Bipolar Disorder: Gutiérrez B

Vázquez GH, Strejilevich S, García Bonetto G, Cetkovich-Bakmas M, Zaratiegui R, Lagomarsino A, Goldchluk A, Kalina E, Herbst L, Gutiérrez B, Anonymous00416. · Departamento de Neurociencias, Universidad de Palermo, Buenos Aires, Argentina. · Vertex. · Pubmed #16601825 No free full text.

Abstract: The consensus guidelines of argentine experts in the treatment of bipolar disorders are the result of three days of work of the 10 main local experts under the organization of the Argentine Association of Biological Psychiatry (AAPB). It was adopted a mixed criterion for its preparation: all the recent data of the evidence medicine based published until now were discussed and were balanced with the knowledge acquired from clinical experience of the local experts on the bipolar field. It presents general recommendations and suggested therapeutic sequences for the phase of maintenance, the manic/hypomanic or mixed episode and the depressive episode. These have been divided according to the classification in type I and II; with or without rapid cycling. Since the group of experts identified the delay and miss-diagnoses like the most important barrier for a suitable treatment enclosed a series of recommendations for differential diagnosis of bipolar disorders.

Gutiérrez B, Rosa A, Papiol S, Arrufat FJ, Catalán R, Salgado P, Peralta V, Cuesta MJ, Fañanás L. · Unitat d'Antropologia, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain. · Am J Med Genet B Neuropsychiatr Genet. · Pubmed #17427184 No free full text.

Abstract: The synaptic vesicular monoamine transporter (SVMT) plays a key role in monoaminergic neurotransmission determining the size of neurotransmitter vesicular pools available for exocytotic release. Recently, several lines of evidence have suggested that altered functions of SVMT may be involved in the pathogenesis of certain neuropsychiatric diseases, including psychotic and mood disorders. In the present study, we tested the potential involvement of SVMT gene variants in the etiology of schizophrenia and bipolar disorder. Five different SNPs (T440G, C1368T, T2666C, A2683C, and A745G) were included in the analysis covering a region of about 35 kb along the SVMT gene. Analyses were performed in a case-control sample consisting of 88 bipolar patients, 107 subjects with schizophrenia, and 164 controls. Two risk haplotypes for both schizophrenia and bipolar disorder in SVMT gene were identified. Particularly, 2666T-2683A-745G (TAG) and 2666C-2683C-745A (CCA) combinations were significantly more frequent in both bipolar and schizophrenic patients than in controls. UNPHASED package estimated haplotype effects for all patients yielded relative risks of 4.1 (95%CI: 1.83-9.21) for TAG combination and 2.336 (95%CI: 1.28-4.26) for CCA haplotype. Conversely, 2666T-2683C-745A (TCA) and 2666C-2683A-745G (CAG) haplotypes seemed to protect against these mental disorders, since the estimated frequency in control chromosomes was 12% whilst such haplotypes were not observed in any bipolar or schizophrenic subject (P < 0.0000). Our results strongly suggest that SVMT gene or certain regions of it may constitute a genetic substrate of susceptibility for both schizophrenia and bipolar disorder.

Gutiérrez B, Arias B, Gastó C, Catalán R, Papiol S, Pintor L, Fañanás L. · Unitat d'Antropologia, Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain. · Psychiatr Genet. · Pubmed #15564894 No free full text.

Abstract: Monoamine oxidase A (MAOA) has been suggested to be involved in human behaviour and physiology due to its key role in the metabolism of several different biological amines including the neurotransmitters serotonin, norepinephrin and dopamine.Recently, a 30 bp repeat in the MAOA gene promoter (uMAOA) has been demonstrated to be polymorphic and to affect transcriptional activity.In the context of an association case-control study design, we analysed the uMAOA polymorphism in 389 unrelated patients affected by severe mood disorders (88 bipolar subjects and 301 major depressive individuals) and in 156 controls. No association was found between the uMAOA locus and bipolar disorder or major depression. However, an increase of high-activity uMAOA alleles was found in major depression female patients presenting a seasonal pattern (chi2=3.013, P=0.05) or psychotic symptoms in their episodes (chi2=2.679, P=0.07). In female bipolar disorder patients, long alleles were associated with longest times of admission (F=4.604, P=0.037). A trend for association with seasonal pattern was also defined in this group (data not corrected for multiple testing). Our results suggest that MAOA gene variation may modulate the expression of some clinical aspects of severe mood disorders, especially in females, and support the existence of a genetic and aetiologic heterogeneity underlying the diagnoses of bipolar disorder and major depression.

Gutiérrez B, Arranz MJ, Huezo-Diaz P, Dempster D, Matthiasson P, Travis M, Munro J, Osborne S, Kerwin RW. · Department of Clinical Neuropharmacology, Institute of Psychiatry, Denmark Hill, London SE5 8AF, UK. · Schizophr Res. · Pubmed #12363396 No free full text.

