Cognitive impairments and predominant polarity in bipolar disorder: a cross-sectional study.

BACKGROUND: Bipolar disorder (BD) patients exhibit cognitive impairments during euthymic states. Studies suggest that manic episodes may be correlated to cognitive impairments. The present study investigated the relationship between predominant polarity and the cognitive deficits frequently detected in bipolar patients. We hypothesize that mania predominant polarity (MPP) patients should exhibit greater cognitive impairments in comparison to depressive (DPP) and indefinite predominant polarity (IPP) patients and healthy control (HC) individuals. METHODS: The study evaluated 55 euthymic BD patients, type I and II, and 31 HCs. Patients were divided into 3 groups: MPP (n = 17), DPP (n = 22), and IPP (n = 16), and compared regarding demographic and clinical variables, and performance on a 7-test neuropsychological battery. RESULTS: MPP patients demonstrated greater cognitive impairments in alternating attention, verbal fluency, and delayed memory in comparison to DPP, IPP, and HC. Compared to HC, IPP patients exhibit cognitive deficits in verbal fluency and alternating attention and DPP patients solely in verbal fluency. Furthermore, DPP patients did not exhibit, in none of the seven neuropsychological tests, significant poorer performances than MPP or IPP patients, although having significant more episodes than MPP patients. CONCLUSION: MPP patients exhibit increased cognitive impairments in comparison to DPP, IPP, and HC subjects. Manic episodes may play an important role in the development of cognitive deficits and thus, in potential neuroprogression. Predominant polarity may be an important specifier for predicting future cognitive impairments.

Facial emotion recognition in euthymic patients with bipolar disorder and their unaffected first-degree relatives.

BACKGROUND: Facial emotion recognition (FER) is an important task associated with social cognition because facial expression is a significant source of non-verbal information that guides interpersonal relationships. Increasing evidence suggests that bipolar disorder (BD) patients present deficits in FER and these deficits may be present in individuals at high genetic risk for BD. The aim of this study was to evaluate the occurrence of FER deficits in euthymic BD patients, their first-degree relatives, and healthy controls (HC) and to consider if these deficits might be regarded as an endophenotype candidate for BD. METHODS: We studied 23 patients with DSM-IV BD type I, 22 first-degree relatives of these patients, and 27 HC. We used the Penn Emotion Recognition Tests to evaluate tasks of FER, emotion discrimination, and emotional acuity. Patients were recruited from outpatient facilities at the Institute of Psychiatry of the University of Sao Paulo Medical School, or from the community through media advertisements, had to be euthymic, with age above 18years old and a diagnosis of DSM-IV BD type I. RESULTS: Euthymic BD patients presented significantly fewer correct responses for fear, and significantly increased time to response to recognize happy faces when compared with HC, but not when compared with first-degree relatives. First-degree relatives did not significantly differ from HC on any of the emotion recognition tasks. CONCLUSION: Our results suggest that deficits in FER are present in euthymic patients, but not in subjects at high genetic risk for BD. Thus, we have not found evidence to consider FER as an endophenotype candidate for BD.

Gray matter volumes in patients with bipolar disorder and their first-degree relatives.

Bipolar disorder (BD) is highly heritable. First-degree relatives of BD patient have an increased risk to develop the disease. We investigated abnormalities in gray matter (GM) volumes in healthy first-degree relatives of BD patients to identify possible brain structural endophenotypes for the disorder. 3D T1-weighted magnetic resonance images were obtained from 25 DSM-IV BD type I patients, 23 unaffected relatives, and 27 healthy controls (HC). A voxel-based morphometry protocol was used to compare differences in GM volumes between groups. BD patients presented reduced GM volumes bilaterally in the thalamus compared with HC. Relatives presented no global or regional GM differences compared with HC. Our negative results do not support the role of GM volume abnormalities as endophenotypes for BD. Thalamic volume abnormalities may be associated the pathophysiology of the disease.

(1)H-MRS of hippocampus in patients after first manic episode.

