Alexandre Duarte Gigante

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

Gigante AD, Bond DJ, Lafer B, Lam RW, Young LT, Yatham LN. Brain glutamate levels measured by magnetic resonance spectroscopy in patients with bipolar disorder: a meta‐analysis. Bipolar Disord 2012: 14: 478–487.

Brain glutamate levels measured by magnetic resonance spectroscopy in patients with bipolar disorder

Gigante AD, Bond DJ, Lafer B, Lam RW, Young LT, Yatham LN. Brain glutamate levels measured by magnetic resonance spectroscopy in patients with bipolar disorder: a meta‐analysis. Bipolar Disord 2012: 14: 478–487.

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.

Decreased mRNA expression of uncoupling protein 2, a mitochondrial proton transporter, in post-mortem prefrontal cortex from patients with bipolar disorder and schizophrenia.

Although the neurobiological basis of bipolar disorder (BD) remains unknown, mitochondrial dysfunction, oxidative stress and oxidative cell damage have been identified in this disease. Uncoupling proteins (UCP) are proton carriers located in the inner membrane of the mitochondria involved in controlling the production of mitochondrial reactive oxygen species (ROS). Therefore, in this study we wished to investigate the involvement of UCP in BD. We analyzed the RNA and protein levels of UCP2 in the dorsolateral prefrontal cortex (DLPFC) of subjects with BD and schizophrenia (SCZ) and assessed the potential relationship between the antioxidant superoxide dismutase (SOD1 and SOD2) and UCP2 in the same region. Our results showed a downregulation of UCP2 mRNA levels in the DLPFC of subjects with BD and SCZ. There were no differences in UCP2 protein, SOD1 and SOD2 levels between patients and controls. Although more studies are necessary, our results suggest that UCP2 is not been used as a compensatory mechanism to oppose the higher levels of oxidative stress found in BD and SCZ.

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 halo-peridol, 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.

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.

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

Abstract 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 (1H-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 1H-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.

Psychiatric and clinical correlates of rapid cycling bipolar disorder: a cross-sectional study

Objective: Rapid cycling (RC) is a feature of bipolar disorder (BD) that has been associated with worse outcome and more severe disability. Our goal was to investigate the association of demographic and clinical factors with RC. Methods: We compared RC and non-rapid cycling (NRC) BD patients from the Brazilian Research Network in Bipolar Disorder (BRN-BD) regarding age at onset of BD; total number of episodes; previous number of manic, depressive, mixed, and hypomanic episodes; polarity of the first episode; gender; number of suicide attempts; number of lifetime hospitalizations and lifetime history of at least one hospitalization; family history of mood disorder; clinical comorbidities such as hypothyroidism, hyperthyroidism, seizures; and current use of medications such as lithium, anticonvulsants, antipsychotics, and antidepressants. Results: We studied 577 patients and found that 100 (17.3%) met the criteria for RC in the year before the investigation. RC patients had earlier age at onset, longer duration of disease, more lifetime depressive and manic episodes, higher number of suicide attempts, and higher rate antidepressant use. Conclusion: The presence of RC in the previous year was associated with specific clinical characteristics closely related to worse outcome in the course of BD.

Rapid cycling bipolar disorder is associated with a higher lifetime prevalence of migraine.

of 2.7 – one that does differ clearly from the 1.9 ratio quantified by Wakefield for all 46 symptoms. Specificity and differentiation are now observed, seemingly annulling Wakefield’s ‘disconfirmation’ charge. While we interpret our LCA as differentiating depressive disease (i.e. bipolar and unipolar melancholia) from residual non-melancholic and normative mood states, Wakefield seeks to interpret our data according to an alternative binary model (i.e. complicated patho-suggestive vs. general-distress symptom types) and claims that his analyses of our data more confirm his hypothesis. We suggest that readers might make their own judgments about how best to interpret the issues and domains under examination. In conclusion, we thank Wakefield for his spirited interest and in adding another challenge to DSM-5’s criteria for melancholia. G. Parker and D. Hadzi-Pavlovic School of Psychiatry, University of NSW, Sydney, NSW and Black Dog Institute, Sydney, NSW, Australia E-mail: g.parker@unsw.edu.au