To align the neuropsychological functioning of our adult euthymic patient group with that reported in previous studies on euthymic bipolar disorder (BD), we used a neuropsychological battery that examined sustained attention (Rapid Visual Information Processing Task), verbal memory (California Verbal Learning Task), executive functioning (Intradimensional-Extradimensional Shift Task, Barrett Impulsivity Task, and Framing Task), and emotion responsiveness/regulation (Positive Affect/Negative Affect Scales, Behavioral Inhibition/Behavioral Activation Scale, and Affective Lability/Affective Intensity Scales) in patients versus healthy volunteers (HV). Our results corroborated existing evidence of reduced sustained attention, impaired verbal memory and executive functioning, and abnormal emotional responsiveness and regulation in euthymic BD relative to healthy controls (Chapter 2). To investigate how abnormal development of brain function in BD leads to deficits in decision-making, motor inhibition, and response flexibility, we examined child and adult BD using a novel risky decision-making task, and used cross-sectional (age x diagnosis) functional magnetic resonance (fMRI) designs to examine neural activation associated with motor inhibition and response flexibility in BD relative to HV. During the risky decision-making task, adult euthymic BD patients were no different from healthy controls in their proportion of risky lottery choices over a range of competing lotteries. This matched behavioral performance was associated with similar prefrontal and striatal brain activation between the patient and control groups during response, anticipation, and outcome phases of decision-making (Chapter 3). These results are different from previous studies that have shown increased risk taking during decision-making in euthymic BD. Similarly, young BD patients were no different from age-matched healthy and patient controls in their pattern of decision making during the risky choice task. This was evidenced by a similar number of risky lottery selections over the range of changing expected values between the young BD group and control groups (Chapter 4). Using a cross-sectional, fMRI analytic design during the stop signal task, we found that child and adult BD showed similar behavioral performance to child and adult HV during motor inhibition. However, this matched behavioral performance was associated with abnormal neural activation in patients relative to controls. Specifically, during unsuccessful motor inhibition, there was an age group x diagnosis interaction, with BD youth showing reduced activity in left and right ACC compared to both age-matched HV and adult BD, and adult BD showing increased activation in left ACC compared to healthy adults. During successful motor inhibition there was a main effect of diagnosis, with HV showing greater activity in left VPFC and right NAc compared to BD (Chapter 5). These neuroimaging data support existing laboratory-based evidence of motor inhibition impairments in BD relative to HV, and indicate brain dysregulation during motor control is important to BD pathophysiology. A previous behavioral study showed impaired response flexibility in young BD patients relative to age-matched controls when using the change task. Here, we used the change task during fMRI to examine response flexibility in child and adult BD compared to child and adult HV. We found that patient and control groups showed similar change signal reaction times in response to change cues. However, this matched behavioral performance was associated with abnormal age group x diagnosis activations in brain regions important in signal detection, response conflict, response inhibition, and sustained attention. Specifically, during successful change trials, child BD participants showed frontal, parietal, and temporal hyperactivation relative to healthy children and adult BD, while adult BD showed hypoactivation in these regions relative to healthy adults. These novel fMRI findings during the change task indicate impaired neural activation during response flexibility may be important to the pathophysiology of BD development.

A study was conducted in which a computerized battery of information processing tasks (called the COGLAB) was administered to three subject groups: patients with schizophrenia, patients with bipolar disorder, and normal controls. The tasks included Mueller-Lyer illusion, reaction time, size estimation, Wisconsin Card Sort, backward masking. and Asarnow Continuous Performance.

