Cognitive Performance in First-Degree Relatives of Individuals With vs Without Major Depressive Disorder

Abstract

IMPORTANCE Findings of cognitive impairment in major depressive disorder (MDD), including remitted MDD, raise the question whether impaired cognition is part of preexisting vulnerability rather than a consequence of MDD or its treatment. To our knowledge, no meta-analyses have been published on cognitive impairment in first-degree relatives of individuals with MDD.OBJECTIVE To compare cognitive performance between individuals with and without family history of MDD.STUDY SELECTION Original articles that reported data on cognition in first-degree relatives of individuals with MDD compared with controls with no family history of major mental illness.DATA EXTRACTION AND SYNTHESIS Means and SDs were extracted, and standardized mean differences (SMD) between relatives and controls were calculated for each measure of cognitive performance. The relative-control differences in overall cognition and in specific cognitive domains were synthesized in random-effects meta-analyses with robust variance estimation that allows including multiple correlated measures of cognition within each study. Heterogeneity was quantified with τ 2 . Publication bias was assessed with funnel plots and Egger intercept. MAIN OUTCOMES AND MEASURES Performance on cognitive tests.RESULTS Across 284 measures of cognition in 54 nonoverlapping samples including 3246 relatives of people with MDD (mean age 15.38 years, 57.68% females) and 5222 controls (mean age 14.70 years, 55.93% females), relatives of people with MDD performed worse than controls across all measures of cognition (SMD = −0.19; 95% CI, −0.27 to −0.11; P < .001). Domain-specific meta-analyses showed similar size of relative-control difference in most domains of cognition, including Full-Scale IQ (SMD = −0.19), verbal intelligence (SMD = −0.29), perceptual intelligence (SMD = −0.23), memory (SMD = −0.20), academic performance (SMD = −0.40), and language (SMD = −0.29). Study characteristics were not significantly associated with observed between-group differences. There was no evidence of publication bias. CONCLUSIONS AND RELEVANCEA general impairment in cognition is a feature of familial disposition for MDD. Cognition may contribute to early identification of risk for depression and may be examined as potential target for early intervention. 11. Rasic D, Hajek T, Alda M, Uher R. Risk of mental illness in offspring of parents with schizophrenia, bipolar disorder, and major depressive disorder: a meta-analysis of family high-risk studies.

Observed psychopathology in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia

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Dispositional negativity, cognition, and anxiety disorders: An integrative translational neuroscience framework

“…In a nationally representative sample of 2,605 American adults, decrements in set shifting, updating, and inhibition conferred robust risk of developing generalized anxiety disorder (GAD) across the 9-year follow-up period (e.g., Odds Ratios for Updating > 6.00; Zainal & Newman, 2018). Likewise, a recent meta-analysis uncovered evidence of cognitive impairment—including lower IQ (−0.19 SD) and academic performance—in first-degree relatives of individuals with MDD (N = 8,468) (MacKenzie, Uher, & Pavlova, in press ), suggesting a causal role. Conversely, there is emerging evidence that interventions targeting cognitive control can ameliorate anxiety symptoms, reinforcing the conclusion that executive control deficits causally contribute to the development of pathological anxiety (e.g., Cohen, Daches, Mor, & Henik, 2014; Cohen, Mor, & Henik, 2015).…”

Executive dysfunction in depression in adolescence: the role of inflammation and higher body mass

“…Dysfunction across a broad range of cognitive functions, such as verbal memory and executive functioning, is a reliable correlate of depression in children, adolescents, and adults (Rock et al ., 2013; Snyder, 2013; Wagner et al ., 2015). However, it also has been observed prior to first onset, in unaffected first-degree relatives of depressed individuals, and when depression has remitted (Rock et al ., 2013; Scult et al ., 2017; MacKenzie et al ., 2018). Thus, it remains unclear whether, in addition to being a correlate of depression, cognitive dysfunction is a risk factor for depression, a consequence of depression, or whether both depression and cognitive dysfunction are caused by a common underlying process (Allott et al ., 2016; Mac Giollabhui et al ., 2018).…”