Schizophrenia is defined as a mental condition in which a person shows two or more of the symptoms like delusions, hallucinations, disorganised speech, grossly disorganised or catatonic behaviour and negative symptoms, for at least six months. And schizophrenia can easily be mistaken with other similar mental disorders like schizophreniform, schizoaffective disorder and schizophrenia spectrum. Schizophrenia is considered as one of the domain of the schizophrenia spectrum whereas schizoaffective disorder is distinct from schizophrenia because of presence of mood swings between extremes of elevated mood and depression in schizoaffective disorder. Similarly, schizophreniform is distinguished from schizophrenia by the duration of presence of psychotic symptoms or in other words by duration of presence of symptoms being less than 6 months in case of schizophreniform (American Psychiatric Association, 2016).
Schizophrenia can impair social, occupational, educational aspects of a person`s life and also affects the overall health and wellbeing along with self-care. Early diagnosis and management of the illness can help reduce the risk of suicide which has been found to be extremely high in patients with schizophrenia due to inability to cope with the psychological changes affecting the interpersonal, academic or occupational functioning. Furthermore, development of schizophrenia is classified into three stages; prodromal phase, acute phase and continuous symptoms and are manifested by negative symptoms, positive symptoms and resistance to conventional antipsychotic medications, respectively (Katie Evans, Debra Nizette, and Anthony O`Brien, 2016, p.340-365). This essay will discuss about two non-pharmacological treatment options for schizophrenia; Cognitive Behaviour Therapy (CBT) and Family Intervention, with major focus on CBT and less focus on family interventions.
Cognitive Behavioural Therapy (CBT) is gaining more popularity these days because of its advantages over the antipsychotic medications and their associated severe adverse effects such as weight gain, blank mask-like expressions, drooling, akathisia, tardive dyskinesia, etc., which are also found to be the main reason behind medication non- compliance in patients with schizophrenia.CBT acknowledges the fact that recovery from schizophrenia is supported by emphasis on the topic of living well by building personal resources and skills, identifying personal strengths or developing a positive identity. CBT is a scientific approach and has number of assumptions and principles which enforces the overarching principle that cognition causally influence emotional experiences and behaviours (Stefan G. Hofmann, Gordon J.G. Asmundson, 2017). CBT`s principles are believed to have been derived from behavioural, cognitive and social learning theories which are associated with exposure therapy, constructivism theory and social learning theory, respectively. Behavioural interventions like cognitive training have been found effective for individuals with cognitive deficits as a major symptom of schizophrenia and have significantly reduced the impact on their social and occupational functioning (Stefan G. Hofmann, Gordon J.G. Asmundson, 2017). CBT helps to direct thoughts and perception of an individual in such a way that the behaviour of individual is changed to adjust the symptoms of the illness and prevent it from recurring in future. Therefore, CBT helps to develop positive habits which may or can influence their symptoms and drives the focus from illness towards the strengths and abilities of the person, which ultimately helps to improve the self-esteem and goal achievement of recovery. Identifying what are the stressors and triggers of distress or manifestation of symptoms and developing coping mechanism or ways to avoid them is taken as a crucial theme while developing care plan under CBT and person-centred care and recovery-orientated practice are also considered. During a study on CBT-based adherence intervention with a PE-based psychotherapy among patients early in their course of illness, CBT has been found out to be more effective intervention to address medication adherence in early phases of schizophrenia. (Peter Weiden, Douglas Turkington, Jennifer Beaumont, Marko Mihailovic, 2019). Studies conducted on effectiveness of CBT have concluded that CBT is not the first-line treatment for schizophrenia but can contribute as enforcement on prevention of relapse and can produce or magnify the therapeutic implications if used along with other pharmacological treatment options. For example; weight gain due to side effect of antipsychotic medications can be acknowledged and managed properly with development of compensatory behaviours like regular exercise, scheduled eating habit, etc., which ultimately prevents or reduces the risk of medication non-adherence (Carmen Valiente, Regina Espinosa, AlmudenaTruchartAlmudenaTrucharte, JuanNieto, LeticiaMartínez-Prado, 2019).
Despite of these advantages, CBT however has been proven to be ineffective against negative symptoms of schizophrenia such as apathy, lack of emotion, poor or nonexistent social functioning, etc., and CBT has also been found to be not that effective but somehow significant in prevention of transition into psychosis in those patients who were at high risk (Jauhar, S., Laws, K., & McKenna, P. (2019). Therefore the efficacy of CBT in treatment of schizophrenia still remains as a subject that needs further research on.
Similarly, family interventions (FI) are found to be remarkably effective in preventing relapse and reducing the severity of manifestation of symptoms of schizophrenia and therefore recommended along with CBT in current treatment guideline, The National Institute for Clinical Excellence (NICE). (Gillian Haddock, Emily Eisner, Candice Boone , Gabriel Davies, Catherine Coogan, and Christine Barrowclough, 2014). The key elements of FI were found to be common therapeutic factors along with some coping skills training and education on the mental condition and the management option, provided by the family heraist or a mental health nurse or some other relevant health professional and are proved to be effective in promoting cognitive and emotional changes in family members and the carers. Grácio, J., Gonçalves, P. M., & Leff, J. (2018).
Family intervention (FI) may consist of psycho-education, stress reduction, emotional processing, cognitive reappraisal and structures problem solving. A therapeutic relationship is made with the care givers or the family members of the affected one and professionals delivering these interventions must have significant training in delivery of the intervention and must also take into account of the whole family`s preference for either single-family intervention or multi-family group intervention. Caqueo-Urízar, A., Rus-Calafell, M., Urzúa, A., Escudero, J., & Gutiérrez-Maldonado, J. (2015). Although family psycho-educational interventions including FI have an impressive evidence based results in treatment of schizophrenia, challenges in their implementation including the engagement of families is equally prevalent. Understanding the experiences of families regarding the FI is considered as a vital factor that could possibly increase the involvement of family members and help to eradicate the challenges of implementation of FI.
To conclude, anti-psychotic medications are the most preferred and most used treatment of schizophrenia, but because of their side-effects and adherence issues, alternative/supportive methods like CBT and FI are gaining more popularity are being studied and accounted as significant methods in treating schizophrenia.
Reference list
American Psychiatric Association(2016). Diagnostic and Statistical Manual of Mental Disorder. Retrieved from https://dsm.psychiatryonline.org/pb-assets/dsm/update/DSM5Update2016.pdf
Evans, K., Nizette, D., & O’Brien, A. (2016). Psychiatric and mental health nursing. Retrieved from https://ebookcentral.proquest.com
Stefan G. Hofmann, Gordon J.G. Asmundson,The Science of Cognitive Behavioral Therapy,Academic Press,2017,Pages 591-610,ISBN9780128034576,https://doi.org/10.1016/B978-0-12-803457-6.00036-2.(http://www.sciencedirect.com/science/article/pii/B9780128034576000362)
Peter Weiden, Douglas Turkington, Jennifer Beaumont, Marko Mihailovic, S98. Can CBT-based interventions address medication adherence in early phases of schizophrenia? results from a pilot rct comparing a cbt-based vs. psychoeducation-based intervention, Schizophrenia Bulletin, Volume 45, Issue Supplement_2, April 2019, Pages S343–S344, https://doi.org/10.1093/schbul/sbz020.643
Carmen Valiente, Regina Espinosa, AlmudenaTruchartAlmudenaTrucharte, JuanNieto, LeticiaMartínez-Prado, 2019). The challenge of well-being and quality of life: A meta-analysis of psychological interventions in schizophrenia. Schizophrenia Research. https://doi.org/10.1016/j.schres.2019.01.040
Jauhar, S., Laws, K., & McKenna, P. (2019). CBT for schizophrenia: A critical viewpoint. Psychological Medicine, 49(8), 1233-1236. doi:10.1017/S0033291718004166].
Grácio, J., Gonçalves, P. M., & Leff, J. (2018). Key Elements of a Family Intervention for Schizophrenia: A Qualitative Analysis of an RCT. Family Process, 57(1), 100–112. https://doi-org.wallaby.vu.edu.au:4433/10.1111/famp.12271
Caqueo-Urízar, A., Rus-Calafell, M., Urzúa, A., Escudero, J., & Gutiérrez-Maldonado, J. (2015). The role of family therapy in the management of schizophrenia: challenges and solutions. Neuropsychiatric disease and treatment, 11, 145–151. doi:10.2147/NDT.S51331
Haddock, G., Eisner, E., Boone, C., Davies, G., Coogan, C., & Barrowclough, C. (2014). An investigation of the implementation of NICE-recommended CBT interventions for people with schizophrenia. Journal of Mental Health, 23(4), 162–165. https://doi-org.wallaby.vu.edu.au:4433/10.3109/09638237.2013.869571
The aim of this essay is to outline how treatment for schizophrenia has changed quite significantly over time. Schizophrenia is a chronic mental illness which affects the brain (RANZCP, 2019). Approximately 1% of the world’s population has schizophrenia (Mentalhelp.net, 2019). It usually appears around the ages of 16 to 30 years. It affects men and women equally but is usually seen at a younger age in males (Brain & Behaviour Research Foundation, 2019). For a person to be diagnosed with schizophrenia that must have two or more of the following symptoms, with each present for a significant portion of time during a month period (Behavenet.com, 2019). The most common symptoms for schizophrenia are delusions and hallucinations, they are considered positive symptoms as they are not seen in healthy people. Hallucinations are experiences and sensations that others cannot comprehend, they may seem real, urgent and vivid. Roughly 70% of people with schizophrenia experience them. Delusions are known as beliefs that conflict with reality. The other symptoms include disorganized speech, being grossly disorganized and a few negative symptoms. These negative symptoms are called this as it is an “absence as much as a presence”, inexpressive faces, blank looks, lack of interest in the world and other people and an inability to feel pleasure (Psycom.net – Mental Health Treatment Resource Since 1986, 2019). No single cause has been identified, but several factors have been shown to associated with its onset. Some causes included are complications during pregnancy or birth that cause structural damage to the brain, chemical imbalance of dopamine from a person’s genetic predisposition to the Illness, Predisposition to schizophrenia can run in families, stressful incidents and harmful alcohol and other drug use may trigger psychosis in people who are vulnerable to developing schizophrenia (Www1.health.gove.au, 2019).
John Nash was one of the greatest thinkers in mathematics of the 20th century. He was born on June 13th, 1928. While teaching in 2958 the first signs of schizophrenia became noticeable. Nash would disappear for days and then have no explanation on where he was. He would often make visitors stand in front of the door as he believed that there were people following him. Nash continued to work but over the year from 1958-1959 his behaviour became increasingly worse. It got to the point were his wife decided to talk to a psychiatrist, whom acknowledged that Nash had what they called ‘nervous breakdown’. He was offered to stay at hospital because of his illness but he had convinced himself that he was the leader of a world movement for peace that only he knew existed. Nash’s mother visited him and became very disturbed at his mental state. He had a stable upbringing and has a circle of close friends during his adolescence. Having schizophrenia effected his life quite drastically as he was admitted to hospital for quite a significant amount of time. After he was let out of that confinement he still had to go for constant consultations about his illness and how to monitor it. His family around him became very disturbed by his actions. He would often have very weird conversations with his wife and often say meaningless sentences to her (living with Schizophrenia, 2019).
To get an official diagnosis for schizophrenia a person much show two of the following symptoms for a month. Delusions, hallucinations, incoherence of speech and disorganization(Psycom.net – Mental Health Treatment Resource Since 1986, 2019). The tests used now to diagnose schizophrenia are urine or blood tests to rule out any alcohol or drug abuse. They then take tests that can scan your body and brain, for example MRI and CT scans that could help rule out other problems like brain tumours (Cleveland Clinic, 2019). John Nash was diagnosed with paranoid schizophrenia based on his delusions that were persecutory. At this period of time it was a habit to put the blame of his illness on his earlier life. Nash’ first known symptoms of schizophrenia was “paranoia and erratic behaviour. According to his wife, he developed the idea that all men who wore red ties were included in a communist conspiracy against him”. Old treatments such as electric shock and insulin shock were still very popular at this time, but the new antipsychotic drugs brought hope to everyone. The early trials of this drug demonstrated that this could be an option (living with Schizophrenia, 2019).
Treatment for schizophrenia has changed drastically over the year. Most older treatments were aimed at controlling the patients disturbed behaviour rather than trying to cure the illness or alleviate the suffering of the patients. Some countries like Germany took this to drastic measures during the Nazi era and led acts of forced sterilisation and genocide. Another drastic treatment was prefrontal leucotomy which is a removal of the part of the brain that processes emotions, this was very controversial but were performed for more then two decades not just for schizophrenia but also for manic depression and bipolar disorder. Other past treatments include fever therapy, sleep therapy, gas therapy and electroconvulsive (ECT) or electroshock treatment (Psychology Today, 2019). Some past treatments have been developed and are being used now but the general idea of the treatment has been kept. For a person to be admitted to hospital they must have severe symptoms and be in what’s known as a crisis period. This is not because they are putting others in danger but instead themselves. Suicide risk is high and about 10% of people with schizophrenia take their own lives. The hospital creates a plan to help manage them back to normal mental state. Another reason they are admitted to hospital is to try out new medication and the effects that has on them. John Nash was put on chlorpromazine and this began showing lots of improvement in a short time. This was all while in confinement but after around 50 days he began outpatient treatment (living with Schizophrenia, 2019). If this happened before this time period Nash may not have had access to antipsychotic drugs as they would not have been invented yet. He may have even been subject to genocide as that was some form of treatment in the Nazi era.
