Martinus Theodorus van de Bilt

Lithium increases plasma brain-derived neurotrophic factor in acute bipolar mania: a preliminary 4-week study.

Several studies have suggested an important role for brain-derived neurotrophic factor (BDNF) in the pathophysiology and therapeutics of bipolar disorder (BPD). The mechanisms underlying the therapeutic effects of lithium in BPD seem to involve a direct regulation of neurotrophic cascades. However, no clinical study evaluated the specific effects of lithium on BDNF levels in subjects with BPD. This study aims to investigate the effects of lithium monotherapy on BDNF levels in acute mania. Ten subjects with bipolar I disorder in a manic episode were evaluated at baseline and after 28 days of lithium therapy. Changes in plasma BDNF levels and Young Mania Rating Scale (YMRS) scores were analyzed. A significant increase in plasma BDNF levels was observed after 28 days of therapy with lithium monotherapy (510.9±127.1pg/mL) compared to pre-treatment (406.3±69.5pg/mL) (p=0.03). Although it was not found a significant association between BDNF levels and clinical improvement (YMRS), 87% of responders presented an increase in BDNF levels after treatment with lithium. These preliminary data showed lithiums direct effects on BDNF levels in bipolar mania, suggesting that short-term lithium treatment may activate neurotrophic cascades. Further studies with larger samples and longer period may confirm whether this biological effect is involved in the therapeutic efficacy of lithium in BPD.

Connection, a microcomputer program for storing and analyzing structural properties of neural circuits

The application of a microcomputer-based system (the Connection system) designed to deal with neuroanatomical information commonly analyzed by researchers and involved in the study of structural properties of neural circuits is presented. This system can be employed at first as a readily-accessible database containing physiological and anatomical data from nuclei of the central nervous system which define a network with up to 45 elements and their subdivisions and connections. Once the database from a specific network is built and stored in a file, routines of this system can be used to classify the nuclei in term of their afferents and efferents and also to display all possible pathways linking any pair of nuclei and their respective length (number of synapses). The role of such a system as an auxiliary tool in neuroanatomical and electrophysiological research is discussed by presenting the results obtained from the analysis of the neural circuits involved in cardiovascular function control in higher vertebrates.

Early improvement of psychotic symptoms with lithium monotherapy as a predictor of later response in mania

Although lithium has been the first line agent in the treatment of bipolar disorder (BD), few studies have evaluated lithiums efficacy in mania with psychosis and its association with later response. Furthermore, given the widespread concern about antipsychotic side effects, answering a question about whether lithium alone can manage to treat both psychotic and non-psychotic mania seems a very relevant one. The present study addresses the antipsychotic efficacy of lithium monotherapy in acute mania and early improvement of psychotic symptoms as a predictor of later response of manic symptoms. Forty-six patients presenting a manic episode (32 with psychotic features and 14 subjects without psychotic features) were treated for 4 weeks with lithium monotherapy and evaluated weekly using the Young Mania Rating Scale (YMRS). Subjects with rapid cycling, substance abuse/dependence, or mixed episodes were excluded. The overall antimanic efficacy of lithium in psychosis vs. non-psychosis groups was evaluated. In addition, early improvement of psychotic symptoms and its prediction of subsequent response (>50% decrease in total YMRS scores) or remission were evaluated. Lithium showed a similar efficacy in both psychosis and non-psychosis mania. Early improvement of psychotic symptoms was associated with clinical response and remission at endpoint.

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.

Poverty, low education, and the expression of psychotic-like experiences in the general population of São Paulo, Brazil

The aim of our study was to assess psychotic-like experiences in the general population aged 18-30 years old of the city of São Paulo, Brazil. A household survey was conducted with 1950 young-adults randomly drawn from the citys general population. The validated 92-item Portuguese version of the Prodromal Questionnaire (PQ) was used for face-to-face interviews. Latent class analysis was conducted. Mean age was of 24 years; 51.1% of the sample was of women. Mean total score on the PQ was 22.06 (SD=17.16). Considering a suggested cut-off of 14 in the positive subscale, 30.8% of individuals were above the threshold for ultra-high risk for psychosis detection. Latent class analysis resulted in a three classes clusterization. Class 1 (20%; n=390) had the highest overall PQ scores (mean=49.31,SD=10.783), class 2 (43%; n=835) had intermediate scores (mean=23.37,SD=6.56), and class 3 (37%; n=721) had the lowest scores (mean=5.81,SD=3.74). Class 1 had significantly more individuals with less education and significantly more individuals with lower socioeconomic class. Poverty and low education might be associated with the psychotic expression in the general population, amplifying their actions on the psychosis gradient in developing countries. The psychosis continuum might be constituted by three distinct quantitatively different classes.

