The empirical study selected is “Environment and Vulnerability to Major Psychiatric Illness: A Case Control Study of Early Parental Loss in Major Depression, Bipolar Disorder and Schizophrenia” by Agid et al. (1999). The purpose of Agid et al.’s study was to examine early parental loss (EPL) as a risk factor in three mental health disorders, bipolar disorder (BPD), major depression (MD), and schizophrenia, in comparison to healthy control subjects. The authors justify their study by describing how EPL as a risk factor for mental illness is not well understood. The authors utilized a review of the literature to develop five hypotheses for their case control study which were intended to understand the different dimensions of EPL and its role in psychiatric illnesses. The authors essentially sought to characterize how these different elements relate to EPL and its influence in the risk of mental illnesses. This pertinent for BPD and MD, given that environmental factors like trauma and grief are known contributors (National Institute of Mental Health [NIMH], 2016; NIMH, 2018).
To examine these hypotheses, the authors conducted a quantitative case controlled study which featured statistical analysis. Patients with BPD, MD, and schizophrenia were recruited from participating hospitals based on consecutive admissions and visits to follow-up clinics at those hospitals (Agid et al., 1999). The healthy control subjects were randomly recruited from neighborhood community centers associated with the hospitals and staff members and their family members of the Hadassah-Hebrew University Medical Center. In terms of protecting human subjects, the authors sought written informed consent from all participants, and the study had been approved by the Helsinki Committee/Internal Review Board of the Hadassah-Hebrew University Medical Center as part of a multi-locational, composite research initiative regarding vulnerability factors for mental illness (Agid et al., 1999).

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In terms of analyzing the data, a variety of approaches were employed. The authors evaluated the matched pairs for their unit of analysis rather than individuals. The authors used Mantel Haenszel odds ratio estimates for calculating EPL rates; McNemar’s testing was conducted to establish significant levels. One-sided p values were used; Bonferonni correction for multiple testing was employed where appropriate. Chi-square or Fisher exact test were used for categorical variables; Wilcoxon-Mann Whitney test was used for ordinal variables. Group variables were identified in terms of mean ± standard deviation. Data was summarized in a series of tables with appropriate narrative explanation. Given the quantitative nature of the study, this was an appropriate approach to presenting the numerical findings.

With regard to the discussion of the findings and their implications, the authors observed that their findings suggest EPL increases the risk of developing MD as an adult; rates of EPL were significant among patients with BPD; and rates of EPL among individuals with schizophrenia were also significant. This suggests that EPL is in fact a significant risk factor for the development of psychiatric illness. This is in line with published risk factors associated with BPD and MD (NIMH 2016; NIMH, 2018).

In terms of recommendations, the authors do not make any regarding future research. They connect their findings with other studies, indicating how their results reflect or support the findings of those studies, namely those which are genetic and/or neurobiological in nature. This lack of recommendations – even just for future study – is a troubling aspect in an otherwise interesting and enlightening study regarding the complexity of psychiatric illness. Though the authors do not explicitly acknowledge it, it seems that their participants might have been predominantly Jewish, so one questions how much generalization could be applied to the authors’ findings. Other than this, this study was well-written and fascinating.

  • Agid, O., Shapira, B., Zislin, J., Ritsner, M., Hanin, B., Murad, H., … & Lerer, B. (1999).
    Environment and vulnerability to major psychiatric illness: a case control study of early parental loss in major depression, bipolar disorder and schizophrenia. Molecular Psychiatry, 4(2), 163-172.
  • National Institute of Mental Health. (2016, April). Bipolar disorder. Mental Health Information. Retrieved from
  • National Institute of Mental Health. (2018, February). Depression. Mental Health Information. Retrieved from