Genetic polymorphisms of the serotonin transporter are not related with depression in temporal lobe epilepsy caused by hippocampal sclerosis.

BACKGROUND: Mood disorders are the most frequent psychiatric disorders in patients with temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS). The pathophysiological mechanisms in common between TLE and mood disorders include abnormalities in the serotonergic pathway. We aimed to evaluate the association between serotonin transporter genetic polymorphisms - 5-HTTLPR and 5-HTTVNTR - and the presence of mood disorders in patients with TLE-HS. METHODS: We evaluated 119 patients with TLE-HS, with and without psychiatric disorder; 146 patients diagnosed with major depressive disorder (MDD), and 113 healthy volunteers. Individuals were genotyped for the 5-HTTLPR and 5-HTTVNTR polymorphisms. RESULTS: No difference was observed between the TLE-HS groups, healthy controls, and MDD without epilepsy. There was a correlation between the 12-allele of the 5-HTTVNTR and the family history of patients with epilepsy with TLE-HS (p = 0.013). CONCLUSIONS: In this study conducted in two Brazilian centers, the serotonin transporter polymorphisms evaluated cannot be associated with depressive disorder in patients with TLE-HS. Still, they do have some influence over some clinical characteristics of epilepsy in TLE-HS. These data may not be reproduced in other populations with distinct ethnic characteristics.

Genetic polymorphisms of the 5HT receptors are not related with depression in temporal lobe epilepsy caused by hippocampal sclerosis.

BACKGROUND: Temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS) is the most frequent form of drug-resistant epilepsy in adults. Mood disorders are the most frequent psychiatric comorbidities observed in these patients. Common pathophysiological mechanisms of epilepsy and psychiatric comorbidities include abnormalities in the serotonin pathway. The primary goal of this study was to determine the possible association between polymorphisms of genes encoding the serotonin receptors 5HT1A (rs6295), 5HT1B (rs6296), and 5HT2C (rs6318) and the presence of mood disorders in patients with TLE-HS. Our secondary goal was to evaluate the possible association between these variants and susceptibility to develop seizures in TLE-HS. METHODS: We assessed 119 patients with TLE-HS, with and without psychiatric comorbidities; 146 patients with major depressive disorder; and 113 healthy volunteers. Individuals were genotyped for the rs6295, rs6296, and rs6318 polymorphisms. RESULTS: No difference was observed between the group with TLE-HS, healthy controls, and the group with major depressive disorder without epilepsy regarding the polymorphisms that were evaluated. There was no correlation between rs6318, rs6295, rs6296, and epilepsy-related factors and history of psychiatric comorbidities. CONCLUSIONS: Our work suggests that the studied polymorphisms were not related to the presence of TLE, psychiatric comorbidities in TLE, and epilepsy-related factors.

Dorsal Anterior Cingulate Lactate and Glutathione Levels in Euthymic Bipolar I Disorder: 1H-MRS Study.

OBJECTIVE: Oxidative stress and mitochondrial dysfunction are 2 closely integrated processes implicated in the physiopathology of bipolar disorder. Advanced proton magnetic resonance spectroscopy techniques enable the measurement of levels of lactate, the main marker of mitochondrial dysfunction, and glutathione, the predominant brain antioxidant. The objective of this study was to measure brain lactate and glutathione levels in bipolar disorder and healthy controls. METHODS: Eighty-eight individuals (50 bipolar disorder and 38 healthy controls) underwent 3T proton magnetic resonance spectroscopy in the dorsal anterior cingulate cortex (2x2x4.5cm(3)) using a 2-D JPRESS sequence. Lactate and glutathione were quantified using the ProFit software program. RESULTS: Bipolar disorder patients had higher dorsal anterior cingulate cortex lactate levels compared with controls. Glutathione levels did not differ between euthymic bipolar disorder and controls. There was a positive correlation between lactate and glutathione levels specific to bipolar disorder. No influence of medications on metabolites was observed. CONCLUSION: This is the most extensive magnetic resonance spectroscopy study of lactate and glutathione in bipolar disorder to date, and results indicated that euthymic bipolar disorder patients had higher levels of lactate, which might be an indication of altered mitochondrial function. Moreover, lactate levels correlated with glutathione levels, indicating a compensatory mechanism regardless of bipolar disorder diagnosis.

