For children, neurocognitive maturation differed significantly among those with familial high risk (FHR) for schizophrenia compared with those with FHR for bipolar disorder (BD) and population-based controls (PBCs). These findings were published in JAMA Psychiatry.

Data for this analysis were sourced from the Danish High Risk and Resilience Study. Participants were identified through the Danish Civil Registration System and Danish Psychiatric Central Research Register. Children who had at least one biological parent with schizophrenia spectrum psychosis (n=170) or BD (n=103) were matched by age, gender, and location with children who did not have FHR for either condition (n=178) and underwent neurologic assessment using 24 instruments in 2013-2016 and a follow-up assessment in 2017-2020. Differences in neurocognitive maturation were evaluated based on familial risk.

The schizophrenia, BD, and PBC groups were aged mean 11.96 (SD, 0.27), 11.94 (SD, 0.21), and 11.93 (SD, 0.23) years; 52.35%, 56.31%, and 53.93% were girls; and 10.00%, <4.90%, and 0% were living outside the home, respectively.

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Children with FHR for either condition had significantly lower Children’s Global Assessment Scale total scores (CGAS; both P <.001) and higher Child Behavior Checklist total scores (CBCL; both P <.001) compared with the PBC cohort.

No time-by-group interactions were significant after correction for multiple comparisons, indicating comparable neurocognitive maturation between 7 and 11 years of age.

At the 4-year follow-up, the children with FHR for schizophrenia had significantly lower scores on 7 of the 24 assessments compared with PBCs. No significant differences were observed between the children with FHR for BD compared with PBCs.

Compared between FHR groups, children at risk for schizophrenia had significantly lower scores on 5 of the 24 assessments.

In an explorative analysis, there was a significant correlation between the change in CBCL scores and change in Trail Making Test (TMT) letter sequencing (r, -0.15; P =.002), explaining 2.3% of the variance.

This study may have been limited by not stratifying patients on the basis of the severity of their parents’ symptoms.

The study authors concluded, “Findings of this prospective cohort study suggest that numerous neurocognitive impairments were detectable early in development in children at FHR of schizophrenia and appeared stable during the ages of 7 and 11 years. This suggests that being at familial high-risk of schizophrenia may affect the basis of neurocognitive development but does not disrupt neurocognitive development during middle childhood.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Knudsen CB, Hemager N, Greve AN, et al. Neurocognitive development in children at familial high risk of schizophrenia or bipolar disorder. JAMA Psychiatry. 2022;e220465. doi:10.1001/jamapsychiatry.2022.0465

This article originally appeared on Psychiatry Advisor