Male Bipolar Disorder Research Articles

Alterations in pituitary adenylate cyclase-activating polypeptide in major depressive disorder, bipolar disorder, and comorbid depression in Alzheimer's disease in the human hypothalamus and prefrontal cortex.

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) is involved in the stress response and may play a key role in mood disorders, but no information is available on PACAP for the human brain in relation to mood disorders. PACAP-peptide levels were determined in a major stress-response site, the hypothalamic paraventricular nucleus (PVN), of people with major depressive disorder (MDD), bipolar disorder (BD) and of a unique cohort of Alzheimer's disease (AD) patients with and without depression, all with matched controls. The expression of PACAP-(Adcyap1mRNA) and PACAP-receptors was determined in the MDD and BD patients by qPCR in presumed target sites of PACAP in stress-related disorders, the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). PACAP cell bodies and/or fibres were localised throughout the hypothalamus with differences between immunocytochemistry and in situ hybridisation. In the controls, PACAP-immunoreactivity-(ir) in the PVN was higher in women than in men. PVN-PACAP-ir was higher in male BD compared to the matched male controls. In all AD patients, the PVN-PACAP-ir was lower compared to the controls, but higher in AD depressed patients compared to those without depression. There was a significant positive correlation between the Cornell depression score and PVN-PACAP-ir in all AD patients combined. In the ACC and DLPFC, alterations in mRNA expression of PACAP and its receptors were associated with mood disorders in a differential way depending on the type of mood disorder, suicide, and psychotic features. The results support the possibility that PACAP plays a role in mood disorder pathophysiology.

Different oxytocin and corticotropin-releasing hormone system changes in bipolar disorder and major depressive disorder patients.

SummaryBackgroundOxytocin (OXT) and corticotropin-releasing hormone (CRH) are both produced in hypothalamic paraventricular nucleus (PVN). Central CRH may cause depression-like symptoms, while peripheral higher OXT plasma levels were proposed to be a trait marker for bipolar disorder (BD). We aimed to investigate differential OXT and CRH expression in the PVN and their receptors in prefrontal cortex of major depressive disorder (MDD) and BD patients. In addition, we investigated mood-related changes by stimulating PVN-OXT in mice.MethodsQuantitative immunocytochemistry and in situ hybridization were performed in the PVN for OXT and CRH on 6 BD and 6 BD-controls, 9 MDD and 9 MDD-controls. mRNA expressions of their receptors (OXTR, CRHR1 and CRHR2) were determined in anterior cingulate cortex and dorsolateral prefrontal cortex (DLPFC) of 30 BD and 34 BD-controls, and 24 MDD and 12 MDD-controls. PVN of 41 OXT-cre mice was short- or long-term activated by chemogenetics, and mood-related behavior was compared with 26 controls.FindingsSignificantly increased OXT-immunoreactivity (ir), OXT-mRNA in PVN and increased OXTR-mRNA in DLPFC, together with increased ratios of OXT-ir/CRH-ir and OXTR-mRNA/CRHR-mRNA were observed in BD, at least in male BD patients, but not in MDD patients. PVN-OXT stimulation induced depression-like behaviors in male mice, and mixed depression/mania-like behaviors in female mice in a time-dependent way.InterpretationIncreased PVN-OXT and DLPFC-OXTR expression are characteristic for BD, at least for male BD patients. Stimulation of PVN-OXT neurons induced mood changes in mice, in a pattern different from BD.Funding10.13039/501100001809National Natural Science Foundation of China (81971268, 82101592).

Downregulation of long non-coding RNAs in patients with bipolar disorder.