ESPECTRA: searching the bipolar spectrum in eating disorder patients.

BACKGROUND: Bipolar Disorder (BD) is a chronic, recurrent and highly prevalent illness. Despite the need for correct diagnosis to allow proper treatment, studies have shown that reaching a diagnosis can take up to ten years due to the lack of recognition of the broader presentations of BD. Frequent comorbidities with other psychiatric disorders are a major cause of misdiagnosis and warrant thorough evaluation. METHODS/DESIGN: ESPECTRA (Occurrence of Bipolar Spectrum Disorders in Eating Disorder Patients) is a single-site cross-sectional study involving a comparison group, designed to evaluate the prevalence of bipolar spectrum in an eating disorder sample. Women aged 18-45 years will be evaluated using the SCID-P and Zurich criteria for diagnosis and the HAM-D, YOUNG, SCI-MOODS, HCL-32, BIS-11, BSQ, WHOQoL and EAS instruments for rating symptoms and measuring clinical correlates. DISCUSSION: The classificatory systems in psychiatry are based on categorical models that have been criticized for simplifying the diagnosis and leading to an increase in comorbidities. Some dimensional approaches have been proposed aimed at improving the validity and reliability of psychiatric disorder assessments, especially in conditions with high rates of comorbidity such as BD and Eating Disorder (ED). The Bipolar Spectrum (BS) remains under-recognized in clinical practice and its definition is not well established in current diagnostic guidelines. Broader evaluation of psychiatric disorders combining categorical and dimensional views could contribute to a more realistic understanding of comorbidities and help toward establishing a prognosis.

Analysis of a possible association between oral lichen planus and drug intake. A controlled study.

OBJECTIVES: To investigate whether daily systemic and/or topical medication contributes to the development of oral lichen planus (OLP) lesions. STUDY DESIGN: The study involved 110 OLP patients and 76 control subjects, matched by age, race and sex. The analyzed data included medical records, drug intake and topical medication. Criteria for analysis of drug intake included: (1) ATC-code drug classification; (2) number of different drugs used daily in the categories of monopharmacy (1 drug), minor polypharmacy (2-4 drugs), and major polypharmacy ( > 5 drugs); and (3) drugs implicated in lichenoid reactions (DILRs). RESULTS: Sixty (54.5%) of the 110 OLP patients reported daily medication (prior to the appearance of the OLP lesion) compared to 52 (68.4%) of the 76 control subjects. No statistical difference was found between the two groups in terms of systemic diseases, number of medicated individuals in the categories of mono- and polypharmacy, nor use of DILRs (P > 0.05). Regarding the clinical forms and site of involvement, a statistically significant difference was only found for the clinical erosive form of OLP, seen more frequently in non-DILR (P = 0.04) and nonmedicated OLP patients (P = 0.02) than in DILR OLP patients. Daily use of topical oral medication was reported by 2 (1.8%) OLP patients and 1 (1.3%) control subject. CONCLUSIONS: It seems that the use of systemic medication does not lead to a significant increase in the incidence of OLP lesions. For their part, lichenoid drug reactions are likely to occur only in a very low percentage of patients.

SIGMA-VB: Validity and reliability of the Brazilian Portuguese version of the Montgomery-Åsberg Depression Rating Scale using the Structured Interview Guide for the MADRS.