Schizophrenia requires a lifelong treatment even when symptoms have subsided. Anti-psychotic medications are the most common treatment for schizophrenia. This affects the brain neurotransmitter dopamine (Mayoclinic.org, 2019). This chemical has effects on changing your behaviour, mood and emotions. By using these antipsychotics, it can suppress or prevent you from hallucinations and delusions. Antipsychotics are not always affective and out of every 10 people it is said that 8 people will experience an improvement. The first antipsychotic drug, chlorpromazine first became available in the 1950s and this was the first glimpse of hope for schizophrenia sufferers. It is still one of the most commonly used treatments today, but it also has serious side effects like blurred vision, depression, uncontrollable shaking and muscle stiffness. Since antipsychotic drugs, the use of electroconvulsive therapy has become increasingly rare, but it is a safe and humane way that I highly effective in treatment of sever mood symptoms that do not respond to medication (Sane.org, 2019). ECT is a very effective way to ease symptoms of schizophrenia. Electroconvulsive therapy is done by sending a finely controlled electric current though electrodes for a very short time causing a brief seizure in your brain (WebMD, 2019). During the 1940s and 1950s John Nash may also have been treated with insulin coma treatment. Insulin coma therapy used to be a type of schizophrenia treatment in which patients were repeatedly injected with large doses of insulin to make them go into a coma. It was found that as a patient would come out of the coma it would improve their mental illness. If Nash had been treated with insulin coma therapy, he would have experienced side affects such as restlessness or drowsiness and perspiration. It was also common for seizures to occur before or during the coma. Some of the psychiatrist saw seizures as a good thing and patients were also given electroconvulsive therapy whilst in the coma.
The main changes for treatment of schizophrenia is that newer treatments are aimed at relieving the suffering and curing the illness. Treatments before the 1950 when antipsychotics were invented were to control the disturbed behaviour. Treatments changed from fever therapy being the most common to antipsychotics nowadays being the most common. Fever therapy was carried out by injecting patients with fever producing diseases. Normally injected with malaria and because of this deadly disease about 15% of patients who were treated with fever therapy ended up dying from the procedure (Science Friday, 2019). Although the number of deaths fever therapy was the very first effective treatment that could help alleviate the sever symptoms of mental illnesses. This shows the main changes being that although they could help alleviate the suffering of the patient, they still had 15% of people using fever therapy die, but nowadays with antipsychotic drugs there is no deaths so it is a lot more effective. There is no known cure for schizophrenia but ten years after diagnosis 50% of people with schizophrenia are either recovered or improved to the point that they can work and live on their own. 25% are better but need help from a strong support network to get by. 15% are not better and most of these are in the hospital. 10% see no way out of their pain and die from suicide (WebMD, 2019). Many people that have schizophrenia do return to a more normal lifestyle, have a job and live independently. For someone who has recovered from the severe symptoms of schizophrenia it is important for them to continue medication. Many people stop their medication as it has died down and seem like it has gone away but schizophrenia is a chronic illness and requires ongoing care (BrightQuest Treatment Centers, 2019). For John Nash the possibility for full recovery was a pretty low chance as he stopped his medication without telling anyone. This would have made his condition worse than it started off as. If left untreated, schizophrenia can cause extreme physical, emotional and behavioural problems that affect every area of the person’s life (CenterPointe Hospital, 2019). For John Nash this was clear from 1958-1959 when his behaviour became increasingly worse.
References
Cleveland Clinic. (2019). Schizophrenia Diagnosis and Tests | Cleveland Clinic. [online] Available at: https://my.clevelandclinic.org/health/diseases/4568-schizophrenia/diagnosis-and-tests
Psychology Today. (2019). A Brief History of Schizophrenia. [online] Available at: https://www.psychologytoday.com/au/blog/hide-and-seek/201209/brief-history-schizophrenia
Sane.org. (2019). Antipsychotic medication. [online] Available at: https://www.sane.org/information-stories/facts-and-guides/antipsychotic-medication
BrightQuest Treatment Centers. (2019). Can Schizophrenia Be Cured? – BrightQuest Treatment Centers. [online] Available at: https://www.brightquest.com/schizophrenia/can-schizophrenia-cured/
Www1.health.gov.au. (2019). Department of Health | What causes schizophrenia?. [online] Available at: https://www1.health.gov.au/internet/publications/publishing.nsf/Content/mental-pubs-w-whatschiz-toc~mental-pubs-w-whatschiz-cau
WebMD. (2019). Electroconvulsive Therapy (ECT) and Mental Illness. [online] Available at: https://www.webmd.com/schizophrenia/electroconvulsive-therapy#1
Behavenet.com. (2019). Diagnostic criteria for Schizophrenia | Behavenet. [online] Available at: https://behavenet.com/diagnostic-criteria-schizophrenia
Science Friday. (2019). From Fever Cure to Coma Therapy: Psychiatric Treatments Through Time – Science Friday. [online] Available at: https://www.sciencefriday.com/articles/from-fever-cure-to-coma-therapy-psychiatric-treatments-through-time/
RANZCP. (2019). Schizophrenia. [online] Available at: https://www.yourhealthinmind.org/mental-illnesses-disorders/schizophrenia
Mayoclinic.org. (2019). Schizophrenia – Diagnosis and treatment – Mayo Clinic. [online] Available at: https://www.mayoclinic.org/diseases-conditions/schizophrenia/diagnosis-treatment/drc-20354449
WebMD. (2019). Schizophrenia Prognosis. [online] Available at: https://www.webmd.com/schizophrenia/schizophrenia-outlook
Mentalhelp.net. (2019). Schizophrenia Symptoms, Patterns and Statistics and Patterns. [online] Available at: https://www.mentalhelp.net/schizophrenia/statistics/
Psycom.net – Mental Health Treatment Resource Since 1986. (2019). Schizoprenia: Understanding Hallucinations and Delusions. [online] Available at: https://www.psycom.net/schizophrenia-hallucinations-delusions/
Brain & Behavior Research Foundation. (2019). What Is Schizophrenia? An Overview of Schizophrenia Signs, Symptoms and Treatments. [online] Available at: https://www.bbrfoundation.org/what-is-schizophrenia-signs-symptoms-treatments
Living With Schizophrenia. (2019). John Nash – Living With Schizophrenia. [online] Available at: https://www.livingwithschizophreniauk.org/john-nash/
G protein-coupled receptors majorly include biochemical pathways that facilitate scientist to contribute lots of researches related to diseases such as; psychiatric illnesses-multiple personality,bipolar,depression,anxiety and final example of describing relationship is schizophrenia[1].Recently,clinical examinations of GPCR(G protein-coupled receptors) are exponentially rising up in genetics and pharmacology.As a brief explanation of how GPCR are related to schizophrenia is to provide by neurotransmitters and signaling pathways in brain.An alteration of neurotransmitters and neuropeptide in GPCR involved in frontal cortex, hippocampus, hypothalamus and brainstem that affect cognitive skills and motor developments (Lisa A. Catapona&Husseini K.Manji, 2009).Schizophrenia has immensely impact on human’s social and psychological life.Improvement of a drug which is cohorently related to psychiatric diseases has initiated in 1950 and 1960 by scientists,after all researchers about psychiatry have detected relationships with molecular biology,genetics and pharmocology that define as renewed studies are followed by.Thanks to GPCR,several drugs may affect human brain system that highly responsible of psychiatric diseases then diminish failures of psychiatric diseases in general schizophrenia,this paper aims to explain what GPCR implements to clarify what type of receptors tightly include. Furthermore, ,bipolar disorder ,manic-depressive disorders, dysthymia are referred mood disorders that mainly physiological disorders,nowadays more than 450 millions in 8 billion people suffer from mental illnesses,however schizophrenia can not be categorized in the statement of mood disorders,in the abstract mood disorders are deeply involved. [1],[2]
According to The World Health Organization,mental disorders are assessed that disabling brain cells and relating cells cause psychiatric illnesses,evaluations have demonstated more than 40% people in USA related to it.Also diversity of psychomotor activity procures many subjects that are depressed mood, suicidal ideation, anhedonia-the disability of feeling pleasure- (Lisa A. Catapona&Husseini K.Manji, 2009).Developments of medical drugs such as; antidepressant curing psychiatric illnesses that affect serotonin inhibitors, attaining hormones; norepinephrine, dopamine and serotonin. [3]
Schizophrenia is a disorder affecting nervous system of a human during the lifetime,occures roundly 1% of human population that results in same percent both woman and man (Lisa A. Catapona&Husseini K.Manji, 2009). As reported in studies about how criteria affects the probability of schizophrenia is related to genetics that human who already has relationship between family relevants possibly more correlates than human in normal population.Symptoms of schizophrenia diagnosed by psychiatrists using some tests as symptoms are readily recognized,In the event; delusions, hallucination and avolition have impact on patients suffering from schizophrenia.Now that,newly found drugs decreasing the effect of schizophrenia assume positive subject about drugs which discover through GPCR.
Dopamine Receptors
Dopamine is major hormone what exactly cause schizophrenia explaining that dopamine is correlated to motor activity,balancing the pleasure level of human,motivation of human.If all these great matters disturbed, schizophrenia,manic depressive disorder and depression readily make human brain’s system exist less effective. [4]The dopamine hypothesis of schizophrenia clarified that in researches of psychiatry,this hypothesis provided lots of subject which is in schizophrenia and other disorders. [5]The Dopamine Hypothesis 1 is explained there,also version two and three occur in drugs found for schizophrenia that inevitable ideas have discovered as treatments of diseases have been insufficient.Moreover, antipsychotic medications are accessed for treating schizophrenia.
Dopamine D2 Receptors are inhibited by variation of hyperactivity of limbic dopaminergic transmission that facilitates motor activity,signaling pathways,cause dopamine to release in brain which is exactly similar symptoms of schizophrenia.Numerous researches are indicated that alteration of dopamine receptors-D2 receptors procure beginning of psychiatric disorders-schizophrenia.According to some reports,D2 receptors can not be distinguished the treatments of all patients who suffer from schizophrenia,almost 70% replents of D2 receptors enable patients to be treat by antipsychotic medications (Lisa A. Catapona&Husseini K.Manji, 2009). [7]
Dopamine D3 Receptors
The D3 receptor polymorphism have been adjusted by lots of studies about schizophrenia that are Ser9Gly which is extensively most known polymorphism recognized by schizophrenia treatments.However all examination of D3 receptor polymorphism- Ser9Gly has not been correlated to responses which enable scientist to ascertain of repling drug cure.[9] Many D3 receptors have been encountered similar results that could not be distinguish any tie between D3 receptors and schizophrenia. [10] [13],[14]
Polymorphisms of Dopamine D2 Receptors
Widespreadly,Dopamine D2 receptors have several polymorphisms that focus on Ser311Cys polymorphism, 141C Ins/Del polymorphism which is located in D2 receptor’s promoter region. [6]In addition to necessary polymorphisms that generally used for recent polymorphisms of schizophrenia, C957T,His313 and the Taq1A polymorphisms are affilitated.Plenty of analysis spanning that relate to major D2 receptors has identified for schizophrenia’s treatment. [8], [11], [12]
Serotonergic Receptors
G protein-coupled receptors has intercorporated to serotonergic receptors that enable debate about how serotonergic receptors are effectively impact on schizophrenia,several medications has applied patients suffering from schizophrenia in order to obtain any responses of how schizophrenia may be diminished through drugs applying. 5HT1A and 5HT2A receptors that can be prioritized in GPCR’ serotonergic receptors. . [15] Moreover,some studies are inferred that 5HT1A operates with dopamine antagonists (Lisa A. Catapona&Husseini K.Manji, 2009).
McCune-Albright Syndrome
McCune-Albright Syndrome is a very scarce genetic disorder that affects only a small proportion of the population. It mainly targets skin, endocrine system and bones. It is also associated with fibrous dysplasia, accompanied by two additional symptoms; defects in skin pigmentation and deficiencies in the regulation of some hormonal glands which later disturbs the growth rate, sexual development and some certain metabolic activities. Fibrous Dysplasia (FD), is a condition resulting from the occurrence of aberrant scar-like fibrous tissue in the bones in any area through the body.[1] The occurrence of fibrous lesions weakens the bones and make them prone to fractures and also it may cause chronic pain.[1] The underlying reason of MAS is a random genetic mutation that occurs in the GNAS1 gene and its reason is still unknown.[2] However, it’s known that MAS is not a genetically inherited mutation indicating that it is a post-zygotic somatic mutation.[2] Even though this syndrome has a wide range of symptoms, some of them may vary from individual to individual and in different scales of severity, since MAS is a syndrome that shows a mosaic genetic pattern.