OBJECTIVES: The investigation of the pathophysiology of bipolar disorder in patients at disease onset is a strategy to avoid the confounding effect of progression of disease or duration of treatment. Our purpose was to investigate in vivo neuronal metabolites in the hippocampus of bipolar disorder patients using proton magnetic resonance spectroscopy ((1)H-MRS) within 3 months after their first manic episode. METHODS: Fifty-eight BD I patients meeting DSM-IV criteria following their first episode of mania and 27 healthy subjects were studied using (1)H-MRS with a 3.0 T Philips Achieva scanner. Voxels with 30 × 15 × 15 mm were placed in the hippocampus on both sides of the brain and the signal was collected using a PRESS sequence with TE = 35 ms and TR = 2000 ms. Data analysis was performed using the LC Model software. RESULTS: N-Acetyl-aspartate (NAA), choline (Cho), myo-inositol (mI), creatine (Cre) and glutamine + glutamate (Glx) levels were compared between the groups and no statistically significant differences were found. CONCLUSIONS: Our results suggest that early in the course of BD there are no alterations in neuronal metabolism or vulnerability in the hippocampus after the first manic episode.

Estudo do hipocampo de portadores de transtorno afetivo bipolar após o primeiro episódio de mania através do uso da espectroscopia por ressonância magnética de próton (1H-ERM) / Study of the hippocampus of bipolar disorder patients after the first episode of mania using proton magnetic resonance spectroscopy (1H-MRS)

A investigação da fisiopatologia do transtorno bipolar em pacientes no início da doença é uma estratégia para evitar um potencial efeito de confusão associado à duração da doença, presença de múltiplos episódios de alteração do humor e tratamento medicamentoso. Nosso objetivo foi investigar, in vivo, metabólitos neuronais do hipocampo de portadores de transtorno afetivo bipolar (TAB) usando a espectroscopia por ressonância magnética de próton (1H-ERM) logo após o seu primeiro episódio de mania. Para isso, foram estudados cinqüenta e oito pacientes com TAB tipo I, classificados de acordo com os critérios do DSM-IV (APA, 2000), após o primeiro episódio de mania e 27 indivíduos saudáveis utilizando a 1H-ERM com um aparelho Philips Achieva de 3T. Voxels com 30X15X15 mm foram posicionados no hipocampo em ambos os lados do cérebro e o sinal foi adquirido utilizando uma sequência PRESS com TE = 35ms e TR = 2000ms. A análise dos dados foi realizada utilizando o programa LC Model. Os níveis de N-acetil-aspartato, compostos de colina, mio-inositol, creatina e glutamina + glutamato (Glx) foram comparados entre os grupos e não foram encontradas diferenças estatisticamente significativas entre eles. Esses achados sugerem que no início do curso do TAB não há alterações no metabolismo neuronal ou vulnerabilidade no hipocampo após o primeiro episódio maníaco.

The investigation of the pathophysiology of bipolar disorder in patients at disease onset is a strategy to avoid a potential confounding effect associated with disease duration, presence of multiples mood episodes and pharmacological treatment. Our purpose was to investigate, in vivo, neuronal metabolites in the hippocampus of bipolar disorder (BD) patients using proton magnetic resonance spectroscopy (1H-MRS) soon after their first manic episode. We studied fifty-eight BD I patients meeting DSM-IV (APA, 2000) criteria following their first episode of mania and 27 healthy subjects using 1H-MRS with a 3.0 T Philips Achieva scanner. Voxels with 30X15X15 mm were placed in the hippocampus on both sides of the brain and the signal was collected using a PRESS sequence with TE = 35ms and TR = 2000ms. Data analysis was performed using the LC Model software. N- Acetyl-Aspartate, choline compounds, myo-inositol, creatine and glutamine + glutamate (Glx) levels were compared between the groups and no statistically significant differences were found. These results suggest that early in the course of BD there are no alterations in neuronal metabolism or vulnerability in the hippocampus after the first manic episode.

Brain glutamate levels measured by magnetic resonance spectroscopy in patients with bipolar disorder: a meta-analysis.