OBJECTIVE: The Montgomery-Åsberg Depression Rating Scale (MADRS) is widely used to assess depression severity. The Structured Interview Guide for the MADRS (SIGMA) was created to standardize MADRS assessment. The objective of this study was to translate and validate the original SIGMA into a Brazilian Portuguese version (SIGMA-VB). METHODS: We translated and cross-culturally validated the original SIGMA into the SIGMA-VB, and assessed its psychometric properties using data from 93 adult outpatients enrolled in the Integral Assessment in Unipolar Depression (AIUNI) trial. Participants were assessed by two raters on five visits over 8 weeks. We calculated multiple interrater reliability indexes for the SIGMA-VB and used the Hamilton Depression Hating Scale (HAM-D) for validation purposes. RESULTS: According to the SIGMA-VB, participants had moderate depression at baseline followed by mild depression at 8 weeks. We found over 90% of correlation between scores attributed by different raters using the SIGMA-VB. Correlations between the SIGMA-VB and the HAM-D were above 66%. CONCLUSION: Our findings confirm that the SIGMA-VB is a valid and reliable instrument to assess depression severity in clinical research and practice. Its interrater reliability was similar to that of a previously published Japanese version of the SIGMA.

Double Blinded Randomized Trial of Subcutaneous Trigeminal Nerve Stimulation as Adjuvant Treatment for Major Unipolar Depressive Disorder.

BACKGROUND: More than 30% of major depressive disorder patients fail to respond to adequate trials of medications and psychotherapy. While modern neuromodulation approaches (ie, vagal nerve stimulation, deep brain stimulation) are yet to prove their efficacy for such cases in large randomized controlled trials, trigeminal nerve stimulation (TNS) has emerged as an alternative with promising effects on mood disorders. OBJECTIVE: To assess efficacy, safety, tolerability, and placebo effect duration of continuous subcutaneous TNS (sTNS) in treatment-resistant depression (TRD). METHODS: The TREND study is a single-center, double-blind, randomized, controlled, phase II clinical trial. Twenty unipolar TRD patients will receive V1 sTNS as adjuvant to medical therapy and randomized to active vs sham stimulation throughout a 24-wk period. An additional 24-wk open-label phase will follow. Data concerning efficacy, placebo response, relapse, and side effects related to surgery or electrical stimulation will be recorded. We will use the HDRS-17, BDI-SR, IDS_SR30, and UKU scales. EXPECTED OUTCOMES: The main outcome measure is improvement in depression scores using HAM-17 under continuous sTNS as adjuvant to antidepressants. Active stimulation is expected to significantly impact response and remission rates. Minor side effects are expected due to the surgical procedure and electrical stimulation. The open-label phase should further confirm efficacy and tolerability. DISCUSSION: This study protocol is designed to define efficacy of a novel adjuvant therapy for TRD. We must strive to develop safe, reproducible, predictable, and well-tolerated neuromodulation approaches for TRD patients impaired to manage their lives and contribute with society.

Resolution of sexual dysfunction during acute treatment of major depression with milnacipran.

OBJECTIVE: The sexual function and enjoyment questionnaire (SFEQ) was developed to assess and detect changes in sexual function in men and women. The aim of the present study was to use the SFEQ to evaluate the effects of the serotonin-noradrenaline reuptake inhibitor, milnacipran, in the treatment of depression in two culturally different populations. METHODS: The SFEQ was employed in two studies investigating milnacipran in the treatment of major depression: a 12-week open study in Brazil and a 6-week randomised controlled study in Europe. RESULTS: At endpoint, 61.3% (Brazil) and 78.4% (Europe) of patients had >or=50% reduction of baseline Hamilton Depression Rating (HAMD) score. All SFEQ items showed improvements in sexual function in both studies at endpoint, 60% (Brazil) and 56% (Europe) of patients stating that their sexual desire was as great as or greater than it had been before their depressive episode. CONCLUSIONS: Milnacipran appears to improve sexual function in parallel with improvement in other symptoms of depression. The SFEQ is a sensitive instrument for measuring changes in sexual function and appears to be unaffected by cultural differences as shown by similar findings in Brazil and Europe.

