Schizophrenia Genetic and Environmental Factors

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Table of Contents

Introduction
General Overview
Schizophrenia: Important Factors
How to Manage Schizophrenia
Conclusion
References

Introduction

Since antiquity mankind has been faced with the challenge of dealing with several psychological disorders as well as diseases. Most of the diseases and disorders interfere directly with the normal functioning of the body system. The effects of these diseases are usually manifested through one’s day to day behaviour or mental symptoms.

Psychiatric disorders refers to any behavioural or psychological symptoms that renders an individual very much distressed, causes paralyses which result in high exposure to pain, disability, or may sometimes cause death (Williams, Owen, & O’Donovan, 2009). Schizophrenia has been categorized by the World Health Organisation as the 7^th greatest cause of disability in the world (Savina & Orlova, 2003).

Many common disorders of adult life have been found to follow complex patterns of inheritance. In order for a condition to be considered a psychiatric disorder, the mentioned manifestations must be experienced for over a fortnight.

Schizophrenia, for instance, is one of the many heritable disorders with a rather complex genetic architecture interacting with the factors in the surrounding (Winterer, Egan, Raedler, Sanchez, Jones, Coppola, & Weinberger, 2003).

The research paper explores schizophrenia by providing a general overview, a comprehensive discussion of clinical synopsis, genetics and environmental factors in relation to schizophrenia, limitations of the methods of analyses, and a clear demonstration of analytical and conceptual approach. It explains three genetic and two environmental factors associated with schizophrenia as well as available options for managing the disorder.

General Overview

Schizophrenia is one of the most common psychological disorders especially in the developed countries like the United States with an estimated prevalence rate of 1% (Williams et al., 2009). Epidemiologically, it is a chronic and causes severe mental illness, harsh, and a brain-paralyzing disorder (Frangou, 2008). Schizophrenia is usually characterized by illusions or the improper perception of what is otherwise real.

The individual suffering from schizophrenia has been found to constantly experience auditory delusions, thinking and talking in a haphazard way, and other different forms of hallucinations. Schizophrenia usually confers important morbidity and disability (about 1.0% and 0.3%-1.7% worldwide respectively) and is identified by the emergence of psychotic symptoms (Frangou, 2008).

Moreover, the patient exhibits cognitive discrepancies, antisocial tendencies, and flat affect. The manifestations of initial stages of schizophrenia commonly start at early adulthood especially for men (Savina & Orlova, 2003). Most significant to note is that this mental illness can only be diagnosed using the personal experiences and overt behavior of the patient. This is due to the fact that its laboratory test is yet to be discovered.

Schizophrenia: Important Factors

Genetic Factors

Current research findings reveal that there is a strong evidence for a significant genetic link to schizophrenia (Frangou, 2008). Many researchers have come to agree that many genes of small significance are responsibility for the high heritability (about 83%) of the disorder.

Some of the genes that have been associated with incidences of schizophrenia include Neuregulin 1 (NRG 1), Disrupted in Schizophrenia (DISC 1), the DTNBP 1, the catechol-O-methyl transferase (COMT), CHRNA 7, and so on. It has been established through recent research that these genes have an impact on the several processes that regulate the synaptogenesis and connectivity of the neurons.

This process may play a role in the creation of subtle abnormalities in molecular aspects (Williams et al., 2009). Consequently, it leads to inefficiency in the functioning of the brain system that causes the schizophrenic symptoms (Frangou, 2008). Three of the major gene factors are discussed in the following paragraphs.

NRG1 Gene

Of all the known psychiatric diseases, schizophrenia remains to be one of the most devastating of them in some parts of the world. A lot of resources have been channeled towards conducting research into the nature of the disease.

Most of the studies have always focused on the functioning of the dopamine and serotonin systems albeit with minimal success (Li, Collier & He, 2006). However, recent studies have implicated a number of possible ways with neuregulin 1 (NRG 1) gene also referred to as heuregulin (Li et al., 2006).

It has been established through a number of genome-wide scans that the NRG 1 is found at 8p21-p12 which is the best replicated connectivity loci for schizophrenia. The NRG 1 gene is a pleiotropic growth factor and is crucial for the development and functioning of the nervous system (Li et al., 2006).

The gene plays a major role when it comes to modulating the migration of neural, gliogenesesis, synaptogenesis, neuronglia communication, myelinatuin, as well as transmission through the neurons in the brain and other body systems. NRG 1 is a large and complex gene and spans about 1.2 Mb with a minimum of 30 exons and 9 possible promoters.

