Neurochemical differences between bipolar disorder type I and II in superior temporal cortices: A proton magnetic resonance spectroscopy study.

BACKGROUND: Despite the diagnostic challenges in categorizing bipolar disorder subtypes, bipolar I and II disorders (BD-I and BD-II respectively) are valid indices for researchers. Subtle neurobiological differences may underlie clinical differences between mood disorder subtypes. The aims of this study were to investigate neurochemical differences between bipolar disorder subtypes. METHODS: Euthymic BD-II patients (n = 21) are compared with BD-I (n = 28) and healthy comparison subjects (HCs, n = 30). Magnetic Resonance Imaging (MRI) and proton spectroscopy (1H MRS) were performed on a 3T Siemens Tim Trio system. MRS voxels were located in the left/right superior temporal cortices, and spectra acquired with the single voxel Point REsolved Spectroscopy Sequence (PRESS). The spectroscopic data were analyzed with LCModel (Version 6.3.0) software. RESULTS: There were significant differences between groups in terms of glutamate [F = 6.27, p = 0.003], glutamate + glutamine [F = 6.08, p = 0.004], inositol containing compounds (Ino) (F = 9.25, p < 0.001), NAA [F = 7.63, p = 0.001] and creatine + phosphocreatine [F = 11.06, p < 0.001] in the left hemisphere and Ino [F = 5.65, p = 0.005] in the right hemisphere. Post-hoc comparisons showed that the BD-I disorder group had significantly lower metabolite levels in comparison to the BD-II and the HC groups. LIMITATIONS: This was a cross-sectional study with a small sample size. In addition, patients were on various psychotropic medications, which may have impacted the results. CONCLUSIONS: Neurochemical levels, in the superior temporal cortices, measured with 1H-MRS discriminated between BD-II and BD-I. Although further studies are needed, one may speculate that the superior temporal cortices (particularly left hemispheric) play a critical role, whose pathology may be related to subtyping bipolar disorder.

Increased oxidative stress in the mitochondria isolated from lymphocytes of bipolar disorder patients during depressive episodes.

The present study aims to investigate the oxidative stress parameters in isolated mitochondria, as well as looking at mitochondrial complex activity in patients with Bipolar Disorder (BD) during depressive or euthymic episodes. This study evaluated the levels of mitochondrial complex (I, II, II-III and IV) activity in lymphocytes from BD patients. We evaluated the following oxidative stress parameters: superoxide, thiobarbituric acid reactive species (TBARS) and carbonyl levels in submitochondrial particles of lymphocytes from bipolar patients. 51 bipolar patients were recruited into this study: 34 in the euthymic phase, and 17 in the depressive phase. Our results indicated that the depressive phase could increase the levels of mitochondrial superoxide, carbonyl and TBARS, and superoxide dismutase, and could decrease the levels of mitochondrial complex II activity in the lymphocytes of bipolar patients. It was also observed that there was a negative correlation between the Hamilton Depression Rating Scale (HDRS) and complex II activity in the lymphocytes of depressive bipolar patients. In addition, there was a positive correlation between HDRS and superoxide, superoxide dismutase, TBARS and carbonyl. Additionally, there was a negative correlation between complex II activity and oxidative stress parameters. In conclusion, our results suggest that mitochondrial oxidative stress and mitochondrial complex II dysfunction play important roles in the depressive phase of BD.

Biochemical abnormalities in basal ganglia and executive dysfunction in acute- and euthymic-episode patients with bipolar disorder: A proton magnetic resonance spectroscopy study.