Cognitive outcomes of TMS treatment in bipolar depression: Safety data from a randomized controlled trial.

BACKGROUND: Bipolar depression (BD) is a highly prevalent condition associated with marked cognitive deficits that persist even in the euthymic phase of the illness. Pharmacological treatments for BD might further aggravate cognitive impairment, highlighting the need of developing interventions that present cognitive safety. In this study, we evaluated the cognitive effects of H1-coil (deep) transcranial magnetic stimulation (TMS) in patients with treatment-resistant bipolar depression. METHODS: Fourty-three patients were randomized to receive 20 sessions of active (55 trains, 18 Hz, 120% resting motor threshold intensity) or sham rTMS within a double-blind, sham-controlled trial. A battery of 20 neuropsychological assessments, grouped in 6 domains (attention and processing speed, working memory and executive function, inhibitory control, language, immediate verbal memory, and long-term verbal memory) was performed at baseline and after 4 and 8 weeks of trial onset. Depressive symptoms were assessed with the 17-item Hamilton Rating Scale for Depression. RESULTS: Cognitive improvement was shown for all cognitive domains. It occurred regardless of intervention group and depression improvement. For the language domain, greater improvement was observed in the sham group over time. No correlations between depression (at baseline or during treatment) and cognitive improvement were found. LIMITATIONS: Absence of healthy control group. CONCLUSION: The results of this exploratory study provide evidence on the cognitive safety of H1-coil TMS for BD patients. Putative pro-cognitive effects of rTMS in BD were not observed and thus should be further investigated.

Treatment of Bipolar Depression with Deep TMS: Results from a Double-Blind, Randomized, Parallel Group, Sham-Controlled Clinical Trial.

Bipolar depression (BD) is a highly prevalent condition with limited therapeutic options. Deep (H1-coil) transcranial magnetic stimulation (dTMS) is a novel TMS modality with established efficacy for unipolar depression. We conducted a randomized sham-controlled trial to evaluate the efficacy and safety of dTMS in treatment-resistant BD patients. Patients received 20 sessions of active or sham dTMS over the left dorsolateral prefrontal cortex (H1-coil, 55 18 Hz 2 s 120% MT trains). The primary outcome was changes in the 17-item Hamilton Depression Rating Scale (HDRS-17) from baseline to endpoint (week 4). Secondary outcomes were changes from baseline to the end of the follow-up phase (week 8), and response and remission rates. Safety was assessed using a dTMS adverse effects questionnaire and the Young Mania Rating Scale to assess treatment-emergent mania switch (TEMS). Out of 50 patients, 43 finished the trial. There were 2 and 5 dropouts in the sham and active groups, respectively. Active dTMS was superior to sham at end point (difference favoring dTMS=4.88; 95% CI 0.43 to 9.32, p=0.03) but not at follow-up. There was also a trend for greater response rates in the active (48%) vs sham (24%) groups (OR=2.92; 95% CI=0.87 to 9.78, p=0.08). Remission rates were not statistically different. No TEMS episodes were observed. Deep TMS is a potentially effective and well-tolerated add-on therapy in resistant bipolar depressed patients receiving adequate pharmacotherapy.

Melatonin levels in drug-free patients with major depression from the southern hemisphere.

