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    Mental Illness

    Introduction To What Extent Can Schizophrenia Be Attributed to Biological Versus Environmental Factors?

    The World Health Organization (WHO) describes schizophrenia as a severe mental disorder characterised by distortions in thinking, perception, emotions, language, sense of self and behaviour (The WHO Factsheet for Schizophrenia; 2016). Schizophrenia is a deteriorating illness which starts usually between age of 16 and 30 years. Even though, the signs and symptoms of schizophrenia are well-defined and clinically identified, yet its nature, aetiology, and the choice of therapy remains a mystery for clinicians. The researchers consider that schizophrenia is caused by an interplay of genetic, behavioural and environmental factors.

    However, the role and extent of each of these factors attributable in developing schizophrenia is not fully understood (Cariaga-Martinez, A., & Alelú-Paz, R; 2017).  The clinical studies done so far to evaluate the natural history of schizophrenia indicate that biological factors or genetic constitution of a person is an important factor that steers the development of this complex mental illness. Whereas, presence of environmental and behavioural factors amplifies the chances of an individual to have schizophrenia. Multiple environmental factors like obstetric complication, adverse child rearing, drug abuse, season of birth, child abuse, migration/ethnicity, prenatal/postnatal infections, head injury, urbanization, maternal malnutrition, social adversity, maternal stress, and ill-fated life events are found to be associated with onset of schizophrenia (Haggerty, J; 2016).

    The incidence and prevalence of schizophrenia clearly indicates a strong genetic association of this disease. Researches states that an average person has only 1% the chances of having schizophrenia in his lifetime, however the risk increases to 12% if one of the parent is schizophrenic. Alarming is the fact the risk of developing schizophrenic is as high as 39%for an individual whose both of parents are schizophrenic.

    The risk is further elevated to 47% if both parents and the identical twin of a person is suffering from schizophrenia. Likewise, the risk is 8% if one of the sibling is schizophrenic, while it is 14% if one has a schizophrenic fraternal twin(Haggerty, J; 2016).  A recent clinical study also stated that the inheritability of schizophrenia for monozygotic twins is about 80%, with a high concordance rates of about 40–50% (Castellani, C.A.; 2015). The findings of this study and the previously described statics clearly indicates that genetic factor is by far the most important regulating factor for development of schizophrenia.  

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    Contradicting to these findings, the adoption studies shows that environmental factors also significantly involved in onset of schizophrenia. It was found in these studies that there is an elevated risk for psychosis in offspring adopted by schizophrenic parents, similar findings were observed with individual with schizophrenic foster parents (Gejman PV, 2009). Another study stated that the risk of transmission of schizophrenia was similar among offspring of schizophrenia mothers, whether they were raised by the biological (schizophrenic) parent or an adoptive (non-schizophrenic) parent. These findings indicate that irrespective of the genomic make-up of an individual the risk of developing schizophrenia can be altered by modifying the environmental factors of the disease.

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    A genetic study done to describe the aetiology of schizophrenia suggested thatthe 677C—>T polymorphism is present at higher levels in patients with schizophrenia than the general population.  However, the further studies done to elucidate failed to replicate the finding of this study (Regland B; 1997).

    The recent genomic-wide association studies (GWAS) were the largest set of studies done to evaluate the nature and extent of association of genetic polymorphism with schizophrenia. the study compared the genomes of 37,000 schizophrenics against 113,000 healthy individuals. The findings of this study revealed 128 genome wide significant single nucleotide polymorphisms (SNP) and 108 genome wide loci in schizophrenic individuals. Additionally, structural variations such as microdeletions and microduplications were also identified in a subgroup of patients. The microdeletions were identified on 1q21.1, 2p16.3, 3q29, 15q13.3 and 16p11.2 as well as a large deletion were on 22q11.21 and a single microduplication on 16p11.2. These findings provide substantial evidences about the role of genetic factors in development of schizophrenia.

