title: White matter integrity as a predictor of response to treatment in first episode psychosis.
abstract: The integrity of brain white matter connections is central to a patient's ability to respond to pharmacological interventions. This study tested this hypothesis using a specific measure of white matter integrity, and examining its relationship to treatment response using a prospective design in patients within their first episode of psychosis. Diffusion tensor imaging data were acquired in 63 patients with first episode psychosis and 52 healthy control subjects (baseline). Response was assessed after 12 weeks and patients were classified as responders or non-responders according to treatment outcome. At this second time-point, they also underwent a second diffusion tensor imaging scan. Tract-based spatial statistics were used to assess fractional anisotropy as a marker of white matter integrity. At baseline, non-responders showed lower fractional anisotropy than both responders and healthy control subjects (P < 0.05; family-wise error-corrected), mainly in the uncinate, cingulum and corpus callosum, whereas responders were indistinguishable from healthy control subjects. After 12 weeks, there was an increase in fractional anisotropy in both responders and non-responders, positively correlated with antipsychotic exposure. This represents one of the largest, controlled investigations of white matter integrity and response to antipsychotic treatment early in psychosis. These data, together with earlier findings on cortical grey matter, suggest that grey and white matter integrity at the start of treatment is an important moderator of response to antipsychotics. These findings can inform patient stratification to anticipate care needs, and raise the possibility that antipsychotics may restore white matter integrity as part of the therapeutic response.
authors.affiliation: 1 Department of Psychosis Studies, Institute of Psychiatry, King's College London, UK.
authors.forename: Tiago
authors.initials: T
authors.lastname: Reis Marques
authors.forename: Heather
authors.initials: H
authors.lastname: Taylor
authors.forename: Chris
authors.initials: C
authors.lastname: Chaddock
authors.forename: Flavio
authors.initials: F
authors.lastname: Dell'acqua
authors.forename: Rowena
authors.initials: R
authors.lastname: Handley
authors.forename: A A T Simone
authors.initials: AA
authors.lastname: Reinders
authors.forename: Valeria
authors.initials: V
authors.lastname: Mondelli
authors.forename: Stefania
authors.initials: S
authors.lastname: Bonaccorso
authors.forename: Marta
authors.initials: M
authors.lastname: Diforti
authors.forename: Andrew
authors.initials: A
authors.lastname: Simmons
authors.forename: Anthony S
authors.initials: AS
authors.lastname: David
authors.forename: Robin M
authors.initials: RM
authors.lastname: Murray
authors.forename: Carmine M
authors.initials: CM
authors.lastname: Pariante
authors.forename: Shitij
authors.initials: S
authors.lastname: Kapur
authors.forename: Paola
authors.initials: P
authors.lastname: Dazzan
mesh_terms: D000328:Adult; D016880:Anisotropy; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D038801:International Classification of Diseases; D008137:Longitudinal Studies; D008297:Male; D001523:Mental Disorders / Q000150:complications; D011237:Predictive Value of Tests; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000473:pathology*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents
keywords: antipsychotic drugs; diffusion tensor imaging; psychosis; schizophrenia; white matter