The secretion of melatonin has been shown as abnormal in some depressed patients, but most such studies were conducted in the northern hemisphere and with severely depressed inpatients. The aim of this study was to evaluate melatonin excretion profiles in major depressive outpatients from São Paulo, Brazil, individually matched to well-screened healthy volunteers to examine whether melatonin abnormalities are also present in patients from the southern hemisphere, and in less severely ill patients. We analyzed 32 drug-free, depressed outpatients and 32 psychiatrically healthy volunteers matched for age and gender. We also examined a set of 15 drug-free depressed outpatients and 15 healthy volunteers that were matched not only for age and gender, but also for body mass index and season, all factors known to influence melatonin excretion in humans. All patients fulfilled DSM-IV criteria for major depression. We evaluated major urinary metabolite of melatonin, 6-sulphatoxymelatonin (aMT6s), produced over 24 h and divided into four periods (06:00-12:00, 12:00-08:00, 18:00-24:00 and 24:00-06:00 h). aMT6s measurements during the 24 and 6 h intervals were similar in the 32 depressed patients and 32 healthy volunteers matched for age and gender; further matching for body mass index and season did not alter the results. Our study supports others in which depressed patients were found to have similar melatonin levels than healthy volunteers. Melatonin excretion has been considered a physiological index for noradrenergic function, which in some studies were found to be altered than depressed patients. It is conceivable that the alteration of nocturnal melatonin in depressed patients occurs only in more severe depression.

Efficacy of hormone therapy with and without methyltestosterone augmentation of venlafaxine in the treatment of postmenopausal depression: a double-blind controlled pilot study.

OBJECTIVE: This study evaluated the augmentation of venlafaxine with hormone therapy in the treatment of postmenopausal depression. The hormones evaluated were estrogen (0.625 mg) in combination with medroxyprogesterone acetate (2.5 mg) and methyltestosterone (2.5 mg). DESIGN: Seventy-two menopausal women (mean age: 53.6 +/- 4.27 years) diagnosed with depression (Montgomery-Asberg Depression Rating Scale [MADRS] scores > or = 20) were treated with venlafaxine and one of the following hormone therapy combinations, in a double-blind regimen: estrogen + medroxyprogesterone + methyltestosterone (group 1, n = 20); estrogen + medroxyprogesterone acetate (group 2, n = 20); methyltestosterone only (group 3, n = 16); and no hormone therapy (group 4, n = 16). Study duration was 24 weeks. Primary efficacy outcome was remission according to the MADRS, whereas secondary efficacy measures included the Clinical Global Impression (CGI), Blatt-Kupperman Index, and Women's Health Questionnaire (WHQ). RESULTS: Forty-eight patients completed the study. All groups showed significant improvement from baseline. Group 3 demonstrated significant improvement on the MADRS compared with placebo (group 4) at weeks 20 (P = 0.048) and 24 (P = 0.030); effect size 8.04 (0.83; 15.26) (P = 0.029), but also had the highest dropout rate. Groups 1 and 3 had significant CGI improvement rates compared with placebo: 42.23% (P = 0.012) and 44.45% (P = 0.08), respectively. There were no differences in the WHQ or BKI scores among the groups. CONCLUSIONS: Methyltestosterone 2.5 mg had the highest effect size compared with placebo, but the high dropout rate prevented its efficacy from being determined. Estrogen plus medroxyprogesterone, combined with methyltestosterone or otherwise, demonstrated a trend toward increased efficacy of venlafaxine. Further larger-scale clinical trials are needed to elucidate the findings of this pilot study.

De la resistencia a la transformación: una revisión de la resiliencia en el deporte / From Resistance to Transformation: A Review of Resilience in Sports

Resumen Se realizó una revisión de literatura acerca de los aportes investigativos de la resiliencia en el deporte entre los años de 2010 y 2020 en una muestra de 239 artículos que respondieron a criterios de inclusión como: artículos originales, de revisión de literatura, estudios cualitativos, cuantitativos o mixtos publicados; tesis o trabajos de grado y capítulos de libro. La búsqueda se realizó en las bases de datos de PubMed, Ebsco Host, Science Direct, Scopus, PsyINFO. Se encontró que la investigación y aportes de la resiliencia en el deporte son numerosos y aplicados a una gran diversidad de modalidades deportivas y a nivel de actividad física, deporte formativo y competitivo. Se encontraron predominantemente estudios cuantitativo-descriptivos; sin embargo se destacan diversos enfoques metodológicos. Se observó además que los estudios se orientaron hacia las poblaciones de adultos y adolescentes, y un tercer foco de interés son las revisiones de literatura. Los campos en los que se exploró la resiliencia en el deporte se asociaron al desempeño en competencia, afrontamiento de la adversidad, situaciones estresantes, o de burn out, como dimensión motivacional. Se concluye con la necesidad de realizar estudios específicos por práctica deportiva, tipos de deporte y fenómenos psico-sociales relacionados como la influencia de la recuperación de lesiones, estados anímicos y situaciones adversas extradeportivas y extra-competición.

