Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study.

BACKGROUND: Lithium is a first-line treatment in bipolar disorder, but individual response is variable. Previous studies have suggested that lithium response is a heritable trait. However, no genetic markers of treatment response have been reproducibly identified. METHODS: Here, we report the results of a genome-wide association study of lithium response in 2563 patients collected by 22 participating sites from the International Consortium on Lithium Genetics (ConLiGen). Data from common single nucleotide polymorphisms (SNPs) were tested for association with categorical and continuous ratings of lithium response. Lithium response was measured using a well established scale (Alda scale). Genotyped SNPs were used to generate data at more than 6 million sites, using standard genomic imputation methods. Traits were regressed against genotype dosage. Results were combined across two batches by meta-analysis. FINDINGS: A single locus of four linked SNPs on chromosome 21 met genome-wide significance criteria for association with lithium response (rs79663003, p=1·37 × 10(-8); rs78015114, p=1·31 × 10(-8); rs74795342, p=3·31 × 10(-9); and rs75222709, p=3·50 × 10(-9)). In an independent, prospective study of 73 patients treated with lithium monotherapy for a period of up to 2 years, carriers of the response-associated alleles had a significantly lower rate of relapse than carriers of the alternate alleles (p=0·03268, hazard ratio 3·8, 95% CI 1·1-13·0). INTERPRETATION: The response-associated region contains two genes for long, non-coding RNAs (lncRNAs), AL157359.3 and AL157359.4. LncRNAs are increasingly appreciated as important regulators of gene expression, particularly in the CNS. Confirmed biomarkers of lithium response would constitute an important step forward in the clinical management of bipolar disorder. Further studies are needed to establish the biological context and potential clinical utility of these findings. FUNDING: Deutsche Forschungsgemeinschaft, National Institute of Mental Health Intramural Research Program.

Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study.

Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.

Correlation between insight dimensions and cognitive functions in patients with deficit and nondeficit schizophrenia.

Previous studies have shown correlations between poor insight and neurocognitive impairment in schizophrenia. Deficit schizophrenia has been associated with worse cognitive functioning and poorer insight. This study aimed at investigating the relationship between insight dimensions (measured by Schedule for the Assessment of Insight-Expanded Version and its factors) and specific neurocognitive functions (assessed through a battery of neuropsychological tests) considering separately patients with deficit (n=29) and nondeficit schizophrenia (n=44), categorized according to the Schedule for the Deficit Syndrome. We found that working memory correlated positively and significantly with awareness of mental illness in both groups. In nondeficit group, awareness of mental illness correlated additionally with verbal fluency and attention. If confirmed by further studies, these results may have important consequences, such as the need of tailoring differently cognitive rehabilitation for each group.

Insight controlled for cognition in deficit and nondeficit schizophrenia.

Patients with deficit schizophrenia have worse cognition and poorer social functioning compared to the nondeficit ones. Insight is another domain in which these two groups might differ, but data on insight impairment in deficit versus nondeficit schizophrenia are still scarce. We compared 29 patients with deficit schizophrenia to 44 nondeficit patients and found a tendency to poorer insight in the deficit group. However such tendency disappeared when analysis was controlled for cognition, a domain in which both groups differed significantly. This finding reinforces the pressing need for simultaneous assessment of the several dimensions or domains of schizophrenic psychopathology.

Anorexia nervosa and Wernicke-Korsakoff syndrome: a case report.

