Cortical structures and their clinical correlates in antipsychotic-naïve schizophrenia patients before and after 6 weeks of dopamine D2/3 receptor antagonist treatment

Psychol Med. 2019 Apr;49(5):754-763. doi: 10.1017/S0033291718001198. Epub 2018 May 8.


Background: Schizophrenia has been associated with changes in both cortical thickness and surface area, but antipsychotic exposure, illness progression and substance use may confound observations. In antipsychotic-naïve schizophrenia patients, we investigated cortical thickness and surface area as well as mean curvature before and after monotherapy with amisulpride, a relatively selective dopamine D2/3 receptor antagonist.

Methods: Fifty-six patients and 59 matched healthy controls (HCs) underwent T1-weighted 3T magnetic resonance imaging. Forty-one patients and 51 HCs were re-scanned. FreeSurfer-processed baseline, follow-up values and symmetrized percentage changes (SPC) in cortical structures were analysed using univariate analysis of variance. Clinical measures comprised psychopathology ratings, assessment of functioning and tests of premorbid and current intelligence. We applied false discovery rate correction to account for multiple comparisons.

Results: At baseline, groups did not differ in cortical thickness or surface area; however, curvature in the left hemisphere was higher in patients (p = 0.015). In both patients and HCs, higher curvature was associated with lower premorbid (p = 0.009) and current intelligence (p 0.43). Cortical thickness SPC was negatively associated with symptom improvement (p = 0.002).

Conclusions: Schizophrenia appears associated with subtle, yet clinically relevant aberrations in cortical structures. Mean curvature holds promise as a sensitive supplement to cortical thickness and surface area to detect complex structural brain abnormalities.

Trial registration: NCT01154829.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / pharmacology*
  • Case-Control Studies
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / pathology*
  • Denmark
  • Dopamine Antagonists / pharmacology*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Psychiatric Status Rating Scales
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Dopamine D3 / drug effects
  • Receptors, Dopamine D3 / metabolism
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / drug therapy*
  • Schizophrenia / pathology*
  • Young Adult


  • Antipsychotic Agents
  • Dopamine Antagonists
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3

Associated data