Neurocognition in youth and young adults under age 30 at familial risk for schizophrenia: a quantitative and qualitative review

Abstract

Introduction: Neurocognitive dysfunction is a central feature of schizophrenia and is observed during all phases of the illness. Because schizophrenia is known to run in families, studying neurocognitive function in first-degree, nonpsychotic relatives has been a widely utilised strategy for almost 50 years for understanding presumed "genetic risk". Studying nonpsychotic relatives ("familial high-risk", or FHR) allows for identification of cognitive vulnerability markers independent of confounds associated with psychosis.

Methods: Prior meta-analyses have elucidated the level and pattern of cognitive deficits in the premorbid, prodromal, and postonset periods of psychosis, and in relatives regardless of age. However, no prior quantitative analyses have specifically focused on studies of young first-degree relatives of individuals with schizophrenia who have not passed through the peak age illness risk (<age 30). The English language literature of neuropsychological studies of first-degree relatives for schizophrenia was identified up to 15 May 2011.

Results: From 33 studies, 28 studies met our criteria for quantitative review, utilising >70 individual tests and 250 variables.

Conclusions: In general, young FHR individuals demonstrated deficits with a moderate level of severity compared with healthy controls. The largest average effect sizes (ESs), based on tests given in at least three independent studies, were on estimates of Full Scale IQ (d= -0.777), followed by Vocabulary (d= -0.749) and single word reading tests (d= -0.698) (often used as estimates of IQ). Measures of declarative memory, sustained attention, working memory and others had more modest ESs. Deficits were milder than in established schizophrenia, but often as severe as in clinical high-risk or putatively prodromal participants and in older relatives examined in prior meta-analyses. Additionally, while assessed from a more limited literature, youth at FHR for schizophrenia tended to show worse neurocognitive functioning than those at FHR for affective psychosis. This suggests that genetic risk for schizophrenia as reflected in a positive FHR carries an especially heavy impact on cognitive ability.

Figure 1

Average effect sizes by domain comparing those at family high-risk for schizophrenia to controls IQ: intelligence quotient, full scale and estimated; VS ability: Visual Spatial Ability, averaged tests include: Performance IQ and Block Design; Declar Mem: Declarative memory, averaged tests include: Story Recall, RAVLT Delayed Recall, RAVLT T1-T5; PM speed: perceptual motor speed, averaged tests include: Digit Symbol, Stroop interference score, Trail Making Time to Execute Part A, Trail Making Time to Execute Part, d2 Concentration Test; Verbal Ling: Verbal Linguistic Ability, averaged tests include: Verbal IQ Score, Comprehension, Information, Similarities, NART & WRAT Reading, Total Fluency, Letter Fluency, and Vocabulary; Exec Funct: Executive Functioning, averaged tests include: WCST Perseverative Errors/Responses, WCST Total Errors, WCST Completed Categories, Picture Arrangement; STW Memory: short-term working memory, averaged tests include: Arithmetic, Total Digit Span, Digit Span Forward, Digit Span Backward; Vig Sust Attn: Vigilance and Sustained Attention, averaged tests include: CPT-IP numbers d’ and CPT-IP shapes d’