Research findings released indicated that an association exists between NRG 1 and schizophrenia as a result of positional mapping of a connection peak on the chromosome 8pin Icelandic families (Savonenko, A. V., Melnikova, T., Laird, F. M., Stewart, K. A. et al., 2008).

The haplotype HAP(ICE) located at the 5’ end of the gene whose core is at risk was made up of 5 SNPs (SNP8NRG221132, SNP8NRG221533, SNP8NRG241930, SNP8NRG243177, SNP8NRG433E1006) and two microsatellites (478B14-848, 420M91395), was found to be closely linked to the onset of schizophrenia in the Icelandic people and was also reproduced in the Scottish population (Li et al., 2006).

Follow up investigations by other researchers have found the same results even though they have used family-based association designs (Li et al., 2006). However, others have found conflicting results particularly on the basis of race.

In an attempt to reconcile the conflicting outcomes and to explain the genetic architecture that exists between NRG 1 and schizophrenia, the most recent meta-analysis uses the results for the most regularly analysed NRG 1 markers from both relevant associations based on population and or family.

Generally, it has been found from research that all of the six individual polymorphisms and the haplotypes at risk in NRG 1indicated a very strong and positive relationship with schizophrenia. However, gene heterogeneity is the principle characteristic of the investigation of complex disorders (Li et al., 2006). Some of the causes of heterogeneity could be the variety in demographic and clinical diagnosis.

This study, however, was limited first by the lack of confidence in the samples used so as to avoid replication as well as due to genetic heterogeneity of schizophrenia. Secondly, the results may have differed due to ethnic and varying geographical location causing variance in observed allele and especially frequencies of haplotype (Li et al., 2006). A third explanation of the variations may be due to difference in sampling.

Furthermore, environmental conditions may also affect results obtained. From the above discussion, it is evident that research has proved that NRG 1 in one of the pathogenesis of schizophrenia and is a gene in the brain glutamine system (Savonenko, Melnikova, Laird, Stewart et al., 2008). This kind of knowledge is important to different fields; it has scientific implications, clinic and for the public good.

DTNBP1 Gene

At the dawn of the 21^st century, several new susceptibility genes for schizophrenia were determined. The detection was by achieved by conducting association studies. Researchers have proposed that a number of these genes may end up converge upon schizophrenia risk on functional basis(Jonsson, Saetre, Vares, Andreou, & Larsson, 2008).

For instance, dystrobrevin-binding protein 1 (DTNBP1; chromosome location 6p22.3), D-amino-acid oxidase (DAO; 12q24), DAO activator (DAOA), and neuregulin 1 (NRG1; 8p12-21).

In an attempt to replicate the studies, single-nucleotide polymorphisms of these genes were evaluated in three independent schizophrenia population case-control samples. Some DTNBP1 and 3 GRM3 SPNs did not show significant associations to schizophrenia.

A study by Fanous, Riley, Aggen, Neale, O’Neill, Walsh, & Kendler (2005), sought to find out whether a haplotype in the DTNBP1 gene which was initially associated with schizophrenia not only enhances the susceptibility to psychotic disorders but also to a clinically specific type of psychotic disorder (Narr, Szeszko, Lencz, et al., 2009).

The study concluded that variation in DTNBP1 gene may be a predisposing factor to a type of psychotic disease associated with increased negative symptoms (Burdick, Lencs, Funke, Finn et al., 2006). It supports the assertion that has existed before; that genetic factors do affect the clinical heterogeneity of schizophrenia as a psychotic disorder (Narr, Szeszko, Lencz, Woods et al., 2009).

The study is important because it helps in understanding the impact of genetic variation is specific genes, such as DTNBP1, in causing or enhancing psychotic illness vulnerability despite the fact that the cause of the gene aberrations in the genes is yet to be known and hence implications on treatment (Williams, O’Donovan, & Owen, 2005).

CHRNA7 Gene

The alpha-7-nicotinic receptor subunit gene (CHRNA7) has been associated with schizophrenia and other cognitive deficits (De Luca, Likhodi, Van, Kennedy & Wong, 2006). It is found at chromosome 15q13-14, which is a region initially linked with schizophrenia.

Researchers in the field of genetic association as well as mRNA7 expression investigations have implicated CHRNA7 in schizophrenia. The study findings indicate that the ratios of alpha7 to alpha7-like mRNA levels in bipolar disorder as well as schizophrenia are much lower than that in controls. The bipolar subjects show the highest magnitude of alteration.