INTRODUCTION: Wernicke's encephalopathy is an acute, potentially fatal, neuropsychiatric syndrome resulting from thiamine deficiency. The disorder is still greatly under-diagnosed, and failure to promptly identify and adequately treat the condition can lead to death or to the chronic form of the encephalopathy - Korsakoff's syndrome. Wernicke's encephalopathy has traditionally been associated with alcoholism but, in recent years, there has been an increase in the number of clinical settings in which the disorder is observed. CASE PRESENTATION: We report the case of a 45-year-old Caucasian woman who arrived at the emergency room presenting signs of marked malnutrition and mental confusion, ataxic gait and ophthalmoplegia. Main laboratory test findings included low serum magnesium and megaloblastic anemia. Brain magnetic resonance imaging revealed increased T2 signal in the supratentorial paraventricular region, the medial regions of the thalamus and the central and periaqueductal midbrain. The diagnosis of Wernicke's encephalopathy was made at once and immediate reposition of thiamine and magnesium was started. The patient had a long history of recurrent thoughts of being overweight, severe self-imposed diet restrictions and self-induced vomiting. She had also been drinking gin on a daily basis for the last eight years. One day after admittance the acute global confusional state resolved, but she presented severe memory deficits and confabulation. After six months of outpatient follow-up, memory deficits remained unaltered. CONCLUSION: In this case, self-imposed long-lasting nutritional deprivation is thought to be the main cause of thiamine deficiency and subsequent encephalopathy, but adjunct factors, such as magnesium depletion and chronic alcohol misuse, might have played an important role, especially in the development of Korsakoff's syndrome. The co-morbidity between eating disorders and substance abuse disorders has emerged as a significant health issue for women, and the subgroup of patients with anorexia nervosa who also misuse alcohol is probably at a particular risk of developing Wernicke-Korsakoff syndrome. The present case report highlights this relevant issue.

Hazardous use of alcohol among undergraduate students at a public university

BACKGROUND. The potentially harmful consequences of alcohol use among undergraduates have become a growing concern in recent years. OBJECTIVES. This study aimed to determine the prevalence of hazardous use of alcohol in this population and to identify demographic and psychosocial factors associated with this pattern of consumption. METHODS. This was a cross-sectional study using an anonymous and self-completed questionnaire in the classroom. The questionnaire was administered to 1,290 enrolled male and female students, which comprised a proportional sample of the main areas of knowledge at University of Campinas. The questionnaire produced sociodemographic and psychosocial profiles and the Alcohol Use Disorders Identification Test was used to detect hazardous use of alcohol. RESULTS. The prevalence of hazardous use of alcohol among the study participants was 24%. Male gender, subjective perceived social support in case of difficulties, being sexually active, not dating, having smoked tobacco cigarettes or marijuana, and having used other illicit psychoactive substances were associated with hazardous use of alcohol. DISCUSSION. Variables related to gender, sexuality, affective partnerships, and consumption of other psychoactive substances were associated with hazardous use of alcohol, which was identified in a quarter of the evaluated students, and indicate the need for strategies to prevent and to treat problems.

Formas deficitária e não deficitária da esquizofrenia não diferem quanto à sazonalidade de nascimentos nas regiões Sul e Sudeste do Brasil / Deficit and non-deficit schizophrenia do not differ regarding season of birth in Brazilian Southern and Southeast regions

Objetivos: Entre os pacientes com esquizofrenia originários do hemisfério norte, observa-se um excesso de 5 por cento-10 por cento de nascimentos no inverno e na primavera. Entretanto, entre os pacientes com a forma deficitária da doença, há uma pequena sobrerrepresentação de nascimentos no verão. Neste estudo, buscou-se verificar se tais associações se repetem entre os pacientes com esquizofrenia nascidos nas regiões Sudeste e Sul do Brasil. Métodos: Setenta e seis pacientes com esquizofrenia foram avaliados quanto a características sociodemográficas e psicopatológicas e categorizados quanto à presença da síndrome deficitária. Pacientes com e sem síndrome deficitária foram comparados quanto à estação de nascimento. Adicionalmente, compararam-se características psicopatológicas entre pacientes nascidos nas quatro estações do ano. Resultados: A distribuição de nascimentos de acordo com as estações não apresentou diferenças significativas. Entre pacientes com síndrome deficitária, dois terços nasceram no verão e outono, mas essa diferença não alcançou significância estatística. Não foram encontradas diferenças psicopatológicas relacionadas à estação do ano de nascimento. Conclusão: Nas regiões Sul e Sudeste do Brasil, não foi observado o excesso de nascimentos no verão entre pacientes ESquizofrênicos com síndrome deficitária, bem como não foi constatado excesso de nascimentos no inverno e primavera no grupo geral de pacientes com esquizofrenia.