To be more specific, FD/MSA Syndrome is resulted from a mutation in the GNAS gene which actually codes for the cAMP pathway-associated G-protein, GSα, that occurs in the early embryonic stages of the somatic cells.[3] Therefore, it is not inherited. On the other hand, it does not necessarily mean that the whole set of an affected individual’s GNAS1 gene products are mutated, rather it displays a “mosaic pattern” meaning that the affected individuals encounter both normal and abnormal copies of the gene. [2] Although it is not known what triggers this mutation yet, studies have shown that it occurs sporadically in a population.[3] Additionally, the severity of the syndrome is dependent on the ratio of normal cells to mutant ones.[3] Due to GSα’s biological function, as ubiquitin signaling molecule, even a slight change in its property may eventually cause alterations in the related tissues; bones, skin, endocrinal glands, digestive system and so on. The GNAS1 gene is located on the chromosome “20q13.2” and it normally codes for the G-protein.[2] In MAS, mutations in the Arg201Cys or Arg201His residues result in overproduction of cAMP due to continuous activation of the GSα. [4] Eventually, the excessive amounts of cAMP derives the formation of the symptoms as the outcome. [4] Furthermore, the rate of those symptoms can be distinctive upon individuals by either displaying the major ones or may not show any symptom at all. As mentioned before, polyostotic fibrous dysplasia is one of the major symptoms directly associated with MAS. It generally affects more than one skeletal sites through the body while generally showing a unilateral pattern.[3] Additionally, FD may cause neurological dysfunctions that result in the loss of hearing and vision due to the disruption of of optic and auditory nerves. [2] There are also some skin-related symptoms like “café-au lait” spots, which are resulted from a deficiency in pigmentation. Those spots are abnormally expressed and restricted on one side, like it is divided by a midline, of the body and the accumulation of them my increase with ageing.[5] The last major class of symptoms is endocrinal glands. In a healthy individual, endocrine system is responsible from the regulation of growth, sexual development and some metabolic activities. MAS usually causes an early puberty (gonadotropin independent precocious puberty), which yields in the development of sexual characteristics at very young ages. [2] Studies have confirmed that the females have 50% more tendency for precocious puberty. [2]
The diagnosis may be detected at birth depending on the severity of the visible abnormal symptoms like “café-au lait” spots. On the contrary, in most of the cases the diagnosis is not attained until the precocious puberty occurs at the late phases of infancy. Diagnosis can be performed based on physical symptoms or by the use of clinical tests like x-ray studies or blood tests.[2] The treatment procedure is individualized and shaped by the symptoms of the patient. The treatment procedure usually consists of the combination of therapeutics, psychological support, the efforts of dermatologists, orthopedists and endocrinologists.[2]
GPCR Drug Discovery
As mentioned before, GPCRs are signal transmitters and they are located in the plasma membrane of the cell. Their ability to interact with different signaling elements in a broad range including proteins, peptides, hormones, neurotransmitters, lipids even smaller elements like protons; makes them unique proteins, and around 800 of GPCRs are encoded in the human genome.[1] Beside that, activated G proteins are able to influence high amount of secondary messengers. It indicates they have a major impact in the cell regulation. [2]
Five protein families are targeted by drugs: GPCRs, kinases, nuclear hormone receptors, ion channels and proteases.[3] GPCR targeted drugs constitute major percentage of the therapeutic drug industry. They perceive 27% of the global market of therapeutic drugs and 34% of the total drugs -statistical data is given in 2017- approved by FDA. Approved drugs target ~100 different GPCRs. Furthermore ~300 new unapproved drugs are being tested in clinics, that target other GPCRs.[4] GPCRs vary under sub-groups depending on several features [5] ; type of the signaling molecules, homology and receptor families.[4] Mutations in GPCRs drive organisms to have numerous diseases considering to this diversity, which also leads to production and designment of different therapeutic drugs.[4] According to Figure 1, GPCR agents are mostly targeted for hypertension, allergy, schizophrenia and depression by approved drugs. In contrast diabetes, Alzheimer, asthma, Parkinson disease and obesity are the rising diseases that account for drugs in trial. It shows that GPCR based studies have a large potential to eliminate many type of diseases.[1]
Structure of GPCRs are highly convenient for designing drugs, the reason behind is the orthosteric binding site. The site is located on the extracellular side of the GPCR and it has a deep cleft. Features -shape, size and amino acid structure- of orthosteric site enable small synthetic molecules to bind with GPCR.[6] Small synthetic molecules function in two ways, by inhibiting the function of GPCR (which is mentioned as antagonists) or by triggering the activation of GPCR (which is also mentioned as agonists). Development of drug does not require additional bioengineering procedure to cross plasma membrane, since GPCRs are located in the plasma membrane of cells. Furthermore dynamic architecture of GPCR make them suitable drug targets.[1] If agonists are not present, GPCRs still have a basal activity to activate their functioning, yet activated GPCRs increase in the presence of. [1]
Additionally, GPCR targeted drugs are developed more likely for the popular diseases (allergy, hypertension, schizophrenia, depression and obesity) within the society and for the emerging novel diseases (multiple sclerosis, hypocalcaemia and smoking cessation).[4] As stated before GPCRs can be targeted for majority of the diseases and they are important elements of cells and biochemistry.
Each year, almost 44 million Americans experience a mental disorder. In fact, mental illnesses are among the most common conditions affecting health today. The good news is that most people who have mental illnesses, even serious ones, can lead productive lives with proper treatment. Mental illnesses are some of the most misunderstood afflictions in today’s society. Too many people think of mental illness as a “weakness.” These are true illnesses and brain diseases. Mental illnesses are illnesses that affect the way a person thinks, acts, and feels. Like most illnesses, they have included biological, psychological, and environmental roots. The more severe mental illnesses are primarily diseases of the brain that cause distorted thinking, feelings, or behavior.
What is schizophrenia? Defining this illness is not easy. Schizophrenia is a extremely complex and serious mental illness. The illness interferes with the mental functioning of a person and makes the people who suffer from it at some point become out of touch with reality. This is an intricate disorder and psychologists are still not one hundred percent sure about this illness, there are still many things they need and want to figure out. Although there is no exact definition scholars and other knowledgeable people learn and still research this topic. “What We Now Know About Schizophrenia” written by Patrick O’Brien (1978) gives us the following definition of schizophrenia using the Diagnostic and Statistical Manual of Mental Disorders,
Although a very scientific description, O’Brien tells us exactly what the condition consists of and even gives us a frame of time that the illness has to be present in order to be diagnosed.
The essential features of this group of disorders are: disorganization of a previous level of functioning, symptoms involving multiple psychological processes; the presence of certain psychotic features during the active phase of the illness; the absence of a full affective syndrome concurrent with or developing prior to the active phase of the illness, a tendency towards chronicity, and the disturbance is not explainable by any of the Organic Mental Disorders. … always involves at least one of the following: delusions, hallucinations, or certain characteristic types of thought disorder. No single clinical feature is unique to the condition or evident in every case or at every phase of the illness, except that by definition the diagnosis is not made unless the period of illness has persisted for at least six months (pgs. 33, 34).
There are five different subtypes of schizophrenia. The first one is paranoid schizophrenia in this type the person is very suspicious of others and has both delusions and hallucinations. Disorganized schizophrenia is the second type, which involves emotions, and moods that are not fitting to the situation at hand and verbal mumble or jumbled speech pattern. A case where the person is negative, isolated, and deeply withdrawn is known as catatonic schizophrenia. In residual schizophrenia the person does not currently have delusions, hallucinations, or speech patterns but they are lacking motivation in day-to-day living and interest in life. The last type is undifferentiated schizophrenia. This person meets the criteria for the general description of schizophrenia but they do not stand out in any of the other above subtypes of schizophrenia.
The main causes dealing with the condition of schizophrenia are environmental factors, bio chemical factors, genetic factors, and stressful events. Genetics are a strong influence on whether a family member might have this illness however it is absolutely not a decisive factor. “Individuals with a first-degree relative (parent or sibling) who has schizophrenia have a 10 percent chance of developing the disorder, as opposed to the 1 percent chance of the general population.” (Smith & Segal n.d. para 25) As said by O’Brien (1978) in the novel “What We Now Know About Schizophrenia” he tells us how “the role heredity plays…probably determines a predisposition to certain extraordinary ways of reacting and feeling. Why one person becomes psychotic and another doesn’t isn’t known at the present.” (p. 169) Although it is not one hundred percent proven today it is an aspect that is not be overlooked. Environmental factors include prenatal or infantile exposure to a viral infection, loss or separation from parents at an early age, and physical or sexual abuse when in childhood. Genetics along with environmental factors have “important implications for designing drugs that can act as environmental modulators and/or for identifying potentially preventive measures that can be undertaken.”(Picker 2005, p. 3 para. 3) Death of a loved one, growing up or living in poverty, frequent changes in jobs, schools, or relationships, are stressful factors that can increase the onset or affect the onset of the illness. Chemical imbalances in the brain play an important role as the cause of schizophrenia. The brain neurotransmitters either have a functioning problem in which they send too many or too little chemical messages. To identify a cause of schizophrenia is very tricky as described by Patrick O’Brien (1978) when he says “there are numerous competing hypotheses as to the cause of the psychoses of unknown origin…all of these theories are at present speculations which may or may not turn out to be implicated in the schizophrenic-type psychotic disorders in some individuals.”(p. 187)
Symptoms may vary in all the different subtypes as explained above but nevertheless there are two different kinds of symptoms in schizophrenia, positive or negative. Signs of this disease can be debilitating however they are usually treatable. There are four main positive symptoms disturbances of thought, hallucinations, illusions, and delusions. A delusion is an idea that is clearly and obviously untrue however an idea that becomes strong and firmly held in a schizophrenic’s brain. These bizarre fantasies can be delusions of persecution, reference, grandeur, or control. A person who is having a delusion may believe they are a person of high authority or royalty or in a high job position. A common delusion is also when a person believes someone is spying on or tracking you, or thinking aliens are invading or attacking. Hallucinations are misconceptions or exaggerations of sounds or sensations conceived as real. Auditory hallucinations are the most common. This is when someone perceives their inner voice or a voice inside their head as coming from an outside source. Experiences of heightened awareness are known as illusions. This includes thinking things are closer than they appear or hearing a familiar voice and it seems unrecognizable. A person whose speech is jumbled, one who changes the subject rapidly without reason, or cannot connect thought logically or put sentences together coherently has disturbances within their thoughts. Disturbances in thought can furthermore include inability to concentrate and someone who is easily distracted. “In contrast to the positive symptoms which refer to abnormal behaviors that are present, negative symptoms of schizophrenia refer to normal behaviors that are absent.”(Smith & Segal n.d. para 16) Negative Symptoms include lack of some or all of the following: expression, eye contact, enthusiasm or determination, motion and speech, self-care, or conversation tactics.
Schizophrenia is an incurable illness. However treatment can be very effective and helpful. It can be made so people with this disorder can lead high-functioning, normal lives. As Patrick O’Brien (1978) explains in his book “since most of the time intensive community support is not available, hospitalization then becomes the most helpful alternative” (p.244) in treating schizophrenia. Hospitals are usually used for immediate intervention. The most effective treatment involves a combination of medication, rehabilitation, and treatment of any other psychological problems. Psychotherapy can be a good start to treatment. This can help patients set small goals, lead to a good medication plan, and help make sure they are maintaining their drugs. Family therapy sessions are proven to reduce relapse rates. Medication works to fix the chemical imbalance in the brain. The drugs used in psychiatric treatment are minor tranquilizers, antidepressants, the antimanic drug lithium, and major tranquilizers.
Schizophrenia is a chronic mental illness and has an immense impact on individuals themselves and even furthermore their families. This can be a tragic disorder however when taken care of and treated properly people who have it can be fully functional. It takes great patience, understanding, and support to deal with this illness as well as to be involved with it and I commend anyone who lives with it themselves or has a family member affected by it.
References
Chiko, B. (n.d.). An Introduction to Schizophrenia . Schizophrenia Information. Retrieved November 18, 2010, from www.schizophrenia.com/ami/index.html
O’Brien, P. (1978). The Disordered Mind; What We Know About Schizophrenia. Englewood Cliffs: Prentice-Hall, Inc..
Picker, J.. (2005, August 1). The Role of Genetic and Environmental Factors in the Development of Schizophrenia – Psychiatric Times. Psychiatric Times. Retrieved November18,2010,fromhttp://www.psychiatrictimes.com/schizophrenia/content/article/10168/52516
Smith, M., & Segal, R. (n.d.). Understanding Schizophrenia: Signs, Symptoms, Causes, and Effects. Helpguide.org: Understand, Prevent and Resolve Life’s Challenges. RetrievedNovember18,2010,fromhttp://helpguide.org/mental/schizophrenia_symptom.htm
What is Schizophrenia?-An Illness Not Understood. (n.d.). mental-health-matters.com. Retrieved November 18, 2010, frommentalhealthmatters.com/schizophrenia/408-what-is-schizophrenia
Many biological necessities that human take, such as eating foods or interacting with others can vary from one culture to another. Asian people mainly consume rice while western people consume wheat and they both are totally acceptable. Interaction with others is more diverse: Every culture has a unique style of showing their emotions. However, it seems sleeping has a small—perhaps no—difference among many religion, cultures or nations that exist in this world. As sleeping is universal and uniform action of human, its function and roles are crucial to the life of humanity.
