Shared Neurocognitive Dysfunctions in Young Offspring at Extreme Risk for Schizophrenia or Bipolar Disorder in Eastern Quebec Multigenerational Families

Abstract

HRSZ and HRBP shared several aspects of their cognitive impairment. Our data suggest that the extremely high genetic and familial loading of these HRs may have contributed to a quantitatively increased magnitude of the cognitive impairments in both HR subgroups, especially in memory. These offspring at heightened risk present difficulties in processing information that warrant preventive research.

Childhood abuse and neglect may induce deficits in cognitive precursors of psychosis in high-risk children

“…50 Our observation that exposure in the young offspring of parents with schizophrenia or BD would induce similar cognitive dysfunctions is consistent with observations that these 2 adult disorders share many genetic, phenotypic and endophenotypic characteristics 15,51 and that the young offspring of parents with schizophrenia or BD display common cognitive impairments. 9,16,27 The offspring of parents with schizophrenia or BD are likely to carry a genetic vulnerability expressed in greater biological sensitivity to stress, 52 thus sensitizing them to abuse and neglect. They would pay a heavier developmental toll at 2 levels: they are likely to carry a genetic vulnerability and are also likely to be exposed to trauma, which are both risk factors for serious and recurring mental illness.…”

“…1,2,9 Cognitive dysfunctions are central to schizophrenia and BD, [10][11][12][13] and recent data suggest that the cognitive decline begins in childhood. 14,15 The cognitive impairments that are typically shared by patients with schizophrenia and BD 12,16,17 have a genetic basis, 18,19 which does not preclude environmental influences from further impacting the developmental trajectory. Abuse and neglect are known to have a negative influence on cognitive functioning in community samples of healthy adults 20,21 and children/adolescents 22,23 as well as in patients with psychosis.…”

“…8,24,25 Congruent with other studies, [26][27][28] we have reported that children from densely affected multigenerational families who had a parent affected by schizophrenia or BD had fullscale IQ impairments as well as deficits in specific cognitive domains, such as visual and verbal episodic memory, working memory and executive functions of initiation. 12,16 These domains are among the most impaired in adult patients and are consistently found to be associated with schizophrenia and BD. 19,29,30 Based on 25 years of findings, we recently reported that phenotype, endophenotypes and genetic findings in these families were very similar to results in sporadic samples, 15 supporting the findings of others that the familial and nonfamilial forms of illness share mechanisms.…”

Affective Processing in Pediatric Bipolar Disorder and Offspring of Bipolar Parents

“…In particular, previous studies in BD have consistently shown a robust effect of negative stimuli on cognitive processing Passarotti et al 2011;Pavuluri et al 2012). 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.…”

Familiarity and recollection processes in patients with recent-onset schizophrenia and their unaffected parents

“…According to the Consortium on the Genetics of Schizophrenia, the key cognitive functions of attention, working memory and episodic memory meet the criteria for selecting an endophenotype (Gur et al, 2007; for criteria, see Gottesman and Gould, 2003). Among these potential candidate endophenotypes, episodic memory -memory for personally experienced events that are embedded in a particular spatial and temporal context (see Tulving, 1985) -may be particularly promising because it is the cognitive process that is most impaired both in patients with SZ (Saykin et al, 1991;Heinrichs and Zakzanis,1998) and in their unaffected relatives (Sitskoorn et al, 2004;Maziade et al, 2009). …”