MicroRNAs (miRNAs) are a family of small non-coding RNAs that regulate gene expression at both the mRNA and protein levels. MiRNAs have been shown to affect neuronal differentiation, synaptosomal complex localization and synapse plasticity, all functions thought to be disrupted in schizophrenia. We investigated the expression of 667 miRNAs (miRBase v.13) in the prefrontal cortex of individuals with schizophrenia (SZ, N = 35) and bipolar disorder (BP, N =35) using a real-time PCR-based Taqman Low Density Array (TLDA). After extensive QC steps, 441 miRNAs were included in the final analyses. At a FDR of 10%, 22 miRNAs were identified as differentially expressed between cases and controls, 7 dysregulated in SZ and 15 in BP. Using in silico target gene prediction programs, the 22miRNAs were found to target brain-specific genes contained within networks overrepresented for neurodevelopment, behavior, and SZ and BP disease development. Given that miRNAs can bind to their targets with imperfect complementarity, computational prediction of true miRNA:mRNA interactions has been difficult and therefore, functional validation of miRNA:mRNA interactions has been relatively sparse. Thus, it was the goal of this study to demonstrate biological functionality of miRNAs on their targets by evaluating transcriptional and translational levels of gene expression(real-time PCR, western blot) as well as determining miRNA target-site specificity (luciferase reporter gene assays). We investigated two miRNAs, miR-132 and miR-137, both of which have been shown to regulate neuronal function and development, and are believed to be associated with schizophrenia from two distinct avenues of research, miR-132 from expression studies and miR-137 from genetic studies. We demonstrated miR-132 down-regulates NTF3, DISC1, and GRIK5 at the transcript level and down-regulates GRIK5 at the protein level as well. Furthermore, we demonstrated miR-137 down-regulates TCF4, CACNA1C, CDK6, ANK3, and ZNF804A at the transcript level, and down-regulates TCF4, CACNA1C, and CDK6 at the protein level. Going further, we also demonstrated miR-137 binds specifically to target sites in the 3'-UTR of CACNA1C, TCF4, and CDK6, suggesting repression of these genes is directly mediated by miR-137. In total, this study provides strong evidence that miRNA dysregulation may contribute to schizophrenia pathogenesis.

Abstract FUNCTIONAL AND BIOCHEMICAL CONSEQUENCES OF SINGLE NUCLEOTIDE POLYMORPHISMS IN THE HUMAN VESICULAR MONOAMINE TRANSPORTER 1 GENE (SLC18A1) By Sally Gamal Shukry, B.S. A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Biology at Virginia Commonwealth University. Virginia Commonwealth University, 2012 Major Advisor: Jennifer K. Stewart Associate Professor and Graduate Director, Department of Biology Single nucleotide polymorphisms (SNP) in the human VMAT1 gene (SLC18A1) have been associated with schizophrenia in three different populations: Han Chinese, Western European and Japanese. Effects of these mutations on transport function of the hVMAT1 protein have not been reported. The goal of this study was to investigate functional and biochemical differences in human VMAT1 proteins with a threonine or proline at amino acid position 4 (Thr4Pro) and a serine or threonine at position 98 (Ser98Thr). COS1 cells were transfected with variant SNPs coding for 4Thr/98Ser, 4Pro/98Ser, or 4Thr98Thr. Western blotting demonstrated robust over expression of the genes and no differences in electrophoretic mobility of the proteins. Maximal transport of serotonin by the VMAT1 protein with 4Pro/98Ser was less than that of the 4Thr/98Ser or the 4Thr/98Thr. Response of the 4Pro/Ser98 to the VMAT inhibitor reserpine was lower than that of the 4Thr/98Thr. These findings suggest mechanisms for human VMAT1 links to schizophrenia.

Titel: Anhörigas erfarenheter av att leva med en person med bipolär sjukdom. Bakgrund: Bipolär sjukdom är en psykisk sjukdom som ungefär 60 miljoner människor världen över drabbas av. I Sverige uppges 1-2 procent av befolkningen någon gång under livet drabbas av bipolär sjukdom. Sjukdomen medför många komplicerade beteenden och gör livssituationen för de anhöriga komplex. Syfte: Syftet med litteraturstudien var beskriva anhörigas erfarenheter av att leva med en person som har bipolär sjukdom. Metod: En litteraturstudie genomfördes med åtta vetenskapliga artiklar med kvalitativ ansats. Dessa analyserades och sammanställdes för att sedan bli litteraturstudiens resultat. Artikelsökningen gjordes i databaserna; CINAHL, PubMed, Scopus och PsycINFO. Resultat: Resultatet sammanställdes i fyra kategorier; anhörigas känslor och tankar kring de drabbade och till sjukdomens yttringar, förändringar i dagligt liv, svårigheter att få stöd från omgivningen och syn på framtiden samt tillhörande underkategorier. Konklusion: Erfarenheterna av att leva med en person med bipolär sjukdom är många och varierande. Brist på stöd, information och förståelse från sjukvården är återkommande i litteraturstudien. Callista Roys adaptionsteori har använts i diskussionen. / Title: Relatives’ experiences of living with a person with bipolar disorder. Background: Bipolar disorder is a mental illness that affects about 60 million people worldwide. In Sweden, 1-2 percent of the population are reported at some point during life to suffer from bipolar disorder. The disease causes many complicated behaviors and makes the life situation of the relative’s complex. Aim: The aim of this study is to describe the close relative’s experiences of living with a person that is diagnosed with bipolar disorder. Method: A literature study was conducted with eight scientific articles with a qualitative approach. These were analyzed and compiled to be the result of the literature study. The article search was made in these databases; CINAHL, PubMed, Scopus and PsycINFO. Result: The result was compiled in four categories; relative’s feelings and thoughts about the affected and the expressions of the disease, changes in everyday life, difficulties to get support from the society and visions of the future and associated subcategories. Conclusion: The experience of being a close relative to a person with bipolar disorder are many and varying. A lack of support, information and understanding from health care is recurrent in the literature study. Callista Roy’s adaption theory has been used in the discussion.

