Bipolar Subjects Research Articles

The Huntington's Disease Gene in an Italian Cohort of Patients with Bipolar Disorder.

Huntington's disease (HD) is characterized by motor, cognitive and psychiatric manifestations and caused by an expansion of CAG repeats over 35 triplets on the huntingtin (HTT) gene. However, expansions in the range 27-35 repeats (intermediate allele) can be associated with pathological phenotypes. The onset of HD is conventionally defined by the onset of motor symptoms, but psychiatric disturbances can precede the motor phase by up to twenty years. The aims of the present study are to identify HD patients in the pre-motor phase of the disease among patients diagnosed with bipolar disorders and evaluate any differences between bipolar patients carrying the normal HTT allele and patients with the expanded HTT gene. We assessed the HTT genotype in an Italian cohort of 69 patients who were affected by either type 1 or type 2 bipolar disorder. No patient was found to be a carrier of the pathological HTT allele, but 10% of bipolar subjects carried an intermediate allele. Carriers of the intermediate allele were older at the onset of psychiatric symptoms than non-carriers. The pathological HTT gene was not associated with bipolar disorder, while we found a higher frequency of the intermediate allele among the bipolar population with respect to healthy controls. The identification of this subset of bipolar subjects has implications for the clinical management of patients and their family members and promotes further investigation into possible pathological mechanisms common to both HD and bipolar disorder.

Managing anxiety disorders in bipolar patients

Anxiety disorders are among the main comorbidities encountered in patients with bipolar disease. Numerous clinical and epidemiological studies show an increased prevalence of anxiety pathologies (generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, panic disorder, and post-traumatic stress disorder) in bipolar subjects compared to the frequencies in the general population. Anxiety disorders are not without consequences on the evolutionary course of the mood disorder, including a significant reduction in euthymia time and less sensitivity to conventional medicinal therapies.

Comorbidities of anxiety disorders in bipolar patients: therapeutic complexity

IntroductionNumerous clinical and epidemiological studies show that the rate of comorbidity of anxiety disorders is high in bipolar patients compared to the general population. This is associated with a poorer prognosis, poorer functioning and higher suicidal risk. Anxiety comorbidity should therefore be carefully investigated.ObjectivesOur main objectives are to explore the therapeutic complexity of anxiety disorders in patients with bipolar disorder To investigate the existence of psycho-pathological links and vulnerabilities between bipolar disorder and anxiety disorders.Methodsthrough a clinical vignette and a review of the existing literature on the comorbidity of anxiety disorders and bipolar disorders, and the resulting therapeutic issuesResultsAnxiety comorbidity is quite common in the bipolar population. In the American National Comorbidity Survey (NCS), lifetime comorbidity is close to 90%. Two recent French clinical studies show the existence of at least one anxiety disorder in approximately 25% of bipolar subjects (24% and 27.2%), which will have an impact on the course of the bipolar disorder, with a particular increase in the risk of suicide, hence the importance of adequate treatment. This treatment faces two obstacles: the risk of manic episodes under antidepressants and the risk of dependence on benzodiazepines. Emphasis is also placed on non-drug approaches, including cognitive-behavioural and psycho-educational therapies.ConclusionsAnxiety comorbidity is not without consequence on the evolution of bipolar disorder. Its particularly high prevalence means that it cannot be neglected or ignored in current practice.Disclosure of InterestNone Declared

Mania associated olfactory dysfunction: A comparison between bipolar subjects in mania and remission