The abnormal function of signaling cascades is currently a candidate in the pathophysiology of bipolar disorder (BD). One of the factors involved in activating these signals is oxidative stress. Some long non-coding RNAs (lncRNA) are involved in the oxidative stress. In this study, we compared expression levels of lincRNA-p21, lincRNA-ROR, and lincRNA-PINT in the peripheral blood mononuclear cells (PBMC) from BD patients (n = 50) and healthy individuals (n = 50). Expression levels of lincRNA-p21, lincRNA-ROR, and lincRNA-PINT were significantly reduced in patients with BD compared to controls. In sex-based analyses, down-regulation of these lncRNAs was revealed only in male BD patients compared to male healthy subjects. Also, in BD patients, all three lncRNAs showed a significant pairwise positive correlation in expression level. The area under curve values for lincRNA-p21, lincRNA-ROR, and lincRNA-PINT was 0.66, 0.75, and 0.66, respectively. Thus, the ROC curve analysis showed that lncRNA-ROR might serve as a diagnostic biomarker for distinguishing between BD patients and controls. Altogether, the current study proposes a role for lincRNA-p21, lincRNA-ROR, and lincRNA-PINT in the pathogenesis of bipolar disorder. Moreover, the peripheral expression of these lncRNAs might be useful as potential biomarkers for BD.

Significant reduction of long non-coding RNAs expression in bipolar disorder

Long non-coding RNAs (lncRNAs) have been recently emerged as critical modulators of oxidative stress pathway. Likewise, rising evidence currently highlights dysfunction of oxidative stress pathways in bipolar disorder (BD) patients.In the current study, we evaluated the expression levels of H19, SCAL1 (LUCAT1), RMST, MEG3 and MT1DP lncRNAs in the PBMC from 50 patients with BD and 50 control subjects (male/female ratio in each group: 70%/30%). Expression levels of SCAL1, RMST and MEG3 but not H19 and MT1DP were considerably decreased in BD patients compared with healthy individuals. Such significant decrease in the expression of MEG3, RMST and SCAL1 was only reported in male BD patients compared with male controls. Substantial pairwise correlations were observed between expression levels of these lncRNAs in BD subjects. The area under curve values for RMST, MEG3 and SCAL1 were 0.70, 0.63 and 0.61 respectively. On the basis of this finding, RMST had the best efficiency in the discrimination of disease status between BD patients and controls. Taken together, the current results suggest a role for MEG3, RMST and SCAL1 lncRNAs in the pathogenesis of BD. In addition, peripheral expression levels of these lncRNAs might serve as potential peripheral markers for BD.

Impulsivity in tramadol dependence and bipolar I disorder patients: a comparative study

Background Tramadol has become widespread in Egypt. Impulsivity is recognized as a factor in the initiation and maintenance of substance use disorders. Moreover, bipolar disorder (BD) is commonly associated with impulsivity. Impulsivity seems to be relatively independent of mood state and is higher in individuals with past history of substance use. So, comparing impulsivity in BD and tramadol dependence is needed to determine if there is any difference. Impulsivity was evaluated by the Barratt Impulsiveness Scale in 30 male patients with BD in partial remission without any comorbid substance use disorder and age-matched 30 male patients with tramadol dependence in partial remission. Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID1), addiction severity index, Young Mania Rating Scale, andEysenck’s Personality Questionnaire were used.Results There was no difference among BD and tramadol dependence groups of patients on subscales attentional and motor impulsivity measures. However, the male tramadol dependence patient group scored higher than the male BD patient group for total and nonplanning impulsivity scores.Conclusion This study found that BD and tramadol dependence patients were similar on attention and motor impulsivity subscales but on the total score and nonplanning subscale, patients with tramadol dependence are more impulsive than patients with BD. Increased tendency to criminal behavior is associated with the increase in total and motor scores of Barratt Impulsiveness Scale in tramadol dependence patients as well as with the total scores of Young Mania Rating Scale in BD patients. Moreover, the severity of mania is correlated with the attentional domain of impulsivity.