It is obvious that without sleeping, humans feel “lower affective well-being,” such as the feeling tired or stressed. On the other hand, people who sleep well have a tendency to show positive well-being state (Wrzus et al, 2014). Then, up to what extent, does sleeping affect our mental health? And how well do people with various mental illnesses sleep compared to the normal people?
Schizophrenia is one of the most well known mental illnesses that current people face. According to the American Psychiatric Association, schizophrenia can be defined as follows: a chronic brain disorder that can include delusion, hallucination, trouble with thinking and concentration (Yao et al, 2000). As schizophrenia is a rising illness on which research began decades ago, there are no medications that can fully recover it. Therefore it is necessary to understand the new illness from various approaches, such as genetics, behavior research or psychological approach.
Then, does a bad sleep quality result in schizophrenia? Or does schizophrenia cause malfunctioning sleep? Background Information about Sleep Disorder and Schizophrenic Symptoms
Unlike depression, schizophrenia is categorized as psychosis, more than neurosis (such as ADHD). This indicates that schizophrenia probably is occurred for many reasons, such as biochemical, physiological and psychological problems. Fortunately, currently, one of the most well-known causes of schizophrenia is the excess secretion of dopamine (Feinberg, 1982). Patients of schizophrenia showed increased numbers of neurotransmitter level, but it is yet to be determined why dopamine has increased. Still, current medical cures that can be given to the patients are dopamine-inhibiting doses. Scientists have found that abnormal secretion and distribution of neurotransmitters, for example, dopamine, serotonin, and glutamate causes a decrease in brain cortex from the brains of patients with schizophrenia. However, this cure can only be effective when the administration has occurred in the early stage of illness. If the duration of untreated psychosis increases, it becomes significantly harder to rehabilitate.
This research will investigate the relationship between the quality of sleep and the symptoms of schizophrenia. However, sleep quality is a complex phenomenon that is difficult to define and measure objectively (Buysse et al, 1988). Daily usage of the word “sleep quality” generally includes qualitative aspects of sleep, such as depth of sleep and how restful the sleep is. Therefore it is necessary to quantify them by using the following variables: sleep duration, sleep latency or number of arousals (Buysse et al, 1988).
Pittsburgh Sleep Quality Index, PSQI, one of the well-known sleep quality indexes, is developed by Buysse in 1988. It assesses the quality of sleep and discriminates “good” sleepers and “poor” sleepers by (Buysse et al, 1988). It consists of 19 questionnaires and each is weighed on 0-3 scales. The measures show a strong correlation with related sleep constructs (Mollayeva et al, 2016).
Discussions about Sleep and Schizophrenia Relationship
In order to investigate how patients with schizophrenia sleep and how they are affected by the sleep they have, this research incorporates many past data.
Sleep disturbances, such as long sleep latency and high total awake time, which destroys the circadian rhythm, are identified to be one of the major contributing factors for the development of psychosis in young people, including schizophrenia (Ruhrmann et al, 2010).
So, do malfunctioning activities of sleep of schizophrenic patients cause the symptoms of schizophrenia, or the opposite causation and result relationship is occurring?
Sleep Disorder and Circadian Rhythm
About 80% of the patients with schizophrenia experience sleep disorder that disrupts their circadian rhythm, yet very little is known about the relationship between sleep and the circadian rhythm (Wulff et al, 2012). Compared to people without schizophrenia who suffer sleep disorder, significant circadian rhythm disruptions occurred in the patients. Out of 20 patients researched, half of them showed misalignment of melatonin cycles and irregular sleep epochs (Wulff et al, 2012).
Also, another research about sleep quality of 321 patients of schizophrenia, precisely patients who were diagnosed as schizophrenia but never received treatment, comparatively showed negative results of sleep compared to 331 healthy subjects (Chouinard et al, 2004). According to the research, the meta-analysis Chouinard and the researchers investigated about the treated patients with schizophrenia had following disorders with comparison to the healthy subjects: Increased sleep latency, decreased total sleep time and decreased sleep efficiency (using sleep efficiency index, SEI). On the other hand, however, only the group that is consisted of untreated patients with schizophrenia showed high total awake time (Chouinard et al, 2004). These results conclude that the symptoms related to sleep quality of schizophrenia patients are not necessarily the consequence of neuroleptic treatments, meaning that the sleep disturbances that the patients’ experience are an intrinsic feature of schizophrenia.
Symptoms of Schizophrenia Due to the Absence and Disturbance of Sleep
It is well known by many of past researches that the functions of sleep are stabilization, enhancement, integration, recognition, and processing the recent memories. While memory consists of many different features such as perceptual, verbal and emotional memories, the processes enhance the durability, flexibility, and automation of these memories (Stickgold et al, 2007).
While sleep of healthy people can perform active processing of memories, the schizophrenia patients’ sleep is malfunctioning in terms of memory processing: A group of medicated patients with schizophrenia showed reduced recall of the Rey-Osterrieth Complex Figure, a test of memory, along with reduced sleep latency and efficiency (Goder et al, 2004). Also, Goder found that slow wave activity of sleep positively correlated with both better performances of neuropsychological measures in healthy subjects. In contrast, treated schizophrenia patients, who initially showed reduced slow wave activity, showed relatively few significant correlations with slow wave activity. These results concluded that the absence of sleep for patients with schizophrenia definitely affects the brain function, especially the process of memory. Furthermore, the research suggests that the deficits the patients of schizophrenia experience is due to the deactivation of memory consolidation processes that occurs during sleep rather than the amount, latency or distribution sleep hours (Manoach et al, 2004).
Although past data have been considering poor sleeping quality as the main reason for having the negative symptoms of schizophrenia, the next researches will view the relationship between sleeping and the symptoms from the other side.
Opposite Cases: Symptoms of Schizophrenia That Causes Sleep disorder
Hallucination, one of the symptoms that people with schizophrenia suffer, including both visual and auditory, is considered to be a symptom that affects sleep disorder (Wilson et al, 2012). Patients with psychosis may get little daylight because they tend to keep curtains closed during the day because of a perception of threat from outside and finding general stimulation they receive in the day time may be distressing therefore prefer to be awake in quieter periods (Wilson et al, 2012). Many researchers argue that the effects of medication or deprivation of sleep cause symptoms of schizophrenia. However, there may be a possibility of the opposite relationship, the symptoms of schizophrenia consequently cause sleep deprivation.
From this research, another variable, environment that patients live, can actually manipulate the quality of sleep. Wilson suggests that it is important to take the environment of healthy subjects and schizophrenic patients into account when evaluating sleep and the symptoms of schizophrenia relationship.
Qualitative Category of Sleep Disorder: Nightmares and Schizophrenia
Although nightmare is extremely difficult to quantify, it definitely is one of the important categories that indicate the status of human health. Although the cause of nightmare remains unclear, many past data assume that stress is the main cause among many other causes (Picchinoi et al, 2002).
According to Levin and Raulin in 1991, the word “nightmare” can be defined as “a scary dream that awakens the dreamer from sleep.” Based on the definition, Levin in 1998, conducts research to clarify the relationship between nightmare and schizophrenia. Levin assessed participants with the following categories: physical anhedonia, perceptual aberration, thought disorder, magical ideation, ambivalence, social fear, and somatic symptoms. Also, the participants completed BDI, STAI, and SD, the schizotypy scales to sort themselves to different groups based on the scales (Levin, 1998). Consequently, Levin concluded that frequent nightmare subjects were observed to have a higher possibility of having schizophrenia. Also, the frequent nightmare subjects had a significantly higher measure of trait anxiety (Levin, 1998).
This research indicates that the people with frequent nightmares are associated with “cognitive slippage and perceptual distortion, and consequently may reflect a phenotype of an underlying vulnerability trait for schizotypy” (Levin, 1998).
Another research of the relationship between nightmare and schizophrenia, conducted in 1987 by Hartmann, suggest that frequent nightmare subjects scored higher on Minnesota Multiphasic Personality Inventory test (MMPI) compared to control group of the observation, that rarely encounter nightmares. According to the interview Hartmann conducted, the frequent nightmare sufferers can be explained as “sensitive and showed schizophrenic spectrums but also showed artistic and creative tendencies and interests, in contrast to the other groups” (Hartmann et al, 1987).
Summary
This research paper investigated the relationship between quality of sleep and the symptoms of schizophrenia from various perspectives. Although many current researchers have tendency to view malfunctioning sleeping, such as long sleep latency, short sleep duration or absence of REM sleep as causes of the negative symptoms of schizophrenia. However, there are still numerous studies that have found low sleep quality as a consequence of schizophrenic symptoms.
In general, the fact that sleeping and schizophrenia are related in some kind of form is apparent (although it is yet to be known that which one is suitable for cause of the other). Many researchers that consider malfunctioning sleep as the cause of schizophrenia tried to justify that people with low sleep quality have a higher possibility of having schizophrenia. Therefore many experiments of this form investigated the risk of schizophrenia in healthy subjects.
On the other hand, researches that have tried to view sleep malfunctioning as symptoms of schizophrenia actively investigated patients with schizophrenia and their environment. Through these researches, sleeping disorders of schizophrenia were known to be influenced by the environment that the patients were in, such as the irregular rhythm of life pattern (circadian rhythm disruptions), which eventually damages the quality of sleep.
Conclusion and Discussion of limitations
The main goal for this research is to view the relationship between sleep quality and schizophrenia from various perspectives and determine which one serves as a cause for the other. Initially, this research predicted that sleep disorder causes schizophrenia rather than schizophrenia causing sleep disorder. To conclude, this cannot be determined, but it is evident that two-variable relationship is very weak to justify: there are many variables such as environment and nightmares, which need to be considered when discussing sleep and schizophrenia. Also, this research fails to investigate the variables as quantitative variables as sleeping and symptoms of schizophrenia are very subjective and can appear in various forms. Especially, a nightmare is hardly observable, and the researches that are related to nightmare only sort levels of nightmares in subjective forms. This absence of definite nightmare measures (and any other qualitative sleeping categories, especially dreams) makes very hard to compare and contrast to other researches.
Overall, it is evident that low sleep quality can lead to schizophrenia, but its specific measures and numbers remain unknown. (1952 words)
References
Chouinard, S., Poulin, J., Stip, E., & Godbout, R. (2004). Sleep in untreated patients with schizophrenia- a meta-analysis. Schizophrenia bulletin, 30(4), 957-967.
Doi, Y., Minowa, M., Uchiyama, M., Okawa, M., Kim, K., Shibui, K., & Kamei, Y. (2000). Psychometric assessment of subjective sleep quality using the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J) in psychiatric disordered and control subjects. Psychiatry research, 97(2-3), 165-172.
Feinberg, I. (1982). Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence?. Journal of psychiatric research, 17(4), 319- 334.
Goder, R., Boigs, M., Braun, S., Friege, L., Fritzer, G., Aldenhoff, J. B., and Hinze-Selch, D. (2004). Impairment of visuospatial memory is associated with decreased slow wave sleep in schizophrenia. J. Psychiatr. Res. 38, 591–599.
Hartmann, E., Russ, D., Oldfield, M., Sivan, I., & Cooper, S. (1987). Who has nightmares?: The personality of the lifelong nightmare sufferer. Archives of General Psychiatry, 44(1), 49-56.
Levin, R. (1998). Nightmares and schizotypy. Psychiatry, 61(3), 206-216.
LEVIN, R., and RAULIN, M. Preliminary evidence for the proposed relationship between frequent nightmares and schizotypal symptomatology. Journal of Personality Disorders (1991) 5:8-14. LEVIN, R., and RAULIN, M. A closer examination of the relationship between frequent nightmares and self-reported schizotypy in a nonclinical population. Manuscript submitted for publication, 1997.
Manoach, D. S., Cain, M. S., Vangel, M. G., Khurana, A., Goff, D. C., and Stickgold, R. (2004). A failure of sleep-dependent procedural learning in chronic, medicated schizophrenia. Biol. Psychiatry 56, 951–956.
Mollayeva, T., Thurairajah, P., Burton, K., Mollayeva, S., Shapiro, C. M., & Colantonio, A. (2016). The Pittsburgh sleep quality index as a screening tool for sleep dysfunction in clinical and non-clinical samples: A systematic review and meta-analysis. Sleep Medicine Reviews, 25, 52-73.
Peigneux, P. , Laureys, S. , Delbeuck, X. & Maquet, P. (2001). Sleeping brain, learning brain. The role of sleep for memory systems. Neuroreport, 12(18), A111-A124.
