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We investigated cerebral structural connectivity and its relationship to symptoms in never-medicated individuals with first-onset schizophrenia using diffusion tensor imaging (DTI).
We recruited subjects with first episode DSM-IV schizophrenia who had never been exposed to antipsychotic medication (n=34) and age-matched healthy volunteers (n=32). All subjects received DTI and structural magnetic resonance imaging scans. Patients' symptoms were assessed on the Positive and Negative Syndrome Scale. Voxel-based analysis was performed to investigate brain regions where fractional anisotropy (FA) values significantly correlated with symptom scores.
In patients with first-episode schizophrenia, positive symptoms correlated positively with FA scores in white matter associated with the right frontal lobe, left anterior cingulate gyrus, left superior temporal gyrus, right middle temporal gyrus, right middle cingulate gyrus, and left cuneus. Importantly, FA in each of these regions was lower in patients than controls, but patients with more positive symptoms had FA values closer to controls. We found no significant correlations between FA and negative symptoms.
The newly-diagnosed, neuroleptic-naive patients had lower FA scores in the brain compared with controls. There was positive correlation between FA scores and positive symptoms scores in frontotemporal tracts, including left fronto-occipital fasciculus and left inferior longitudinal fasciculus. This implies that white matter dysintegrity is already present in the pre-treatment phase and that FA is likely to decrease after clinical treatment or symptom remission.
Patients with major depressive disorder are found to show selective attention biases towards mood-congruent information. Although previous studies have identified various structural changes in the brains of these patients, it remains unclear whether the structural abnormalities are associated with these attention biases. In this study, we used voxel-based morphometry (VBM) to explore the structural correlates of attention biases towards depression-related stimuli.
Seventeen female patients with major depressive disorder and 17 female healthy controls, matched on age and intelligence, underwent magnetic resonance imaging (MRI). They also performed positive-priming (PP) and negative-priming (NP) tasks involving neutral and negative words that assessed selective attention biases. The reaction time (RT) to a target word that had been attended to or ignored in a preceding trial was measured on the PP and NP tasks respectively. The structural differences between the two groups were correlated with the indexes of attention biases towards the negative words.
The enhanced facilitation of attention to stimuli in the PP task by the negative valence was only found in the depressed patients, not in the healthy controls. Such attention biases towards negative stimuli were found to be associated with reduced gray-matter concentration (GMC) in the right superior frontal gyrus, the right anterior cingulate gyrus and the right fusiform gyrus. No differential effect in inhibition of attention towards negative stimuli in the NP task was found between the depressed patients and the healthy controls.
Specific structural abnormalities in depression are associated with their attention biases towards mood-congruent information.
Diffusion tensor imaging (DTI) can be used to investigate cerebral structural connectivity in never-medicated individuals with first-episode schizophrenia.
Subjects with first-episode schizophrenia according to DSM-IV-R who had never been exposed to antipsychotic medication (n=25) and healthy controls (n=26) were recruited. Groups were matched for age, gender, best parental socio-economic status and ethnicity. All subjects underwent DTI and structural magnetic resonance imaging (MRI) scans. Voxel-based analysis was performed to investigate brain regions where fractional anisotropy (FA) values differed significantly between groups. A confirmatory region-of-interest (ROI) analysis of FA scores was performed in which regions were placed blind to group membership.
In patients, FA values significantly lower than those in healthy controls were located in the left fronto-occipital fasciculus, left inferior longitudinal fasciculus, white matter adjacent to right precuneus, splenium of corpus callosum, right posterior limb of internal capsule, white matter adjacent to right substantia nigra, and left cerebral peduncle. ROI analysis of the corpus callosum confirmed that the patient group had significantly lower mean FA values than the controls in the splenium but not in the genu. The intra-class correlation coefficient (ICC) for independent ROI measurements was 0.90 (genu) and 0.90 (splenium). There were no regions where FA values were significantly higher in the patients than in the healthy controls.
Widespread structural dysconnectivity, including the subcortical region, is already present in neuroleptic-naive patients in their first episode of illness.
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