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

Abstract

The current focus on identifying genes which predispose to psychiatric illness 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 parental loss and psychopathology in adult life has intrigued psychiatrists for most of this century. We report a case control study in which rates of EPL, due to parental death or permanent separation before the age of 17 years were 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 pairs). Loss of parent during childhood significantly increased the likelihood of developing MD during adult life (OR = 3.8, P = 0.001). The effect of loss due to permanent separation (P = 0.008) was more striking than loss due to death, as was loss before the age of 9 years (OR = 11.0, P = 0.003) compared to later childhood and adolescence. The overall rate of EPL was also increased 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 psychosocial, medical and clinical characteristics of subjects with and without a history of EPL, within the larger patient groups from which the matched samples were drawn (MD, n = 136; BPD, n = 107; SCZ, n = 160), yielded few significant findings. Among the controls (n = 170), however, subjects who had experienced EPL, 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 reported more physical illness (P = 0.03-0.001). Long term neurobiological 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, including corticotrophin releasing factor gene expression, have received particular attention. Analogous processes may be implicated in the effect of EPL on human 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 rendered vulnerable as a consequence of the stress.

The dynamics of attachment insecurity and paranoid thoughts: An experience sampling study

“…It has consistently been reported that psychosis is associated with a wide range of early adverse experiences . Some of these experiences of parental separation (Agid et al, 1999) neglect Sitko et al, 2014) victimisation through means of sexual abuse (Read et al, 2005), and of being unwanted at birth (Myhrman et al, 1996) may result in disruptions to the development of early secure attachment relationships, and may subsequently lead to the development of incoherent self/others beliefs that fluctuate over time.…”

Decreased cortisol awakening response after early loss experience

“…This seminal observation was subsequently confirmed in a large number of epidemiological, twin and case-control studies demonstrating that loss of a parent due to death or separation increases the risk for major depression in adulthood (Agid et al, 2000). Early loss experience (ELE) was also found to predispose for a variety of other psychiatric disorders, including bipolar disorder, anxiety disorders, schizophrenia, and alcohol abuse (Agid et al, 1999;Kendler et al, 1992Kendler et al, , 2002a. There is also evidence for a relationship between ELE and physical illnesses, functional somatic syndromes and several health risk behaviors (Lowman et al, 1986;Felitti et al, 1998;Agid et al, 1999).…”

“…Early loss experience (ELE) was also found to predispose for a variety of other psychiatric disorders, including bipolar disorder, anxiety disorders, schizophrenia, and alcohol abuse (Agid et al, 1999;Kendler et al, 1992Kendler et al, , 2002a. There is also evidence for a relationship between ELE and physical illnesses, functional somatic syndromes and several health risk behaviors (Lowman et al, 1986;Felitti et al, 1998;Agid et al, 1999).…”

Importance of Studying the Contributions of Early Adverse Experience to Neurobiological Findings in Depression

“…Childhood abuse has also been associated with earlier-onset and more chronic depression ). In addition, parental loss predominantly due to parental separation has also been found to increase the risk for major depression in casecontrol and epidemiological studies (Agid et al, 1999). Twin studies have provided concordant findings (Kendler et al, 1992(Kendler et al, , 1993(Kendler et al, , 2002.…”