This study can be of great importance. It is possible to measure the mRNA levels of alpha 7-nicotinic receptor subunit (CHRNA7) separately from that of pseudo-gene CHRFAM7A. This can be done by quantitatively using sequence-specific fluorescent primers in real-time PCR (De Luca et al., 2006).

Also, CHRNA7 expression in dorsolateral prefrontal cortex is not different between schizophrenia subjects, those with bipolar disorder or unaffected controls. Moreover, the ratio of CHRNA7: CHRFAM7A mRNA levels do not differ in bipolar subjects particularly when compared to those subjects with schizophrenia or those unaffected controls.

There are some limitations that are inherent in this particular case. Medical treatment, use of nicotine and agonal events can significantly change the levels of mRNA in human postmortem tissue.

This can potentially confound disease effects. Secondly, the expression of the ready functional mRNA transcripts of CHRNA7 and CHRFAM7A were not measured (De Luca et al., 2006). On the hand, sample sizes for such studies are normally quite small due to the fact that it is difficult to get postmortem human brain tissue.

Environmental Factors

Family Interaction

Researchers in the field of psychiatric disorders have over the past few decades developed literature on how the family environment affects the short-term course taken by a disorder after the individual is released from the hospital (Kopelowicz, Lopez, Zarate, O’Brien, Gordon, Chang, & Gonzales-Smith, 2006).

It has been found that the released person will react differently depending to the degree to which relatives verbalised criticism, hostility, or emotional over-engagement directed to the patient which is referred to as expressed emotion(EE) (Kopelowicz et al., 2006).

This incident will result in relapse of the patient followed by rehospitalisation within one year of being released. Consequently, the finding has led to the development of meaningful family intervention attempts to help psychiatric patients especially those with schizophrenia recover and join the family upon being discharged from hospital.

Many researchers have ventured deeper with an aim of understanding the relationships among EE and the course of illness as well as its relation to relapse. Interpersonal interaction between the patient and the rest of the family members or relatives is also of significance to researchers in this field.

They have also conducted cross-cultural research of families and how they contribute to the advancement in understanding the role of families as far as schizophrenia is concerned. Culture has emerged to be very influential in shaping the how family members interact especially perception of illness and emotional reactions (Kopelowicz et al., 2006).

Other researchers have established that overcrowding at home may be a risk factor for those with schizophrenia (Wahlbeck, Osmond, Forsen, Barker, & Eriksson, 2001). This study is important since it helps understand the relationship between EE and relapse, family interaction and relapse, and EE and family interaction. The findings also help families adjust to the needs of their patient without causing any relapse.

However, the conclusions from the study may not be generalisable due to the small sample use. Also, the study interviewed only one relative yet family interaction comprises of many people and hence the need for longitudinal study so as to capture different parties involved in the interaction network.

Use of Drugs

Substance abuse has been associated with schizophrenia especially the use of cannabis sativa, amphetamines as well as cocaine. Research findings reveal that more than half of those suffering from the disorder abuse drugs. Investigations by researchers in this field have concluded that cannabis plays the role of a causative agent while other drugs are abused as a ‘coping’ strategy.

This is mainly because schizophrenia is characterised by depression, feeling lonely, and general anxiety (Frangou, 2008). Cannabis is highly addictive and poses a great risk of psychotic illnesses. Continued use of the drug increases the risk of developing schizophrenia.

How to Manage Schizophrenia

Many theories concerning schizophrenia have been put forward. Some of the factors that are associated with the onset of schizophrenia include the individual’s genetic background and the environmental conditions that one is exposed to at the earlier stages of growth and development (Frangou, 2008).

Moreover, neurobiology which involves the study of the nervous system and the social and mental processes has been identified as playing a major role in the development of schizophrenia.

It is important, however, to note that the root causes of schizophrenia have not yet been fully established but continuous research has brought some sense of hope as far as its treatment is concerned (Frangou, 2008).

According to Frangou, modern antipsychotic medication is basically the foundation of known pharmacological treatment of schizophrenia (2008). Current antipsychotic medications seek to eliminate the symptoms associated with the schizophrenia and allow the patient to live a normal life in the society.

Although the older types of anti-psychotics are in use today, most current ones which include clozapine are very effective in the treatment of acute symptoms. For individuals who are genetically prone to this particular disorder, the use of some medicinal drugs or those that are meant to be used for recreational purposes may also be the cause or serve to enhance the rate of suffering from schizophrenia.

For example, clozapine reduces the number of white blood cells in the body hence causing an increase in the risk of infections. The side effects of using antipsychotic medication include improper vision, rashes on the skin, increased heartbeat, and can also affect monthly periods among females.

