FAMILIAL LIABILITY FOR ENDOCRINE-METABOLIC DISORDERS AND DEPRESSION

• Background: Endocrine-metabolic disorders are common in individuals with depression. Better understanding of the underlying factors contributing to their concomitant occurrence is needed. This study investigates the familial co-aggregation of depression and endocrine-metabolic disorders and estimates the contribution of genetic and environmental risk factors to their co-occurrence.Methods: We conducted a population-based cohort study using Swedish national data. A total of 2,263,311 individuals born between 1973 and 1996 were included and followed up until death, emigration, or December 31, 2013, whichever occurred first. Each participant was linked to their biological parents, allowing identification of full-, maternal half-, and paternal half-siblings. We investigated clinical diagnoses of depression and endocrine-metabolic disorders diagnosed at any point during the follow-up period, grouping the latter into autoimmune disorders (i.e., hypothyroidism, Graves’ disease, and type 1 diabetes) and non-autoimmune disorders (i.e., type 2 diabetes, obesity, and polycystic ovarian syndrome). Logistic regression and Cox proportional hazards regression were used to estimate the association between endocrine-metabolic disorders and depression within the same individual and across siblings. Quantitative genetic modeling was performed to investigate the relative contribution of genetic and environmental influences.Results: Individuals diagnosed with endocrine-metabolic disorders had significantly higher risk of depression, with odds ratios ranging from 1.43 [95% CI, 1.30-1.57] for Graves’ disease to 2.44 [2.37-2.50] for obesity. Overall, increased risks extended to full- and half-siblings. Quantitative genetic modeling showed that shared genetic factors explained the phenotypic correlations between endocrine-metabolic disorders and depression to different extents (ranging from 36% for autoimmune hypothyroidism, to 74% for obesity), except for type 1 diabetes, for which the association was mainly explained by non-shared environmental factors (84%).Discussion: Endocrine-metabolic disorders and depression co-occur in individuals and display familial co-aggregation. Shared genetic risk factors explained much of this relationship, but unique environmental influences also contributed significantly. These findings expand the current knowledge of the etiological sources of comorbidity between somatic and psychiatric disorders, which could guide future research aiming at identifying the pathophysiological mechanisms and potentially intervention targets.

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MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

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