ObjectivesThe aim of this study was to assess the olfactory functions of patients with bipolar disorder in manic phase and to compare them to those of bipolar subjects in remission and healthy controls. MethodsWe recruited 96 participants divided in 3 groups: bipolar mania (MB), euthymic bipolar in remission (EB) and healthy controls (HC). All participants underwent an assessment of their olfactory functions using the Sniffin’ sticks threshold and identification tests. Odors' pleasantness, intensity, familiarity and emotion were assessed. All participants were screened for the presence of psychiatric disorder through the MINI questionnaire. Clinical evaluation explored dimensions of mania, depression, anxiety respectively through YMRS, MADRS and STAI scales. Anhedonia was explored through the Chapman physical and social anhedonia questionnaire. ResultsPatients in mania had deficits in identifying positive smells compared to bipolar subjects in remission and to healthy controls (MB < EB < HC; p < 0.001). Hedonic (MB < EB = HC; p < 0.001) and emotional (MB < EB = HC; p < 0.001) ratings of positive smells were lower in patients in manic phase compared to remitted subjects or controls. Mania was associated to higher emotion rating of negative smells compared to remitted subjects and controls (MB > EB = HC; p < 0.001). There was no difference between the 3 groups in the ratings of intensity and familiarity of smells, as well as in the olfactory threshold testing. The 3 groups showed no difference in the identification of negative smells. ConclusionsPatients in manic episodes showed deficits in identifying positive odors. They evaluated these smells as less pleasant and less emotional compared to remitted bipolar subjects and healthy controls. These olfactory dysfunctions may constitute potential indicators of manic state. The persistence of olfactory dysfunction in remission phase (deficit in the olfactory identification of positive odors compared to healthy controls) may constitute a potential trait indicator of bipolarity.

The Co-Existence of Anaemia in Chronic Psychiatric Disorders: A Study at Tertiary Care Hospital

Objective: To study the frequency of anaemia in various chronic psychiatric disorders in an adult population.&#x0D; Study Design: Cross-sectional study.&#x0D; Place and study duration: Creek General Hospital, Karachi Pakistan, from Feb to May 2021.&#x0D; Methodology: Two hundred and six patients were enrolled in the outpatient clinics after informed consent. Adult patients of 18 to 50 years who were clinically diagnosed with a psychiatric disorder by a certified psychiatrist and had no organicity were included in the study. Anaemia was defined as haemoglobin less than 13 gm/dl for males and less than 12 gm/dl in females. The severity of anaemia was classified into mild, moderate and severe according to the haemoglobin range by WHO criteria. The type of anaemia was categorized into microcytic, normocytic and macrocytic according to the value of mean corpuscle volume.&#x0D; Results: The overall frequency of anaemia in patients suffering from psychiatric disorders was 126 (61.2%) out of 206 persons. Among the anaemic, 20 (58.8%) had schizophrenia; depression was present in 35 (63.6%), generalized anxiety disorder in 39 (57.4%), somatoform disorders in 20 (62.5%) and 12 (70.6%) in bipolar subjects. Among those who were anaemic, a normocytic value was found in 28 (13.6%) adults, microcytic in 95 (46.0%) patients and macrocytic in 4 (1.9%). The severity of anaemia among anaemic was highest in the mild group. Sixty-nine males (53.6%) and 89 females (65%) were anaemic. (p=0.078). Anaemia was found highest in the 40-50 years age group.&#x0D; Conclusion: Anaemia was frequently found in adults suffering from chronic psychiatric disorders.

Sleep architecture modifications after double chronotherapy: A case series of bipolar depressed inpatients

The aim of this study is to objectively evaluate sleep architecture changes of depressed bipolar subjects treated with chronoterapeutics. Eleven depressed bipolar inpatients received 3 cycles of Total Sleep Deprivation, followed by daily light therapy sessions for one week. Polysomnography was performed before and after the treatment. Depressive symptoms significantly reduced, and sleep architecture changed with significant differences in N2% and N3% and REM density. Change in N3% was also positively correlated to depressive symptoms reduction. Although, previous studies reported sleep architecture changes after chronoterapeutics in unipolar depression, this is the first study to demonstrate changes also in bipolar depressed subjects.