Picchioni, D., Goeltzenleucher, B., Green, D. N., Convento, M. J., Crittenden, R., Hallgren, M., & Hicks, R. A. (2002). Nightmares as a coping mechanism for stress. Dreaming, 12(3), 155-169.
Ruhrmann S, Schultze-Lutter F, Salokangas RKR, Heinimaa M, Linszen D, Dingemans P, et al. Prediction of psychosis in adolescents and young adults at high risk: results from the prospective European prediction of psychosis study. Arch Gen Psychiatry 2010; 67: 241–51.
Stickgold, R., and Walker, M. P. (2007). Sleep-dependent memory consolidation and reconsolidation. Sleep Med. 8, 331–343.
Wilson, S., & Argyropoulos, S. (2012). Sleep in schizophrenia: time for closer attention. The British Journal of Psychiatry, 200(4), 273-274.
Wrzus, C., Wagner, G. G., & Riediger, M. (2014). Feeling good when sleeping in? Day-to-day associations between sleep duration and affective well-being differ from youth to old age. Emotion, 14(3), 624.
Wulff, K., Dijk, D. J., Middleton, B., Foster, R. G., & Joyce, E. M. (2012). Sleep and circadian rhythm disruption in schizophrenia. The British Journal of Psychiatry, 200(4), 308-316
Yao, J. K., Leonard, S., & Reddy, R. D. (2000). Membrane phospholipid abnormalities in postmortem brains from schizophrenic patients. Schizophrenia research, 42(1), 7-17.
Schizophrenia is a severe form of psychological disorder and is considered to be a psychosis. People with schizophrenia are out of touch with reality and tend to not understand what is going on around them and how to interact. People with schizophrenia generally have a hard time interacting with others as their diagnosis gives them severe impairments in thinking; which may cause hallucinations where they hear or see things that are not present. Some patients may experience delusions or irrational belief systems. Often the delusions or hallucinations a patient may experience will strengthen and support one another. Schizophrenia affects 1 percent worldwide and has a strong genetic basis. It is found that stressors may factor in on the onset of the disorder, some being severe poverty and poor parenting could be considered triggers. One-third of people with schizophrenia will attempt suicide and 10 percent will eventually succeed.
Ali Bani-Fatemi took it upon herself to question the connection between childhood trauma and suicide attempt among people diagnosed with schizophrenia. Bani-Fatemi, states in her journal that “Suicide runs in families, with adoption and twin studies indicating that the familial transmission can be attributed to genetic factors. Genetic factors determine a large proportion of the risk for schizophrenia as well, with up to 81% heritability being suggested” (Bani-Fatemi, 169). Genetically, it is found that 10-15 percent of first-degree relatives to a schizophrenic patient will also develop schizophrenia. In fraternal twins if one has schizophrenia, the other has a 15 percent risk of also developing the disorder. In identical twins, if one has schizophrenia, the other’s risk of the disorder increases to 50 percent. As suicide is accountable for 5 percent of death among the schizophrenic, they hold a higher risk of attempting suicide. The hypothesis reached for the study states how schizophrenia risk loci is more delicate to environmental insults which may influence suicidal actions and childhood trauma increases the chances of suicide.
Previous studies explain how trauma is associated in suicide attempt among the schizophrenic. “Among early life adversities, childhood trauma has been associated with suicide attempt in schizophrenia. In our previous study, we found that childhood maltreatment increases the risk for suicide attempt in psychosis when controlling for confounding factors” (Bani-Fatemi, 170). More studies found that patients with childhood trauma have had more severe clinical and psychotic symptoms compared to those with low childhood trauma. It was also found that patients with prior suicide attempts had higher sexual abuse than those without suicide attempts. Patients with high suicidal risk had higher physical neglect than those without suicidal risk. Sexual abuse predicted lifetime suicide attempts, and physical neglect and depression predicted suicidal ideation.
The goal of the study was to determine if there were any connections between polygenic scores with childhood trauma that could lead to suicide attempt within schizophrenics. 224 participants were recruited for the study from the Centre for Addiction and Mental Health, all participants being able to provide written consent. Participants were in the age range 18 to 75 years old, all with white caucasian ancestry. Out of the 224 participants, 93 were suicide attempters and 131 were non-suicide attempters. A suicide attempter was defined as anyone who attempted suicide at least once in his/her lifetime, as assessed by the Columbia Suicide Severity Rating Scale which allows to clearly differentiate between a suicide attempt versus an aborted or interrupted attempt.
Data that was taken from each participant was their sex, age, age of onset, and duration of illness. The Childhood Trauma Questionnaire (CTQ) was given to the participants “to measure the presence and severity of trauma and neglect before the age of 18 years. The CTQ is a self-report inventory that provides a brief and reliable history of abuse and neglect. The questionnaire measures the severity of physical, emotional and sexual abuse, as well as emotional and physical neglect” (Bani-Fatemi, 170). This background knowledge is necessary in order to calculate statistics and get results from the data.
The results from the tests showed that in 131 non-attempters and 93 suicide attempters, “The mean unweighted score in suicide attempters was 95.26(6.47) and in non-attempters was 95.42(6.60) while the mean weighted score in suicide attempters was 0.910 (0.050) and in non-attempters was 0.909(0.048). The maximum difference between the cumulative distributions of unweighted polygenic scores D was 0.1207 with a corresponding P > .05. Furthermore, there was no significant difference in weighted polygenic score distribution between suicide attempters and non-attempters (p > .05)” (Bani-Fatemi, 171). Seeing no significant differences, Bani-Fatemi performed subsidiary analysis due to the extensive data she collected.
While comparing different components of data the results showed that “In our samples, there were 45 multiple attempters (subjects who attempted suicide twice or more lifetime) and 45 non-attempters who never showed suicidal behavior and experienced suicide ideation lifetime. When comparing the weighted scores in non-attempters/non-ideators and multiple attempters we found no difference in polygenic weighted scores and in unweighted polygenic scores D = 0.133 with a corresponding P of: 0.790” (Bani-Fatemi, 171). The differences in unweighted scores from the 45 multiple attempts to non-attempters is slightly higher than the first results of data.
Continuing comparing different levels of suicidal schizophrenics to non-attempters the data showed “There were 31 subjects who committed an attempt that produced high medical damage (3 or 4 medical damage scores at the C-SSRS when considering the most serious attempt lifetime). We performed the comparison with the 45 non-suicide attempters/non ideators considering only the 31 high medical damage attempters. When comparing the weighted polygenic scores for the subjects with high medical damage attempts with non-attempters, we found that the maximum difference between the cumulative distributions, D, is 0.241” (Bani-Fatemi, 171). There was no trend for higher polygenic scores in suicide attempters with high lethality compared to non-attempter/non-ideators.
Bani-Fetami then chose to compare the participants that had a least one violent attempt to the non-attempters. “Among the attempters, there were 38 subjects who had at least one violent attempt lifetime using the classification by Dumais et al., 2005. We compared the violent attempters with the non-attempters/non-ideators and we did not find any differences in weighted polygenic scores, the maximum difference between the cumulative distributions, D, was 0.0982 with a corresponding P of 0.984. When we compared the unweighted polygenic scores, we found that the maximum difference between the cumulative distributions, D, was 0.0924 with a corresponding P of 0.992” (Bani-Fatemi, 171). The differences in the scores was not very high, but also showed a larger difference than other comparisons
The last comparison made was between participants that had high intent to kill themselves justified by the Beck Scale for Suicide Ideation and the non-attempters. The journal following passage from the journal states the results. “We considered the attempters with high intent using the item 21 of the BSS that is characterizing subjects who had high intent to kill themselves in the last attempt. According to this classification, there were around 29 attempters who reported high intent during the last attempt. When we compared the weighted polygenic scores, the maximum difference between the high intent attempters and non-attempters/ non-ideators was not significant (D = 0.1609; P = .712). When we analyzed the unweighted polygenic scores, we found that the maximum difference between the cumulative distributions, D, was 0.1073 with a corresponding P of 0.982” (Bani Fatemi, 171). The results from the high intent to non-attempters shows a slight variation compared to the rest of the data.
Contradicting Bani-Fatemi’s hypothesis, the research found that the polygenic risk score did not predict suicide attempt. Showing that schizophrenia polygenic risk scores are not related with suicide attempt. Variables that may have affected the data is family history of schizophrenia and the amount of suicide attempters in comparison to the sample size. When gathering statistical data the participants used can make a huge difference. If all the participants used were fraternal twins affected with schizophrenia the results could be more valuable.
More research should be done to further the knowledge and prediction of suicide attempts among those with schizophrenia. Both genetic risk and abuse or neglect received during childhood are factors that should be further analysed. Although Bani-Fatemi’ data does not support her hypothesis, genetic risk for schizophrenia with childhood trauma could help predict those who may be at risk for potential suicide attempt in the future. Other studies data contradicts the results Bani-Fatemi received. Each study using participants with different variables. The suicide rate within schizophrenic is high, continuing this research could prevent future suicides. While childhood trauma may be a trigger to schizophrenia, it is hard to relate each individual’s experience and actions to the next.
What is Schizophrenia and the importance of induced pluripotent stem cells:
Schizophrenia is one of the most significant mental illness or disorder that affects the ability of an individual to think, feel and behave. It also interferes with the ability of individual to function in day to day lifestyle. Schizophrenia is characterised by both positive and negative symptom as well as cognitive deficits. It is believed to be heritable neurodevelopmental disease, which affects 1% of the adult population worldwide[4]. There are various anti-psychotic treatments and many new techniques have been developed to overcome this devastating disorder. However, cognitive and negative symptom do persist even after the treatment, which prevents the normal functioning of an individual [4]. Noh et al. demonstrated that Schizophrenia is not a monogenic disease instead there are many multiple risk gene and environmental factors which interacts with each other and produces clinical phenotype. Up until now, it has been bit hard and problematic to understand schizophrenia and it’s developmental mechanism due to inadequacy of the existing model, as animal models are less successful in producing negative and cognitive symptoms[3]. However, recent studies and research have discovered that induced pluripotent stem cells provide a possibility to study schizophrenia in live patient derived neurons[1]. These induced pluripotent stem cells (iPSCs) can be derived from various somatic cells, such as dermal fibroblasts, hair follicles, glutamatergic neurons and other neural subtypes etc. In addition, Shao et al. used this newly discovered approach, induced pluripotent stem cells to understand the mechanism of schizophrenia. To begin the study, 4 transcription factors integrating retroviral vector were transmitted into somatic cells to generate iPSCs[7]Then, cortical interneurons were generated using induced pluripotent stem cells which were derived from relatively small cohort, 14 healthy control and 14 subjects with schizophrenia.
Rationale for each different experimental approaches and the relative findings:
Initially, Shao and his colleagues, used footprint – free modified RNA method to generate iPSCs from healthy and schizophrenia fibroblasts. The generated iPSCs were then reprogrammed using RNA transfection and the modified iPSCs showed morphology which was similar to the human Pluripotent stem cells and they also expressed pluripotent stem cells markers. Later on, the iPSCs were differentiated using the modified protocol which resulted in the generation of homogenous population of Cortical Interneurons (cINs). The phenotype of this newly generated cINs was analysed using real – time PCR analysis and the results were compared with the undifferentiated iPSCs and induced glutamatergic neurons. After the analysis, it was found that cIN-specific genes were highly expressed in cIN groups compared to other cells or Non-cIN markers. This confounding results confirm the identity and homogeneity of the generated cIN cells. The generated cINs were grafted using electrophysiological analysis into the mouse brain to determine if the cINs generated form iPSCs were functional and authentic for the diseases modelling. Both the healthy control and schizophrenia cINs were then transduced with GFPs to allow optogenetic studies in order to view cortical slices of the mouse brain. As result, it was found that grafted cINs showed rapid desensitizing inward currents and sustained outward currents, which supported the expression of both voltage gated Na+ and K+ channels. However, there was no difference between the groups in those voltage dependent channels. In addition, Healthy control and schizophrenia cIN developed into functional cINs, whose neuronal properties are similar to those of endogenous interneurons. Furthermore, the synaptic properties of grafted human cINs were analysed to see if they integrate into adult brain circuitry and receive any synaptic inputs form the host cortical neurons. And as result, it was discovered that the human cINs form both the controls have functional postsynaptic machinery to receive excitatory synaptic inputs from host glutamatergic cortical neurons as well as the grafted cINs also have presynaptic machinery for GABA release but they inhibit host cortical neurons.