Label-free proteomics differences in the dorsolateral prefrontal cortex between bipolar disorder patients with and without psychosis

BackgroundPsychosis is common in bipolar disorder (BD) and is related to more severe cognitive impairments. Since the molecular mechanism of BD psychosis is elusive, we conducted this study to explore the proteomic differences associated with BD psychosis in the dorsolateral prefrontal cortex (DLPFC; BA9). MethodsPostmortem DLPFC gray matter tissues from five pairs of age-matched male BD subjects with and without psychosis history were used. Tissue proteomes were identified and quantified by label-free liquid chromatography tandem mass spectrometry and then compared between groups. Statistical significance was set at q < 0.40 and Log2 fold change (Log2FC) ≥ |1|. Protein groups with differential expression between groups at p < 0.05 were subjected to pathway analysis. ResultsEleven protein groups differed significantly between groups, including the reduction of tenascin C (q = 0.005, Log2FC = −1.78), the elevations of synaptoporin (q = 0.235, Log2FC = 1.17) and brain-specific angiogenesis inhibitor 1-associated protein 3 (q = 0.241, Log2FC = 2.10) in BD with psychosis. The between-group differences of these proteins were confirmed by Western blots. The top enriched pathways (p < 0.05 with ≥ 3 hits) were the outgrowth of neurons, neuronal cell proliferation, growth of neurites, and outgrowth of neurites, which were all predicted to be upregulated in BD with psychosis. LimitationsSmall sample size and uncertain relationships of the observed proteomic differences with illness stage and acute psychosis. ConclusionsThese results suggested BD with psychosis history may be associated with abnormalities in neurodevelopment, neuroplasticity, neurotransmission, and neuromodulation in the DLPFC.

Oxidative Status in Bipolar Disorder (BD) and Its Correlation with Age, Gender and Body Mass Index (BMI)

Bipolar disorder (BD) is a chronic psychiatric illness which molecular foundations have yet to be elucidated. Oxidative stress appears to be a promising field of study to understand the formation of this disease in molecular level. The objective was to investigate the oxidative status of BD and its association with age, gender and body mass index (BMI). A cross-sectional study was conducted in a tertiary university hospital in Cheras, Malaysia on 55 patients with BD diagnosed using Mini Neuropsychiatric Interview (MINI). Peripheral markers of oxidative stress which include superoxide dismutase (SOD), glutathione peroxidise (GPx), catalase (CAT), malondialdehyde (MDA) and DNA damage were examined in subjects with BD (n=55) and compared to healthy controls (n=28). BD patients had significantly higher concentrations of MDA compared to healthy controls (p<0.001). Concentration of MDA was significantly higher in BD patients aged 40 and above compared to those aged 39 years and below (p<0.05). The concentration of MDA did not show significant difference between male and female BD patients, likewise between patients with BMI below and above 25. The percentage of normal DNA in healthy controls was significantly higher than that of BD patients (p<0.001), while percentage of mildly and severely damaged DNA in BD patients was significantly higher than that of healthy controls (mildly damaged: p<0.001; severely damaged: p<0.001). The severity of DNA damage in the BD patients was similar when compared between age, gender and BMI. SOD activity of BD patients was found to be comparable to that of healthy subjects as well as when compared between gender and age, but was significantly lower in subjects with BMI above 25 (p<0.05). CAT activity was significantly higher in BD patients compared to controls (p<0.001), while no significant difference was found when compared between gender, age and BMI. GPx activity did not show significant difference when compared between BD and healthy controls, gender, age and BMI. Multiple linear regression analysis showed that the percentage of normal DNA increases with age in BD patients (p<0.001), while the percentage of damaged DNA decreases with age (mildly damaged: p<0.002; severely damaged: p<0.001). Percentage of normal and damaged DNA are not significantly correlated with BMI, while all antioxidative enzymes (SOD, GPx, CAT) and MDA concentration did not show significant correlation with age and BMI. In conclusion, age and BMI are associated with the oxidative status of BD patients regardless of gender.

Risk of obstructive sleep apnea in patients with bipolar disorder: A nationwide population-based cohort study in Taiwan.

