Working memory and attention deficits in adolescent offspring of schizophrenia or bipolar patients: Comparing vulnerability markers

Abstract

Background Working memory deficits abound in schizophrenia and attention deficits have been documented in schizophrenia and bipolar disorder. Adolescent offspring of patients may inherit vulnerabilities in these brain circuits and may show deficit performance in these cognitive domains. Here we assess impairments in offspring of schizophrenia (SCZ-Offspring) or bipolar (BP-Offspring) patients compared to controls (HC) with no family history of mood or psychotic disorders to the second degree. Methods Three groups (n=100 subjects; range:10–20 yrs) of HC, SCZ-Offspring and BP-Offspring gave informed consent. Working memory was assessed using a delayed spatial memory paradigm with two levels of delay (2s & 12s); sustained attention processing was assessed using the Continuous Performance Task-Identical Pairs version. Results SCZ-Offspring (but not BP-Offspring) showed impairments in working memory (relative to HC) at the longer memory delay indicating a unique deficit. Both groups showed reduced sensitivity during attention but only BP-Offspring significantly differed from controls. Conclusions These results suggest unique (working memory/dorsal frontal cortex) and potentially overlapping (attention/fronto-striatal cortex) vulnerability pathways in adolescent offspring of patients with schizophrenia and bipolar disorder. Working memory and attention assessments in these offspring may assist in the clinical characterization of the adolescents vulnerable to SCZ or BP.

Cortical thickness, volume and surface area in patients with bipolar disorder types I and II

“…[3][4][5][6][7][8][9] Moreover, we observed that patients with BDI and BDII had abnormally low volume and/or thickness in medial occipital brain regions, including the cuneus, pericalcarine and lingual cortices. These findings are in line with previously reported deficits in visual processing and perception [36][37][38][39][40] -unrelated to lithium use 41,42 -and also with deficits in working memory tasks 10,[43][44][45][46] that partly engage visual areas of the medial occipital cortex. [47][48][49][50] Hence, it is not farfetched to assume that previously observed deficits in visual tasks in patients with BD might be partly related to neuroanatomical abnormalities in medial occipital brain regions.…”

Affective Processing in Pediatric Bipolar Disorder and Offspring of Bipolar Parents

“…Although current literature does not view such biases as primary endophenotypic markers of BD, both healthy pediatric BD offspring (Gotlib et al 2005) and adult siblings of BD patients exhibit affective processing biases toward negative stimuli in tasks of impulse control (Clark et al 2005;Klimes-Dougan et al 2006;Maziade et al 2009;Brand et al 2012). Similar to patients with BD, at-risk individuals display deficits in sustained attention and executive functioning (Zalla et al 2004;Frangou et al 2005;Klimes-Dougan et al 2006;Trivedi et al 2008;Kulkarni et al 2010;Diwadkar et al 2011) which suggests that cognitive deficits and affective processing biases could be interrelated, and may constitute markers of vulnerability to BD.…”

Bipolar disorder ANK3 risk variant effect on sustained attention is replicated in a large healthy population

“…Of note, no associations could be detected in this study between rs10994336 risk variant and other aspects of cognitive functioning, such as general intellectual ability, episodic memory, decision making and response inhibition, indicating a rather selective effect on the sustained attention phenotype. Sustained attention deficits as measured with different versions of the CPT task have been consistently observed among BD patients and their offspring (Clark et al , 2002; Diwadkar et al , 2011, Burdick et al , 2011) and are likely to constitute a fundamental behavioral feature of BD pathophysiology. In addition, several genetic loci have been associated with CPT performance in clinical and non-clinical populations (Blasi G et al , 2011), suggesting that inter-individual sustained attention variability is at least in part attributable to complex genetic influences.…”