To suffer from bipolar disorder can cause significant distress. Bipolar disorder causes severe shifts in mood. The person can, apart from having a normal mood, experience depressive episodes or a highly elevated mood – hypomania or mania. Psychoeducation as a complement to medicine treatment can help persons manage their disorder and reduce severe changes in mood. Little is known about psychoeducation programs in the country as a whole. Knowledge about these programs can be useful for evaluation and can contribute to valuable insights. The aim of this study was to survey the setup and content of psychoeducation programs for people with bipolar disorder in outpatient care in the country. To accomplish this a cross-sectional study was made through a web-based questionnaire sent to staff involved in outpatient psychoeducation. The Swedish National Quality Register for Bipolar Disorder – BipoläR contributed with contact information to the outpatient clinics. All 234 clinics involved were linked to BipoläR, 56 answers were returned resulting in the following information: Most of the psychoeducation programs were group-based. The major part used programs designed by themselves. Nurses were the most frequently staff involved. The mean amount of time for education delivery was 12 hours. The psychoeducation content was rich in important aspects related to the disorder. The programs were delivered through lectures and discussion. The conclusion of this study was the emphasis on group-based programs developed at the clinics, the quality content of programs and the possible need for more evidence-based programs. / Bipolär sjukdom kan vara svår att leva med då den medför stora variationer i personens sinnesstämning. Ett sätt att underlätta kan vara medverkan i patientutbildningsprogram som tillägg till medicinsk behandling. Detta kan bidra till ökad förståelse för sjukdomen och dess individuella uttryck och därmed göra den mer hanterbar. På flera öppenvårdsmottagningar för personer med bipolär sjukdom runt om i Sverige bedrivs patientutbildning. Någon sammanhållen beskrivning av utbildningarna finns inte. I samråd med personal hos Nationellt kvalitetsregister för personer med bipolär affektiv sjukdom (BipoläR) bedömdes dessa utbildningar vara intressanta att undersöka. Forskning har påvisat att patientutbildningsprogram har positiva effekter för att motverka depression, hypomani och mani vid bipolär sjukdom. Programmen kan se olika ut men utbildning i grupp verkar generellt ge bättre utfall än individuell utbildning. Det är oklart hur utbildningarna i landet ser ut och vi har därför valt att i denna studie kartlägga upplägg och innehåll i dessa utbildningar. Specialistsjuksköterskan i psykiatrisk vård ansvarar bland annat för att stödja patienter och deras anhöriga till lärande och beslutsfattande genom undervisning. Patientutbildning för personer med bipolär sjukdom ligger inom psykiatrisjuksköterskans kompetensområde och sjuksköterskan kan vara en lämplig förmedlare av sådan utbildning. En kartläggning av patientutbildningsprogrammen kan utgöra grund för utvärdering och därmed bidra till utveckling av det psykiatriska vårdandet. Syftet med denna undersökning var att kartlägga upplägg och innehåll i patientutbildningar för personer med bipolär sjukdom inom den psykiatriska öppenvården runt om i landet. Detta gjordes via en webbenkätundersökning riktad till personal involverade i patientutbildning på öppenvårdsmottagningar anslutna till BipoläR. Resultatet visade att de flesta utbildningar var grupputbildningar. Största delen av mottagningarna använde sig av egenutformade utbildningsprogram. Sjuksköterskor var den personalkategori som oftast gav patientutbildning, följt av läkare och psykologer. Utbildningarna hade ett medelvärde på 12 timmars utbildningstid. Erfarenhetsutbytet i utbildningarna sågs som ett värdefullt inslag. Studiens slutsatser var att enkätsvaren tyder på att det i landet fanns en övervikt av gruppbaserade utbildningsprogram för personer med bipolär sjukdom. De flesta mottagningar utformade sina egna program. Utbildningarna var innehållsmässigt rika på viktiga ämnen relaterade till olika aspekter av bipolär sjukdom. De verkade i genomsnitt även vara tidsmässigt tillräckligt långa för att kunna förmedla sitt innehåll. Sjuksköterskor var den personalkategori som oftast var involverad i patientutbildningarna och kunde därmed ge ett betydande bidrag i dessa. Det kan vara värdefullt med en tydligare evidensbas i utbildningarna.