Previous studies have found a high prevalence of risk factors for obstructive sleep apnea (OSA) in patients with bipolar disorder (BD). This study aimed to determine whether BD patients are associated with an increased risk of incident OSA. Using the National Health Insurance Research Database of Taiwan, 3650 BD patients and 18 250 non-BD controls matched by sex and age were enrolled between 2000 and 2010 and followed until the end of 2013. Patients who developed OSA confirmed by a polysomnographic examination during the follow-up period were identified. Cox regression analysis was performed to examine the risk of OSA between BD patients and comparative controls. BD patients were prone to developing OSA in the crude analysis (hazard ratio [HR]: 1.63, 95% confidence interval [CI]: 1.07-2.49). After adjusting for demographics and comorbidities, the HR declined and was only marginally significant (HR: 1.54, 95%CI: 0.99-2.37). The stratification analysis by sex revealed that the risk trend with BD and subsequent OSA was mainly contributed by male BD patients (HR: 1.72, 95%CI: 1.02-2.91) and female BD patients weakened the overall association. Additionally, this study found that older age, higher income, living in urbanized areas, and some metabolic comorbidities were potential risk factors for developing OSA. This study shows that male BD patients are associated with an increased risk of OSA, which has direct implications for the development of targeted prevention interventions or the implementation of a screening algorithm for OSA to reduce its negative health impact.

Sensorimotor Gating in Depressed and Euthymic Patients with Bipolar Disorder: Analysis on Prepulse Inhibition of Acoustic Startle Response Stratified by Gender and State.

Prepulse inhibition (PPI) of the acoustic startle reflex is an operational measure of sensorimotor gating. The findings on PPI deficits in bipolar disorder (BD) are inconsistent among studies due to various confounding factors such as gender. This study aimed to assess sensorimotor gating deficits in patients with BD stratified by gender and state (depressed/euthymic), and to explore related clinical variables. Subjects were 106 non-manic BD patients (26 BD I and 80 BD II; 63 with depression and 43 euthymic) and 232 age-, gender-, and ethnicity-matched (Japanese) healthy controls. Depression severity was assessed using the Hamilton Depression Rating Scale-21. The electromyographic activity of the orbicularis oculi muscle was measured by a computerized startle reflex test unit. Startle magnitude, habituation, and PPI were compared among the three clinical groups: depressed BD, euthymic BD, and healthy controls. In a second analysis, patients were divided into four groups using the quartile PPI levels of controls of each gender, and a ratio of the low-PPI group (<1st quartile of controls) was compared. Effects of psychosis and medication status were examined by the Mann-Whitney U test. Clinical correlates such as medication dosage and depression severity with startle measurements were examined by Spearman's correlation. Male patients with depression, but not euthymic male patients, showed significantly lower PPI at a prepulse of 86 dB and 120 ms lead interval than did male controls. More than half of the male patients with depression showed low-PPI. In contrast, PPI in female patients did not differ from that in female controls in either the depressed or euthymic state. Female patients with active psychosis showed significantly lower PPI than those without psychosis. Female patients on typical antipsychotics had significantly lower PPI, than those without such medication. PPI showed a significant positive correlation with lamotrigine dosage in male patients and lithium dosage in female patients. These findings suggest that sensorimotor gating is impaired in male BD patients with depression. However, we obtained no evidence for such abnormalities in female BD patients except for those with current psychosis. The observed associations between medication and startle measurements warrant further investigation.

Cingulate abnormalities in bipolar disorder relate to gender and outcome: a region-based morphometry study [corrected

Structural magnetic resonance imaging (MRI) studies reported gray matter (GM) loss in bipolar disorder (BD) in cingulate cortices, key regions subserving emotional regulation and cognitive functions in humans. The aim of this study was to further explore cingulate GM volumes in a sizeable group of BD patients with respect to healthy controls, particularly investigating the impact of gender and clinical variables. 39 BD patients (mean Age = 48.6 ±9.7, 15 males and 24 females) and 39 demographically matched healthy subjects (mean Age = 47.9 ± 9.1, 15 males and 24 females) underwent a 1.5T MRI scan. GM volumes within the cingulate cortex were manually detected, including anterior and posterior regions. BD patients had decreased left anterior cingulate volumes compared with healthy controls (F = 6.7, p = 0.01). Additionally, a significant gender effect was observed, with male patients showing reduced left anterior cingulate cortex (ACC) volumes compared to healthy controls (F = 5.1, p = 0.03). Furthermore, a significant inverse correlation between right ACC volumes and number of hospitalizations were found in the whole group of BD patients (r = -0.51, p = 0.04) and in male BD patients (r = -0.88, p = 0.04). Finally, no statistically significant correlations were observed in female BD patients. Our findings further confirm the putative role of the ACC in the pathophysiology of BD. Interestingly, this study also suggested the presence of gender-specific GM volume reductions in ACC in BD, which may also be associated to poor outcome.