OBJECTIVES: Bipolar disorder (BD) is a common and highly disabling disease characterized by substantial cognitive and functional impairment. The exact neurobiological mechanisms underlying the expression of symptoms in this condition remain unknown but there is growing evidence that glutamate might play an important role. Using proton magnetic resonance spectroscopy (¹H-MRS), a number of studies have examined brain glutamate/glutamine levels in patients with bipolar disorder, but they have produced conflicting results. The objective of this paper was to conduct a systematic review and meta-analysis of the literature on brain glutamate/glutamine in BD as measured by ¹H-MRS. METHODS: A Medline search for the period January 1980-April 2010 was conducted to identify published studies that used ¹H-MRS to measure glutamate + glutamine (Glx), the Glx/creatine (Cr) ratio, glutamate (Glu), or the Glu/Cr ratio in any brain region in adult or child/adolescent patients with BD and healthy subjects. A meta-analysis of the pooled data was conducted. RESULTS: BD patients were found to have increased Glx compared to healthy subjects when all brain areas were combined. This finding remained true in medicated and non-medicated patients, and in frontal brain areas in adults. There was a non-significant trend (p = 0.09) for an increase in whole-brain Glx/Cr and Glu in patients compared with healthy subjects. No significant difference was found in Glu/Cr. CONCLUSIONS: The results of this meta-analysis suggest that brain Glx levels are elevated in BD patients and support the idea that glutamate might play an important role in the pathophysiology of BD.

Long-acting injectable antipsychotics for the maintenance treatment of bipolar disorder.

Depot antipsychotics have been used as a strategy to reduce non-adherence to medications in schizophrenia and bipolar disorder (BD). This article reviews the literature on the efficacy and safety of first- and second-generation depot antipsychotics (FGDA and SGDA, respectively) for the maintenance treatment of BD. Although FGDA have been studied in BD, they have not been approved for use in this disease. Among the SGDA, only depot risperidone has been studied and approved for the maintenance treatment of BD. We found eight studies on FGDA (three on flupenthixol, two on depot haloperidol, one on fluphenazine and flupenthixol, two on a mix of diverse antipsychotics) and ten studies on SGDA (all on depot risperidone). Differences in efficacy and safety were found between the two classes of depot antipsychotics. Although FGDA may be effective in reducing manic relapses, they possibly increase the risk of worsening depression. Depot risperidone is effective as a maintenance treatment in BD with effect noted predominantly for preventing mania. However, no worsening in depression was observed. Depot risperidone also is better tolerated than FGDA, mainly in relation to extrapyramidal symptoms. Studies with the new depot antipsychotics, olanzapine pamoate and paliperidone palmitate, are needed in BD patients. Further, there is currently little information on the metabolic changes (apart from bodyweight gain) that may occur with the use of depot risperidone in patients with bipolar disorder, and this issue needs further investigation.

Morphometric post-mortem studies in bipolar disorder: possible association with oxidative stress and apoptosis.

Despite extensive research in the last decades, the pathophysiology of bipolar disorder (BD) remains unclear. Access to post-mortem brain tissue of subjects who had BD offers an opportunity to investigate neurobiology and this approach has led to some progress, particularly, due to the availability of more sophisticated molecular and cellular biological methodologies and well characterized brain collections over the past decade. Here we review the findings of morphometric post-mortem studies in BD and interpret them in the context of a potential physiopathological mechanism involving oxidative stress and apoptosis. A review of the literature was conducted to identify post-mortem studies that investigated cellular changes such as number, density and size of neurons and glia, in brains of subjects with BD. We found decreased density of neurons and glia and decreased size of neurons in frontal and subcortical areas of the brain. Based on recent studies that found evidence of increased apoptosis and oxidative stress in BD, we hypothesize that the cell abnormalities described are due to an increase in the apoptotic process that can be triggered, through its intrinsic pathway, by the existence of an exacerbated production of reactive oxygen species and oxidative damage in the disease.