>Magister Scientiae - MSc / INTRODUCTION: Sustained attention is known to be dysfunctional in psychotic disorders. Sustained attention is the ability to remain focused on a specific time-locked stimulus within a task. We aimed to determine whether there are specific group differences between CON and three psychotic disorders: SCZ, MPD and BPD, then to determine differences between these psychotic disorders. This included differences in behavioural performance and prominent electrophysiological event-related potential (ERP) wave components during cueing and target processing of a visual sustained attention task. Further we aimed to characterize ERP waveform component relationships across and within these groups for demographics, substance use, behavioural performance, and clinical variables, the last limited to the psychotic groups. Lastly, we investigated the effects of prescribed medications on ERP wave components within the psychotic groups. METHODOLOGY: 103 participants (29 schizophrenia (SCZ), 28 bipolar disorder with a history of psychosis (BPD), 21 methamphetamine-induced psychotic disorder (MPD), and 30 controls (CON)) underwent electroencephalography (EEG) record while completing a visual continuous performance task. Participants were presented with 60 trials with three consecutive S’s, the presentation of the third S required a behavioural response. Prominent ERP waveform components were extracted from cues and target stimulus. Group differences were determined by ANOVA with Bonferroni post-hoc correction or multivariate Kruskal-Wallis test dependent on data distribution. Relationships between ERP wave components were determined appropriate with Spearman’s Rank order correlation analyses. RESULTS: (1) MPD reported higher use of substances compared to CON, SCZ and BPD. SCZ behavioural performance was poorer compared to CON which was shown by their longer response times, reduced accuracy and increased errors of omission. Clinically, MPD was found to have a shorter duration of illness compared to SCZ. Then SCZ was found to have more positive symptoms compared to BPD whereas BPD had more negative symptoms compared to SCZ. For the first cue, wave component differences were found only over the left hemisphere, for P100 amplitude over the frontal cortex, P300 amplitude over the central cortex, and N170 amplitude over the parietal cortex. For the presentation of the second cue, differences noted for all groups were localised to the frontal and central brain regions, for P100 and N170 ERP waveforms. For the target stimulus wave component differences were found over the prefrontal, frontal and parietal brain regions, within CON, SCZ, BPD and MPD. (2) For the first cue, education positively correlated with the N170 left parietal amplitude in CON and P300 right parietal amplitude in MPD. During the second cue, the left parietal N170 latency in SCZ correlated positively with education and the left central P300 latency correlated negatively with education in MPD. The age on the day of testing correlated positively with the target left frontal P300 latency in MPD. For the first cue, substance use positively correlated with the left and right parietal P300 latency and negatively for the right parietal P100 amplitude in SCZ. In MPD, a negative correlation was noted across left and right prefrontal N170 and P300 amplitudes, and positive correlation for the left prefrontal P300 latency in MPD. For the target stimulus, correlations were evident for the left and right parietal N70, N170 amplitudes, P300 latency, the right parietal P100 amplitude and left central P300 latency in SCZ. For the first cue, in SCZ PANSS total score correlated positively with left and right central P300 amplitudes and the left parietal P300 amplitude. For the second cue; in MPD, the PANSS negative symptom score, positively correlated with the P100 and N170 left parietal amplitude, left and right parietal P150 amplitude, left central and right parietal P300 amplitude. For the target, the Hamilton depression rating scale correlated positively with the left and right frontal P300 amplitude in MPD and then negatively with the right parietal P300 amplitude in SCZ. Behavioural performance in CON, positively correlated with the left parietal N70, P100, P150 and N170 amplitude the number of correct responses, and left central N170 amplitude. While the number of impulsive responses correlated negatively with the left parietal N70, P100, P150 and N170 and the left central N170 amplitude of CON. For the second cue, behavioural performance was related to the fronto-parietal relationship across all groups. For the target stimulus, impulsive responses positively correlated