Frontal fasciculi and psychotic symptoms in antipsychotic-naive patients with schizophrenia before and after 6 weeks of selective dopamine D2/3 receptor blockade

Psychotic symptoms are core clinical features of schizophrenia. We tested recent hypotheses proposing that psychotic, or positive, symptoms stem from irregularities in long-range white matter tracts projecting into the frontal cortex, and we predicted that selective dopamine D2/3 receptor blockade w...

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Published in:	Journal of psychiatry & neuroscience Vol. 41; no. 2; pp. 133 - 141
Main Authors:	Ebdrup, Bjørn H., Raghava, Jayachandra M., Nielsen, Mette Ø., Glenthøj, Birte, Rostrup, Egill
Format:	Journal Article
Language:	English
Published:	Canada Canadian Medical Association 01.03.2016 NRC Research Press Joule Inc Cooperative Education Association 8872147 Canada Inc
Subjects:	Acute Disease Adult Anisotropy Antipsychotic Agents - therapeutic use Brain Brain - diagnostic imaging Brain - drug effects Diffusion Magnetic Resonance Imaging Diffusion Tensor Imaging Dopamine Antagonists - therapeutic use Dopamine receptors Dosage and administration Drug interactions Female Follow-Up Studies Humans Image Processing, Computer-Assisted Male Observations Patients Physiological aspects Psychiatric Status Rating Scales Psychiatric/Mental Health Psychiatry Psychotic Disorders - diagnostic imaging Psychotic Disorders - drug therapy Psychotic Disorders - metabolism Psychotic Disorders - psychology Receptors, Dopamine D2 - metabolism Receptors, Dopamine D3 - antagonists & inhibitors Receptors, Dopamine D3 - metabolism Research Paper Schizophrenia Schizophrenia - diagnostic imaging Schizophrenia - drug therapy Schizophrenia - metabolism Schizophrenic Psychology Schizophrenics Studies Sulpiride - analogs & derivatives Sulpiride - therapeutic use Treatment Outcome White Matter - diagnostic imaging White Matter - drug effects
ISSN:	1180-4882, 1488-2434, 1488-2434
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Summary:	Psychotic symptoms are core clinical features of schizophrenia. We tested recent hypotheses proposing that psychotic, or positive, symptoms stem from irregularities in long-range white matter tracts projecting into the frontal cortex, and we predicted that selective dopamine D2/3 receptor blockade would restore white matter. Between December 2008 and July 2011, antipsychoticnaive patients with first-episode schizophrenia and matched healthy controls underwent baseline examination with 3 T MRI diffusion tensor imaging and clinical assessments. We assessed group differences of fractional anisotropy (FA) using voxelwise tract-based spatial statistics (TBSS) and anatomic region of interest (ROI)–based analyses. Subsequently, patients underwent 6 weeks of antipsychotic monotherapy with amisulpride. We repeated the examinations after 6 weeks. We included 38 patients with first-episode schizophrenia and 38 controls in our analysis, and 28 individuals in each group completed the study. At baseline, whole brain TBSS analyses revealed lower FA in patients in the right anterior thalamic radiation (ATR), right cingulum, right inferior longitudinal fasciculus and right corticospinal tract (CT). Fractional anisotropy in the right ATR correlated with positive symptoms (z = 2.64, p = 0.008). The ROI analyses showed significant associations between positive symptoms and FA of the frontal fasciculi, specifically the right arcuate fasciculus (z = 2.83, p = 0.005) and right superior longitudinal fasciculus (z = −3.31, p = 0.001). At re-examination, all correlations between positive symptoms and frontal fasciculi had resolved. Fractional anisotropy in the ATR increased more in patients than in controls (z = −4.92, p < 0.001). The amisulpride dose correlated positively with FA changes in the right CT (t = 2.52, p = 0.019). Smoking and a previous diagnosis of substance abuse were potential confounders. Long-term effects of amisulpride on white matter were not evaluated. Antipsychotic-naive patients with schizophrenia displayed subtle deficits in white matter, and psychotic symptoms appeared specifically associated with frontal fasciculi integrity. Six weeks of amisulpride treatment normalized white matter. Potential re-myelinating effects of dopamine D2/3 receptor antagonism warrant further clarification.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 These authors contributed equally to this work.
ISSN:	1180-4882 1488-2434 1488-2434
DOI:	10.1503/jpn.150030