Pituitary gland shrinkage in bipolar disorder: The role of gender

BackgroundHyperactivity of the Hypothalamic-Pituitary-Adrenal Axis (HPAA) has been consistently reported in mood disorders. However, only few studies investigated the Pituitary gland (PG) in Bipolar Disorder (BD) and the results are so far contrasting. Therefore, the aim of this study is to explore the integrity of the PG as well as the role of gender and the impact of clinical measurements on this structure in a sample of BD patients compared to healthy controls (HC). Methods34 BD patients and 41 HC underwent a 1.5 T MRI scan. PG volumes were manually traced for all subjects. Psychiatric symptoms were assessed by means of the Brief Psychiatry Rating Scale, the Hamilton Depression Rating Scale and the Bech Rafaelsen Mania Rating Scale. ResultsWe found decreased PG volumes in BD patients compared to HC (F = 24.9, p < 0.001).Interestingly, after dividing the sample by gender, a significant PG volume decrease was detected only in female BD patients compared to female HC (F = 9.1, p < 0.001), but not in male BD compared to male HC (F = −0.12, p = 0.074). No significant correlations were observed between PG volumes and clinical variables. ConclusionsOur findings suggest that BD patients have decreased PG volumes, probably due to the long-term hyperactivity of the HPAA and to the consequent strengthening of the negative feedback control towards the PG volume itself. This alteration was particularly evident in females, suggesting a role of gender in affecting PG volumes in BD. Finally, the absence of significant correlations between PG volumes and clinical variables further supports that PG disruption is a trait feature of BD, being independent of symptoms severity and duration of treatment.

Atherogenic index of plasma as a cardiovascular risk marker in manic, depressive, and euthymic stages of bipolar disorder.

Individuals with bipolar disorder (BD) frequently suffer from cardiovascular disease (CVD), and it is a leading cause of mortality. Clinicians use routine laboratory tests, including a lipid profile, to predict cardiovascular risk. In addition, a particular lipid ratio, the atherogenic index of plasma (AIP), is a sensitive, new parameter that can be used to assess highrisk groups. To our knowledge, this is the first study evaluating cardiovascular risk via AIP in different stages of BD. The study group consisted of male patients with BD who were in a manic, depressive, or euthymic state, and age- and gender-matched healthy controls. Lipid profiles were analyzed and the AIP parameter of logarithm of triglyceride (TG) / high-density lipoprotein cholesterol (HDLc) was calculated for all of the participants. The significance level was set at p<0.05. A total of 44 BD patients experiencing a manic episode, 35 depressive BD patients, 42 euthymic patients, and 41 healthy controls matched for age, gender, and smoking status were enrolled in the study. The AIP level was significantly different between groups (p=0.009). Pairwise comparisons of the groups revealed that the AIP level of depressive patients was significantly higher than that of the manic, euthymic, and control groups (p=0.013, p=0.048, and p=0.021, respectively). The AIP level was positively correlated with body mass index, waist circumference, metabolic syndrome, total cholesterol, low-density lipoprotein, and triglyceride level, and was negatively correlated with the HDLc level. In this study, male BD patients in a depressive episode demonstrated an increase in cardiovascular risk. The significant correlations between AIP and other conventional cardiovascular risk factors indicate that AIP may be more useful to identify individuals with BD at high risk for CVD than absolute lipid parameters.