with the left parietal N70 latency in SCZ. Overall response time negatively correlated with the right parietal P300 latency for SCZ. (3) Medication was found to affect ERP wave components during the sustained visual attention task. For the first cue FGA’s increased the left central P100 amplitude in both SCZ and BPD and decreased the left parietal P100 amplitude in SCZ only. The use of antipsychotics increased the right parietal N70 and left central P100 amplitudes in BPD, specifically the right prefrontal N170 amplitude was increased with the use of SGA’s. Then clozapine use increased the left frontal P100 amplitude in SCZ. For the second cue, SGA’s decreased the right parietal P150 amplitude in SCZ but in MPD the right parietal P150 amplitude was increased with haloperidol use, and FGA. SGA’s increased the left parietal P300 latency in BPD and sodium valproate decreased the left prefrontal P300 latency. For the target stimulus, SGA’s decreased the right parietal P100, P150 and left parietal P150 amplitudes and increased the left central P300 latency in BPD. CONCLUSION: (1) sustained attentional performance is poorer in SCZ. Our study adds to previous studies showing attention processing deficits in SCZ, are evident during cueing of a sustained attention tasks; (2) substance use was found to slow cognitive processing, education improved executive function and information processing, and symptom severity was associated with dysfunction of prefrontal and frontal cortices; (3) antipsychotic medication was related to improved processing of salient information. These data support the current literature and provide novel insights to the attentional processing deficits during cueing in the psychotic disorders.

Bakgrund: Förekomsten av bipolär sjukdom uppskattas vara upp till 1,5 % av världens befolkning. Denna population drabbas i stor utsträckning av välfärdssjukdomar som metabolt syndrom, diabetes och hjärt- och kärlsjukdomar. Idag är förstahandsbehandlingen vanligtvis stämningsstabiliserande psykofarmaka, sömnpreparat och antipsykotiska läkemedel. Syfte: Syftet var att beskriva fysisk aktivitet hos vuxna personer med bipolär sjukdom. Metod: En allmän litteraturstudie gjordes på tio vetenskapliga artiklar som bearbetades genom textanalys. Resultat: Analysen resulterade i kategorierna: Hälsoeffekter av fysisk aktivitet, Erfarenheter av fysisk aktivitet och Motivation för fysisk aktivitet. Resultatet påvisade i första kategorin att regelbunden fysisk aktivitet minskade skoven av mani och depression. I andra kategorin framkom det att aktiviteter som föredrogs var rytmiska och monotona, såsom löpning, cykling, promenad eller simning. Tredje kategorin påvisade att en förtroendefull relation mellan patient och allmänsjuksköterskan var betydande vid depressiva perioder. Sjuksköterskan fungerade också som stöd för vardagsstrukturen och till att motivera till fysisk aktivitet. Slutsats: Fysisk aktivitet kan symtomlindra och förbättra den fysiska och psykiska hälsan. Fysisk aktivitet bör vara en självklar del i omvårdnadsarbetet och utbildning om dess effekt bör ges till både sjuksköterskestudenter och yrkesverksamma sjuksköterskor. Mer forskning behövs för att se hur fysisk aktivitet på sikt påverkar läkemedelsbehandling och samsjukligheten med välfärdssjukdomar. / Background: The prevalence of bipolar disorder is estimated to be 1,5 % of the world's population and this patient group have a higher risk to be affected of welfare diseases such as metabolic syndrome, diabetic and cardiovascular diseases. The primary treatment of bipolar disorder are psychopharmacologic drugs. Aim: The aim of this study was to describe physical activity among adults with bipolar disorder. Result: Categories that appeared were: Health effects of physical activity, Experience of physical activity and Motivation for physical activity. First category showed that regularly performed physical activity reduced the episodes of mania and depression. Second category showed that preferred activities were of rhythmic and monotone nature like running, cycling, walking or swimming. Third category showed that a confiding relationship between the patient and their registered nurse were of importance during depressive episodes, functioned as support for daily routines and motivate for physical activity. Conclusion: Physical activity reduces symptoms and improve both physical and mental health. Physical activity should be a manifested treatment in nursing and education of its effect should be given to both nurse-students and registered nurses. More research is required about how physical activity affect treatment and the occurrence of welfare diseases in a long-term perspective.

