Schizophrenia and other psychotic disorders Fractional anisotropic changes of the corpus callosum associated with antipsychotic treatment in first-episode antipsychotic drug-naive patients with schizophrenia

摘要

BACKGROUND: Schizophrenia is a serious brain illness that indicates many abnormalities in the functions of the brain’s fiber connections such as assessing the reality, thought, emotion and cognition. These fibers effect cognitional functions by connecting cortical and subcortical areas and networks formed by them. Aberrant brain connectivity especially in the prefrontal and temporal heteromodal cortex has been suggested as the essential mechanism underlying the disease. In this study, it is intended to investigate the post- and pre-treatment changes with diffusion tensor imaging MRI (DTI-MRI) in the splenium and genu regions of the corpus callosum in patients diagnosed with first-episode schizophrenia according to the DSM-IV-TR. METHOD: Between June 2009 and February 2010, 18 patients with psychotic symptoms were recruited from the outpatient unit of the GMMA Haydarpasha Research and Training Hospital. These patients had been diagnosed with first-episode schizophrenia (n=7) or schizophreniform disorder (n=11) and matched inclusion criteria. Patients with schizophreniform disorder as initial diagnosis were reevaluated after 6 months, and this time schizophrenia diagnosis was a ascertained. By means of implementation of SCID-II, additional diagnoses for personality disorder were excluded. Two of the 18 patients who had been admitted to the study were excluded because of being diagnosed with short-term psychotic disorder, and two patients were unable to proceed because of incompatibilitywith MRI device. Three participants with schizophrenia were excluded from this study because of unsatisfactory image data due to head and body movement in the follow-up MRI scan. DTI-MRI was obtained from participants at baseline and after 4 weeks of standard antipsychotic treatment follow-up. A ‘difference color-coded fractional anisotropy (FA) map’ for each of the 11 patients was calculated from the 4-week follow-up and the baseline splenium and genu FA ROI (Region of Interest)-based measurements. Finally, this study included participants of whom 14 had completed baseline, 11 both baseline and follow-up experiment and 16 control persons who had no organic or psychiatric disease and whose age, sex and education level was matched with the patient group. Patients included in the study were hospitalized, all tests and measurements were implemented before starting on antipsychotics, then standard antipsychotic treatments (Risperidone (n=12), Paliperidone (n=2)) were continued. Patients’ family histories were received and they were examined mentally, physically and neurologically. Initially liver, kidney and thyroid functions of all patients were examined. In addition, structural brain abnormalities were evaluated during the DTI measurements. To be eligible, criteria of involvement for either patients or healthy control subjects were: between 18 and 45 years old, being right-handed, first application to psychiatry, at least primary school graduate, no abuse of nicotine or caffeine, no DSM-IV-TR Axis I and Axis II comorbidity, a written consent (for patients by first-degree relatives). Criteria for being excluded: clinically conspicuous medical or neurological illness, having received antipsychotic treatment at the time of application or before or having used benzodiazepine longer than two weeks, for necessity of ECT (Electroconvulsive therapy), an incompatibility with MRI device and communication because of language problems and illnesses. The study was started after submitting the study protocol to the Istanbul Clinical Research Ethics Board and receiving approval from there (Number of decision: 2009-CC-040/11.12.2009) DTI Image Analysis: FA maps were calculated with Siemens? syngo VE27A SL0109 Syngo Multimodality Workplace AG 2007 according to Basser et al. Major eigenvector linear maps were transformed into color codes. In the second stage, in advance of measurements 3D correction (Eddy Current Correction) was implemented to remove artifacts of emerging images. ROI radiuses were determined as 2 mm in the genu, 3 mm in the splenium. Hereby FA values were calculated accurately. Statistic Evaluation: Acquired parameters from the study were evaluated with Statistical package for Social Sciences for Windows 16.0 (SPSS 16.0). Study parameters were expressed with average±standard deviation and percentage values. Group differences were assessed at baseline using independent group Student’s t-tests or χ2-tests, whereas longitudinal changes between the baseline and follow-up time points in the patients’ group was examined using paired Student’s t-tests. Significance level was based on p0.05). First-episode schizophrenia group’s economic level was lower than in healthy controls (χ2=5.275, p=0.022). DUP was identified as 2.3±1.7 months. Family history for schizophrenia was identified as 28.6%. In the first-episode schizophrenia group, an FA value of the genu region of the corpus callosum was determined as 0.690±0.124 and 0.834±0.042 for th