The Heredity of Mental Disorders

Elizabeth (Shuxuan) Li ’25, Neuroscience, 22F

If you were a prospective parent with a mental disorder, would your children be more at risk for your specific condition or mental illnesses in general?

Mental health data from Dr. Jill Goldstein’s research team showed that children at risk for any psychological condition often developed the same disorder as their parents (Goldstein et al., 2010). In other words, the heredity of psychological conditions is “disorder-specific” (Spang et al., 2022). Curiously, another finding published only three months later backed up the alternative theory: parents with any mental disorder increase their children’s risk for the “full-spectrum” of psychiatric conditions, according to Dr. Kimberlie Dean (Dean et al., 2010). The studies both tracked two generations over decades, yet their conclusions contrast each other. Between disorder-specific and full-spectrum inheritance, determining the most likely theory would help researchers and psychiatrists better attribute the risks for a range of psychological conditions.

Among the broad categories of mental conditions are schizophrenia-psychosis spectrum (SPS) disorders and affective psychoses (AP). SPS disorders are characterized by frequent hallucinations and losing touch with reality, while APs involve episodes of depression in addition to hallucinations. For children of parents with SPS disorders, Goldstein found that they had almost six times more risk for SPS disorders but not for APs. Conversely, children of parents with APs were fourteen times more likely to develop APs but not SPS disorders. However, this disorder-specific effect was called into question only three months later. Research on the entire population of Denmark found that SPS and APs in parents predicted more risk for not only their own condition but also for the full spectrum of psychiatric illnesses (Dean et al., 2010).

When the methods of the two studies are explored in depth, the full-spectrum pattern of inheritance seems to be rooted in stronger evidence than disorder-specific inheritance. In terms of participant demographic, Dean et al.’s population consisted of every person born in Denmark between 1980 and 1994. Roughly 50,000 had mental health troubles before turning thirty, and 1,000 of their parents also had at least one condition. The pattern of disorders from these 51,000 people generated the full-spectrum inheritance conclusion. Compared to Dean et al.’s massive sample size, Goldstein worked with only a few hundred parents and offspring from select medical centers in the US. Since larger and more comprehensive samples tend to increase the precision of study estimates, Dean and colleagues’ claim on full-spectrum inheritance seems more statistically robust. Moreover, the large population enabled Dean’s team to track the mental health history of mothers and fathers, whereas Goldstein only analyzed data from mothers. Since the risk of developing SPS and APs varies by sex,excluding fathers could have skewed the results for the supposed disorder-specific inheritance (Aleman et al., 2003).

In addition to a substantial sample size, the wide range of disorders studied by Dean and colleagues (2010) also provides more support for the full-spectrum inheritance theory. Dean’s team tracked nine categories of mental illnesses, including but not limited to SPS disorders, APs, anxiety disorders, personality disorders, and substance misuse. In contrast, Goldstein only accounted for AP and SPS disorders, eliminating the possibility to investigate inheritance patterns across other conditions. From Goldstein et al.’s data (2010), there is no way of knowing whether the second generation could have also been at risk for other disorders like depression. Hence, the lack of measures other than SPS and APs further reduces the credibility of the disorder-specific hypothesis.

Interestingly, the two authors referenced the same studies on the heredity of mental illnesses—the Copenhagen and New York High-Risk Projects—to support different theories (Parnas et al., 1993; Erlenmeyer-Kimling, 1997). Both the Copenhagen and New York Projects found that children of mothers with schizophrenia have elevated risks not only for schizophrenia, but also for a range of psychotic, affective, and personality disorders. Whereas Dean et al. (2010) properly presented these conclusions in her article, Goldstein et al. (2010) only extracted the data relevant to SPS and APs.

The field of psychology has struggled to understand why the full-spectrum inheritance of mental disorders exists in the first place. Since both genes and the environment impact brain development, their interaction makes it difficult for researchers to attribute any singular factor to a mental condition. At the moment, psychologists are far from being able to pinpoint an exact group of genes for most psychiatric conditions (Cloninger, 2002).

While genetics influence one’s susceptibility to mental disorders, recent work has also focused on the environmental influences on psychological health. Many factors have yet to be studied extensively, including the loss of a parent, childhood maltreatment, and parenting quality. How might one’s later experiences interact with genes to trigger or prevent a mental illness? Is it realistic to expect a perfect theory on the causes of each disorder? Future research in psychological health may require a reclassification of mental disorders as well as a reorganization of how people understand psychiatry (Kawa & Giordano, 2012).

References

Aleman, A., Kahn, R. S., & Selten, J. (2003). Sex Differences in the Risk of Schizophrenia: Evidence from Meta-analysis. Archives of General Psychiatry, 60(6), 565–571. https://doi.org/10.1001/archpsyc.60.6.565

Cloninger, C. R. (2002). The Discovery of Susceptibility Genes for Mental Disorders. Proceedings of the National Academy of Sciences, 99(21), 13365–13367. https://doi.org/10.1073/pnas.222532599

Dean, K., Stevens, H., Mortensen, P. B., Murray, R. M., Walsh, E., & Pedersen, C. B. (2010). Full Spectrum of Psychiatric Outcomes Among Offspring With Parental History of Mental Disorder. Archives of General Psychiatry, 67(8), 822–829. https://doi.org/10.1001/archgenpsychiatry.2010.86

Erlenmeyer-Kimling, L., Adamo, U. H., Rock, D., Roberts, S. A., Bassett, A. S., Squires-Wheeler, E., Cornblatt, B. A., Endicott, J., Pape, S., & Gottesman, I. I. (1997). The New York High-Risk Project: Prevalence and Comorbidity of Axis I disorders in Offspring of Schizophrenic Parents at 25-year Follow-up. Archives of General Psychiatry, 54(12), 1096-1102. https://doi.org/10.1001/archpsyc.1997.01830240052008

Goldstein, J. M., Buka, S. L., Seidman, L. J., & Tsuang, M. T. (2010) Specificity of Familial Transmission of Schizophrenia Psychosis Spectrum and Affective Psychoses in the New England Family Study’s High-Risk Design. Archives of General Psychiatry, 67(5), 458–467. https://doi.org/10.1001/archgenpsychiatry.2010.38.

Parnas, J., Cannon, T. D., Jacobsen, B., Schulsinger, H., Schulsinger, F., & Mednick, S. A. (1993) Lifetime DSM-III-R Diagnostic Outcomes in the Offspring of Schizophrenic Mothers: Results from the Copenhagen High-Risk Study. Archives of General Psychiatry, 50(9), 707-714. https://doi.org/10.1001/archpsyc.1993.01820210041005

Spang, K. S., Thorup, A. A. E., Ellersgaard, D., Hemager, N., Christiani, C., Burton, B. K., Gantriis, D., Greve, A., Gregersen, M., Mors, O., Nordentoft, M., Jepsen, J. R. M., Obel, C., & Plessen, K. J. (2022). The Strengths and Difficulties Questionnaire Is of Clinical Significance Regarding Emotional and Behavioral Problems in 7-Year-Old Children With Familial Risk of Schizophrenia or Bipolar Disorder and Population-Based Controls the Danish High Risk and Resilience Study-VIA 7; A Population-Based Cohort Study. Frontiers in Psychiatry, 13, 861219. https://doi.org/10.3389/fpsyt.2022.861219