Hisae Ono

Association between Catechol-O-Methyltransferase Functional Polymorphism and Male Suicide Completers

Suicide has been suggested to involve catecholaminergic dysfunction and to be related to genetics. Catechol-O-methyltransferase (COMT) 158Val/Met polymorphism (GenBank Accession No. Z26491) is a polymorphism of the gene encoding COMT, a major enzyme in catecholamine inactivation. The COMT 158Val/Met polymorphism affects COMT activity, that is, the alleles encoding Val and Met are associated with relatively high and relatively low COMT activity, respectively. In this study, we hypothesized that the COMT 158Val/Met polymorphism is associated with suicide. The study population consisted of 163 suicide completers (112 males and 51 females). We found that the genotype distribution of the COMT 158Val/Met polymorphism was significantly different between male suicide completers and male controls (p=0.036), while the frequency of the Val/Val genotype, a high-activity COMT genotype, was significantly less in male suicide completers than in male controls (OR: 0.52; 95% CL: 0.31–0.89; p=0.016). However, this was not the case in females. Our results suggest that the Val/Val genotype is a protective factor against suicide in males.

Tryptophan hydroxylase immunoreactivity is altered by the genetic variation in postmortem brain samples of both suicide victims and controls.

Several lines of evidence suggest that a partly genetically controlled serotonergic dysfunction is involved in the biological pathogenesis of suicide. In this study, we measured tryptophan hydroxylase (TPH) immunoreactivity as a pre-synaptic marker, and serotonin receptor 2A (5HT2A receptor) density as a post-synaptic marker in the serotonergic system in 10 postmortem brains of suicide victims. We also examined whether TPH gene polymorphisms (A218C and A-6526G polymorphisms) could affect TPH immunoreactivity and 5HT2A receptor gene polymorphism (A-1438G polymorphism) could affect 5HT2A receptor density in 28 postmortem brain samples. No significant differences were found in TPH immunoreactivity or 5HT2A receptor density between suicide victims and controls. The AA genotype of the A218C polymorphism of the TPH gene showed higher TPH immunoreactivity along with lower 5HT2A receptor density than did any other genotypes in the postmortem brains of both suicide victims and controls. Our findings suggest that the A218C polymorphism of the TPH gene can be expected to provide new insights not only for neurobiological studies of suicide, but also for research into the behavioral characteristics that may be associated with serotonergic dysfunction.

Serotonin 2A receptor gene polymorphism is not associated with completed suicide.

Several lines of evidence indicate that a serotonergic dysfunction is involved in the biological susceptibility to suicide. Recently, the A-1438G polymorphism of the serotonin 2A (5-HT2A) receptor gene has been suggested to be associated with suicide, but the results are inconsistent. We examined whether the A-1438G polymorphism of the 5-HT2A receptor gene was associated with suicide itself using 151 Japanese completed suicides. No significant difference in genotype distribution or allele frequencies of the polymorphism was found between the completed suicides and the comparison group. We conclude that the A-1438G polymorphism of the 5-HT2A receptor gene is not likely to have a major effect on the biological susceptibility of suicide.

Tryptophan hydroxylase gene polymorphisms are not associated with suicide

Several lines of evidence suggest a serotonergic dysfunction involved in the biological susceptibility of suicide. Abnormalities of serotonergic markers such as 5-hydroxyindoleacetic acid and prolactin response to fenfluramine have been demonstrated in suicide subjects. Tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin biosynthesis, is one of the most important regulating factors in the serotonergic system. Recently, polymorphisms of the TPH gene have been identified and some of these polymorphisms have been suggested to be associated with suicide, but the results are still inconsistent. We examined whether the -6526A/G polymorphism in the promoter region and the 218A/C polymorphism in intron 7 of the TPH gene were associated with suicide using 132 Japanese suicide victims. No significant difference in genotype distribution and allele frequencies of these polymorphisms was found between the suicide victims and the controls. We concluded neither the -6526A/G polymorphism nor the 218A/C polymorphism of the TPH gene is likely to have a major effect on the susceptibility of suicide. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:861-863, 2000.

Lack of an association between 5-HT6 receptor gene polymorphisms and suicide victims

Abstract  An association between serotonergic dysfunction in the brain and suicidal behavior has previously been suggested. The high affinity of some antipsychotic and antidepressant drugs to serotonin 6 (5‐HT6) receptors, and the predominant localization of 5‐HT6 receptors in some limbic regions, suggest that 5‐HT6 receptors play a role in the pathogenesis of suicide. The objective of the present study was to examine the association between suicide victims and two polymorphisms of the 5‐HT6 receptor gene: a biallelic polymorphism (267C/T) in exon 1 and a trinucleotide repeat polymorphism ([GCC]2/3) in the 5′‐upstream region of the gene. The two polymorphisms were genotyped in 163 suicide victims and 166 controls, and the distribution of genotype and allele frequencies between the two groups were compared. Haplotype frequencies of these two polymorphisms were estimated from genotypic data by the maximum‐likelihood method. In both polymorphisms, there were no significant differences in genotype or allele frequencies between the suicide victims and the controls. Moreover, there were no significant differences in the haplotype distributions of these polymorphisms between the two groups. These findings suggest that it is unlikely that the 5‐HT6 receptor gene is involved in the susceptibility to suicide.

