Neurocognitive performance in family-based and case-control studies of schizophrenia

Abstract

Background: Neurocognitive deficits in schizophrenia (SZ) are established and the Consortium on the Genetics of Schizophrenia (COGS) investigated such measures as endophenotypes in family-based (COGS-1) and case-control (COGS-2) studies. By requiring family participation, family-based sampling may result in samples that vary demographically and perform better on neurocognitive measures.

Methods: The Penn computerized neurocognitive battery (CNB) evaluates accuracy and speed of performance for several domains and was administered across sites in COGS-1 and COGS-2. Most tests were included in both studies. COGS-1 included 328 patients with SZ and 497 healthy comparison subjects (HCS) and COGS-2 included 1195 patients and 1009 HCS.

Results: Demographically, COGS-1 participants were younger, more educated, with more educated parents and higher estimated IQ compared to COGS-2 participants. After controlling for demographics, the two samples produced very similar performance profiles compared to their respective controls. As expected, performance was better and with smaller effect sizes compared to controls in COGS-1 relative to COGS-2. Better performance was most pronounced for spatial processing while emotion identification had large effect sizes for both accuracy and speed in both samples. Performance was positively correlated with functioning and negatively with negative and positive symptoms in both samples, but correlations were attenuated in COGS-2, especially with positive symptoms.

Conclusions: Patients ascertained through family-based design have more favorable demographics and better performance on some neurocognitive domains. Thus, studies that use case-control ascertainment may tap into populations with more severe forms of illness that are exposed to less favorable factors compared to those ascertained with family-based designs.

Figure 1

Neurocognitive performance of COG-1 and COGS-2 participants: Mean (±95% Confidence Interval) accuracy (left panel) and speed (right panel) of patients are presented in z-scores compared to the respective control groups (z-scores for response times are inverted for speed so that higher scores always reflects better performance). SZ = Schizophrenia, HCS = Healthy Comparison Subjects; ABF = Abstraction and Mental Flexibility, ATT = Attention, WM = Working Memory, VME = Word Memory, FME = Face Memory, SME = Spatial Memory, SPA = Spatial Processing, EMO = Emotion Identification, SM = Sensori-Motor, MOT = Motor Speed.