Fine mapping of a schizophrenia susceptibility locus at chromosome 6q23: increased evidence for linkage and reduced linkage interval.

We previously reported an autosomal scan for schizophrenia susceptibility loci in a systematically recruited sample of Arab Israeli families. The scan detected significant evidence for linkage at chromosome 6q23 with a nonparametric LOD score (NPL) of 4.60 (P=0.000004) and a multipoint parametric LOD score of 4.16. In order to refine this finding we typed 42 additional microsatellite markers on chromosome 6q between D6S1570 (99.01 cM from the pter) and D6S281 (190.14 from the pter) in the same sample (average intermarker distance approximately 1.7 cM). In the 23 cM region between D6S1715 and D6S311, markers were more closely spaced ( approximately 1.1 cM). Multipoint nonparametric and parametric and single point linkage analyses were performed. The peak NPL rose to 4.98 (P=0.00000058) at D6S1626 (136.97 cM), immediately adjacent to D6S292 (NPL 4.98, P=0.00000068), the marker that gave the highest NPL in the original genome scan, under the broad diagnostic category. The putative susceptibility region (NPL-1) was reduced from 12.0 to 4.96 cM. The peak multipoint parametric LOD score was 4.63 at D6S1626 under a dominant genetic model, core diagnostic category and the LOD-1 interval was 2.10 cM. The maximum single point LOD score (3.55, theta=0.01) was also at D6S1626 (dominant model, core diagnostic category). Increased evidence for linkage in the same sample as in the original genome scan and consistent localization of the linkage peak add further support for the presence of a schizophrenia susceptibility locus at chromosome 6q23. Moreover, the markedly reduced linkage interval greatly improves prospects for identifying a schizophrenia susceptibility gene within the implicated region.

A double blind study showing that two weeks of daily repetitive TMS over the left or right temporoparietal cortex reduces symptoms in patients with schizophrenia who are having treatment-refractory auditory hallucinations.

The aim of this study was to evaluate the effect of repetitive transcranial magnetic stimulation (rTMS) on the left and right temporoparietal cortex compared with sham stimulation in schizophrenic patients with treatment-refractory auditory hallucinations (AH). Thirty-nine patients with schizophrenia with treatment-refractory AH were allocated randomly to one of three groups: daily left, right, and sham rTMS groups. rTMS was applied to the TP3 or 4 regions with the aid of the electroencephalography 10-20 international system at 1 Hz for 20 min per day for 10 treatment days. Symptoms were evaluated using the Auditory Hallucination Rating Scale (AHRS), the Positive and Negative Symptoms Scale (PANSS), the Clinical Global Impression--Severity (CGI-S), and Clinical Global Impression--Improvement (CGI-I) scale. For the time effect (within-subject comparison), there were significant changes in the frequency of AHs, positive symptoms of PANSS, and CGI-I. A between-group comparison revealed significant differences in the positive symptoms of PANSS, and CGI-I scores. Post hoc analysis revealed that both the right- and left-side rTMS treatment groups exhibited better CGI-I scores compared to the sham-stimulated group. This study suggests that 10 days of low-frequency rTMS applied daily for 20 min to either temporoparietal cortex significantly reduces the symptoms in patients with schizophrenia who are having refractory AH, but the left sided rTMS is not superior to right or sham rTMS.