Abstract: Clozapine is a potent antagonist of 5-HT3 receptors, which are ligand-gated ion channels that mediate rapid excitatory responses in the central nervous system. Two different isoforms of 5-HT3 receptor subunit genes (HTR3A and HTR3B) have been identified. They have been assigned to chromosome 11q23.1-q23.2, a region which in the past has been linked to schizophrenia and bipolar disorder.In this study, we performed a systematic mutation screening of the 5-HT3A and 5-HT3B receptor genes and tested the variants for association with clozapine response in a sample of 266 clozapine-treated patients. Two polymorphisms at the 5-HT3A gene and five new variants in the 5-HT3B gene were finally detected. Of these, only the more frequent mutations (178-C/T and 1596-A/G in 5-HT3A and a CA-repeat in 5-HT3B) were genotyped in our clozapine sample. Association analysis showed similar allele and genotype distributions among clozapine responders and nonresponders.These results make unlikely the possibility that 5-HT3A and 5-HT3B receptor genes underlie variation in clinical response to clozapine. However, the promoter regions of both genes have yet to be investigated.

Gutiérrez B, Arias B, Papiol S, Rosa A, Fañanás L. · Unitat d'Antropologia, Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona, Diagonal 645, 08028 Barcelona, Spain. · Neurosci Lett. · Pubmed #11502363 No free full text.

Abstract: Two recently described adjacent DNA polymorphisms [(GT)12-18 and (CT)4-5] in the 5'-regulatory region of 5-HT2C receptor gene were analysed in a sample of 88 bipolar patients and 162 controls, all of Spanish origin. Statistical analyses revealed no overall allele or genotype associations with the disease. A haplotype analyses between the (GT)12-18/(CT)4-5 motif and a Cys23Ser variant of the 5-HT2C gene (which had previously been genotyped in the same sample) showed similar distributions between cases and controls. Only a slight increase of s-Ser23 haplotype was found in the subgroup of bipolar women with family history of psychiatric illness (OR=1.24 [95%CI: 1.12-1.38]).

Arias B, Collier DA, Gastó C, Pintor L, Gutiérrez B, Vallès V, Fañanás L. · Unitat d'Antropologia, Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona, Diagonal 645, 08028, Barcelona, Spain. · Neurosci Lett. · Pubmed #11311505 No free full text.

Abstract: In the present study, genetic variation of the 5-HT5A receptor was analyzed in patients affected by affective disorders and healthy controls. The sample consisted of 181 patients with major depression, 88 patients with bipolar affective disorder (BP) and 157 unrelated controls (C), all of Spanish origin. Two polymorphisms (-19G/C and 12A/T) in the 5-HT5A receptor gene were analyzed by polymerase chain reaction amplification and subsequent enzyme digestion. No genotype, allele or haplotype differences were found when we compared patients and controls. When clinical variables were considered as possible tools for detecting genetic heterogeneity, no differences were found. Our results suggest that the polymorphisms analyzed in the 5-HT5A receptor gene do not play a major role in the pathogenesis of affective disorders.

Vallès V, Van Os J, Guillamat R, Gutiérrez B, Campillo M, Gento P, Fañanás L. · Servei de Psiquiatria, Consorci Sanitari de Terrassa, Carretera de Torrebonica, 08227 Terrassa, Barcelona, Spain. · Schizophr Res. · Pubmed #10742646 No free full text.

Abstract: BACKGROUND: It has been reported that relatives of probands with severe, psychotic forms of bipolar illness have increased rates of schizophrenia but not the relatives of individuals with milder, non-psychotic forms of disorder. In this study, we examined the prevalence of psychiatric disorders in the first degree relatives of a sample of 103 inpatients with bipolar disorder and in a matched control sample of 84 healthy individuals. METHOD: Relatives of cases and controls were interviewed using the FH-RDC to determine familial morbid risk for schizophrenia and bipolar disorder. Age- and sex-adjusted morbidity risks were calculated in both samples according to the method of Strömgren. RESULTS: The morbid risks for both bipolar disorder (4.9%) and schizophrenia (2.8%) were higher in relatives of patients than in relatives of controls (0.3% and 0.6% respectively). The relative risks were 14.2 [95% confidence interval (CI)=3.1-64.2] for bipolar disorder and 4.9 (95% CI=1.3-18.8) for schizophrenia. Relatives of women with early onset of bipolar illness had the highest morbid risks for both bipolar illness and schizophrenia. The presence of more than one patient with bipolar disorder in a family increased the risk for schizophrenia nearly fourfold (RR=3.5, 95% CI=1.2-10.2). There was no additional effect of presence of psychotic features. CONCLUSION: Our results suggest that the transmission of psychosis is not disorder-specific. Bipolar illness characterised by a high familial loading is associated with increased risk of schizophrenia in the relatives.

Papiol S, Rosa A, Gutiérrez B, Martín B, Salgado P, Catalán R, Arias B, Fañanás L. · No affiliation provided · J Med Genet. · Pubmed #14985387 links to  free full text

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