Abstract A literature review was conducted on the research contributions on resilience in sports between 2010 and 2020 in a sample of 239 articles, which responded to inclusion criteria such as original articles; literature reviews; qualitative, quantitative, or mixed published studies; thesis or degree works; and book chapters. The search was carried out in PubMed, Ebsco Host, Science Direct, Scopus, and PsycINFO databases. It was found that research and contributions on resilience in sports are numerous and applied to a great diversity of sports modalities and at the level of physical activity and formative and competitive sports. Quantitative-descriptive studies were predominantly found; however, different methodological approaches are highlighted. It was also observed that the studies were oriented towards adult and adolescent populations, and a third focus of interest is literature reviews. The fields in which resilience in sports was explored were associated with performance in competition, coping with adversity, stressful situations, or burnout, as a motivational dimension. It is concluded that it is necessary to carry out specific studies by sports practice and types of sports, and the related psycho-social phenomena, such as the influence of injury recovery, moods, and adverse extra-sports and extra-competition situations.

Panorama científico de la relación entre la violencia intrafamiliar y de género y la resiliencia familiar: posibilidades, retos y límites / Scientific Overview of the Relation between Domestic and Gender Violence and Family Resilience: Possibilities, Challenges and Limits

Resumen En el marco de la investigación titulada "Resiliencia en víctimas de violencia intrafamiliar y de género Fase 1", realizada por el programa de Psicología de la Universidad Santo Tomás de Aquino (Bogotá, Colombia), se realizó una revisión de literatura, que describió el estado del arte de las investigaciones y estudios reflexivos publicados entre los años de 2015 y 2019 con respecto a la resiliencia familiar frente a la violencia intrafamiliar y de género (vifg). Se obtuvieron resultados preliminares de 3160 documentos, que fueron depurados a 74 artículos, que respondieron a criterios de inclusión como: Artículos Originales, de Reflexión, Revisión de literatura, Estudios Cualitativos, Cuantitativos o Mixtos publicados entre 2015 y 2019. La búsqueda se realizó en las bases de datos: PubMed, Ebsco Host, Science Direct, Scopus, Psyinfo, sage, Sprinter, y Taylor & Francis. Se encontró una tendencia de estudios aplicados, cualitativos, descriptivos con población participante femenina, infantil y adolescente con reporte de violencia intrafamiliar, realizados en Estados Unidos, Reino Unido y Canadá. Sin embargo, se pudo observar que la literatura hace referencia indirecta a la resiliencia familiar, pues en mayor medida se refiere al afrontamiento, recuperación y factores protectores, como fenómenos de interés relacionados con la vifg. Se concluye que aún son pocos los estudios en los que se incluya explícitamente el fenómeno del género en la vif, que describen la emergencia de la resiliencia familiar y alternativas de intervención para su desarrollo.

Abstract In the frame of the first phase of the research titled "Resilience in Victims of Domestic and Gender Based Violence", carried out by the Psychology academic program at the Santo Tomas University (Bogota, Colombia), a literature review was carried out which described the State of the Art of studies published between 2015 and 2019 regarding Family Resilience against Domestic and Gender-based Violence. There were preliminary results gathered from 3160 documents, which were later reduced to 74 articles according to the following criteria: original articles, rational thinking, literature review, and qualitative data, quantitative data, or mixed methods research published between 2015 and 2019. The research was carried out using the following Databases: PubMed, Ebsco Host, Science Direct, Scopus, PsyINFO, sage, Sprinter, and Taylor & Francis. A particular trend has been identified as a result of the research, with a large set of studies using mostly applied, qualitative and descriptive data of female, child and teenager participants who have reported cases of domestic violence, conducted in the United States, the United Kingdom, and Canada. However, it was observed that the literature makes indirect reference to family resilience, since for the most part it refers to coping mechanisms, recovery, and protective factors as phenomena of interest related to Domestic and Gender-based Violence. It is concluded that there are still very few studies which, while describing the emergence of family resilience and intervention alternatives for its development, explicitly include a gender approach or gender-related elements in cases of domestic violence.