Cerebrospinal fluid metabolomics identifies a key role of isocitrate dehydrogenase in bipolar disorder: evidence in support of mitochondrial dysfunction hypothesis.

Although evidence for mitochondrial dysfunction in the pathogenesis of bipolar disorder (BD) has been reported, the precise biological basis remains unknown, hampering the search for novel biomarkers. In this study, we performed metabolomics of cerebrospinal fluid (CSF) from male BD patients (n=54) and age-matched male healthy controls (n=40). Subsequently, post-mortem brain analyses, genetic analyses, metabolomics of CSF samples from rats treated with lithium or valproic acid were also performed. After multivariate logistic regression, isocitric acid (isocitrate) levels were significantly higher in the CSF from BD patients than healthy controls. Furthermore, gene expression of two subtypes (IDH3A and IDH3B) of isocitrate dehydrogenase (IDH) in the dorsolateral prefrontal cortex from BD patients was significantly lower than that of controls, although the expression of other genes including, aconitase (ACO1, ACO2), IDH1, IDH2 and IDH3G, were not altered. Moreover, protein expression of IDH3A in the cerebellum from BD patients was higher than that of controls. Genetic analyses showed that IDH genes (IDH1, IDH2, IDH3A, IDH3B) and ACO genes (ACO1, ACO2) were not associated with BD. Chronic (4 weeks) treatment with lithium or valproic acid in rats did not alter CSF levels of isocitrate, and mRNA levels of Idh3a, Idh3b, Aco1 and Aco2 genes in the rat brain. These findings suggest that abnormality in the metabolism of isocitrate by IDH3A in the mitochondria plays a key role in the pathogenesis of BD, supporting the mitochondrial dysfunction hypothesis of BD. Therefore, IDH3 in the citric acid cycle could potentially be a novel therapeutic target for BD.

Clinical Implications of White Matter Lesions in Overweight Male Individuals with Bipolar Disorder

Cerebral white matter lesions (WML) have been found in normal aging, vascular disease and several neuropsychiatric conditions. Correlations of volumetric measured WML with clinical parameters in men with Bipolar Disorder (BD) have been described in a currently submitted work of our study group. As we try to elucidate common pathways between obesity/metabolic syndrome and BD we reinvestgated our data in the context of obesity. In a cross-sectional study 100 euthymic individuals (52 male, 48 female) with BD were enrolled to undergo brain magnetic resonance imaging using 3T including a FLAIR sequence for volumetric assessment of WML-load using FSL-software. Additionally, clinical characteristics and psychometric measures including Structured Clinical Interview according to DSM-IV were evaluated. Partial correlation analysis (WML-load with lifetime number of manic/depressive episodes) were performed in 4 different groups (male normalweight, male overweight/obese, female normalweight, female overweight/obese) In overweight/obese men only (n=41), the number of manic/hypomanic episodes ( r =0.85 ; p< 0.001) as well as depressive episodes ( r =0.55; p <0.001) correlated positively with WML-load. WML-load strongly correlated with the number of manic episodes in overweight male BD patients, suggesting that overweight men might be more vulnerable to mania in the context of cerebral white matter changes.

Sex-specific urinary biomarkers for diagnosing bipolar disorder.

Sex-based differences are prominent in affective disorders, but there are no biomarkers available to support sex-specific, laboratory-based diagnostics for male and female bipolar disorder (BD) patients. Here, a NMR-based metabonomic approach was used to preliminarily identify sex-specific urinary metabolite biomarkers for diagnosing male and female BD patients. A male-specific biomarker panel consisting of four metabolites (α-hydroxybutyrate, choline, formate, and N-methylnicotinamide) effectively discriminated between male BD and healthy controls (HC) subjects, achieving an area under the receiver operating characteristic curve (AUC) of 0.942. A female-specific biomarkers panel consisting of four metabolites (α-hydroxybutyrate, oxalacetate, acetone, and N-methylnicotinamide) effectively discriminated between female BD and HC subjects, achieving an AUC of 0.909. The male-specific biomarker panel displayed low discriminatory power in the female group, and the female-specific biomarker panel displayed low discriminatory power in the male group. Moreover, several other metabolites showed different trends between male and female BD subjects. These findings suggest that male and female BD patients have distinct biomarker fingerprints and that these two sex-specific biomarker panels may serve as effective diagnostic tools in distinguishing male and female BD patients from their healthy counterparts. Our work may provide a window into the mechanisms underlying the pathoetiology of BD in both men and women.