The AREDOC project and its implications for the definition and measurement of the bipolar disorders: A summary report

Judging that the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) criteria for defining mania/hypomania (and thus bipolar I/II disorders, respectively) would benefit from review, we formed an expert taskforce to derive modified criteria for consideration. The aim of this paper is to summarise the component stages and detail the final recommended criteria. We first sought taskforce members' views on the Diagnostic and Statistical Manual of Mental Disorders criteria and how they might be modified. Next, members recruited patients with a bipolar I or II disorder, and who were asked to judge new definitional options and complete a symptom checklist to determine the most differentiating items. The latter task was also completed by a small comparison group of unipolar depressed patients to determine the mood state items that best differentiate unipolar from bipolar subjects. Subsequent reports overviewed analyses arguing for bipolar I and II as being categorically distinct and generated empirically derived diagnostic criteria. Alternatives to all the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) criteria were generated. Modifications included recognising that impairment is not a necessary criterion, removing hospitalisation as automatically assigning bipolar I status, adding an irritable/angry symptom construct to the symptom list, deleting a mandatory duration period for manic/hypomanic episodes, and requiring a greater number of affirmed symptoms for a bipolar diagnosis to manage the risk of overdiagnosis. Granular symptom criteria were identified by analyses and constructed to assist clinician assessment. A potential bipolar screening measure was developed with analyses showing that it could clearly distinguish bipolar versus unipolar status, whether symptom items were assigned as having equal status or weighted by their quantified diagnostic contribution. While requiring further validation, we suggest that the revised criteria overcome several current Diagnostic and Statistical Manual of Mental Disorders (5th ed.) limitations to defining and differentiating the two bipolar sub-types, while still respecting and preserving the Diagnostic and Statistical Manual of Mental Disorders template. It will be necessary to determine whether the bipolar screening measure has superiority to currently accepted measures.

Increased Asymmetric Perfusion of the Cerebral Cortices and Thalamus Indicates Individuals at Risk for Bipolar Disorder: A Family Cohort Single Photon Emission Computed Tomography Neuroimaging Study.

Bipolar disorder is a significant mental illness affecting over 4 million people in North America and approximately 46 million worldwide. While the onset of bipolar disorder is typically in late adolescence and early adulthood, the correct diagnosis can be delayed for several years. This delay can result in inappropriate pharmaceutical interventions, loss of career or productivity, suicide, family hardship, and unnecessary expense. Moreover, prolonged untreated or inappropriately treated bipolar disorder may cause damage to the brain. Early diagnosis is a critical need to circumvent the damage, suffering, and expense caused by the current delay. Brain perfusion single photon emission computed tomography (SPECT) neuroimaging reveals visual correlates of brain function. Herein, a family cohort all with bipolar disorder is described and their symptoms correlated with findings on the individual SPECT brain scans. The family consisted of two parents and three children (one female). The scans were interpreted by a panel of experts. Then a post hoc region-of-interest (ROI) analysis was conducted on SPECT data normalized to the cerebellum maximum with comparison to similarly normalized data from a normative sample. These findings support two distinct patterns of SPECT perfusion scan changes that can be found in individuals with bipolar disorder. In addition, these findings indicate that SPECT scan findings may be predictive of individual risk for progressing to symptomatic bipolar disorder. While preliminary, the findings in this cohort support the need for larger, diverse cohort studies of bipolar and control subjects to assess the predictive value of these particular SPECT perfusion findings in bipolar disorder.

Factors associated with lifetime suicide attempts in bipolar disorder: results from an Italian nationwide study

The purpose of the present study was to detect demographic and clinical factors associated with lifetime suicide attempts in Bipolar Disorder (BD). A total of 1673 bipolar patients from different psychiatric departments were compared according to the lifetime presence of suicide attempts on demographic/clinical variables. Owing to the large number of variables statistically related to the dependent variable (presence of suicide attempts) at the univariate analyses, preliminary multiple logistic regression analyses were realized. A final multivariable logistic regression was then performed, considering the presence of lifetime suicide attempts as the dependent variable and statistically significant demographic/clinical characteristics as independent variables. The final multivariable logistic regression analysis showed that an earlier age at first contact with psychiatric services (odds ratio [OR] = 0.97, p < 0.01), the presence of psychotic symptoms (OR = 1.56, p < 0.01) or hospitalizations (OR = 1.73, p < 0.01) in the last year, the attribution of symptoms to a psychiatric disorder (no versus yes: OR = 0.71, partly versus yes OR = 0.60, p < 0.01), and the administration of psychoeducation in the last year (OR = 1.49, p < 0.01) were all factors associated with lifetime suicide attempts in patients affected by BD. In addition, female patients resulted to have an increased association with life-long suicidal behavior compared to males (OR: 1.02, p < 0.01). Several clinical factors showed complex associations with lifetime suicide attempts in bipolar patients. These patients, therefore, require strict clinical monitoring for their predisposition to a less symptom stabilization. Future research will have to investigate the best management strategies to improve the prognosis of bipolar subjects presenting suicidal behavior.