O impacto da flutuação dos hormônios esteróides sobre o curso do Transtorno Afetivo Bipolar durante a vida reprodutiva das mulheres é pouco estudado. Encontramos ainda muitas lacunas no conhecimento quanto a sua apresentação clínica e as suas implicações na evolução do Transtorno Afetivo Bipolar, especialmente sua associação com a ciclagem rápida e o seu valor preditivo para recorrência. Métodos: Mulheres com Transtorno Afetivo Bipolar (tipos I, II ou sem outra especificação) participantes do Systematic Treatment Enhancement Program for Bipolar Disorder, com idade entre 16 e 40 anos, foram divididas em dois grupos: com e sem relato de exacerbação pré-menstrual do Transtorno Afetivo Bipolar na avaliação inicial do estudo. Estes grupos foram comparados em relação às características clínicas do Transtorno Afetivo Bipolar, de vida reprodutiva e tratamento na entrada do estudo. Longitudinalmente, foi comparado o tempo de recorrência entre as pacientes que iniciaram o estudo eutímicas utilizando análise de sobrevivência Kaplan Meier e a regressão de Cox. O número de episódios entre as pacientes que foram seguidas por um período de um ano também foi comparado. Resultados: Das 706 mulheres que completaram o questionário, 490 (69,4%) relataram exacerbação pré-menstrual. Na entrada do estudo, quando comparadas ao grupo sem exacerbação pré-menstrual, as mulheres com exacerbação pré-menstrual encontravam-se mais deprimidas, apresentavam mais comorbidades psiquiátricas, sintomas do humor com uso de contraceptivos hormonais, ciclos menstruais irregulares, e estavam recebendo menos tratamento farmacológico. Mulheres com exacerbação pré-menstrual também relataram mais episódios de humor durante o ano anterior e eram mais susceptíveis de apresentar ciclagem rápida neste mesmo período. Na avaliação prospectiva, entre as mulheres que iniciaram o estudo eutímicas (exacerbação pré-menstrual n = 66, sem exacerbação pré-menstrual n = 63), o grupo com exacerbação pré-menstrual teve um tempo de recaída mais rápido ao se incluir estados subsindrômicos associados a recaídas em mania, depressão ou estado misto. O tempo médio de recidiva de 50% da amostra foi de 4,5 meses para as mulheres com a exacerbação pré-menstrual, em comparação com 8,5 meses para as do grupo sem exacerbação pré-menstrual (p = 0,02). A exacerbação prémenstrual também foi um fator significativamente associado a maior gravidade dos sintomas depressivos e de elevação do humor entre as mulheres com um ano de seguimento. Conclusões: As mulheres com Transtorno Afetivo Bipolar que relataram exacerbação pré-menstrual apresentaram uma maior comorbidade psiquiátrica, maior número de episódios do humor no ano anterior e ciclagem rápida. A avaliação prospectiva mostrou uma taxa de recorrência maior, mais estados subsindrômicos e maior número de episódios, mas não ciclagem rápida, nas mulheres do grupo exacerbação pré-menstrual. Nossos resultados sugerem que a exacerbação pré-menstrual pode ser considerada um marcador clínico preditor de um fenótipo clínico mais complexo e associado a uma pior evolução da doença em mulheres em idade reprodutiva com Transtorno Afetivo Bipolar. / The impact of hormonal fluctuation during the menstrual cycle on the course of bipolar disorder in women is poorly studied. We also found many gaps in knowledge about its clinical presentation and its implications for the evolution of Bipolar Disorder, especially the association with rapid cycling and its predictive value for recurrence. Methods: Women with Bipolar Disorder (types I, II or Not Otherwise Specificated ) participants Systematic Treatment Enhancement Program for Bipolar Disorder, aged between 16 and 40, were divided into two groups: with and without reports of Premenstrual Exacerbation of Bipolar Disorder in the baseline assessment. These groups were compared to clinical features of BD, reproductive life and treatment at study entry. The time difference of recurrence between groups who were euthymic at the baseline assessment were done with survival analysis Kaplan Meier\'s survival curve and Cox regression models. The number of episodes between the patients who were followed for a period of one