Ming-Hsien Hsieh

More severe sustained attention deficits in nonpsychotic siblings of multiplex schizophrenia families than in those of simplex ones

Sustained attention deficits measured by the Continuous Performance Test (CPT) have been proposed as an endophenotype of schizophrenia. However, little is known about whether sustained attention deficits in first-degree relatives of schizophrenic patients are associated with familial loading for schizophrenia. We examined 107 parents and 84 siblings of simplex schizophrenia families as well as 72 parents and 56 siblings of multiplex schizophrenia families, all nonpsychotic, using the Diagnostic Interview for Genetic Studies and two sessions of the CPT (undegraded and degraded). The effect of perceptual load was assessed using the residual of the regression of the degraded score on the undegraded one. Statistical models that can adjust for familial correlations were used to compare the CPT performance of relatives between the two types of families. Siblings from multiplex families exhibited worse performance on the degraded CPT and less proficiency in processing the perceptual load than those from simplex families. No such difference was observed for the parents on either CPT version. We concluded that sustained attention along with perceptual load processing is more impaired in the siblings of schizophrenic patients with high familial loading and that this finding might be useful for future genetic dissection of schizophrenia.

No association evidence between schizophrenia and dystrobrevin-binding protein 1 (DTNBP1) in Taiwanese families

Several linkage studies have shown significant linkage of schizophrenia to chromosome 6p region, which includes the positional candidate genes, Dystrobrevin-binding protein 1 (DTNBP1). The aim was to examine the association evidence of the candidate gene in 693 Taiwanese families with at least two affected siblings of schizophrenia. We genotyped nine SNPs of this gene with average intermarker distance of 17 kb. Intermarker linkage disequilibrium was calculated with GOLD. Single locus and haplotype association analyses were performed with TRANSMIT program. We found no significant association between schizophrenia and DTNBP1 either through single locus or haplotype analyses. We failed to replicate the association evidence between DTNBP1 and schizophrenia and this gene may not play a major role in the etiology of schizophrenia in this Taiwanese family sample.

Shared and distinct alterations of white matter tracts in remitted and nonremitted patients with schizophrenia

Patients with schizophrenia do not usually achieve remission state even after adequate antipsychotics treatment. Previous studies found significant difference in white matter integrity between patients with good outcomes and those with poor outcomes, but difference is still unclear at individual tract level. This study aimed to use a systematic approach to identify the tracts that were associated with remission state in patients with schizophrenia. We evaluated 91 patients with schizophrenia (remitted, 50; nonremitted, 41) and 50 healthy controls through diffusion spectrum imaging. White matter tract integrity was assessed through an automatic tract‐specific analysis method to determine the mean generalized fractional anisotropy (GFA) values of the 76 white matter tract bundles in each participant. Analysis of covariance among the 3 groups revealed 12 tracts that were significantly different in GFA values. Post‐hoc analysis showed that compared with the healthy controls, the nonremission group had reduced integrity in all 12 tracts, whereas the remission group had reduced integrity in only 4 tracts. Comparison between the remission and nonremission groups revealed 4 tracts with significant difference (i.e., the right fornix, bilateral uncinate fasciculi, and callosal fibers connecting the temporal poles) even after adjusting age, sex, education year, illness duration, and medication dose. Furthermore, all the 4 tracts were correlated with negative symptoms scores of the positive and negative syndrome scale. In conclusion, our study identified the tracts that were associated with remission state of schizophrenia. These tracts might be a potential prognostic marker for the symptomatic remission in patients with schizophrenia.

T182. SHARED AND DISTINCT ALTERATIONS IN THE WHITE MATTER TRACTS OF REMITTED AND NON-REMITTED PATIENTS WITH SCHIZOPHRENIA

Abstract Background Antipsychotic drugs are the standard treatment for schizophrenia; however, the treatment outcomes vary. Different treatment outcomes may be attributed to the genetic and molecular heterogeneity of patients, which may be represented in the white matter structures of the brain. In the present study, we assessed the association between white matter tract integrity and treatment outcomes in patients with schizophrenia. Methods We evaluated 96 patients with schizophrenia (remitted, 53; non-remitted, 43) and 50 healthy controls through diffusion spectrum imaging with a 3 Tesla magnetic resonance imaging scanner. Patients were categorized into the remission and non-remission groups according to the criteria proposed by The Remission in Schizophrenia Working Group (RSWG) on the basis of PANSS scores. White matter tract integrity was assessed through an automatic tract-specific analysis method to determine the mean generalized fractional anisotropy (GFA) values of the 76 white matter tract bundles in each participant. Results Analysis of covariance revealed that 7 tracts, namely the bilateral fornices, the bilateral uncinate fasciculi, and the callosal fibers (CFs) of the bilateral temporal poles, bilateral hippocampi, and bilateral amygdalae, had significantly different GFA values among the 3 groups. Posthoc between-groups analysis showed that the non-remission group had lower GFA values in all 7 tracts than the control group; the remission group had lower GFA values than the control group only in 4 tracts, namely the bilateral fornices and the CFs of the bilateral temporal poles, and bilateral hippocampi. Compared with the remission group, the non-remission group had lower GFA values in all 7 tracts. Discussion All 7 tracts that were altered in the non-remission group are a part of the limbic system, which supports various functions, including emotions, memory, and learning. Our results suggest that patients who had poor outcomes to antipsychotic treatments might have more severe disruptions in the limbic system. The 7 altered tracts in the non-remission group are compatible with those reported in previous studies on white matter or gray matter alterations. In a cross-sectional tractography-based study on 3 pairs of association fibers (i.e., the cingulum, superior longitudinal fasciculus, and uncinate fasciculus), Luck et al reported that compared with patients with good outcomes, patients with poor outcomes had reduced FA in the uncinate fasciculus and superior longitudinal fasciculus. Marques et al performed a longitudinal study using tract-based spatial statistics and reported that non-responders had more tracts with a significantly lower FA than did the responders, particularly in the uncinate fasciculus and corpus callosum. In addition to the uncinate fasciculus, we also observed reduced fiber integrity in the bilateral fornices and the CFs of the bilateral temporal poles, bilateral hippocampi, and bilateral amygdalae; these tracts connect the gray matter in the limbic system. Jääskeläinen et al revealed that a reduction in gray matter volume in the frontal and limbic areas is associated with overall poor outcomes. In addition, Van Haren et al reported significantly reduced gray matter volumes in the frontal and temporal cortices of the individuals with poor outcomes. Because the gray matter regions are anatomically connected by the fiber tracts, gray matter reduction in the limbic system might affect the interconnecting fiber tracts; this finding accords with the findings of the present study. In conclusion, differences in the severity of white matter tract alterations in the remission and non-remission groups might indicate biologically distinct subgroups in schizophrenia.

Comparative effect of antipsychotics on risk of self-harm among patients with schizophrenia

To investigate the association of different antipsychotic treatments with hospitalization due to self‐harm among patients with schizophrenia.