Sudden Cognitive Decline in Bipolar Mood Disorder Patient with Underlying Severe Tardive Dyskinesia After the Failure of His Deep Brain Stimulation Device Battery

Bipolar disorder (BD) is a chronic mood disorder associated with multiple comorbidities. Structural and functional abnormalities in these subjects’ brains have been related to cognitive deficits correlated with the severity of the mood symptoms. These deficits are also present in euthymic states, indicating a trait characteristic. Bipolar subjects would risk developing tardive dyskinesia due to being exposed to long periods of antipsychotic treatment. Unfortunately, the presence of tardive dyskinesia is also associated with worsening cognition. One treatment option for severe tardive dyskinesia is deep brain stimulation that has also been implicated with cognitive decline. We present a case of Bipolar disorder with underlying cognitive impairment, who had a deep brain stimulation device inserted for severe tardive dyskinesia. He was admitted to a depressive phase and was noted to have a sudden worsening of cognitive impairment following his deep brain stimulation device battery running low. Possible explanations discussed for this unexpected observation are attributed to a further deterioration of his tardive dyskinesia following the device failure and depressive episode, which causes added pseudo-cognitive deficit signs.

Inferior frontal gyrus seed-based resting-state functional connectivity and sustained attention across manic/hypomanic, euthymic and depressive phases of bipolar disorder

ObjectiveSeed-based resting-state functional connectivity (rs-FC) of inferior frontal gyrus (IFG), as well as sustained attention cognitive deficit are consistently reported to be impaired in bipolar disorders. However, whether these deficits exist across mood states and euthymic state are lacking. We compared rs-FC of IFG and sustained attention of bipolar patients in (hypo) mania, depression and euthymia, with controls. We also explored the interrelationships between clinical, cognitive, and imaging measurements. MethodsParticipants included 110 bipolar subjects: 46 manic/hypomanic, 35 euthymic, and 29 depressed, matched with 41 healthy controls (HCs) underwent structural magnetic resonance imaging (MRI) and resting-state functional MRI scans. Seed-based functional connectivity analyses were performed focused on bilateral IFG seeds. Clinical symptoms and sustained attention function were measured. Stepwise linear regression analysis was conducted to explore predictors of sustained attention measurements. ResultsIncreased rs-FC between right IFG and bilateral frontal pole/superior frontal gyrus, precuneus, and posterior cingulate gyrus, as well as decreased rs-FC between right IFG and sensorimotor areas, anterior middle cingulate gyrus were found in all three bipolar subgroups compared with HCs. Impaired sustained attention measurement was found in bipolar manic/hypomanic and depressive subgroups compared with HCs. Linear regression analyses revealed a significant impact of the manic symptoms and psychotic symptoms on the performance of sustained attention task. ConclusionsOur results revealed that IFG seed-based resting-state functional networks involved in emotion regulation and cognitive function were trait-like deficit in bipolar patients. Higher manic levels and psychotic symptoms were predictors of a worse sustained attention performance.

Structural brain network differences in bipolar disorder using with similarity-based approach.

Objective: Previous studies have shown differences in the regional brain structure and function between patients with bipolar disorder (BD) and healthy subjects, but little is known about the structural connectivity between BD patients and healthy subjects. In this study, we evaluated the disease-related changes in regional structural connectivity derived from gray matter magnetic resonance imaging (MRI) scans. Methods: The subjects were 73 patients with BD and 80 healthy volunteers who underwent 3-Tesla MRI. Network metrics, such as the small world properties, were computed. We also performed rendering of the network metric images such as the degree, betweenness centrality, and clustering coefficient, on individual brain image. Then, we estimated the differences between them, and evaluate the relationships between the clinical symptoms and the network metrics in the patients with BD. Results: BD patients showed a lower clustering coefficient in the right parietal region and left occipital region, compared with healthy subjects. A weak negative correlation between Young mania rating scale and clustering coefficient was found in left anterior cingulate cortex. Conclusions: We found differences in gray matter structural connectivity between BD patients and healthy subjects by a similarity-based approach. These points may provide objective biological information as an adjunct to the clinical diagnosis of BD.