BACKGROUND: Recent studies found abnormal biochemical metabolism and executive cognitive deficits in acute bipolar disorder (BD). However, the evidence concerning in euthymic BD is limited. Thus, a comparison between acute and euthymic BD is conductive to better understanding the association between cognition and the outcome of neuroimaging. This study sought to investigate the relationship between the executive function and the biochemical metabolism in acute- and euthymic-episode BD patients and delineate the prominent endophenotype of BD. METHODS: Three groups of participants were recruited in this study: 30 BD patients with an acute depressive episode, 22 euthymic BD patients, and 31 healthy controls. All participants were interviewed using the Structured Clinical Interview for DSM-IV, and underwent two-dimensional multivoxel proton magnetic resonance spectroscopy (1H-MRS) to obtain the bilateral metabolite levels in the lenticular nucleus of basal ganglia(BG). The ratios of N-acetylaspartate (NAA)/creatine (Cr) and Choline-containing compounds (Cho) /Cr ratios were calculated. Executive function was assessed by using the Wisconsin Card Sorting Test (WCST) and Trail Making Test, Part-B(TMT-B). RESULTS: The comparison of biochemical changes showed that the NAA/Cr ratios in bilateral lenticular nucleus in both acute and euthymic BD patients was significantly lower than that in healthy controls at a confidence level of p<0.05. In the comparison of executive function, both acute and euthymic BD patients showed significantly decreased numbers of categories completed, and increased numbers of total errors, perseverative and noperseverative errors, and TMT-B uptake compared to the healthy controls at a confidence level of p<0.05. There were no significant differences between the acute BD and euthymic BD groups in the biochemical metabolite ratios and executive function. We found that the NAA/Cr ratio in the left in BG in the acute -episode BD patients was positively correlated with the number of categories completed, whereas it was negatively correlated with the total errors and TMT-B uptake. There was no correlation between the NAA/Cr and Cho/Cr ratios in the bilateral BG and the scores of SWCT and TMT-B in euthymic-episode BD patients. LIMITATION: The sample size was relatively small and not all the euthymic-episode patients are the ones with an acute episode. CONCLUSIONS: Our findings suggest that biochemical abnormalities in the lenticular nucleus and the executive dysfunction may occur early in the course of BD, and persist during remission, and are the most likely markers of endophenotypes of BD. The dysfunction of the neuronal function in the lenticular nucleus may be correlated with the cold dysfunction in patients with acute BD.

Depressive, anxiety and hypomanic symptoms in schizophrenia may be driven by tryptophan catabolite (TRYCAT) patterning of IgA and IgM responses directed to TRYCATs.

The aim of this study was to delineate the associations between the tryptophan catabolite (TRYCAT) pathway and affective symptoms in schizophrenia. Towards this end we measured immunoglobulin (Ig)A and IgM responses to relatively noxious TRYCATs, namely quinolinic (QA), xanthurenic (XA), picolinic (PA) acid and 3-OH-kynurenine (3HK), and generally protective TRYCATs, namely anthranilic (AA) and kynurenic (KA) acid in 80 patients with schizophrenia and 40 healthy controls. The Hamilton Rating Scale for Depression (HDRS) and anxiety (HAMA), Young Mania Rating Scale (YMRS) as well as the Positive and Negative Symptoms Scale of Schizophrenia (PANSS) were measured. Depression, anxiety and hypomanic as well as negative and positive symptoms were associated with increased IgA responses to PA. Increased IgA responses to XA were associated with anxiety, hypomanic and negative symptoms. Moreover, depressive, anxiety, hypomanic and negative symptoms were characterized by increased IgA responses to the noxious (XA+3HK+QA+PA)/protective (AA+KA) TRYCAT ratio. All symptom dimensions were associated with increased IgM responses to QA, while depressive, anxiety, positive and negative symptoms were accompanied by lowered IgM responses to 3HK. Hypomanic symptoms were additionally accompanied by lowered IgM responses to AA, and negative symptoms by increased IgM responses to KA. In conclusion, both shared and distinct alterations in the activity of the TRYCAT pathway, as well as its regulatory factors and consequences, may underpin affective and classical psychotic symptoms of schizophrenia. Increased mucosa-generated production of noxious TRYCATs, especially PA, and specific changes in IgM-mediated regulatory activities may be associated with the different symptom dimensions of schizophrenia.

Cyclothymic temperament and glucose metabolism in the right superior parietal lobule.

Cyclothymic temperament possesses a central dimension that includes rapid fluctuations in mood and emotional instability, and it is regarded as a prodromal state of bipolar disorder. The aim of the present study is to explore the neural correlates of cyclothymic temperament. We used the data of 55 healthy participants in our previous study and analyzed the association between cyclothymic temperament scores rated by the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire (TEMPS-A) and the uptake of [18F]-FDG measured by positron emission tomography (PET). A whole brain analysis revealed a cluster of [18F]-FDG uptake significantly and positively associated with cyclothymic temperament scores, located in the right superior parietal lobule (SPL). Even after adjustment for relevant factors, there remained a significant cluster of [18F]-FDG uptake with cyclothymic temperament scores in the right SPL. In ROI analyses, there were similar significant peaks in the right SPL in association with cyclothymic temperament scores. These findings suggest that the right superior parietal lobule may be one of the neural correlates of cyclothymic temperament.