year was also compared. Results: Of 706 women who completed the questionnaire, 490 (69.4%) reported premenstrual exacerbation. At study entry, compared to those without premenstrual exacerbation, women with premenstrual exacerbation were more depressed, had more psychiatric comorbidities, mood symptoms with the use of hormonal contraceptives, irregular menstrual cycles, and were receiving less drug treatment. Women with premenstrual exacerbation also reported more mood episodes during the previous year and were more likely to state rapid cycling in the same period. In a prospective evaluation among women who started the study in euthymic mood state (premenstrual exacerbation n = 66, without premenstrual exacerbation n = 63), the premenstrual exacerbation group had a smaller time to relapse when associated subsyndromal mood states to relapse in mania, depression or mixed state. The median time to relapse of 50% of the sample was 4.5 months for women with premenstrual exacerbation, compared with 8.5 months for the group without premenstrual exacerbation (p = 0,02). The premenstrual exacerbation was also a significantly positive factor for a greater severity of depressive symptoms and elevation of mood among women with one year of follow-up. Conclusions: Women with Bipolar Disorder who reported premenstrual exacerbation had a higher psychiatric comorbidity, greater number of episodes of mood in the previous year and rapid cycling. Prospective evaluation showed a higher rate of recurrence, more states and more subsyndromal episodes, but not rapid cycling among women in the premenstrual exacerbation. Our results suggest that premenstrual exacerbation can be considered a clinical marker predictor of a worse clinical phenotype and associated with a worst disease progression in women of reproductive with bipolar affective disorder

Objetivo: Identificar os medicamentos preferidos no Brasil para tratar o transtorno bipolar e a opinião dos psiquiatras brasileiros sobre a litioterapia. Métodos: Um questionário de múltipla escolha com 14 itens foi desenvolvido para estudar estas questões. Foram enviados 10.059 questionários para psiquiatras brasileiros. Resultados: 820 psiquiatras (8,6%) responderam aos questionários. Lítio foi a medicação de primeira escolha em todas as fases do transtorno. Antipsicóticos foram a segunda escolha no tratamento da mania, superando os anticonvulsivantes. Antidepressivos foram a segunda medicação mais utilizada nos episódios depressivos. Mais de 80% de psiquiatras acreditam que o lítio é um medicamento seguro e de fácil manejo. Características epidemiólogicas como região de origem, alto nível educacional, grande experiência clínica e interesses acadêmicos podem ter influenciado tais resultados. Conclusão: Lítio é o medicamento de primeira linha no tratamento do transtorno bipolar no Brasil, a despeito do que ocorre em outros países. Apesar deste panorama favorável, algumas dificuldades podem ser identificadas como a falta de conhecimento sobre o lítio por profissionais da área de saúde mental e pacientes. / Objective: Identify preferred drugs to treat bipolar disorder in Brazil and the impressions of Brazilian psychiatrits about lithium therapy. Methods: A 14 items multiple-choice questionnaire was developed to answer this issue. Questionnaires were posted to 10,059 Brazilian psychiatrists. Results: 820 psychiatrists (8.6%) have answered the questionnaires. Lithium was the preferred medication used in all phases of the disorder. Antipsychotics were second choice in treatment of mania, overcoming anticonvulsants. Antidepressants were the second more used medication for depressive episode. More than 80% of psychiatrists believe that lithium is a safe drug and there is no difficult to handle with. Epidemiological characteristics such region of origen, high degree, large clinical practice and academic interests may influenced those results. Conclusion: Lithium is the first line drug to treat bipolar disorder in Brazil, despite what occur in others countries. Although this favorable panel, some difficults can be identified as mental health professional and patients\' lack of information about lithium.