A Prospective Comparison of Bipolar I and II Subjects With and Without Comorbid Alcohol Dependence From the COGA Dataset.

Objective: Comorbidity of alcohol use disorders in bipolar subjects is high as indicated by epidemiological and clinical studies. Though a more severe course of bipolar disorder in subjects with comorbid alcohol dependence has been reported, fewer studies considered the longitudinal course of alcohol dependence in bipolar subjects and the prospective course of comorbid bipolar II subjects. Beside baseline analysis, longitudinal data of the COGA (Collaborative Study on Genetics in Alcoholism) were used to evaluate the course of bipolar I and II disordered subjects with and without comorbid alcohol dependence over more than 5 years of follow-up.Methods: Characteristics of bipolar disorder, alcohol dependence and comorbid psychiatric disorders were assessed using semi-structured interviews (SSAGA) at baseline and at a 5-year follow-up. Two hundred twenty-eight bipolar I and II patients were subdivided into groups with and without comorbid alcohol dependence.Results: Of the 152 bipolar I and 76 bipolar II patients, 172 (75, 4%) had a comorbid diagnosis of alcohol dependence. Bipolar I patients with alcohol dependence, in particular women, had a more severe course of bipolar disorder, worse social functioning and more suicidal behavior than all other groups of subjects during the 5-year follow-up. In contrast, alcohol dependence improved significantly in both comorbid bipolar I and II individuals during this time.Conclusions: A 5-year prospective evaluation of bipolar patients with and without alcohol dependence confirmed previous investigations suggesting a more severe course of bipolar disorder in comorbid bipolar I individuals, whereas bipolar II individuals were less severely impaired by comorbid alcohol use disorder. While severity of alcohol dependence improved during this time in comorbid alcohol-dependent bipolar I patients, the unfavorable outcome for these individuals might be due to the higher comorbidity with personality and other substance use disorders which, together with alcohol dependence, eventually lead to poorer symptomatic and functional clinical outcomes.

Central levels of tryptophan metabolites in subjects with bipolar disorder

The kynurenine pathway of tryptophan degradation produces several neuroactive metabolites such as kynurenic acid (KYNA), quinolinic acid (QUIN), and picolinic acid (PIC) thought to be involved in the pathophysiology of psychosis, major depression, and suicidal behavior. Here, we analyzed cerebrospinal fluid (CSF) concentrations of tryptophan, kynurenine, KYNA, QUIN, and PIC utilizing ultra-performance liquid chromatography – tandem mass spectrometry system (UPLC-MS/MS) in persons with bipolar disorder (n = 101) and healthy controls (n = 80) to investigate if the metabolites correlated with depressive symptoms or to the history of suicidal behavior. Furthermore, we analyzed if genetic variants of the enzyme amino-β-carboxymuconate-semialdehyde-decarboxylase (ACMSD) were associated with the CSF concentrations of PIC and QUIN. We found that CSF KYNA and PIC concentrations, as well as the kynurenine/tryptophan ratio were increased in bipolar disorder compared with controls. CSF PIC concentrations were lower in subjects with a history of suicidal behavior than those without, supporting the hypothesis that low CSF PIC is a marker of vulnerability for suicidality. Bipolar subjects taking antidepressants had higher CSF concentrations of kynurenine and KYNA than subjects not given these medications. A negative association was found between a genetic variant of ACMSD and the ratio of PIC/QUIN, indicating that a polymorphism in ACMSD is associated with excess of QUIN formation at the expense of PIC. The present results confirm that the kynurenine pathway is activated in bipolar disorder, and suggest that shifting the activity of the kynurenine pathway away from QUIN production towards a production of KYNA and PIC might be a beneficial therapeutic strategy.

