Environment and vulnerability to major psychiatric illness: a case controlstudy of early parental loss in major depression, bipolar disorder and schizophrenia

The current focus on identifying genes which predispose to psychiatric illn ess sharpens the need to identify environmental factors which interact with genetic predisposition and thus contribute to the multifactorial causation of these disorders. One such factor may be early parental loss (EPL). The putative relationship between early environmental stressors such as parenta l loss and psychopathology in adult life has intrigued psychiatrists for mo st of this century. We report a case control study in which rates of EPL, d ue to parental death or permanent separation before the age of 17 years wer e evaluated in patients with major depression (MD), bipolar disorder (BPD) and schizophrenia (SCZ), compared to individually matched, healthy control subjects (MD-Control, 79 pairs; BPD-Control, 79 pairs; SCZ-Control, 76 pair s). Loss of parent during childhood significantly increased the likelihood of developing Mn during adult life (OR = 3.8, P = 0.001). The effect of los s due to permanent separation (P = 0.008) was more striking than loss due t o death, as was loss before the age of 9 years (OR = 11.0, P = 0.003) compa red to later childhood and adolescence. The overall rate of EPL was also in creased in BPD (OR = 2.6, P = 0.048) but there were no significant findings in any of the subcategories of loss. A significantly increased rate of EPL was observed in schizophrenia patients (OR = 3.8, P = 0.01), particularly before the age of 9 years (OR = 4.3, P = 0.01). Comparison of psychosociaI, medical and clinical characteristics of subjects with and without a histor y of EPL, within the larger patient groups from which the matched samples w ere drawn (MD, n = 136; BPD, n = 107; SCZ, n = 160), yielded few significan t findings. Among the controls (n = 170), however, subjects who had experie nced EPL, reported lower incomes, had been divorced more frequently, were m ore likely to be living alone, were more likely to smoke or have smoked cig arettes and reported more physical illness (P = 0.03-0.001). Long term neur obiological consequences of early environmental stressors such as maternal deprivation have been extensively studied in many animal species. Recently, enduring changes in hypothalamic-pituitary-adrenal axis function, includin g corticotrophin releasing factor gene expression, have received particular attention. Analogous processes may be implicated in the effect of EPL on h uman vulnerability to psychopathology, via alterations in responsiveness to stress. Genetic predisposition may influence the degree of susceptibility of the individual to the effects of early environmental stress and may also determine the psychopathological entity to which the individual is rendere d vulnerable as a consequence of the stress.