Association between polymorphisms in the type 1 sigma receptor gene and schizophrenia.

Several antipsychotic agents such as haloperidol and rimcazole are known to bind to sigma receptors with high affinity, and evidence for a potential link between sigma receptors and the etiology of schizophrenia has been reported. The present study was conducted to systematically search for nucleotide variants of the type 1 sigma receptor gene in 48 schizophrenics. Two polymorphisms were found: GC-241-240TT in the 5' flanking region and Gln2Pro. These two polymorphisms were in nearly complete linkage disequilibrium with each other. The Pro2 variant of the Gln2Pro polymorphism changes the endoplasmic reticulum retention signal motif. These polymorphisms were examined in an extended sample of schizophrenics (n = 308) and controls (n = 433) and a significant association between the presence of the TT/Pro2 haplotype and schizophrenia was observed (odds ratio = 1.27, P = 0.04).

Two factors of experienced deficits in schizophrenia and their relationships with positive, negative, and depressive symptoms.

Eighty inpatients and 20 outpatients with ICD-10 schizophrenia were assessed with the Manchester Scale (MS) and the scale for the assessment of Subjective Experience of Deficits in Schizophrenia (SEDS). A factor analysis on MS scores yielded a three-factor solution: negative symptoms, positive symptoms, and anxious-depressive factor. On the other hand, a factor analysis on SEDS scores provided a seven-factor solution. The first factor, "awareness of social incompetence (ASI)," positively correlated with the anxious-depressive factor. ASI may reflect a negative cognitive attitude of persons who easily become depressive. The second factor, "subjective cognitive disturbance (SCD)," positively correlated with the positive-symptoms factor. SCD might represent a subtle disturbance, which can also produce positive symptoms. We found no factor on SEDS that correlated with the negative-symptoms factor. It was noted that a selection and comparison of items and the cultural background of subjects should be considered.

Evidence supporting an association between the DRB1 gene and schizophrenia in Japanese.

The authors attempted a replication of earlier studies that detected an association of HLA-DR4 and DR1 with schizophrenia. Japanese patients with schizophrenia (n = 266, DSM-III-R criteria) and Japanese controls (n = 283) were genotyped for DR1 and DR4 alleles using a combination of group-specific polymerase chain reaction (PCR) amplification and PCR-restriction fragment length polymorphism. Significant positive association with HLA-DR1 [odds ratio (OR) = 1.87, corrected p = 0.04] and a negative association with HLA-DR4 (OR = 0.63, corrected p = 0.02) was noted. DR1 and DR4 were independently associated with schizophrenia. The association of the DR1-positive/DR4-negative genotype with schizophrenia was modest (OR = 2.60, 95% confidence intervals = 1.38-4.89, corrected p = 0.008). Thus, these findings support an association of the HLA DRB1 gene locus with schizophrenia in the Japanese population. Since both DR4 and DR1 are positively associated with rheumatoid arthritis, our findings are not simply consistent with the known negative association between schizophrenia and rheumatoid arthritis.

Three grades of subjective experiences in schizophrenia: their phenomenology and implications for initial treatment.

Subjective experiences (SEs) in schizophrenia are sometimes neglected in operationalized diagnostics because schizophrenic patients often distort reality. Nevertheless, they sometimes report the peculiar nature of their experiences in a form of SEs. Two cases are presented to show the characteristic forms of SEs, which represent awareness of disturbed experiences of reality. They correspond to SEs in the third grade (SE3s), while SEs in the first grade consist of general subjective symptoms regarding mental and nervous conditions and those in the second grade indicate awareness of deficits in mental functions. Showing an intermediate nature between real and imaginary, SEs as well as first-rank symptoms perplex patients in the initial stage of the illness. Labeling SE3s as symptoms might successfully reduce the distress and anxiety of patients and be helpful in introducing them to long-lasting pharmacotherapy.

Acute polymorphic psychosis in adults with mild intellectual deficits.

This paper describes two representative cases of acute polymorphic psychotic disorder (APPD) defined in the International Classification of Diseases (ICD)-10 in adults with mild intellectual deficits. The patients showed mild intellectual impairment but had worked diligently for many years without their impairment being noticed by others. Some displayed maladjustments in their childhood and were classified as having intellectual disabilities. With their low self-esteem, precipitating events forced the patients to act inappropriately and, as a result, they became psychotic. Although APPD is supposed to occur without causative stress, an intellectual limitation combined with a certain personality can precipitate such a psychosis. It is noted that APPD might mask intellectual deficit and their precipitating factors and that a relapse could be prevented by advising a member of the patient's family.

Further association study on dopamine D2 receptor variant S311C in schizophrenia and affective disorders.

The dopamine D2 receptor gene is a candidate gene for schizophrenia because the potency of certain neuroleptics correlates with their affinity for this receptor. Case-control studies in 291 schizophrenics, 78 patients with affective disorders, and 579 controls on an association of a molecular variant of S311C of the dopamine D2 receptor with psychiatric disorders were conducted. The frequency of individuals with S311C was significantly higher in schizophrenics with the absence of negative symptoms (17.1%, P < 0.00001), but similar in schizophrenics with the presence of negative symptoms (5.7%, P = 0.46) when compared with the controls (4.1%). The frequency of S311C was significantly higher in familial schizophrenics from one local area but not in those from other areas. It was significant that S311C was frequently present in patients with mood-incongruent psychotic affective disorders (33.3%, P < 0.0001), but not in those with other affective disorders. These data suggest that S311C might be one of the genetic factors for symptomatic dimensions of delusions and hallucinations and might be involved in underlying clinical heterogeneity in schizophrenia and affective disorders.