Influence of genetic variations in IL1B on brain region volumes in bipolar patients and controls

Involvement of the immune system has been implicated in the etiology and pathophysiology of mood disorders, including bipolar disorder. Neuroimaging studies have reported structural brain pathology in bipolar disorder patients, and both levels of and genetic variants in cytokines have been associated with altered volumes of brain regions. The aim of this study was to investigate associations between single nucleotide polymorphisms in the gene coding for the pro-inflammatory cytokine interleukin-1 beta (IL1B) and whole brain grey matter volume, as well as volumes of several brain regions shown to be of importance in mood disorders. Structural magnetic resonance imaging and vertex-based morphometry were used to obtain volume of different brain regions in subjects with bipolar disorder (n=188) and healthy controls (n=54). Four IL1B polymorphisms were genotyped: rs1143623, rs1143627, and rs16944 in the promoter region together with the synonymous variant rs1143634 in the IL1B gene. The genotype distribution did not differ between bipolar subjects and controls. The T allele at rs16944 and the C allele at rs1143627 were associated with increased volumes of the putamen of the left hemisphere in patients and controls, which lends support to the role of this immune system mediator for brain structure.

P.336 Short-term intravenous valproate augmentation in partial/non-responder bipolar subjects with a depressive mixed episode: an observational study

P.336 Short-term intravenous valproate augmentation in partial/non-responder bipolar subjects with a depressive mixed episode: an observational study

Bipolar depression had more atypical depressive symptoms in comparison with unipolar depression

BackgroundDepressive patients with atypical symptoms tend to cause greater functional impairment. This study examined the differences of the atypical depressive symptoms between unipolar and bipolar depressive patients (BP I and BP II). MethodsWe studied 466 depressed patients (262 unipolar and 204 bipolar subjects, in which 122 BP I depression, 82 BP II depression) diagnosed with DSM-IV criteria. Atypical depressive symptoms were also evaluated with DSM-IV criteria for atypical features specifier. Binary logistic regression was used to examine the associations of atypical depressive symptoms with depressive disorders after control of confounding variables. ResultsThe prevalence with any atypical depressive symptoms in unipolar depressive disorder was 32.8 % (86/262), and in bipolar depression was 44.6 % (91/204), X2 = 6.76, P = 0.009. In stepwise binary logistic regression analysis, patients with bipolar depression had more females, more positive psychiatric history, more weight gain or increase in appetite, more interpersonal rejection sensitivity, and more visual values of severest pain. LimitationsThe participants recruited were both inpatients and outpatients in one major hospital which might influence the generality of the study. The cross-sectional research methods can't work out causality. ConclusionsBipolar depression and major depressive disorder exhibit subtle differences in presentation, which may help guide the early intervention, initial diagnosis and the choice of therapy.

Cognitive dysfunctions in patients with bipolar disorder: A comparative study from Western Rajasthan

Background: Cognitive dysfunction is an established entity in bipolar disorder. The affected individuals exhibit wide-ranging deficits involving multiple domains of cognitive functioning. These deficits are associated with poor functional outcome and residual disability in patients. A substantial literature exists globally on cognition in bipolar disorder; however, few studies have been carried out on this subject in India and in Rajasthan. The aim of the study is to compare cognitive functions of bipolar disorder patients and healthy control subjects. Subjects and Methods: This cross-sectional study was conducted at the Psychiatry department of a tertiary care institution on 50 bipolar disorder patients and matched healthy controls subjects who fulfilled the inclusion criteria. The diagnosis was made by DSM-V criteria, and symptom severity was determined by the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HAM-D). After seeking socio-demographic details, all participants were administered the Post Graduate Institute Battery of Brain Dysfunction (PGI-BBD) to assess cognitive functioning. Data collected were subjected to suitable statistical analysis (mean, standard deviation, and chi-square test). Results: The majority of the bipolar disorder patients (54%) were under 35 years of age, were males (60%), were from the urban background (70%), and were married (82%). Bipolar disorder patients performed poorly on all domains of cognitive functioning, i.e. memory, performance and verbal intelligence, and perceptuo-motor skills. Conclusion: The present study affirmed the previous findings of wide-spread cognitive impairment in bipolar disorder patients. Prompt diagnosis and treatment are the key steps to reduce the cognitive morbidity associated with this disorder.

