Module 4: Causes of Psychological Disorders

Psychological disorders have etiologies that are largely multi-factorial, involving complex interactions between genetic and environmental factors. A number of risk factors have been implicated in the development of psychological disorders, but their relative contributions to mental illness are specific to different disorders and individual patients, and a precise cause can rarely be identified on an individual basis.(1) Below is a sampling of some of the variables identified as risk factors in the development of psychological disorders.

Please note that the following list is not an exhaustive list of all factors that may contribute to mental illness, and should not be used as a diagnostic tool. 

Biological and Personal Factors(2)

Environmental Factors(3)

Gene by Environment Interactions: Schizophrenia and Depression

The factors listed above do not act in isolation to contribute to the development of psychological disorders, and the nature of gene by environment interactions is the subject of substantial research. Gene-environment interactions describe the phenomenon by which certain gene variants modulate the effects of environmental factors. However, environmental factors often cause epigenetic changes –chemical modifications that affect how genes are expressed – making it difficult to distinguish environmental from genetic effects. Increased interest in epigenetics has prompted modern psychiatric research to focus on biochemical mechanisms by which environmental factors may influence genetic expression and the onset of psychological disorders.(4) The following studies illustrate the complex nature of gene by environment interactions by providing a sample of research on the causes of schizophrenia and depression, two of the priority mental health conditions identified by the World Health Organization.(5) 


Schizophrenia has long been believed to have a strong genetic component. Twin studies report the concordance rate of schizophrenia (the probability that one twin will have the disorder if the other twin does) to be 45 to 60 % for monozygotic (identical) twins, compared to only 10 to 15 % for dizygotic (fraternal) twins. In a comprehensive review of schizophrenia literature, Husted et al. (2012) emphasize that many studies have also identified a host of environmental risk factors for schizophrenia. For instance, a classic study of the Dutch Hunger Winter (1944-1945) found that exposure to famine early in pregnancy was associated with a significant increase in schizophrenia risk for both male and female offspring. However, because of the retrospective nature of the study, researchers could not determine which of the many variables associated with famine (e.g. nutrient deficiencies, generalized stress, infection, ingestion of toxic substances, or a combination of those factors) contributed to the increased risk of psychosis.(6) Determining the relative contribution of environmental factors to the onset of schizophrenia is further complicated by the interactions between genetic and environmental variables. For instance, Caspi et al. (2005) found that different versions of the catecholamine-O-methyl transferase (COMT) gene, which is involved in the regulation of dopamine release in the prefrontal cortex, affected the degree to which adolescent cannabis use was a risk factor for schizophrenia.(7)        


The genetic contribution to depressive disorders is estimated to be approximately 30 to 40 %.(8) While a variety of environmental characteristics have been identified as risk factors for depression, early life stressors, such as childhood physical or sexual abuse, parental neglect, and loss of a parent, have been shown to significantly increase the probability of developing depression later in life.(9) The effects of early life stressors are influenced by a variety of genes, and the 5-HTTLPR gene, involved in serotonin transporter functioning, has received significant attention. Caspi et al. (2003) found that the short version of the gene, which is associated with a reduction in serotonin transporter function, increased the risk of developing depressive symptoms and suicidality following exposure to stressful life events and maltreatment during childhood.(10) However, results from studies of the 5-HTTLPR gene have not been consistent, and Heim et al. (2012) suggest that such variation occurs because different genetic backgrounds may alter the nature of the 5-HTTLPR gene by environmental interaction. Furthermore, a variety of other genes may influence this interaction, as a number of gene-environment interactions have been reported in recent studies of the 5-HTTLPR gene.(11)

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(1) National Institutes of Health. “Mental disorders”.

(2) Ibid.

(3) Ibid.          

(4) Susser et al. (1996) as cited in Husted, J.A., Ahmed, R., Chow, E.W.C., Brzustowicz, L.M., Bassett, A.S. (2012). Early environmental exposures influence schizophrenia expression even in the presence of strong genetic predisposition. Schizophrenia Research, 137(1-3): 166-168.

(5) World Health Organization (WHO). Mental Health Gap Action Programme (mhGAP): Scaling up care for mental, neurological, and substance use disorders. Retrieved 29 June 2012.

(6) Susser, E., Neugebauer, R., Hoek, H.W., Brown, A.S., Lin, S., Labovitz, D., Gorman, J.M. (1996). Schizophrenia after prenatal famine. Further evidence. Arch. Gen. Psychiatry, 53: 25–31.  As cited in Husted, J.A., Ahmed, R., Chow, E.W.C., Brzustowicz, L.M., Bassett, A.S. (2012). Early environmental exposures influence schizophrenia expression even in the presence of strong genetic predisposition. Schizophrenia Research, 137(1-3): 166-168.

(7) Caspi, A., Moffitt, T.E., Cannon, M., McClay, J., Murray, R., Harrington, H., Taylor, A., Arseneault, L., Williams, B., Braithwaite, A., Poulton, R., Craig, I.W. (2005). Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene-environment interaction. Biol. Psychiatry, 57: 1117–1127.

(8) Heim, C., Binder, E.G. (2012). Current research trends in early life stress and depression: review of human studies on sensitive periods, gene-environment interactions, and epigenetics. Experimental Neurology, 233(1): 102-11.

(9) Ibid.

(10) Caspi, A., Sugden, K., Moffitt, T.E., Taylor, A., Craig, I.W., Harrington, H., McClay, J., Mill, J., Martin, J., Braithwaite, A., Poulton, R. (2003). Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science, 301: 386–389.

(11) Heim et al. (2012)