Objectives: There is a 5 percent-10 percent excess of births in winter and spring among the patients with schizophrenia born in the northern hemisphere. However, in patients with the deficit syndrome of schizophrenia, there is a slight over-representation of births in summer. In this study, we aimed at verifying whether the same patterns are found in patients with schizophrenia born in the Brazilian South and Southeast regions. Methods: Seventy-six patients with schizophrenia were assessed for demographics and psychopathology and also categorized for the presence of deficit syndrome. Patients with deficit and non-deficit schizophrenia were compared for the season of birth. In addition, we compared psychopathological variables between patients born in all four seasons. Results: There was no significant difference in the distribution of births according to the seasons. Although two thirds of the patients with deficit syndrome were born in the summer and autumn, this over-representation did not reach statistical significance. We found no differences regarding psychopathology between patients born in all four seasons. Conclusion: In the South and Southeast regions of Brazil, there was no significant excess of births in the summer between schizophrenic patients with deficit syndrome, neither was an excess of births in winter and spring in the overall sample of patients with schizophrenia.

Insight na psicose: uma análise conceitual / Insight in psychosis: a conceptual analysis

INTRODUÇÃO: No contexto da psiquiatria clínica, insight ou crítica da doença é definida como uma subcategoria do autoconhecimento dos pacientes relativa ao reconhecimento das manifestações patológicas que os afetam e também à apreciação das mudanças que tais manifestações causam na sua interação com o mundo. OBJETIVO: Examinar as formas de apresentação do insight na esquizofrenia e em outras psicoses. MÉTODOS: Análise conceitual, com vinhetas clínicas ilustrativas, da relação entre insight e as diversas dimensões sintomatológicas da esquizofrenia e condições relacionadas, considerando aspectos clínicos, neurocognitivos, psicodinâmicos e transculturais. RESULTADOS: Do ponto de vista conceitual, o construto é conformado pela perspectiva teórica adotada; do ponto de vista clínico, sua apresentação nas psicoses é a resultante da interação com os diferentes domínios sintomatológicos e aspectos subjetivos e culturais do paciente. CONCLUSÃO: A avaliação psicopatológica do insight deve levar em conta a complexidade do fenômeno, o recorte teórico em que está situada e a finalidade clínica com que é realizada.

INTRODUCTION: In the context of clinical psychiatry, insight is defined as a subcategory of self-awareness of patients, which is related to the recognition of the pathological manifestations that affect them and also the appreciation of the changes that these manifestations cause in their interaction with the outside world. OBJECTIVE: To examine the forms of presentation of insight in schizophrenia and other psychoses. METHODS: Conceptual analysis, with illustrative clinical vignettes, of the relation between insight and several symptomatologic dimensions of schizophrenia and related conditions, regarding clinical, neurocognitive, psychodynamic and transcultural aspects. RESULTS: From a conceptual point of view, the construct is shaped by the theoretical approach adopted; from a clinical point of view, its presentation in psychoses is the result of the interaction with different symptomatologic areas and subjective and cultural aspects of the patient. CONCLUSION: Psychopathology assessment of insight must consider the complexity of the phenomenon, the theoretical approach used, and the clinical purpose for which it is done.

God‘s eyes and the schizophrenic hands: listening to a psychiatric patient / Os olhos de Deus e as mãos esquizofrênicas: escutando um paciente psiquiátrico / Les yeux de Dieu et les mains schizophrènes: à l'écoute d'un patient de psychiatrie / Los ojos de Dios y las manos esquizofrénicas: escuchando un paciente psiquiátrico

This article describes the intriguing case of a young female patient first seen in the emergency room and then followed up at the psychiatric outpatient facility of the General Hospital at UNICAMP, Brazil. The cooperation that ensued between psychiatrists and a psychoanalyst toreach a psychopathological diagnosis is also presented here. The differential diagnosis is discussed within a psychiatric framework andthen contributions from listening to the patient’s free associations related to the clarification of her psychopathology are described. The clinical collaboration between psychiatry and psychoanalysis proved effective in this case as a clinical method for approaching the patient.

