Neurological abnormalities among offspring of persons with schizophrenia: relation to premorbid psychopathology

Abstract

Background: Neurological Examination Abnormalities (NEA, often called "neurological soft signs") have been observed in early schizophrenia and may be heritable. We investigated the prevalence, and neurocognitive and psychopathological correlates of NEA among offspring of schizophrenia patients who are at increased genetic risk for this illness.

Methods: Neurological examinations were conducted on high risk (HR, n=74) and healthy comparison subjects (HS, n=86), using the Heinrichs-Buchanan scale. Cognitive-perceptual (CogPer) and repetitive motor (RepMot) subscores, and total NEA scores were computed. All HR and HS were assessed using K-SADS/SCID for diagnoses. Schizotypy was measured using the Magical Ideation and the Perceptual Aberration subscales (Chapman scale), attention using Continuous Performance Test (CPT-IP) and executive functions using the Wisconsin Card Sorting Test (WCST).

Results: CogPer (F(1,160)=7.14, p=0.008) but not RepMot NEA scores were higher in HR subjects compared to HS after controlling for age and sex. CogPer NEA scores were higher in HR subjects with axis I psychopathology compared to those without (F(2,170)-6.41, p=0.002). HR subjects had higher schizotypy scores (composite of the magical ideation and perceptual aberration scales) (F(1,141)=23.25, p=0.000004). Schizotypy scores were negatively correlated with sustained attention and executive functions. In addition, schizotypy was positively correlated with CogPer NEA scores.

Conclusions: Young relatives at increased genetic risk for schizophrenia show more frequent NEA. CogPer but not RepMot NEA scores were elevated, consistent with our prior observation of CogPer NEA being relatively specific for schizophrenia. The observed relationships between NEA, cognitive impairments, schizotypy and axis I disorders suggest that NEA may characterize a subgroup of HR offspring at an elevated risk for psychopathology.

Fig. 1

Average Cognitive–Perceptual NEA scores across HR subjects with axis I psychopathology (HR + P), without psychopathology (HR − P) and healthy subjects. Lines represent 95% confidence interval and the box represents the means.