After the clarification of the authenticity and functionality of the cINs derived from the iPSCs, RNA-sequence analysis was performed to compare transcriptomes of healthy control cINs to schizophrenia cINs after 8 week differentiation. This was done to see if there is any schizophrenia cIN-specific abnormalities exists in gene expression during development. It was discovered that neuronal and cIN markers such as MAP2, DCX and GAD1,VGAT,SST, Lhx6 were highly expressed respectively. However, the expression of nonrelevant markers were relatively low and there was no difference in the expression of this markers between the both, healthy and schizophrenia samples. Later on, real time PCR was used to see if there is any difference in the selected gene, such as PCDH2 between healthy and diseased samples. There was no clear separation between the healthy and schizophrenia samples, but the selected gene PCDHA2 did exhibit significant difference in the expression of gene among the two samples. Due to the involvement of the genetic mutation in the schizophrenia, the size of samples were expanded to 14 healthy and 14 schizophrenia controls. Similar to last time, RNA-sequencing was performed and it was found that apart from PCDHA2, there are many other genes that are downregulated in schizophrenia. These genes include PCDHA3, PCDHA6 and PCDHA8. In addition, the real time PCR further confirmed significant decrease in the expression of PCDHA family members. It was also discovered that PCDHA2 eQTL SNPs were highly associated with schizophrenia and this is further supported by figure 8b of the paper[6]. This association of PCDHA2 supports the idea that there is potential role of schizophrenia risk loci in regulating the gene expression of PCDHA2. However, this aspect of the study did not achieve a statistical significance due to the smaller sample size However a final conclusion was drawn form the study. It was concluded that “schizophrenia risk locus may be related to the regulation of multiple protocadherin family members in addition to PCDHA members”[6]
Later in the study, Pcdha and Pcdhg knock out mice were used to determine the effect of protocadherin hypofunction on cIN development. Pcdhg knock out mouse showed severe lethal phenotype and it was discovered that Pcdhg is critical for the localisation of Pcdha and function. Where as Pcdha knock out mouse showed mild phenotype, however there was significant arborisation deficits in Pcdha knock out cINs upon analysis. This finding was further supported by decrease in neurite number from cell body as well as the total branch number and the neurite length were also reduced in the Pcdha knock out mouse. In addition, there was deficits in the inhibitory synapses formation of prefrontal cortex cINs in Pcdha knock out mice, but there was no significant difference in the excitatory synapses. Overall, it is clearly shown that protocadherin pathway is important for the normal development of cINs in the prefrontal cortex as well as in normal sensorimotor gating. Schizophrenia cINs were further tested to see if they also demonstrate similar phenotypic deficits, similar to those cIN deficits by protocadherin hypofunction in previous study. The healthy control and schizophrenia cINs were infected with a “limiting titer of lentivirus expressing GFP under the ubiquitin promoter”[6]. Analysis of these GFP cells showed that schizophrenia cINs have significant decrease in neurite number from soma, total branch numbers and neurite length compared to healthy cINs. Furthermore, Linear regression analysis revealed weak correlation which exist between the PCDHA family members and arborisation. This suggests that absence of a schizophrenia circuit environment leads to the intrinsic deficit in the formation of inhibitory synapses of schizophrenia cINs. Lastly, the final experiment was conducted to see whether the observes developmental deficits continue to be present in adult post-mortem brain. The analysis of 3rd layer of PV form both healthy and schizophrenia controls showed significant deficits in diseased post-mortem cINs which was indicated by decrease in neurite number from soma, total branch number and neurite length. There was also decrease in inhibitory synapses formation of post-mortem diseased cINs. The result were exactly similar to those of phenotype observed in developmental cINs. The only difference that was observed in adult post-mortem diseased cINs and not in phenotypic developmental cINs was that the excitatory synapses formation was relatively reduced in the post-mortem diseased cINs. This reduction in excitatory synapses can be associated with deficits in the glutamatergic neurons.
Strength and weakness of the experimental approach and contribution to broader field:
The main purpose of study was well achieved as Shao and his colleagues were successful to find that the expression of protocadherins, a family of cell surface proteins which are significantly downregulated in schizophrenia cINs during development. In addition, they also discovered that altered expression of this gene led to disease-relevant phenotypes in knockout mice as well as in human schizophrenia cINs. The conducted experiment also shows the importance of using disease-relevant and homogenous population of cell in order to understand the effect of risk genotypes on both healthy and diseased controls. The study was conducted using human samples, more specifically using neurons that are affected in schizophrenia disease. Also, the study used live tissues except the last approach which used post-mortem brain slices and tissues. In addition, for better result the experiment was repeated and also there was increase in sample size form 8 individuals to 14 individuals. Also, the techniques that were used such as real time PCR which targeted protocadherin genes and other family members of protocadherin genes. However, the sample size chosen for this experiment could have been improve by choosing larger cohort of individual. A larger sample size also provides greater chance to work with more line and achieve more adequate statistical significance which was not possible to achieve using smaller sample size. It was also suggested that using large sample size, the common and rare variants of the schizophrenia disease may converge providing insights into cellular and molecular function of common variants[5]. This insight could results into identification and production of new therapeutic targets for such neuropsychiatric disorder[5]. In addition, it would have been much better to use same or much similar mouse model for the two different approaches, morphological changes in neurons/synapses and other for behaviour. In the study two different mouse models were used. This could have contributed to discrepancies of result, as each has different body structure as well as different morphology.
Furthermore, the study has contributed to the broader field of research and future by introducing new techniques. The study demonstrates the power of using homogenous and functional populations of specific neuronal subtype that are known to be affected in schizophrenia to probe the pathogenesis of schizophrenia[2]. Not only schizophrenia, but this new method of using homogenous populations of cells can be used to study any other developmental disease mechanisms as well as this techniques may provide a pathway for effective therapies or preventions in the future which can prevent the occurrence of such diseases. It was also discovered that PKC inhibitor reverts the schizophrenia cINs back in to normal phenotype. However, the mechanism is unclear but it is suggested that they are other molecules or mechanisms are involved which allows the reversion of the cINs, providing a future direction of research.
There are many questions and decisions that are left unanswered. The very first questions that can be raised is based on the validity of control. For this study, Shao et al. selected Caucasian males to eliminate gender and ethnicity variations. However, apart from these two factors what are other factors that could be introduced or eliminated to obtain valid statistical results? In addition, the last study conducted using post-mortem brain slices also possessed limitation and challenges. The results that were obtained from the study supported the link between schizophrenia and dysregulation in protocadherin pathway. However, it was not known if those model has any other age related disease or any prior known developmental disease mechanisms. In addition, Clozapine was used as first line treatment without gaining any knowledge of the prior history of the individuals. If these individuals selected for the study have been exposed to any different type of drugs previously, then there are chances that the exposure of drug in previous years could have affected the gene expression or neuron structure. These change in gene expression or neuron structure can be interpreted as a disease related phenotype.
In summary, The overall aim of the research was achieved, that there is correlation between protocadherin and schizophrenia disease, however again the exact mechanism is bit unclear and require further research. In addition, Shao et al. were able to identify the genes of PCDHA family that were downregulates in the schizophrenia cINs as well as they were also able to identify the affected pathway in the diseased individual. So, after all the discovery, findings and creating a direction for the future research, Shao et al. have immensely contributed to the broader field of research and the field of developmental disease mechanisms.
References:
Brennand, K.J., Gage, F.H., 2011. Concise Review: the promise of human induced pluripotent stem cell – based studies of schizophrenia. Stem cells 29 (12), 371, 1915 – 1922.
Jacobs, B.M., 2015. Concise Review: A dangerous method? The use of induced Pluripotent stem cells as a model for schizophrenia. Schizophrenia Research 168, 563 – 568.
Jones, C.A., Watson, D.J.G., Fone K.C.F., 2011. Animal models of schizophrenia. Br. J. Pharmacol. 164 (4), 1162 – 1194.
Rajarajan, P., Flaherty, E., Akbarian S., Brennand, K.J., Concise Review: CRISPR – based functional evaluation of schizophrenia risk variants. Schizophrenia Research, https://doi.org/10.1016/j.schres.2019.06.017
Shao Z., et al., 2019, Dysregulated protocadherin – pathway activity as an intrinsic defect in induced pluripotent stem cell – derived cortical interneurons from subjects with schizophrenia. Nature neuroscience, (22), 229 – 242.
Takahashi, K., Yamanaka, s., 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblasts cultures by defined factors. Cell 126(4), 663 – 676.
Schizophrenia is a major psychological disorder whose causes and better means of treatment remain unclear despite its long time existence. This paper offers an in-depth review of related literature to ascertain whether persons with the ailment should be compelled to take medications. The paper finally calls for further research on the disorder in order to come up with better therapeutic methods.
A brief overview of schizophrenia
Dora (2002) indicates that Schizophrenia is a psychological disorder whose symptoms appear in form of auditory hallucinations and delusions. Though many studies have pointed out that its causes are poorly understood, Dora (2002) is of the view that it results from the interplay of the immediate environment that a person is exposed to and the biological predisposition.
Basically, schizophrenia is a disorder that is largely implanted on complex inheritance but requires particular environmental conditions to be manifested. Dora (2002) further indicates that various theories have been employed to try and explain the causes and occurrences of the disorder among people in society.
One such theory is the Becks cognitive theory of emotions. According to the theory, this disorder arises form an individual’s cognitive distortions which culminate to emergence of maladaptive behaviors among them. The theory indicates that for emotional disability to occur in an individual there must be major errors that affect the thought process. The theory therefore offers strong insights that can be used by the medics mostly in the field of clinical psychology.
Treatment and medication
Chan et al (2004) indicate that antipsychotic medication is the first line treatment for patients with schizophrenia. The medication may fail to completely ameliorate cognitive dysfunctions and negative symptoms though effective in reducing the positive effects of the disorder. Even so, patients with schizophrenia may be unwilling to take their medication for various reasons. Many physicians and caretakers have resorted to various means including forceful administration of drugs to control the disorder.
Forceful injection of medication to patients with schizophrenia is a common practice carried out by a number of people. This has been lauded by caregivers as an effective means of administering drugs to patients who are unable or unwilling to take their medication. Chan et al (2004) argue that the use of force in that case is necessary since it is the only option. The argument hinges on the notion that it is critical to consider both the safety of the patient who do not want to take drugs and the public good.
Dora (2002) appears to disagree with Chan et al (2004) view on the use of force to administer drugs by arguing that there are alternative methods that can be employed to treat the patients. One common treatment method is cognitive therapy.
This type of therapeutic treatment helps victims suffering from schizophrenia to identify with the problem and change their dysfunctional thinking and emotional responses. Family therapy and psycho-education further help the affected individuals to deal with the symptoms and fit more effectively in the extended community. Additionally, social skills can be taught to patients so that they can manage themselves well in a bid to coexist with others.
Alternative treatment methods such as use of special diets and glycine supplements can have positive impacts. To sum up, current effectiveness of schizophrenia treatment is a major issue of concern lacks the direct capacity to address the problem of whether to forcefully administer drugs to schizophrenia patients or not. Hence, it becomes hard to use medication with certainty although it leaves the future generations at great risk of the disorder.
References
Chan, R. et al. (2004). Problem-solving ability in chronic schizophrenia. European Archives of Psychiatry and Clinical Neuroscience, 254(4), 236-241.
Dora, W. K. (2002). Trial rights and psychotropic drugs: The case against administering involuntary medications to a defendant during trial. Vanderbilt Law Review, 55(1), 165-218.
The need to understand the complex interplay between a number of variables, including genetics, environmental factors, clinical, psychological and social processes, in the development of brain disorders and the resultant behavioural and cognitive deficiencies informed the urge to evaluate and critique the article by de la Serna and colleagues, titled “Relationship between Clinical and Neuropsychological Characteristics in Child and Adolescent First Degree Relatives of Subjects with Schizophrenia.”
In particular, the topic is of great interest in the study of brain and behaviour because schizophrenia affects the growth and development of many children and adults, not only in terms of their psychological wellbeing but also their cognitive and social skills.
The critiqued article was retrieved from the ScienceDirect database of the Elsevier Databases using the search terms “schizophrenia”, “cognition” and “neuropsychology.”
This particular article stood out from the rest due to the new knowledge it sought to divulge, particularly on the influence of diagnosis for schizophrenia on cognitive variables in children at high risk of developing the mental disorder (de la Serna et al, 2010).
The questions that arose upon reading the abstract of the article included: 1) Is schizophrenia associated more with genetic factors than with environmental processes, and 2) what cognitive and/or behavioural disorders may be predominant in siblings of a family with a history of schizophrenia.
Article Summary
The article under review purposed “…to describe the clinical and neuropsychological characteristics of children and adolescents at high risk for schizophrenia compared to healthy controls, and to investigate the influence of diagnosis on clinical symptoms and cognitive assessment” (de la Serna et al, 2010, p.160).
The authors were informed by the need to fill the dearth in knowledge that existed on drawing the relationship between the diagnoses for schizophrenia on the one hand and cognitive and behavioural manifestations of people considered at high-risk on the other. It is important to note that the authors of the article did not formulate any research questions or hypothesis to guide the study.
The participants for the study included 26 high-risk children who were first-degree relatives of individuals already clinically diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. For comparison purposes, the researchers also engaged 20 control children and adolescents of individuals with no history of any psychotic disorder according to the DSM-IV criteria (de la Serna et al, 2010).
