Neuropsychological Functioning in Adolescents and Young Adults at Genetic Risk for Schizophrenia and Affective Psychoses: Results from the Harvard and Hillside Adolescent High Risk Studies

Abstract

Siblings and offspring of persons with schizophrenia carry elevated genetic risk for the illness and manifest attentional and memory impairments. Because less is known about other neuropsychological functions and their specificity in adolescents, we conducted a genetic high-risk (HR) study of schizophrenia (HR-SCZ) and affective psychosis (HR-AFF). Participants (ages 12-25) were from the Harvard Adolescent High-Risk and Hillside Family studies, including 73 HR-SCZ, 18 HR-AFF, and 84 community controls (CCs) recruited in metropolitan Boston and New York. Groups were compared on overall neurocognitive functioning, 6 domains, and 13 test scores, controlling for age, parental education, and correlated data within families. The HR-SCZ group was significantly impaired overall, while the HR-AFF group demonstrated a trend toward overall impairment. HR-SCZ subjects showed significantly lower Verbal Ability (d = .73) and Executive Functioning/Working Memory (d = .47) than CCs. HR-AFF subjects showed reduced Verbal Ability (d = .64) compared to CCs. Excluding 12 CCs with a parental history of depression (without psychosis) led to larger differences between HR and CC groups across domains. Moreover, HR-SCZ and CC group differences in Verbal Memory (d = .39) and Visual-Spatial (d = .34) became statistically significant. There were no significant differences between HR-SCZ and HR-AFF groups. Data support a modest neuropsychological deficit in persons at genetic HR for psychosis, with a broader range of deficits in HR-SCZ. Future work should assess the relationship of neurocognition to adaptive functioning and possible onset of psychosis in HR samples. Ascertainment criteria for controls may markedly influence results and interpretation of group differences.

Cognitive and Psychiatric Predictors to Psychosis in Velocardiofacial Syndrome: A 3-Year Follow-Up Study

“…Across all tests, lower performance during childhood predicted more prodromal symptoms in adolescence. This finding is entirely consistent with other VCFS research 47 as well as the non-VCFS schizophrenia research [70][71][72][73][74][75][76][77][78][79][80][81][82][83] . Thus, our data are entirely consistent with the extant non-VCFS high risk data; language and executive function deficits in childhood appear to presage which children with VCFS will develop significant prodromal psychotic symptoms in adolescence.…”

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

“…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.…”

Advances in endophenotyping schizophrenia

“…These impairments in genetic high-risk subjects are not confounded by psychosis or medications, and their presence in high-risk children and adolescents provided strong support for a neurodevelopmental model of pre-psychotic vulnerability for schizophrenia (49). There is substantial evidence that measures of sustained attention or vigilance, verbal declarative memory and working memory are valid endophenotypes in schizophrenia.…”