Alternately, psychosocial treatment options have been developed in order to deal with the patients who have become highly resistant to the use of antipsychotic medication (Addington, Piskulic & Marshall, 2010).

Conclusion

The paper has presented a comprehensive discussion of schizophrenia. It has explored the two major causes which are: Genetic factors and environment. The benefits of the studies as well as their weaknesses have also been highlighted. Under genetic, three genes have been discussed and include the NRG1, DTNBP1, and CHRNA7. Environmental factors, on the other hand include family interaction and substance abuse.

The paper has discussed the strategies for managing schizophrenia especially in the modern age where psychosocial treatment options are now becoming popular as traditional medications fail to bring relief to the patient.

References

Addington, J., Piskulic, D., & Marshall, C. (2010) Psychosocial Treatment for Schizophrenia. Current Directions in Psychological Science, 19 (4): 260-263

Burdick, K. E., Lencs, T., Funke, B., Finn, C. T. et al. (January 2006) Genetic variation in DTNBP1 influences general cognitive ability. Human Molecular Genetics, 15, (10): 1563-1568

De Luca, V., Likhodi, O., Van, T., Kennedy, J. L. & Wong, A. H. C. (February 2006) Regulation of alpha7-nicotinic receptor subunit and alpha7-like gene expression in the prefrontal cortex of patients with bipolar disorder and schizophrenia. Acta Psychiatrica Scandinavica, 114: 211-215

Fanous, A. H., riley, B. P., Aggen, S. H., Neale, M. C., O’Neill, F. A., Walsh, D. & Kendler, K. S. (October 2005) Relationship Between a High-Risk Haplotype in the DTNBP1 (Dysbindin) Gene and Clinical Features of Schizophrenia. American Journal of Psychiatry, 162: 1824-1832

Frangou, S. (2008) Psychiatric Disorders: Schizophrenia. Medicine 36 (8) [Peer Reviewed], Pp. 405-409

Jonsson, E. G., Saetre, P., Vares, M., Andreou, D. & Larsson, D. (May, 2008). DTNBP1, NRG1, DAOA, DAO AND GRM3 Polymorphisms and Schizophrenia: An Association Study. Neuropsychology, 59: 142-150

Kopelowicz, A., Lopez, S. R., Zarate, R., O’Brien, M., Gordon, J., Chang, C. & Gonzales-Smith, V. (2006) Expressed Emotions and Family Interactions in Mexican Americans with Schizophrenia. The Journal of Nervous and Mental Disease, 194: 330-334

Li, D., Collier, D. A. & He, L. (2006) Meta-analysis shows strong positive association of the neurogulin 1 (NRG 1) gene with schizophrenia. Human Molecular Genetics, 15 (12): 1995-2002

Narr, K. L., Szeszko, P. R., Lencz, T., Woods, R. P. et al. (2009) DTNBP1 Is Associated with Imaging Phenotypes in Schizophrenia. Human Brain Mapping, 30: 3783-3794

Pae, C., Mandelli, L., De Ronchi, D., Kim, J. et al. (2009) Dysbindin gene (DTNBP1) and schizophrenia in Korean population. European Arch Psychiatry Clinical Neuroscience, 259: 137-142

Savina, T. D. & Orlova, V. A. (2003) “Genetic Determination of Mental Activity Parameters in the Families of Schizophrenia Patients.” Russian Journal of Genetics, 39 (1): 77-86

Savonenko, A. V., Melnikova, T., Laird, F. M., Stewart, K. A. et al. (2008) Alteration of BACE1-dependent NRG1/ErbB4 signalling and schizophrenia-like phenotypes in BACE1-null mice. The National Academic of Sciences of the USA

Wahlbeck, K., Osmond, C., Forsen, T., Barker, D. P., & Eriksson, J. G. (2001) “Associations between childhood living circumstances and schizophrenia: a population-based cohort study.” Acta Psychiatrica Scandinavica, 104: 356-360

Williams, H. J., Owen, M. J., & O’Donovan, M. C. (2009) Schizophrenia genetics: new insights from new approaches. British Medical Bulletin, 91: 61-74

Williams, N. M., O’Donovan, M. C. & Owen, M. (September 2005) Is the Dysbindin Gene (DTNBP1) a Susceptibility Gene for Schizophrenia? Schizophrenia Bulletin, 31 (4): 800-805

Winterer, G., Egan, M. F., Raedler, T., Sanchez, C., Jones, D. W., Coppola, R. & Weinberger, D. R. (November 2003) P300 and Genetic Risk for Schizophrenia. Arch Gen Psychiatry, 60

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