The experimental and the control groups were evaluated and interviewed by a trained clinical psychologist using a semi-structured interview and other rating scales, such as the Conner’s Parent Rating Scales (CPRS-48) to assess psychopathological symptomatology, the Hollingshead Redlich Scale to estimate the socio-economic status, and the Wechsler Intelligence Scale for Children-Forth Edition (WISC-IV to evaluate the intelligence quotient (IQ).
The results of the study demonstrated that 4 in every 10 participants in the experimental group (high-risk) had a diagnosis of one or more psychiatric disorders according to the DSM-IV criteria, with attention deficit/hyperactivity disorder (ADHD) and the generalized anxiety disorder taking the first and second place, respectively (de al Serna et al, 2010).
Another major finding of the study was that high risk children and adolescents scored highly than the control group not only on the prodromal symptoms, behavioural challenges and premorbid adjustment, but also on the majority of other scales intended to measure intelligence, social adjustment, cognition, working memory and logical memory.
Still, the findings demonstrated clinical variations between high-risk children with attention deficit disorder (HR-ADD), high-risk children without attention deficit disorder (HR-NADD), and the control group, particularly in prodromal symptoms, behavioural challenges and premorbid adjustment.
In particular, it was found that HR-ADD children had substantially higher scores on prodromal symptomatology than did HR-NADD participants and the control group, in large part due to attentional difficulties, behavioural inhibition and absence of social competence. According to de la Serna et al (2010), “…cognitive assessment revealed significant differences between HR children and controls on the majority of cognitive domains evaluated: intelligence, working memory, verbal memory and learning” (p. 165).
Equally, the high-risk children achieved considerably lower scores than the control group when their level of intelligence was evaluated using various scales such as the WISC-IV.
The study concluded that “…HR children had elevated rates of prodromal symptomatology, psychopathology and psychiatric diagnosis, especially ADHD, compared to normal controls” (de la Serna et al, 2010, p. 165). Additionally, it was concluded that HR children and adolescents had more cognitive difficulties in IQ, behavioral problems, and other challenges related to the working and logical memory than did the control group.
Lastly, there were no considerable cognitive differences between HR-ADD and HR-NADD subjects, implying that HR samples seem to have a comparable cognitive pattern that is not only widespread in both subgroups but is independent of the underlying clinical diagnosis. However, it is important to note that the study was limited by the small sample size, difficulties in conducting the clinical and cognitive assessment, and lack of demographic information (birth histories) of the experimental and control groups (de al Serna et al, 2010).
Article Critique
As is the case with other published research articles, this particular study has its own merits, particularly in the light of new knowledge on clinical and neuropsychological characteristics of children and adolescents at an elevated risk for schizophrenia when compared to the general population.
The study has also brought into the limelight the influence of diagnosis of schizophrenia on clinical symptoms and cognitive evaluation of individuals with the aim of analyzing the risks involved. These are important findings in schizophrenia research, particularly in the preparation and administration of clinical and psychological interventions to individuals who may be considered at greatest risk of developing the neurodevelopmental disorder.
The article, in my view, is focused and written in a coherent manner, particularly in the introduction section and the review of related literature. However, there exist some obvious limitations that require to be addressed with the view to add more value to the study. First, it has been noted that the researchers utilized very many data collection tools in the methodology section, almost leaving the reader confused.
The researchers are also not clear on the type of research design used, leaving the reader to assume that they might have used a mixed-methods research design since they used semi-structured interviews as well as scales to collect data. The study, in my view, could have been more coherent if the researchers included some research questions or hypotheses.
Sadly, this was not done despite the fact that the researchers dealt with a broad research objective, which could have been fragmented into several research questions to attain clarity of responses.
Although the findings infer causation from a correlational design by virtue of the fact that predisposition towards people with schizophrenia is positively correlated with the development of cognitive and behavioural challenges, it is generally felt that the development of research questions could have enabled the reader to understand the relationships explained in the findings section.
The results are valid in as far as they have been corroborated by other previous studies. However, a larger sample size could have made the results to be more generalizable across a bigger population.
The most important implication that arises from this study is that children and relatives of people with schizophrenia, considered to be high-risk population, can be introduced to preventative interventions early in life as it has been demonstrated that they have a higher chance of developing mental, behavioural, psychological and cognitive impairments than children and adolescents sampled from the general population.
Consequently, the article is not only enjoyable to read but also informative since it comes up with new knowledge that could be used by clinical psychologists to address the symptoms of schizophrenia.
If this research study was to be repeated in the future, it could have been imperative for the researchers to devote more time into the development of an all-inclusive data collection tool to collect the required data from the experimental as well as the control groups. Additionally, it could have been plausible for the researchers to develop a set of key research questions to guide the research process.
As suggested by the authors, “…future research is needed to identify specific cognitive and neuropsychological markers that would predict later onset of schizophrenia and help define clinical groups at enhanced risk” (de al Serna et al, 2010).
In considering the relevance of the article to the course, the idea that brain functions and behavioural orientations are innately linked has been reinforced. It has been demonstrated that some cognitive and behavioural orientations can be explained through genetics.
Personally, it has been learned that schizophrenia definitely has genetic connotations in that children from families with incidences of schizophrenia have been found to be at a high risk of developing behavioural and cognitive difficulties than children from the general population. Such knowledge, in my view, is fundamental in professional practice since it can assist clinical psychologists and counsellors to develop intervention measures to be used by at-risk groups before succumbing to the neurodevelopmental disorder.
Reference List
de la Serna, E., Baeza, I., Toro, J., Andres, S., Puig, O., Sanchez-Gustau, V…Castro-Fornieles, J. (2010). Relationship between clinical and neuropsychological characteristics in child and adolescent first degree relatives of subjects with Schizophrenia. Schizophrenia Research, 116, 159-167
Schizophrenia is as a severe mental illness that is estimated to occur in about 1% of the population (American Psychiatric Association 2000). Schizophrenia is considered a heterogeneous illness because its symptoms, level of impairment and course of illness manifest themselves in different forms.
Primarily, schizophrenia impairs neurocognitive functioning resulting in problems of perception, interpretation, communication and interaction with others. It is also associated with the impairment of the performance of day to day activities, self-care and other social and occupational activities (Ziedonis et al. 2007). Schizophrenia symptoms are categorized into two groups.
The first group exhibits positive symptoms such as disorganized speech and behavior, hallucinations and delusions. The second group exhibits negative symptoms that include cognitive impairment and restricted effect and motivation. These symptoms have a deleterious impact on the social and occupational functioning of the patients (American Psychiatric Association 2000; Weinberger et al. 2007; Ziedonis et al. 2007).
Individuals with a diagnosis of schizophrenia are reported to be highly susceptible to developing nicotine dependence with an estimated prevalence of up 88% (Kelly & McCreadie 2000 & Lasser et al. 2000; Kumari & Postma, 2005; Steinberg & Williams 2007). This rate is particularly concerning when compared to a prevalence of 23% of smokers who do not have mental illness.
Out of the smokers with schizophrenia, over half are described as being heavy smokers smoking more than 25 cigarettes per day (Kelly & McCreadie 2000, Lasser et al. 2000 & Ferron, et al. 2009; Banham & Gilbody 2010). The estimated rate of smoking cessation amongst those with schizophrenia is approximately 8% compared to 31% of those without a major mental illness.
This high prevalence of heavy smoking amongst individuals with schizophrenia is concerning because it puts them at a significantly higher risk of smoking related illness, such as lung cancer, cardiovascular and respiratory diseases (Ziedonis et al. 2003 & Moss et al. 2010).
It is estimated that the life expectancy of smokers with schizophrenia is reduced by 25 years, with smoking related illness being a significant contributing factor (Ziedonis et al. 2003 & Ferron et al. 2009; Kelly et al. 2000; Moss et al. 2010). Over the years, there have been strong indications that heavy cigarette smoking can be linked to schizophrenia and that smoking may have a connection to the neurobiology of schizophrenic illness.
This paper will critically examine the current body of clinical and neurological research that links nicotine dependence to schizophrenia. We will also examine a self-medication, social and environmental explanations for nicotine dependence. Finally, this paper will offer discussions regarding the implications for assessment and intervention.
Self-Medication of Symptoms
Neurobiological research has established an abundance of nicotinic receptors in the prefrontal cortex of the brain with the nicotinic acetylcholine receptor subtype being the main receptor linked to nicotine dependence. Nicotine has been observed to bond with these receptors resulting in formation of dopamine and serotonin.
Raising dopamine levels has been shown to transiently lead to cognitive dysfunction and negative symptoms associated with schizophrenia. This paper will examine the positive and negative symptoms of schizophrenia that are thought to be targets of self-medication.
These include processes that relate to attention and concentration, the P50 Gating Response and Visuospatial Working Memory (Kelly & McCready 2000; Kumari & Postma 2005).
P50 Gating
A common symptom associated with schizophrenia is dysfunctioning of the P50 gating response and it is believed that this is connected to auditory hallucinations. Individuals who do not have a deficit in their P50 gating response can hear more than one sound at the same time, but not all sounds are heard at the same volume. This enables us to focus our attention on what we choose (Kumari & Sharma 2002; Adler et al. 2004).
The neurocognitive deficits associated with a deficit in the P50 gating response can significantly impact on quality of life. It is thought that smoking cigarettes is a method of self-medication to moderate this symptom (Adler et al. 2004; Kumari & Postma 2005; George et al. 2006; Weinberger et al. 2007). Researchers used a controlled study to measure the P50 wave response to auditory stimulation of participants with schizophrenia.
They reported that participants were unable to block the response when a second stimulus was added. However, participants were retested after smoking cigarettes and others chewing 6 mg dose of Nicorette gum. Results from both smoking and chewing Nicorette gum indicated improvement in the P50 wave when an auditory stimulus was added.
This finding indicates that nicotine has the ability to temporarily improve the ability to filter and suppress the response to auditory stimulation (George et. al. 2006). It should however be noted that the improvement is only temporary.
It would be a medical disaster to encourage people with schizophrenia to use smoking as a remedy because it would mean that they smoke frequently to improve their ability to filter. This would not solve the problem and would instead expose the people to a high risk of smoking related complications like lung cancer.
VSWM
A second neurocognitive function that is reported to improve with nicotine is visuospatial working memory (VSWM). Dysfunction of dopamine activity in the anterior cortex has in some cases been linked to Schizophrenia. This dysfunction affects the cognitive process that facilitates visualization of the relative positions of items in the environment.
It requires encoding and remembering location of objects and landmarks. These functions are necessary for allowing performance and motivation to start and complete simple and complex tasks and activities (Snyder 2006). This process is referred to as visuospatial working memory (VSWM). Animal testing reports that VSWM functioning is enhanced with nicotine (George et al. 2006).
It is thought that smoking cigarettes enhances VSWM in people with schizophrenia by increasing dopamine activity (Depatie et al. 2002; George et al. 2006). Symptoms of tobacco withdrawal are reported to impair VSWM with the impairment abated when smoking is resumed (George et al. 2002).
A controlled study using nicotine and functional magnetic resonance scanning (fMRI) by Jacobson and colleagues (2004) reports improvement in participants with schizophrenia’s performance of tasks involving attention and memory when nicotine was administered.
However, the researchers acknowledged that they were unable to state with certainty, whether improved function was associated with nicotine or antipsychotic medication that the participants were taking.
Another study to examine whether nicotine improved attention and VSWM in participants with schizophrenia reported only slight improvement in attention and no improvement reported in any other area of cognitive function (Harris et al. 2004). According to these reports, it cannot be concluded without doubt that nicotine indeed aids in reducing VSWM impairment. Further controlled tests need to be carried out to ascertain this.
Attention and Concentration
It has been reported that nicotine improves the ability to focus attention and concentration in tasks that involve working memory as well as selective attention. This is believed to occur as nicotine stimulates activation and functional connectivity in the prefrontal cortex region of the brain (Jacobsen et al. 2004; Weinberger et al. 2007).
However, results of improved attention and concentration varied when nicotine was administered via different delivery systems. The first study, a controlled double-blind study conducted by Depatie and colleagues (2002), determined that attention and concentration was diminished with overnight nicotine abstinence and improved once a nicotine replacement patch was administered.
In a second study, Weinberger and colleagues (2007) report that in a controlled study, only minimal improvement in attention and concentration was reported when nicotine nasal spray was administered and even less effect noted in a third study with administration of nicotine gum.
These varied results in the tests could be an indication that maybe there is some stimulation that affects and possibly improves attention and concentration but is not necessarily nicotine. Schizophrenic Cigarette smokers can be encouraged to try different natural stimulants and more research done to establish the accurate relationships between the two.
Negative Sx
There are reports that suggest that smoking reduces other negative symptoms of schizophrenia, such as anergia, amotivation and flattened affect (Smith et al. 2002; Tidey & Williams 2007). However, Barnes and colleagues (2006) report that this was not consistent with their research as they found no association of heavy smoking and decreased negative symptoms.
Tidey and Williams (2007) note that there are limited controlled studies comparing smokers with schizophrenia to non-smokers with schizophrenia to determine whether negative symptoms are impacted by nicotine use and cessation.
