The effect of second-generation antipsychotics on basal ganglia and thalamus in first-episode psychosis patients

Eur Neuropsychopharmacol. 2019 Dec;29(12):1408-1418. doi: 10.1016/j.euroneuro.2019.10.004. Epub 2019 Nov 8.


Patients who have recently experienced a first of episode psychosis (FEP) exhibit considerable heterogeneity in subcortical brain volumes. These results become even more divergent when exploring the effect of antipsychotic medication among other clinical and cognitive features. We aimed to contrast volumetric measures in basal ganglia and thalamus in patients with a FEP treated with different second-generation antipsychotics. T1-weighted magnetic resonance images were obtained and subcortical structures were extracted with MAGeT-Brain. Relationships with cognitive functioning were also explored with a Global Cognitive Index obtained, on average, within one month from the scan. Subgroups included: risperidone (n = 26), aripiprazole (n = 22), olanzapine (n = 19) and controls (n = 80). The olanzapine subgroup displayed significant enlargement of the right globus pallidus volume compared with all other groups. Moreover, despite not exhibiting poorer cognitive capacity than the rest of patients, results from a stepwise multiple-regression linear regression analysis identified a significant negative association between right globus pallidus volume and scores on the Global Cognitive Index among these patients. To our knowledge, this is the first study to associate treatment with olanzapine with an increase in globus pallidus volume in a sample of FEP patients with a relatively short time of antipsychotic monotherapy. Such enlargement was also found to be associated with poorer global cognitive functioning. Exploration of the biological underpinnings of this early medication-induced enlargement should be the focus of future investigations since it may lend insight towards achieving a better clinical outcome for these patients.

Keywords: Antipsychotic medication; Cognition; First episode psychosis; Globus pallidus; Magnetic resonance imaging; Subcortical structures.

Publication types

  • Pragmatic Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use*
  • Basal Ganglia / diagnostic imaging*
  • Basal Ganglia / drug effects*
  • Female
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging / methods
  • Male
  • Psychotic Disorders / diagnostic imaging*
  • Psychotic Disorders / drug therapy
  • Thalamus / diagnostic imaging*
  • Thalamus / drug effects*
  • Young Adult


  • Antipsychotic Agents

Grant support