Environment and vulnerability to major psychiatric illness: a case control study
of early parental loss in major depression, bipolar disorder and schizophrenia.
O Agid, B Shapira, J Zislin, M Ritzner, B Hanin, H Murad, T Trudart, M Bloch, U
Heresco-Levy and B Lerer
Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem
91120, Israel
Currently, a central focus of research into serious psychiatric disorders such as depression, bipolar disorder and schizophrenia, is to identify their molecular basis. A major strategy to achieve this objective is to identify susceptibility genes. At the same time, it is well recognized that these are complex disorders and that environmental factors which interact with genetic predisposition are likely to play a pivotal role. Early parental loss (EPL) may be one such factor.
The relationship between early environmental stressors, such as parental loss, and psychopathology in adult life has intrigued psychiatrists for most of this century. This interest has been fueled by the results of animal studies on long-term neurobiological consequences of maternal deprivation early in the life of the animal. These have demonstrated enduring changes in hypothalamic pituitary axis function, including corticotrophin release factor gene expression, as well as a variety of behavioral sequellae. The extension of such findings to humans is tantalizing, but largely unexplored. What is also unclear, in spite of a voluminous literature, is whether adult patients with major psychiatric disorders indeed experience early parental loss to a greater extent than healthy individuals from a similar background.
Agid and colleagues (from the Hadassah - Hebrew University Medical Center, Jerusalem, Israel) have addressed this pivotal question in a carefully controlled study of early parental loss, due to death or permanent separation, in Israeli patients with major depression, bipolar disorder and schizophrenia. Patients were closely matched to control subjects on a variety of variables to insure that findings would not be a consequence of different base risks for early parental loss. The results showed that 29.1% of patients with major depression, 17.7% of those with bipolar disorder and 22.4% of schizophrenia patients had experienced loss of a parent before the age of 17 years, compared to 7.6-7.9% of control subjects. Except for bipolar disorder, where the result was borderline, these differences were highly significant.
Beyond an overall association of psychiatric disorder with early parental loss, certain categories of loss are particularly important. Early loss (before the age of 9 years) has a significantly stronger impact than loss in later childhood and adolescence. Similarly, permanent separation from a parent is more strongly associated with major depression than loss due to death. Loss of mother may be more associated with psychopathology in adult life and the impact of loss may be stronger in females than in males.
Agid et al also observed unexpected consequences of loss in their control subjects who had been carefully screened for a personal or family history of formal psychiatric disorder. Control subjects who had experienced early parental loss reported lower incomes, had been divorced more frequently, were more likely to be living alone, were more likely to smoke or have smoked cigarettes and had more physical illness than control subjects who had not experienced loss.
Association does not imply causation. However, parental loss (particularly in early childhood and due to separation) may be an important environmental link in the chain of biological and environmental factors that render the individual susceptible to major psychiatric disorder, particularly depression. If the results of recent animal studies can be extrapolated, early loss experiences could alter brain function in a way which renders the individual more susceptible to subsequent environmental stressors. In persons genetically predisposed to a disorder such as major depression, this could be a crucial factor in bringing their genetic predisposition to the fore.
For further information on this work, please contact Prof. Bernard Lerer, Professor of Psychiatry, Director, Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah - Hebrew University Medical Center, Ein Karem, Jerusalem 91120, Israel. Phone: 972-2-6777185; Fax: 972-2-6439294; e-mail: lerer@cc.huji.ac.il
In the same issue of Molecular Psychiatry (http://www.stockton-press.co.uk/mp/) there is a News & Views on this work written by Professor Charles Nemeroff, who can also be reached for independent information on the work: Charles B. Nemeroff, MD, PhD, Reunette W. Harris Professor & Chairman, Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine 1639 Pierce Dr., Suite 4000, Atlanta, GA 30322; phone: 404-727-5881; FAX: 404-727-3233; e-mail: cnemero@emory.edu
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Journal
Molecular Psychiatry