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Original Investigation
December 2016

Cognitive Subtypes of Schizophrenia Characterized by Differential Brain Volumetric Reductions and Cognitive Decline

Author Affiliations
  • 1Neuroscience Research Australia, Randwick, New South Wales, Australia
  • 2School of Psychiatry, University of New South Wales, Kensington, New South Wales, Australia
  • 3Schizophrenia Research Institute, Darlinghurst, New South Wales, Australia
  • 4Discipline of Psychiatry, University of Adelaide, Adelaide, South Australia, Australia
  • 5School of Psychology, Flinders University, Adelaide, South Australia, Australia
  • 6Adult Mental Health Services, Northern Adelaide Local Health Network, Adelaide, South Australia, Australia
  • 7School of Medicine, University of Queensland, Brisbane, Queensland, Australia
JAMA Psychiatry. 2016;73(12):1251-1259. doi:10.1001/jamapsychiatry.2016.2925
Key Points

Question  What is the extent to which brain volumetric differences further define intellectually based subgroups of people with schizophrenia?

Findings  In this study of 96 patients, cluster analytical techniques revealed 4 IQ-based subgroups in which all those assessed had significantly reduced inferior parietal volume relative to healthy controls; however, a severely deteriorated subgroup had the most extensive reduction of gray matter volume relative to all groups.

Meaning  Classifying the cognitive heterogeneity associated with schizophrenia can provide a platform to better characterize the neurobiological underpinnings of the illness and its treatment.


Importance  Cognitively distinct subgroups of schizophrenia have been defined based on premorbid and current IQ, but little is known about the neuroanatomical differences among these cognitive subgroups.

Objectives  To confirm previous findings related to IQ-based subgroups of patients with schizophrenia in an independent sample and extend those findings to determine the extent to which brain volumetric differences correspond to the IQ-based subgroups.

Design, Setting, and Participants  A total of 183 participants were assessed at the outpatient settings of Neuroscience Research Australia and Lyell McEwin Hospital from September 22, 2009, to August 1, 2012. Patients were classified using cluster analysis on the basis of current and premorbid IQ differences. Regional magnetic resonance imaging (MRI) brain volumes were compared among the IQ-based subgroups using analysis of covariance with intracranial volume and age as covariates.

Main Outcomes and Measures  Wechsler Adult Intelligence Scale, third edition, scores; Wechsler Test of Adult Reading scores; Positive and Negative Syndrome Scale scores; and MRI brain volumes.

Results  Ninety-six outpatients (mean [SD] age, 35.7 [8.4] years; age range, 18-51 years; 59 men) with schizophrenia or schizoaffective disorder and 87 healthy controls (mean [SD] age, 31.9 [8.4] years; age range, 20-50 years; 46 men) were studied. Sixty-two patients and 67 healthy controls underwent structural MRI of the brain. Cluster analyses revealed 25 putatively preserved patients (26%), 33 moderately deteriorated patients (34%), 27 severely deteriorated patients (28%), and 11 compromised patients (12%). Negative symptom scores were significantly worse in the severely deteriorated group relative to the putatively preserved group (F2,82 = 13.8, P < .001, effect size [ES] = 1.40). Patient subgroups analyzed revealed significantly reduced inferior parietal volume relative to controls (F3,113 = 9.7, P < .001, ES = 0.85-1.24). The severely deteriorated group had significantly reduced total hippocampal (mean [SEM], 8309.6 [175.0] vs 9024.0 [145.5]; P = .01), lingual gyrus (mean [SEM], 11 996.0 [531.5] vs 13 838.1 [441.9]; P = .05), and superior temporal sulcus (mean [SEM], 4697.8 [192.0] vs 5446.0 [159.6]; P = .05) gray matter volumes relative to the putatively preserved group (ES = 0.91-1.10).

Conclusions and Relevance  Using an independent sample, we obtained proportions in each IQ-based subgroup that were similar to our previous work. Inferior parietal volume reduction was characteristic of schizophrenia relative to controls, and the severely deteriorated IQ group had widespread volumetric reductions. Classifying cognitive heterogeneity in schizophrenia provides a platform to better characterize the neurobiological underpinnings of the illness and its treatment.