Insight into schizophrenia: a comparative study between patients and family members

CONTEXTO: A despeito do reconhecimento da importância de fatores socioculturais na crítica da doença, a literatura recente sobre esse tema é escassa. OBJETIVOS: 1) traduzir e adaptar o Schedule for Assessment of Insight (SAI) para a língua portuguesa; 2) utilizar uma versão modificada deste instrumento para avaliar a crítica dos familiares em relação à esquizofrenia; 3) comparar a crítica dos pacientes com a de seus familiares. TIPO DE ESTUDO: Estudo transversal. LOCAL DO ESTUDO: Ambulatório do Projeto Esquizofrenia do Instituto de Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (Projesq). MÉTODOS: 40 pacientes com diagnóstico de esquizofrenia (Manual Diagnóstico e Estatístico de Transtornos Mentais - Quarta edição - DSM-IV) em tratamento ambulatorial e seus respectivos familiares foram entrevistados pela SAI e por uma versão modificada deste instrumento respectivamente. RESULTADOS: Os familiares apresentaram melhores notas que os pacientes nas avaliações parciais e total da SAI [total 13,0 e 8,75 (p < 0,001); aderência 3,9 e 3,4 (p < 0,005); reco-nhecimento da doença 5,5 e 3,5 (p < 0,001); reconhecimento dos fenômenos psicóticos 3,6 e 1,9 (p < 0,001)]. No entanto, quando as notas foram correlacionadas entre cada par paciente-familiar, a única nota parcial que teve uma correlação negativa foi o reconhecimento correto dos fenômenos psicóticos (r = -0,14), enquanto os outros tiveram correlações positivas (total r = 0,401; aderência r = 0,410; reconhecimento da doença r = 0,422). DISCUSSAO: Não houve correlação entre as notas dos familiares e dos pacientes na habilidade de reconhecer os sintomas psicóticos como anormais. Isso pode ser entendido como uma menor influência dos fatores socioculturais nesta dimensão. A presença de características psicopatológicas e neuropsicológicas nos familiares pode ter influenciado estes resultados. O fato de os familiares não terem sido avaliados para estes déficits é uma limitação deste estudo. CONCLUSAO: Diferentes dimensões da crítica da doença não são igualmente influenciadas pela doença e fatores socioculturais. O reconhecimento da doença parece sofrer maior influência dos fatores socioculturais que o componente reconhecimento correto dos fenômenos psicóticos.

Insight into schizophrenia: a comparative study between patients and family members.

CONTEXT: Despite the recognition of the role that sociocultural factors play in the process of acquiring insight, recent research on this issue is scarce. OBJECTIVES: 1) to translate and adapt the Schedule for Assessment of Insight (SAI) to Portuguese; 2) to use a modified version of it to evaluate family members' insight into schizophrenia; 3) to compare patients' insight with family members' insight. TYPE OF STUDY: Cross-sectional study. SETTING: Schizophrenia Project Outpatient Clinic (Projesq), Institute of Psychiatry, Faculdade de Medicina da Universidade de São Paulo. METHODS: 40 patients with schizophrenia (Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition-DSM-IV) undergoing outpatient treatment and members of their respective families were interviewed using the SAI and a modified version of this instrument, respectively. RESULTS: Family members performed better than patients in the total and partial SAI scores [total: 13.0 to 8.75 (p < 0.001); adherence: 3.9 to 3.4 (p < 0.005); recognition of illness: 5.5 to 3.5 (p < 0.001); relabeling of psychotic phenomena: 3.6 to 1.9 (p < 0.001)]. However, when the scores were correlated for each patient-family member pair, the only partial score that had a negative correlation was the relabeling of psychotic phenomena (r = -0.14), while the others had positive correlations (total r = 0.401; adherence r = 0.410; recognition of illness r = 0.422). DISCUSSION: There was a lack of correlation between the scores of family members and patients regarding the ability to relabel psychotic phenomena as abnormal. This might be understood as a smaller influence of sociocultural factors in this dimension than in other dimensions. The fact that family members were not assessed for the presence of psychopathology is a limitation of this study. CONCLUSIONS: Different dimensions of insight are not equally influenced by disease and sociocultural factors. The recognition of illness is more strongly influenced by sociocultural factors than the ability to relabel psychotic phenomena as abnormal.