Are Uric Acid Levels Different from Healthy Subjects in Bipolar Affective Disorder and Schizophrenia?: Relationship Between Clinical Improvement and Episode Severity in Male Patients.

Purinergic system dysfunction has been shown both in patients with bipolar disorder (BD) and those with schizophrenia. The aim of this study was to evaluate whether uric acid levels in male BD patients with manic episode and schizophrenia patients with psychotic relapse differ from healthy male subjects. Secondly to assess whether uric acid levels in both patient groups correlate with episode severity and if a decrease in uric acid levels correlate with clinical improvement. A total of 55 BD patients with manic episode and 59 schizophrenic patients with psychotic relapse were evaluated at baseline and at weeks 1, 2, 3 using the Young Mania Rating Scale (YMRS) and the Positive and Negative Syndrome Scale (PANSS), and their plasma uric acid levels were measured. 60 age-matched healthy males without history of any previous or current psychiatric diagnosis and treatment constituted the control group. In order to determine plasma uric acid levels, blood samples were centrifuged at 3000 × g for 15 minutes, stored at -80°C and measured in milligrams per deciliter. Uric acid levels in both patient groups with manic episode and psychotic relapse were found higher than in healthy controls (f=6.122, p=.027). The difference between repeated measurements of uric acid levels in BD patient group was found to be between baseline and first week measurements (after Bonferroni correction) (p<.001). No correlation was found between YMRS and PANSS scores and uric acid levels at 4 assessment times. Uric acid levels in male BD and schizophrenia patients with manic episode and psychotic relapse were similar with each other, and higher than in healthy males. No correlation was found between uric acid levels and episode severity in both groups. However, for patients with BD, a decrease in uric acid levels between baseline and first week seems to be correlated with clinical improvement.

Association study of LIS1 and TSNAX genes with bipolar disorder in Chinese Han population

To assess the association of neural development-related genes LIS1and TSNAX with bipolar disorder in a Chinese Han population. Three hundred and eight five patients (including 188 males and 197 females) from Guangzhou Brain Hospital with bipolar disorder meeting the Diagnostic and Statistic Manual of Bipolar Disorder (BDI) (Fourth Edition) criteria and 475 healthy controls from the local community were recruited. Ten single nucleotide polymorphisms (SNPs) of the LIS1 and TSNAX genes were genotyped by GoldenGate genotyping assay on an Illumina Beadstation 500 machine. Association analyses of SNPs and haplotypes were performed with Plink 1.07 software. Analysis of the total sample has failed to find any association of SNP or haplotype of the two genes with BDI (P> 0.05). When patients were divided into subgroups with or without psychotic symptom, no significant association of the two genes was found with psychotic BDI or non-psychotic BDI (P> 0.05). No significant association was found between any SNP and haplotype of two genes and female BDI or male BDI, nor were significant association found between age of onset and LIS1 and TSNAX gene polymorphisms. Our results indicated that LIS1 and TSNAX genes are not associated with susceptibility to bipolar I disorder in Chinese Han population.