Increased platelet glycogen sysnthase kinase 3beta in first-episode psychosis

Past studies have linked intracellular pathways related to psychotic disorders to the GSK3B enzyme. This study aimed to investigate GSK3B protein expression and phosphorylation in drug-naïve first-episode psychosis patients (n=43) at baseline and following symptom remission, and in healthy controls (n=77). At baseline GSK3B total level was higher in patients (p<0.001). In schizophrenia spectrum patients (n=25) GSK3B total and phosphorylated levels were higher than in controls and patients with other non-affective psychotic disorders (n=18) (p<0.001; p=0.027; p=0.05 respectively). No enzyme changes were found after clinical remission. The implication of this finding for the biology of psychoses warrants further studies to clarify whether increased GSK3B may be useful as a biomarker for psychosis in general, and schizophrenia in particular.

Hearing spirits? Religiosity in individuals at risk for psychosis—Results from the Brazilian SSAPP cohort

In the last decades, biological and environmental factors related to psychosis were investigated in individuals at ultra-risk for psychosis (UHR) to predict conversion. Although religion relates to psychosis in a variety of ways, it is understudied in subclinical samples. Therefore, we assessed the interplay between religion and prodromal symptoms in 79 UHR and 110 control individuals. They were interviewed with the Duke University Religion Index and the Structured Interview for Prodromal Syndromes (SIPS). Organizational religious activity, a measure of how often someone attends churches/temples, was positively related to perceptual abnormalities/hallucinations (Spearmans rho = 0.262, p = 0.02). This relationship was replicated in a path analysis model (β = 0.342, SE = 0.108, p = 0.002), as well as a link between organizational religious activity and lower ideational richness (β = 0.401, SE = 0.105, p = 0.000) with no influence of sex, age, religious denomination, or socioeconomic class. Intrinsic religious activity was negatively correlated with suspiciousness (SIPS P2) (β = -0.028, SE = 0.009, p = 0.002), and non-organizational religious activity was correlated with higher ideational richness (N5) (β = -0.220, SE = 0.097, p = 0.023). We hypothesize that subjects with subclinical psychosis may possibly use churches and other religious organizations to cope with hallucinations. Indeed, Brazil is characterized by a religious syncretism and a strong influence of Spiritism in the popular culture. The mediumistic idea that some might be able to hear and/or see spirits is probably employed to explain subclinical hallucinations in the lay knowledge. Our results emphasize the importance of assessing religion and other region-specific aspects of various cultures when studying UHR individuals. This sort of assessment would enhance understanding of differences in conversion rates, and would help to transpose prevention programs from high-income countries to other settings.

T51. TREATMENT OF NEGATIVE SYMPTOMS OF SCHIZOPHRENIA WITH TRANSCRANIAL CURRENT STIMULATION (TDCS): RESULTS OF RANDOMIZED, DOUBLE-BLINDED, SHAM-CONTROLLED TRIAL

Abstract Background The negative symptoms of schizophrenia cause significant distress and impairment. The treatment of them is a challenge, with medications having none or little effect. So, new treatments are necessary for this condition. The aim of the study was to ascertain the efficacy of tDCS in treating negative symptoms of schizophrenia Methods This study was designed to be a randomized, sham-controlled, double-blinded trial using tDCS for the treatment of negative symptoms of schizophrenia. One-hundred (here we analyzed only 70% of the sample, the remaining will be presented at the meeting) patients will be enrolled and submitted to ten tDCS session over the left dorsolateral prefrontal cortex (anodal stimulation) and left temporo-parietal junction-left (cathodal stimulation), over 5 consecutive days, with 2 mA of current. Participants were assessed with clinical and neuropsychological tests before and after the intervention. The primary outcome was change (over time and across groups) in the scores of the Negative Subscale of Positive and Negative Symptoms Syndrome (PANSS). Our secondary outcomes consist of others scales as SANSS (Scale of Assessment of Negative Symptoms), Calgary and the AHRS (Auditory Hallucinations Rating Scale). Results From 70% of the sample the active tDCS was significantly superior to sham at endpoint at 6 weeks by negative sub scale of PANSS (mean difference, 3,5 points; SD=6.2; P<.05). The total PANSS and the hallucinations scale had no differences between both groups. The other times of analysis were not found differences between sham and active groups. The others scales (Calgary and SANSS have not being evaluated yet). Discussion The results of our studies suggests a potential role of tDCS for the treatment of negative symptoms of schizophrenia. The effect size was small. This is the biggest study with tDCS for treating negative symptoms of schizophrenia until now. At the meeting all the data will be analyzed (100 patients), it these could change our preliminary results.