    However, further studies are recommended to find out the exact genes which are responsible for onset and progression of this mental illness (Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2014).The major limitations of the GWAS studies was the high chances of getting false positive results due to complex methodology involved. Secondly, the interplay of other factors, particularly environmental factors were not studied, which might have influenced the overall findings.

    As stated earlier, several environmental factors are found to be strongly associated with schizophrenia or psychosis.  The risk of schizophrenia is significantly increased among the new-borns who are exposed to maternal infection like rubella and respiratory infections, born under low socioeconomic class, have significant maternal deprivation due to natural calamity like famine or man-made calamity like war/ riots, obstetric complications, and are born in late winter/early spring.

    A few studies are done which compared the influence of both genetic and environment factors parallelly in individuals with schizophrenia. A study was done to compare the role of genetic factors and environmental factors in development of schizophrenia later in life.  The findings of this study showed that foetal hypoxia or pre-natal insult results in decrease in mass of grey matter and reduced volume of cerebrospinal fluid in foetus brain.  New-borns exposed to such pre-natal events are at high risk of developing schizophrenia irrespective of their healthy genetic constitution and no family history of schizophrenia(Cannon TD, 1993). As mentioned earlier, stress is another environmental factor which pre-disposes an individual with normal genetics to schizophrenia. Stress produces glutamate and dopamine which adversely affects the neurotransmission of brain, thereby resulting in schizophrenia (Palomo T, 2004). It was found that any form of post-natal stress in an individual with genetic factors of schizophrenia accelerate the chances of onset of symptoms.

    While in a normal induvial stress increases the risk of developing schizophrenia. Another independent study was done to evaluate the familial aggregation and heritability of schizophrenia in affected families. The authors of this study concluded that, despite having a strong familial aggregation, an uncertainty was found among the degree of genetic contribution to the phenotypic variance of the disease.The accountability for the phenotypic variance of schizophrenia was found to be as high as 47.3% with presence of known genetic factors, 15.5% for presence of shared environmental factors, and 37.2% for presence of non-shared environmental factors. These findings indicate the relative proportion to which genetic and environmental factors influence the onset and progression of schizophrenia (I-Jun Chou Chang-Fu Kuo; 2016).

    The aetiopathogenesis of schizophrenia is complex and still not well-understood. Though the studies done so far have clearly stated the role of multiple risk factors, yet the evidences clearly demarcating the role of each factors is yet to be elucidated. The evidences collated and analysed so far have concluded that biological predisposition (i.e. genetic compositions) and presence of certain environmental factors (stress, pre-natal trauma etc.) together led to development of schizophrenia. Neither of these two factors solely determine the chances of an individual developing schizophrenia. Hence, both factors are equally related to pathogenesis of this disease and a strong interplay is being suggested for progression or worsening of symptoms.

    A better understanding of these risk factors is necessary for identifying the high-risk individual and for minimizing the chances of development of schizophrenia. Additionally, it is essential that the genetic and environmental factors are studied by further experiments to find out their exact association with the disease which could later help the clinicians to find better therapeutic options for prevention, timely diagnosis and management of schizophrenia.


    • Cannon TD, Mednick SA, Parnas J et al. (1993), Developmental brain abnormalities in the offspring of schizophrenic mothers. I. Contributions of genetic and perinatal factors. Arch Gen Psychiatry, 50(7), 551-564.
    • Cariaga-Martinez, A., & Alelú-Paz, R. (2017). Rethinking the Epigenetic Framework to Unravel the Molecular Pathology of Schizophrenia. International Journal of Molecular Sciences, 18(4), 790. doi:10.3390/ijms18040790.
    • Castellani, C. A., Melka, M. G., Gui, J. L., O’Reilly, R. L. & Singh, S. M. (2015). Integration of DNA sequence and DNA methylation changes in monozygotic twin pairs discordant for schizophrenia. Schizophr. Res., 169, 433–440.


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