Neuroanatomical profiles of treatment-resistance in patients with schizophrenia spectrum disorders

Prog Neuropsychopharmacol Biol Psychiatry. 2020 Apr 20;99:109839. doi: 10.1016/j.pnpbp.2019.109839. Epub 2019 Dec 13.


Widespread structrual abnormalities in subcortical brain regions have been identified in patients with schizophrenia. However, only a few studies have examined the neuroanatomical profiles of patients with treatment-resistant schizophrenia. The aim of this study was to compare differences in subcortical and hippocampal volumes between: (i) treatment-resistant patients who are non-responders to both first-line antipsychotics and clozapine (URS), (ii) treatment-resistant patients who are non-responders to first-line antipsychotics but are responders to clozapine (CLZ-Resp), (iii) responders to first-line antipsychotics (FL-Resp), and (iv) healthy controls. T1-weighted images of 103 participants (27 URS, 29 CLZ-Resp, 21 FL-Resp, and 26 healthy controls) were obtained. Group differences in striatal, thalamic, globus pallidus, amygdala, and hippocampus volumes were examined. Multiple regression analyses were performed to examine the associations between subcortical and hippocampal volumes and participant characteristics. The FL-Resp group showed larger striatal and globus pallidus volumes compared to the URS group and larger post-commissural putamen and globus pallidus volumes compared to healthy controls. The URS group showed smaller thalamic volume compared to healthy controls. There were no subcortical or hippocampal volume differences between the URS and CLZ-Resp groups. Differences in subcortical and hippocampal structural volumes were not related to symptom severity or chlorpromazine antipsychotic dose equivalents. Our findings suggest different structural volume alterations in subcortical brain regions between treatment-resistant schizophrenia and responders to first-line antipsychotics. Whether subcortical structure compromise is a distinct pathophysiological marker of treatment-resistant schizophrenia, or a result of antipsychotic exposure, remains to be explored.

Keywords: Antipsychotics; Clozapine; Hippocampus; Subcortical; Treatment-resistant schizophrenia; Volume.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use*
  • Cross-Sectional Studies
  • Female
  • Hippocampus / diagnostic imaging*
  • Hippocampus / drug effects
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Schizophrenia / diagnostic imaging*
  • Schizophrenia / drug therapy*
  • Schizophrenic Psychology*


  • Antipsychotic Agents