TY - JOUR
T1 - White matter integrity as a predictor of response to treatment in first episode psychosis
AU - Reis Marques, Tiago
AU - Taylor, Heather
AU - Chaddock, Chris
AU - Dell'acqua, Flavio
AU - Handley, Rowena
AU - Reinders, A A T Simone
AU - Mondelli, Valeria
AU - Bonaccorso, Stefania
AU - Di Forti, Marta
AU - Simmons, Andrew
AU - David, Anthony S
AU - Murray, Robin M
AU - Pariante, Carmine M
AU - Kapur, Shitij
AU - Dazzan, Paola
PY - 2014/1
Y1 - 2014/1
N2 - 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.
AB - 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.
KW - Acknowledged-BRC
KW - Acknowledged-BRC-13/14
U2 - 10.1093/brain/awt310
DO - 10.1093/brain/awt310
M3 - Article
C2 - 24253201
SN - 0006-8950
VL - 137
SP - 172
EP - 182
JO - Brain
JF - Brain
IS - 1
ER -