T203. ILLICIT DRUGS USE AND ULTRA-HIGH RISK (UHR) FOR PSYCHOSIS STATUS IN A LATIN-AMERICAN SAMPLE

Abstract Background In recent years, a number of investigations have evaluated the effect of cannabis use on the risk of presenting ultra-high risk for psychosis (UHR) status as well as its influences on transition rate, suggesting a dose-dependent interaction. On the other hand, the association between cocaine (snorted or smoked) - an increasing health issue in several countries worldwide - and the UHR state was not appropriately examined. Also, exposure to other psychotomimetic drugs, as amphetamines and lysergic acid diethylamide (LSD), has not been investigated yet. We sought to examine differences in the prevalence of drug use between UHR subjects and epidemiologic controls (EC). Methods Over 2500 individuals from the city of São Paulo (Brazil), aged between 18 and 30 years old, were screened with the Prodromal Questionnaire. Subjects with scores higher than 18 points in the positive subscale were invited to be thoroughly assessed with the application of SIPS (Structured Interview for Psychosis-Risk Syndromes). Drug use (lifetime use, age of first use and more intense use) was assessed using South Westminster scale. Results 100 individuals presented UHR state; other 110 were enrolled as EC. A subsample of 50 UHR subjects and 82 HC with data on drugs consumption were evaluated herein. UHR subjects history of lifetime drug use was: 19 (38%) cannabis; 5 (10%) snorted cocaine; 1 (2%) crack; 1 (2%) amphetamine; 2 (6.9%) LSD. EC history of lifetime drug use was: 20 (24.4%) cannabis; 6 (7.3%) snorted cocaine; 0 crack; 2 (2.4%) amphetamine; 1 (1.2%) LSD. No differences were observed for snorted cocaine (p=0.589), crack (p=0.379), amphetamine (p=1.0), or LSD (P=0.167). At a trend level, cannabis lifetime use (p=0.096) was more prevalent in the UHR group. Additional analyses showed that UHR subjects initiate cannabis use at earlier age than EC (p=0.006). In this group, 20% of subjects had used cannabis prior to 15 years of age, in comparison to 3.6% in the EC group. Discussion Our results reinforce the view that cannabis use is linked to psychosis risk and that subjects at early age of exposure are at greatest risk. Nonetheless, studies with larger number of participants are warranted to confirm our findings, particularly on the lack of association between less frequently consumed drugs and the UHR for psychosis state.

A randomized clinical trial of home-based telepsychiatric outpatient care via videoconferencing: design, methodology, and implementation

Background Healthcare providers are continuously challenged to find innovative, cost-effective alternatives and to scale up existent services to meet the growing demand upon mental health care delivery. Due to continuous advances in technologies, telepsychiatry has become an effective tool for psychiatric care. In 2012, the Institute of Psychiatry of the University of Sao Paulo Medical School started a randomized clinical trial of home-based telepsychiatric outpatient care via videoconferencing. Objective The objective of this article is to describe the design, methodology and implementation of a pilot project, which aimed to verify the applicability and efficiency of psychiatric attendance via Internet-based videoconferencing in a resource-constrained environment. Methods The project consisted of a 12 months follow-up study with a randomized clinical trial, which compared various quality indicators between home-based telepsychiatric aftercare via videoconferencing and face-to-face aftercare. Results The final sample comprised 107 outpatients (53 in the telepsychiatry group and 54 in the control group). Among 1,227 realized consultations, 489 were held by videoconferencing. Satisfaction with the aftercare by videoconferencing and the medication delivery was high among patients. Attending psychiatrists were satisfied with the assistance by videoconferencing. Discussion The experiences during this pilot project have overall been very positive and psychiatric outpatient care by videoconferencing seems viable to treat patients even in a resource-constrained environment.