It is frequently reported that smoking is associated with regulating mood (Baker et al. 2004; Perkins et al. 2010). In a research conducted by Tidey and Williams (2007) measuring smoking outcome expectancies, it was found that smokers with schizophrenia also shared the perception that smoking alleviated feelings of anxiety and irritability.
However, they suggest that increased irritability and anxiety are symptoms of nicotine withdrawal. If there is an expectation that smoking will reduce anxiety, the smokers will smoke; this will alleviate withdrawal symptoms and might falsely appear to relieve the anxiety and irritability.
Medication Side Effects
In addition to alleviating symptoms of schizophrenia, nicotine is reported as being used as an antidote to unpleasant side effects of neuroleptic medication used to treat schizophrenia (Kelly & McCready 2000; Kumari & Postma 2005). Kumari and Postma (2005) suggest that hydrocarbons in cigarette smoke decrease the efficiency and can shorten the half-life of neuroleptic medication by 50%.
Medication is metabolized quickly and cleared from the system and this is thought to reduce associated side effects. The implication of this is that schizophrenic smokers would need a higher dose of the medicine for the same remedial effect. Some researchers suggest that this under-medication may be an explanation as to why schizophrenia patients who smoke account for more frequent hospitalizations compared to non-smokers.
Also they are reported to experience increased psychiatric symptoms such as hallucinations and delusions during an acute episode compared to non-smokers (Kelly & McCready 2000; Kumari & Postma 2005). A study conducted by Yang and colleagues (2002) at an inpatient psychiatric unit in China administered transdermal nicotine and placebo patches to 30 patients with schizophrenia who were prescribed Haldol.
Their findings reported decreased Haldol related Parkinsonism with the nicotine transdermal patch compared to the placebo patch. In a more recent study of 146 adults with schizophrenia, Barnes and colleagues (2006) found that smoking was associated with decreased tardive dyskinesia as well as akathisia.
However, Smith and colleagues (2002) recommend that research findings be interpreted with caution since there lacks a published research of placebo-controlled studies showing consistent improvement of psychiatric symptoms associated with nicotine use.
Also, in the study conducted by Barnes and colleagues (2006), they reported that the association of nicotine dependence and neuroleptic medication was dependent upon the type of medication used.
Older neuroleptics such as Haldol were associated with high prevalence of smoking, whereas, newer medications such as clozapine saw a reduction in smoking behavior. This is thought to occur because the newer medication increases dopamine and decreases negative symptoms of schizophrenia (Barnes et al. 2006).
There is research that suggests the pathophysiology of the illness itself may increase vulnerability to the initiation and maintenance of nicotine dependence since many begin smoking during the prodromal phase of their illness (deLeon & Diaz 2005). Kelly and McCreadie (2000) suggest that smoking may be a marker for schizophrenia.
Psychosocial factors for high tobacco use and low cessation
Ziedonis and colleagues (2007) suggest that focusing solely on the self-medication explanation may detract researchers from exploring other hypotheses for nicotine dependence.
Socioeconomic factors that increase smoking risks for this population include limited education, poverty, unemployment and peer influence (American Psychiatric Association 2004; Riala et al. 2005). The attitudes towards smoking within the mental health treatment system are also responsible for perpetuating a smoking culture (Williams & Ziedonis 2003).
Unlike the general population, individuals with schizophrenia are often unemployed which increases their idle time and their inability to engage in social activities in which smoking is not acceptable.
Other potential etiologic factors include living with other smokers in group homes, having a fixed low income, having low education, lacking support and being unmarried (American Psychiatric Association 2004). Schizophrenic people could therefore be leaning towards smoking because of psychosocial factors more than any other medical reasons.
In a meta-analysis of smoking and severe mental illness, de Leon and colleagues (2005) propose that a high rate of smoking exceeds the severe mental illness effect. They suggest that decreased smoking in people with schizophrenia is related to high nicotine dependence and cultural factors. Riala and colleagues (2005) suggest that both social and cultural factors can influence the initiation and maintenance of smoking behavior.
Smoking is perceived to be less socially acceptable in India where they report that only 38% of male patients with schizophrenia smoke This rate is even lower for women.
This is significantly lower than the 88% of smokers with schizophrenia in western society. In a meta-analysis of smoking, Riala and colleagues (2005) propose that smoking is more strongly associated with cultural attitudes and availability of cigarettes, rather than being associated with a diagnosis of schizophrenia.
Tobacco Industry
Ferron and colleagues (2009) report that in the United States, smokers with mental illness account for 46% of cigarette sales. The 46% translates into sales revenue amounting to 37 billion dollars and 180 billion cigarettes.
However, there is evidence that the tobacco industry has invested heavily to promote research that supports this and suppress evidence that counters the association Ferron and colleagues (2009) conducted a review of the tobacco industry documents dating 1955 up to 2004. Their analysis revealed the tobacco industry provided financial backing for research that promulgated three messages:
Support for the self- medication hypothesis;
Quitting smoking would lead to deterioration in mental health and
People with schizophrenia are less susceptible to smoking related disease.
The tobacco industry monitored and suppressed research that did not support the industry’s agenda. The tobacco industry has also used the self-medication hypothesis to encourage cigarette use in mental institutions and frustrated efforts to ban cigarette use in hospitals.
These targeted strategies by the tobacco industry increased the barriers to smoking cessation by discounting the effectiveness of smoking cessation treatment for this population and discouraging the implementation of no smoking policies in mental health treatment facilities.
The tobacco industry’s close relationship with mental health research influenced the mental health clinician’s knowledge and attitudes about nicotine use. Although schizophrenia represents 1% in the general population, schizophrenia is primarily treated in mental health settings (Ziedonis et al. 2007).
Supported by research funded by the tobacco industry, smoking was not only perceived as being an acceptable practice on inpatient psychiatric units but also patient smoking was condoned in these settings. Positive patient behaviors were rewarded and reinforced with cigarettes as part of a token economy.
This practice in mental health treatment settings has likely contributed to the high rates of tobacco use and low rates of successful smoking cessation attempts among individuals with schizophrenia (Ziedonis et al. 2003). Patients with serious mental illness have described smoking cigarettes as a fundamental need that was more important than food and even helped them to prevent relapse of schizophrenia (Forchuk et al. 2002).
The self-medication explanation was widely accepted and efforts to change the culture within psychiatric community were met with resistance. In addition to the self-medication rationale, there was a common perception that smoking was one of the few pleasures they could have in their lives (Ziedonis et al. 2007).
Other concerns expressed by health care providers, families and the patients include the potential for exacerbation of mental health symptoms, relapse, anger, aggression and detrimental effect on neuroleptic medications.
Mental health clinicians have been reluctant to accept smoking bans on psychiatric units (Willemsen et al. 2004) despite growing evidence that such bans do not have a negative impact on the management of psychiatric patients in these settings. Furthermore, there was concern regarding the health risk if patient’s continued to smoke while using nicotine replacement therapy.
Another concern expressed was that staff and patients would lose the opportunity to connect and bond while having a cigarette together. Health care providers expressed concern that their patients who are primarily on fixed limited income, would not be able to afford the price of over the counter smoking cessation treatments and that promoting smoking cessation treatment would further marginalize this population.
This argument is easily countered by Steinberg and colleagues’ (2004) findings that in the high tobacco taxation states in the U.S., smoking consumes 27% of people with severe mental illness’s fixed monthly income.
Implications for Assessment
The low motivation for smoking cessation amongst people with schizophrenia may be attributable to three primary factors. The first pertains to the high rate of nicotine dependence amongst this group. The second factor pertains to perceived benefits of smoking which are associated with the self-medication explanation.
Smoking cessation is reported to be a challenge as it is reported that nicotine withdrawal can result in their psychiatric symptoms temporarily worsening. The third factor pertains to an overall lack of support for smoking cessation and unavailability of targeted smoking cessation treatment (Ziedonis et al 2003; Barnes et al. 2006).
Formal institutional and system barriers that further contribute to this problem include restricted formularies and insurance reimbursement for smoking cessation treatments, exceptions to smoking bans in psychiatric facilities and inadequate staff training on smoking cessation (Ziedonis et al. 2003).
Among mental health professionals, training on tobacco dependence treatment is lacking and primary care providers and tobacco control specialists do not focus on this issue, perhaps due to stigma, lack of information or perceived hopelessness regarding abstinence (Ziedonis et al. 2007).
Because patients with schizophrenia often receive treatment in a variety of intensive settings (e.g. psychiatric hospitals, residential facilities, day treatment programs) these settings allow for the delivery of an intensive smoking cessation treatment integrated with mental health care. However, only recently have some psychiatric treatment settings begun to address tobacco use (Ziedonis et al. 2007).
Implications for Intervention
Kelly & McCreadie (2000) suggest that targeted smoking intervention during the first episode of schizophrenia could be beneficial. Although the percentage of smokers in the first episode is equivalent to those with chronic schizophrenia, they found that the number of cigarettes smoked per day was lower.
It was also established that although many patients experience difficulties and may relapse, they are interested in reducing smoking (Forchuk et al. 2002). Individuals with schizophrenia appear to be able to quit tobacco with the support of psychosocial treatment, nicotine dependence treatment medications and social support.
These patients must therefore be supported in these areas and be encouraged to quit smoking. Tobacco companies cannot be expected to spread this message, but they must desist from suppressing this message.
Clinical studies report that different intensity psychosocial treatment interventions have been effective, including one-to-one and group based counseling using modified American Lung Association interventions, cognitive-behavioral therapy approaches, social skills training and contingency monetary reinforcement.
Most of the studies using nicotine replacement or buproprion in this population have included a psychosocial treatment component.
Motivational interviewing for less motivated smokers
Engaging less motivated patients with psychosocial interventions is important given the high rates of tobacco dependence and the smaller number of individuals with schizophrenia who are prepared to quit smoking.
Motivational interviews with personalized feedback (e.g. Carbon monoxide level, personal annual cost of cigarettes, personal medical conditions caused or exacerbated by smoking) was found effective in motivating 32% of smokers with schizophrenia to seek smoking cessation treatment within one month of the single session intervention compared to 11% among those receiving an educational intervention and 0% among those provided with information only (Steinberg, et al. 2004).
From these statistics, it is clear that motivational interviewing is a powerful tool that can be used to motivate schizophrenic patients and convince them to quit smoking.
Interventions for smokers ready to quit
Medication treatment studies on smoking cessation have been primarily small, uncontrolled and usually combined with psychosocial treatments for smoking cessation. Bupropion appears to be tolerated and to help reduce smoking and expired air carbon monoxide (George et al 2002).
Nicotine patch on the other hand appears safe and well-tolerated but has achieved lower than expected long-term abstinence rates (Williams & Hughes 2003) while Nicotine nasal spray appears helpful among schizophrenic individuals (Williams et al. 2004) and may produce short term reduction in schizophrenia symptoms and cognition.
Tobacco dependence outcomes may also be affected by the pharmacological treatment for the mental disorder itself. Treatment with typical antipsychotics, particularly clozapine, has been associated with more successful quit attempts among schizophrenia patients motivated to stop smoking than among those treated with typical antipsychotics (George et al. 2000).
What role does exercise play in the treatment process
Exercise may exert beneficial effects by addressing psychosocial and physiological needs that nicotine replacement alone does not (Williams & Hughes 2003). Exercise has been shown to help in health behavioral change such as aiding women in stopping habits such as smoking and can also reduce aging that is induced by stress. Physical exercise is also important in managing weight after cessation.
The newest FDA-approved remedy for smoking surcease is Varenicline. It preys upon α-4 and β-2 receptors and behaves like a partial resister.
This means that it mildly stimulates the nicotine receptor, but not sufficiently to allow the release of dopamine which is important for the rewarding effects of nicotine (Williams & Hughes 2003). As a resister, Varenicline prevents nicotine from triggering dopamine thereby reducing the urge to smoke.
Behavior based Treatment
Behavioral training is important because it trains patients on what changes to make in their lifestyles to avoid relapse. A synergic effect is achieved with the combined approach of using behavioral and pharmacological treatments.
Harris and colleagues (2004) reported that the impact was bidirectional with decreased functioning in the participants who were smokers and improved functioning in the group that were non-smokers. There is a scarcity of longitudinal research to investigate whether cognitive functioning worsens after confirmed abstinence.
George et al. (2000) reports that one study conducted in 1996 noted an increase in psychotic symptoms after smoking cessation. However, in a controlled study of smoking cessation interventions using bupropion, there was no evidence of worsening psychiatric symptoms (George et al. 2000).
Conclusion
Researchers in these studies admit to have had methodological challenges. Data collection was difficult because the sample sizes were small and the methodologies were cross-sectional.
The high prevalence of tobacco dependence in patients with schizophrenia may be associated with dysfunction in the neurobiology associated with dopamine systems, while there is a focus on the research to suggest that people with schizophrenia smoke to self-medicate the cognitive and clinical symptoms associated with the illness and side-effect profiles of neuroleptic medication (Kelly & McCreadie 2000; deLeon & Diaz 2005; Barnes et al. 2006)
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