Abstract
Depressive symptoms in subjects at Clinical High Risk for Psychosis (CHR-P) or at first-episode psychosis (FEP) are often treated with antidepressants. Our cross-sectional study investigated whether brain morphology is altered by antidepressant medication. High-resolution T1-weighted structural MRI scans of 33 CHR-P and FEP subjects treated with antidepressants, 102 CHR-P and FEP individuals without antidepressant treatment and 55 controls, were automatically segmented using Freesurfer 6.0. Linear mixed-effects modelling was applied to assess the differences in subcortical volume, surface area and cortical thickness in treated, non-treated and healthy subjects, taking into account converted dosages of antidepressants. Increasing antidepressant dose was associated with larger volume of the pallidum and the putamen, and larger surface of the left inferior temporal gyrus. In a pilot subsample of separately studied subjects of known genomic risk loci, we found that in the right postcentral gyrus, the left paracentral lobule and the precentral gyrus antidepressant dose-associated surface increase depended on polygenic schizophrenia-related-risk score. As the reported regions are linked to the symptoms of psychosis, our findings reflect the possible beneficial effects of antidepressant treatment on an emerging psychosis.
Highlights
Appearance of psychosis is considered to be the driving force of multiple debilitating mental disorders, including schizophrenia[1,2], which affects 0.7% of the world population[3]
As there are only a few studies showing an impact of antidepressant medication on volume, thickness and surface[26,51] in Clinical High Risk for Psychosis (CHR-P) and first-episode psychosis (FEP), we investigated the influence of antidepressant dose on the whole-brain
In an analysis of automatically segmented brain regions in CHR-P, FEP and healthy controls, we found a significant (FDR p < 0.05) main effect of current antidepressant dose on the volume of the pallidum and the putamen and surface of the inferior temporal gyrus
Summary
Appearance of psychosis is considered to be the driving force of multiple debilitating mental disorders, including schizophrenia[1,2], which affects 0.7% of the world population[3]. Multiple findings indicate that CHR-P and FEP show similar functional[11] and structural brain abnormalities[9,10,12,13], but it is unclear to what extent they reflect genetics, general distress, medication effects or are unique features associated with the at risk stage of the disorder. CHR-P and FEP individuals often suffer from comorbid depressive and anxiety symptoms[25,26] that can precede[27] or accompany the onset of attenuated positive psychotic symptoms[9,28] These features are the main reason for seeking help at specialized services[29] and the occurrence of these is significantly associated with decreased likelihood of remission from CHR-P30,31. A recent study of affective psychoses[51] did not detect long-term antidepressant effect on any brain regions, – like in other studies – only general presence or absence of antidepressants was used as a predictor
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