Relatamos um intrigante caso de uma jovem paciente atendida no Pronto-Socorro e, depois, no Ambulatório de Psiquiatria do HC-UNICAMP, e descrevemos a colaboração estabelecida entre psiquiatras e psicanalista, com o intuito de realizar um diagnóstico psicopatológico. Discutimos a sintomatologia e o diagnóstico diferencial da paciente em termos médicos e mostramos, a partir de alguns fragmentos da escuta das associações livres do paciente, como o quadro psicopatológico foi finalmente elucidado. A colaboração clínica entre a psiquiatria e psicanálise se mostrou profícua neste caso,como método clínico, na abordagem do sujeito psicopatológico.

Relatamos el caso instigador de una joven paciente tratada en la sala de emergencia y después en la Clínica de Psiquiatría del HC-UNICAMP; describimos también la cooperación establecida entre psiquiatras y psicoanalista para larealización del diagnóstico de la psicopatología. Discutimos la sintomatología y el diagnóstico diferencial de la paciente en términos médicos y mostramos, a partir de algunos fragmentos de la escucha de las asociaciones libres del paciente, cómo elcuadro psicopatológico fue elucidado. La colaboración clínica entre psiquiatría ypsicoanálisis se mostró provechosa en este caso como método clínico en el abordajed el sujeto psicopatológico.

Nous rapportons un cas fascinant d’une jeune patiente traitée à la Salled’Urgence, puis à la Clinique de Psychiatrie de l’Hôpital des Cliniques de l’UNICAMPet décrivons ensuite la collaboration entre psychiatres et psychanalystes pour établirun diagnostic psychopathologique. Nous discutons les symptômes et le diagnostic différentiel de la patiente en termes médicaux et montrons à partir de quelques fragments d’associations libres de la patiente comment le cadre psychopathologique a finalement été élucidé. Dans ce cas, la collaboration clinique entre la psychiatrie etpsychanalyse s’est révélée fructueuse et peut être considérée comme méthode cliniquedans le traitement du sujet psychopathologique.

Neurocysticercosis calcifications in patients with partial epilepsy: is there etiological relevance?

Avalia a relevância das calcificações cerebrais por neurocisticercose em tomografia computadorizada (TC) como a etiologia das crises em pacientes com epilepsia parcial. Avaliamos 45 pacientes consecutivos acompanhados em nosso serviço de epilepsia que apresentavam calcificações cerebrais em TC compatíveis com neurocisticercose. Todos os pacientes foram investigados com eletroencefalogramas (EEG) interictais e ressonância magnética (RM) cerebral. Imagens por RM foram adquiridas nos 3 planos ortogonais, incluindo cortes coronais finos em T1-IR, T2 e sequência volumétrica (3D). Realizamos análise detalhada das imagens de RM em todos os planos ortogonais e por reconstrução multiplanar (RMP). Comparamos a localização das calcificações pela TC com a localização das anormalidades epileptiformes nos EEGs interictais e com a localização das lesões na RM. Lesões estruturais, além das microcalcificações, na RM foram consideradas como epileptogênicas e portanto, como provável etiologia das crises epilépticas das crises epilépticas, quando a semiologia ictal e anormalidades no EEG coincidiram com a localização da lesão. Não houve associação significativa entre localização das calcificações diagnosticadas pela TC com a semiologia ictal, EEG interictal e RM. Por outro lado, houve uma associação significativa entre a localização de atividade epileptiforme focal no EEG e localização de outras lesões diagnosticadas pela RM e invisíveis pela TC, particularmente sinais de esclerose hipocampal pela RM. Apesar da neurocisticercose ser um fator etiológico comum de crises sintomáticas remotas em nosso meio, o achado de microcalficicações na TC não necessariamente implica que estas sejam a causa da epilepsia