Novel missense polymorphism in the regulator of G‐protein signaling 10 gene: analysis of association with schizophrenia

ABSTRACT  Dysfunction of neuronal signal transduction via G‐protein has previously been speculated to be involved in the pathophysiology of schizophrenia. Regulator of G‐protein signaling (RGS) is a protein that acts as a GTPase‐activator for Gα protein. A total of 33 Japanese patients with schizophrenia were screened for mutations in the coding region of the RGS10 gene, and a novel missense polymorphism (Val38Met) in the RGS domain was detected. A case‐control study did not reveal a significant association between this polymorphism and schizophrenia. The results do not provide evidence that the RGS10 gene is involved in biological vulnerability to schizophrenia.

Mutation and association analysis of the DAP‐1 gene with schizophrenia

Glutamate dysfunction has been hypothesized to be involved in the pathophysiology of schizophrenia. The human homolog of Drosophila discs large protein (hDLG) and post‐synaptic density‐95‐associated protein‐1 (DAP‐1) is one of the major proteins that are involved in intracellular signal transduction via N‐methyl‐d‐aspartate receptors. In the present study 33 Japanese patients with schizophrenia were screened for mutations in the DAP‐1 gene. A single nucleotide polymorphism was identified in the DAP‐1 gene (1618A/G). A case–control study using a larger sample of unrelated patients and controls did not reveal a significant association between this polymorphism and schizophrenia. The results do not provide evidence that the DAP‐1 gene is involved in vulnerability to schizophrenia.

Reduced left precentral regional responses in patients with major depressive disorder and history of suicide attempts

Previous neuroimaging studies have revealed frontal and temporal functional abnormalities in patients with major depressive disorder (MDD) and a history of suicidal behavior. However, it is unknown whether multi-channel near-infrared spectroscopy (NIRS) signal changes among individuals with MDD are associated with a history of suicide attempts and a diathesis for suicidal behavior (impulsivity, hopelessness, and aggression). Therefore, we aimed to explore frontotemporal hemodynamic responses in depressed patients with a history of suicide attempts using 52-channel NIRS. We recruited 30 patients with MDD and a history of suicidal behavior (suicide attempters; SAs), 38 patient controls without suicidal behavior (non-attempters; NAs), and 40 healthy controls (HCs) matched by age, gender ratio, and estimated IQ. Regional hemodynamic responses during a verbal fluency task (VFT) were monitored using NIRS. Our results showed that severities of depression, impulsivity, aggression, and hopelessness were similar between SAs and NAs. Both patient groups had significantly reduced activation compared with HCs in the bilateral frontotemporal regions. Post hoc analyses revealed that SAs exhibited a smaller hemodynamic response in the left precentral gyrus than NAs and HCs. Furthermore, the reduced response in the left inferior frontal gyrus was negatively correlated with impulsivity level and hemodynamic responses in the right middle frontal gyrus were negatively associated with hopelessness and aggression in SAs but not in NAs and HCs. Our findings suggest that MDD patients with a history of suicide attempts demonstrate patterns of VFT-induced NIRS signal changes different from those demonstrated by individuals without a history of suicidal behaviors, even in cases where clinical symptoms are similar. NIRS has a relatively high time resolution, which may help visually differentiate SAs from NAs.

Effectiveness of a Simple Individual Psychoeducation Program in a Patient with Bipolar II Disorder

Bipolar II disorder is characterised by recurrent mood episodes of depression and hypomania [1]. Patients with bipolar II disorder show lack of awareness about their illness, because a hypomanic does not significantly influence a patient’s social functioning. Lack of awareness may be a cause to prolong time to diagnosis in bipolar II disorder [2]. The low disease awareness and prolonged time to diagnosis might establish psychopathological features that make difficult the progress of the disease.

The Effect of Interpersonal Counseling for Subthreshold Depression in Undergraduates: An Exploratory Randomized Controlled Trial

Background Subthreshold depression and poor stress coping strategies are major public health problems among undergraduates. Interpersonal counseling (IPC) is a brief structured psychological intervention originally designed for use in primary care to treat depressive patients whose symptoms arose from current life stress. Objectives This study examined the efficacy of IPC in treating subthreshold depression and coping strategies among undergraduates in school counseling. Materials and Methods We carried out an exploratory randomized controlled trial comparing the efficacy of IPC with counseling as usual (CAU). Participants were 31 undergraduates exhibiting depression without a psychiatric diagnosis. Results The Zung Self-Rating Depression Scale total score decreased significantly in the IPC group (n = 15; Z = −2.675, p = .007), but not in the CAU group (n = 16). The task-oriented coping score of the Coping Inventory for Stressful Situations showed a tendency towards a greater increase in the IPC group than in the CAU group (t = 1.919, df = 29, p = .065). Conclusions The IPC might be more useful for student counseling because it can teach realistic coping methods and reduce depressive symptoms in a short period. Further studies using more participants are required.