Auditory-prosodic processing in bipolar disorder; from sensory perception to emotion

ObjectivesAccurate emotion processing is critical to understanding the social world. Despite growing evidence of facial emotion processing impairments in patients with bipolar disorder (BD), comprehensive investigations of emotional prosodic processing is limited. The existing (albeit sparse) literature is inconsistent at best, and confounded by failures to control for the effects of gender or low level sensory-perceptual impairments. The present study sought to address this paucity of research by utilizing a novel behavioural battery to comprehensively investigate the auditory-prosodic profile of BD. MethodsFifty BD patients and 52 healthy controls completed tasks assessing emotional and linguistic prosody, and sensitivity for discriminating tones that deviate in amplitude, duration and pitch. ResultsBD patients were less sensitive than their control counterparts in discriminating amplitude and durational cues but not pitch cues or linguistic prosody. They also demonstrated impaired ability to recognize happy intonations; although this was specific to male's with the disorder. The recognition of happy in the patient group was correlated with pitch and amplitude sensitivity in female patients only. LimitationsThe small sample size of patients after stratification by current mood state prevented us from conducting subgroup comparisons between symptomatic, euthymic and control participants to explicitly examine the effects of mood. ConclusionsOur findings indicate the existence of a female advantage for the processing of emotional prosody in BD, specifically for the processing of happy. Although male BD patients were impaired in their ability to recognize happy prosody, this was unrelated to reduced tone discrimination sensitivity. This study indicates the importance of examining both gender and low order sensory perceptual capacity when examining emotional prosody.

Childhood maltreatment and coping in bipolar disorder.

A personal history of childhood maltreatment has been associated with unfavorable outcomes in bipolar disorder (BD). The impact of early life stressors on the course of BD may be influenced by individual differences in coping skills. The coping construct relies on neurocognitive mechanisms that are usually influenced by childhood maltreatment. The objective of the present study was to verify the association between childhood maltreatment and coping skills in individuals with BD Type 1. Thirty female euthymic outpatients with BD Type 1 were evaluated using the Childhood Trauma Questionnaire and two additional instruments to measure their coping preferences: Ways of Coping Questionnaire (coping strategies) and Brief COPE (coping styles). Reports of physical abuse (B = .64, p < .01) and emotional abuse (B = .44, p = .01) were associated with the use of maladaptive strategies that focused on emotional control. Adaptive strategies and styles of coping, such as focusing on the problem, were chosen less frequently by women who had experienced emotional neglect (B = .53, p < .01) and physical abuse (B = -.48, p < .01) in childhood. The small sample size in the present study prevented subgroup analyses. The sample did not include male BD participants. Our results indicate that early traumatic events may have a long-lasting deleterious influence on coping abilities in female BD patients. Future prospective studies may investigate whether the negative impact of childhood maltreatment over the course of BD is mediated by individual differences in coping abilities.

P.1.e.014 The effects of testosterone on serotonin-1A receptor binding in postmenopausal women

Little is known about the serotonin-1A receptor (5-HT1A) in bipolar depression despite altered 5-HT1A binding in major depressive disorder. Utilizing positron emission tomography (PET) and the radioligand N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide ([Carbonyl-C-11]WAY-100635), 5-HT1A binding was compared between depressed bipolar disorder (BD) and controls.Brain 5-HT1A binding potential (BPF = Bmax/KD, where Bmax = total available receptors, and 1/KD = ligand affinity) was measured in 32 currently depressed, medication-free BD subjects and 47 controls. Participants were genotyped for the 5-HT1A promoter polymorphism C(-1019)G.The bipolar depressed group demonstrated higher 5-HT1A BPF across all regions of interest (ROIs; p = .022). Post hoc analyses indicated that male BD patients had higher 5-HT1A BPF than male controls (p = .025), with higher 5-HT1A BPF found in every region (by 102% in raphe nuclei and 29% to 50% in the forebrain ROIs); whereas, female subgroups did not differ in 5-HT1A BPF (p = .32). Serotonin-1A BPF did not correlate with depression severity. The GG genotype was overrepresented at trend level in the BD group (p = .057). Number of G-allele copies was associated with higher 5-HT1A BPF in raphe (p = .0050), amygdala (p = .022), and hippocampus (p = .041).Higher 5-HT1A BPF in bipolar depressed males suggests higher raphe autoreceptor binding, potentially causing less serotonin release and compensatory upregulation of forebrain postsynaptic 5-HT1A receptors. The raphe effect may be partly genetic. No difference in 5-HT1A BPF between BD and control females may reflect greater effect of prior antidepressant exposure in BD females.