Peripheral markers of oxidative stress and antioxidative defense in euthymia of bipolar disorder--Gender and obesity effects.

INTRODUCTION: Oxidative and nitrosative stress are implicated in the pathogenesis of uni- and bipolar disorder. Herein we primarily sought to characterize markers of oxidative/nitrosative stress during euthymia in adults with bipolar disorder (BD). Oxidative markers were further evaluated in this BD sample in synopsis with excess overweight or obesity and/or comorbid metabolic syndrome (MetS). METHODS: Peripheral markers of oxidative stress [i.e. thiobarbituric acid reactive substance, (TBARS), malondialdehyde (MDA), and carbonyl proteins] and antioxidant markers [e.g. total antioxidative capacity (TAC), superoxide dismutase (SOD), glutathione S-transferase (GST)] were obtained in a cohort of euthymic adults with BD (N=113) and compared to healthy controls (CG) (N=78). Additionally, anthropometric measures included the body mass index (BMI) [kg/m(2)], waist and hip circumference [cm], waist-to-hip-ratio (WHR), waist to height ratio (WtHR) as well as the IDF-defined MetS. RESULTS: The major finding was a significantly decreased TAC in BD compared to the CG (p<0.01; BD: M 1.18, SD 0.47; CG: M 1.39, SD 0.49). MDA was significantly and TBARS by trend higher in the CG compared to the euthymic bipolar test persons (MDA: p<0.01, BD: M 0.70, SD 0.18; CG: M 0.81, SD 0.25; TBARS: p<0.1, BD: M 0.78, SD 0.28; CG: M 0.76, SD 0.30). The antioxidative enzyme GST was significantly elevated in both patients and controls (BD: M 298.24, SD 133.02; CG: M 307.27 SD 118.18). Subgroup analysis revealed that the CG with concurrent MetS and obesity had significantly elevated TAC when compared to CG without concurrent MetS (p<0.05, no MetS: M 1.33, SD 0.50; MetS: M 1.67, SD 0.32), as well as persons with BD with or without current MetS (no MetS: M 1.18, SD 0.44; MetS: M 1.15, SD 0.49). Significant correlations between GST and anthropometric variables were found in male study participants. Multivariate analysis indicated a significant gender effect concerning TBARS values in all patients and CG (p<0.01, females: M 0.73, SD 0.29; males: M 0.83, SD 0.28). CONCLUSION: Euthymic bipolar adults exhibit peripheral evidence of a disturbed biosignature of oxidative stress and antioxidative defense. Male test persons showed significantly higher peripheral markers of oxidative stress than women- female sex may exert protective effects. Furthermore, the biosignature of oxidative stress obtained herein was more pronounced in males with concurrent metabolic disorders. Our results further extend knowledge by introducing the moderating influence of gender and obesity on oxidative stress and BD.

Biological aspect of hyperthymic temperament: light, sleep, and serotonin.

RATIONALE: Hyperthymic temperament is one of several premorbid temperaments putatively associated with bipolar disorder. Several reports suggest that depressive patients with hyperthymic temperament may belong to the proposed soft bipolar spectrum. OBJECTIVES: To investigate biological aspects of hyperthymic temperament, the present study examined daily activity, sleep time, central serotonergic function, and other relevant variables in relation to hyperthymic temperament in healthy subjects. METHODS: Fifty six healthy subjects were monitored via the actigraphy system to measure daily total activity, sleep time, and illuminance. A neuroendocrine challenge test was performed to estimate central serotonergic function. RESULTS: Multiple regression analysis revealed that higher illuminance of daytime, greater fluctuation in sleep time, and lower central serotonergic function significantly and independently predicted hyperthymic temperament scores. CONCLUSIONS: The present findings suggest that light, sleep, and serotonin are crucial factors in understanding hyperthymic temperament, which may be common to bipolar disorder.