Anterior cingulate Glutamate-Glutamine cycle metabolites are altered in euthymic bipolar I disorder.

Bipolar disorder (BD) has been consistently associated with abnormalities in the Glutamate/GABA-Glutamine cycle. Magnetic resonance spectroscopy (MRS) studies have reported increased brain Glutamate (Glu) and Glx (Glu+Glutamine) in subjects with BD. However, data on separate measures of GABA and Glutamine (Gln) in BD are sparse due to overlapping resonant signals. The development of new sequence methods in the quantification of these metabolites has allowed a better understanding of the Glu/GABA-Gln cycle but data on this field of research remains sparse in BD. Eighty-eight subjects (50 euthymic BD and 38 HC) underwent 3T proton magnetic resonance spectroscopy (1H MRS) in the anterior cingulate cortex (ACC; 2×2×4.5cm(3)) using a two-dimensional JPRESS sequence. GABA, Glutamine (Gln) and Glutamate (Glu) were quantified with the ProFit program. Using image segmentation and known creatine (Cre) concentrations for white and grey matter, metabolite concentrations were calculated for the excited MRS voxel. GABA levels did not differ between groups. Gln level was higher in euthymic BD patients than in healthy controls. The Glu level and Glu/Gln ratio were lower in BD patients than in controls. The use of anticonvulsants was associated with Gln increase but did not affect Glu or Glu/Gln. Neither lithium nor antipsychotic use influenced metabolite levels. The ACC MRS findings indicate that the glutamatergic function in euthymic medicated BD patients is altered relative to controls. Whether this feature is a metabolic signature of euthymic BD subjects should be the focus of future studies.

Epistasis between COMT Val158Met and DRD3 Ser9Gly polymorphisms and cognitive function in schizophrenia: genetic influence on dopamine transmission.

OBJECTIVE: To assess the relationship between cognitive function, a proposed schizophrenia endophenotype, and two genetic polymorphisms related to dopamine function, catechol-O-methyl transferase (COMT) Val158Met and dopamine receptor 3 (DRD3) Ser9Gly. METHODS: Fifty-eight outpatients with schizophrenia/schizoaffective disorder and 88 healthy controls underwent neurocognitive testing and genotyping. Analyses of covariance (ANCOVAs) using age, sex, and years of education as covariates compared cognitive performance for the proposed genotypes in patients and controls. ANCOVAs also tested for the epistatic effect of COMT and DRD3 genotype combinations on cognitive performance. RESULTS: For executive functioning, COMT Val/Val patients performed in a similar range as controls (30.70-33.26 vs. 35.53-35.67), but as COMT Met allele frequency increased, executive functioning worsened. COMT Met/Met patients carrying the DRD3 Ser/Ser genotype performed poorest (16.184 vs. 27.388-31.824). Scores of carriers of this COMT/DRD3 combination significantly differed from all DRD3 Gly/Gly combinations (p < 0.05), from COMT Val/Met DRD3 Ser/Gly (p = 0.02), and from COMT Val/Val DRD3 Ser/Ser (p = 0.01) in patients. It also differed significantly from all control scores (p < 0.001). CONCLUSION: Combined genetic polymorphisms related to dopamine neurotransmission might influence executive function in schizophrenia. Looking at the effects of multiple genes on a single disease trait (epistasis) provides a comprehensive and more reliable way to determine genetic effects on endophenotypes.

