Neurocognitive performance as an endophenotype for mood disorder subgroups

Abstract

Background There is growing evidence that neurocognitive function may be an endophenotype for mood disorders. The goal of this study is to examine the specificity and familiality of neurocognitive functioning across the full range of mood disorder subgroups, including Bipolar I (BP-I), Bipolar II (BP-II), Major Depressive Disorders (MDD), and controls in a community-based family study. Methods A total of 310 participants from 137 families with mood spectrum disorders (n=151) and controls (n=159) completed the University of Pennsylvania’s Computerized Neurocognitive Battery (CNB) that assessed the accuracy and speed of task performance across five domains. Mixed effects regression models tested association and familiality. Results Compared to those without mood disorders, participants with BP-I had increased accuracy in complex cognition, while participants with MDD were more accurate in emotion recognition. There was also a significant familial association for accuracy of complex cognition. Mood disorder subgroups did not differ in performance speed in any of the domains. Limitations The small number of BP-I cases, and family size limited statistical power of these analyses, and the cross-sectional assessment of neurocognitive function precluded our ability to determine whether performance precedes or post dates onset of disorder. Conclusions This is one of the few community-based family studies of potential neurocognitive endophenotypes that includes the full range of mood disorder subgroups. There were few differences in neurocognitive function except enhanced accuracy in specific domains among those with BP-I and MDD. The differential findings across specific mood disorder subgroups substantiate their heterogeneity in other biologic and endophenotypic domains.

A Bibliometric Review of Executive Function as Cognitive Endophenotypes in Parents of Children with Neurodevelopmental Disorders

“…After a clear enumeration of criteria on identifying the "endophenotype" in psychiatry and psychology (Gottesman & Gould, 2003), many family studies on ADHD, ASD and Schizophrenia, in particular, were published (Rommelse et al, 2008;Allen et al, 2009;Rommelse et al, 2011). Other areas where this construct was explored are bipolar disorders (Raust et al, 2014), major depression (Merikangas et al, 2017) and anxiety disorders (Müller et al, 2015).…”

Transdiagnostic neurocognitive endophenotypes in major psychiatric illness

“…This approach has also led to discovery of several promising candidate genes of influence [12]. Impairments in working memory, executive functions, set-shifting, decision making, response inhibition and social cognition have been consistently found in affected probands and to varying degree in their unaffected first-degree relatives (FDR) [13][14][15][16][17][18][19][20][21][22][23].…”

“…This approach has also led to discovery of several promising candidate genes of influence [12]. Impairments in working memory, executive functions, set-shifting, decision making, response inhibition and social cognition have been consistently found in affected probands and to varying degree in their unaffected first-degree relatives (FDR) [13–23]. However, nearly all extant research in this area has included individuals from non-multiplex families, and looked at endophenotypes only when the probands are affected with a single, distinct psychiatric illness.…”

The characteristic of cognitive impairments in patients with bipolar II depression and its association with N-acetyl aspartate of the prefrontal white matter

“…However, BD type I and BD type II are pathophysiological different, which is still controversial. Prior studies have noted cognitive deficits in bipolar II depression (4,10) and their first-degree relatives (11), suggesting that cognitive deficits may improve performance as a promising candidate endophenotype of bipolar II depression (12). However, the neural mechanism of cognitive dysfunction in bipolar II depression is still unknown.…”