Lithium efficacy in bipolar depression with flexible dosing: A six-week, open-label, proof-of-concept study.

Lithium has a narrow therapeutic index with a subtle balance between effectiveness and adverse effects. Current guidelines recommend the use of lithium as a treatment for acute bipolar depression; however, the therapeutic range for the treatment has not been fully defined. Recently, the adjunctive lower lithium dose in bipolar depression has revealed potential efficacy; however, no study has investigated it predominantly in monotherapy. In this open-label, proof-of-concept study, 31 individuals with bipolar disorder during a depressive episode were randomized and 29 were followed up for six weeks with flexible lithium dosing. All subjects had a 21-item Hamilton Rating Scale for Depression (HAM-D) score of ≥18 at baseline. Subjects were divided into two groups, with higher (Li ≥0.5 mEq/l) or lower (Li <0.5 mEq/l) blood lithium levels. Response and remission rates were evaluated using the HAM-D scores. Following 6 weeks of lithium treatment, the remission rate for all patients was 62.0%. The plasma lithium levels did not impact the clinical response. However, subjects with higher blood lithium levels had an increased prevalence of nausea, restlessness, headaches and cognitive complaints. The results indicate that the lithium dose for the treatment of bipolar depression in an individual should be based on the clinical efficacy and side-effects. In the context of personalized psychiatric treatments, it is necessary to evaluate the therapeutic action of lithium with individual regimens in order to develop more tolerable and effective treatment approaches.

SIGMA-VB: Validity and reliability of the Brazilian Portuguese version of the Montgomery-Åsberg Depression Rating Scale using the Structured Interview Guide for the MADRS

Objective: The Montgomery-Åsberg Depression Rating Scale (MADRS) is widely used to assess depression severity. The Structured Interview Guide for the MADRS (SIGMA) was created to standardize MADRS assessment. The objective of this study was to translate and validate the original SIGMA into a Brazilian Portuguese version (SIGMA-VB). Methods: We translated and cross-culturally validated the original SIGMA into the SIGMA-VB, and assessed its psychometric properties using data from 93 adult outpatients enrolled in the Integral Assessment in Unipolar Depression (AIUNI) trial. Participants were assessed by two raters on five visits over 8 weeks. We calculated multiple interrater reliability indexes for the SIGMA-VB and used the Hamilton Depression Hating Scale (HAM-D) for validation purposes. Results: According to the SIGMA-VB, participants had moderate depression at baseline followed by mild depression at 8 weeks. We found over 90% of correlation between scores attributed by different raters using the SIGMA-VB. Correlations between the SIGMA-VB and the HAM-D were above 66%. Conclusion: Our findings confirm that the SIGMA-VB is a valid and reliable instrument to assess depression severity in clinical research and practice. Its interrater reliability was similar to that of a previously published Japanese version of the SIGMA.

Leukocyte telomerase activity and antidepressant efficacy in bipolar disorder.

Telomeres are DNA-protein complexes that cap linear DNA strands, protecting DNA from damage. Recently, shorten telomeres length has been reported in bipolar disorder (BD) and depression. The enzyme telomerase regulates telomeres׳ length, which has been associated with cellular viability; however it is not clear how telomerase may be involved in the pathophysiology and therapeutics of BD. In the present study, leukocyte telomerase activity was assessed in 28 medication-free BD depressed individuals (DSM-IV-TR criteria) at baseline and after 6 weeks of lithium therapy (n=21) also matching with 23 healthy controls. There was no difference between telomerase activity in subjects with BD depression (before or after lithium) and controls. Improvement of depressive symptoms was negatively associated with telomerase activity after 6 weeks of lithium therapy. This is the first study describing telomerase activity in BD research. Overall, telomerase activity seems not directly involved in the pathophysiology of short-term BD. Lithium׳s antidepressant effects may involve regulation at telomerase activity. Further studies with larger samples and long-term illness are also warranted.