QEEG - spectral power density of brain regions in predicting risk, resistance and resilience for bipolar disorder: A comparison of first degree relatives and unrelated healthy subjects

BackgroundTemperament stems from the brain circuitry. Genetic differences among people are attributable to differences in neurophysiological function. Affective temperament is proposed endophenotype for bipolar affective disorder. QEEG - spectral power density is thought to be an index of general affective and cognitive brain activity. The association of spectral power density with types of affective temperament may enlighten endophenotypes for bipolar affective disorder disposition. MethodTEMPS-A scale and rest QEEG were done on 25 euthymic patients, their healthy first degree relatives (n = 25) and 25 unrelated healthy control subjects. All patients were on lithium maintenance therapy. ResultsF4 and T4 delta wave activity were similar between patients and first degree relatives, while Pz alpha activity was similar in first degree relatives and unrelated healthy subjects (p = 0.025, p = 0.001, p = 0.010). Cyclothymic and hyperthymic temperament scores were similar between patients and first degree relatives but higher than unrelated healthy subjects (p = 0.015, p = 0.010). F7 beta and F7–O2 high beta power were correlated with hyperthymic and irritable temperaments respectively in bipolar subjects (r = 0.439, 0.387; 0.405, 0.364; 0.226, 0.351). T3-F4-T4 delta powers were correlated with cyclothymic temperament in patients and their first degree relatives (r = 0.443, 0.420, 505). Pz alpha power and hyperthymic temperament were inversely correlated in first degree relatives and unrelated healthy subjects (r = -0.256 and -0.311). ConclusionMedial temporal network may be associated with bipolar affective disorder heritability. On the other hand, left dorsolateral prefrontal beta and high beta activities may be a neural marker for disorder resistance together with right occipital high beta power.

S165. GLUTAMATERGIC ABNORMALITIES IN EARLY SCHIZOPHRENIA AND BIPOLAR DISORDER MEASURED USING WHOLE-BRAIN SPECTROSCOPY

BackgroundGlutamatergic abnormalities in schizophrenia and bipolar disorder gave been identified using proton magnetic resonance spectroscopy (1H-MRS). Although schizophrenia and bipolar disorder are both known to involve extensive brain networks, most MRS studies have been done using single-voxel techniques. In this study we used whole brain 1H-MRS to examine glutamine-plus-glutamate (Glx) in early schizophrenia and bipolar disorder to examine metabolic abnormalities associated with affective and non-affective psychosis and with exposure to antipsychotic medication.MethodsThree dimensional 1H-MRS was acquired in young schizophrenia (SCZ, N=36, 24 M, 22.8±3.9 years, 19 antipsychotic-naïve and 17 antipsychotic-treated), bipolar (N=13, 5 antipsychotic-naïve and 8 antipsychotic-treated), schizoaffective-bipolar type (N= 3, 2 antipsychotic-naïve and 1 antipsychotic-treated) subjects, and healthy controls (HC, N=29, 17M, 23±4.4yrs). Glx, N-acetylaspartate, choline, myo-inositol and creatine group contrasts from all individual voxels that met spectral quality were analyzed in common brain space (voxel-wise p-threshold=0.001), followed by cluster-corrected alpha value (p<0.05). Bipolar subjects (N=13) and schizoaffective-bipolar type (N=3) were combined (SBP) (N=16, 11M, 21.9±2.9yrs, 7 antipsychotic naïve and 9 antipsychotic-treated).ResultsSCZ subjects compared to HC had lower Glx in the left superior (STG) and middle temporal gyri (16 voxels, p=0.04) and increased creatine in two clusters involving left temporal, parietal and occipital regions (32, and 18 voxels, p=0.02 and 0.04, respectively). Antipsychotic-treated and naïve SCZ had similar Glx reductions (8/16 vs 10/16 voxels respectively, but p’s>0.05). However, creatine was higher in antipsychotic-treated vs HC’s in a larger left hemisphere cluster (100 voxels, p=0.01). Also in treated SCZ, choline was increased in left middle frontal gyrus (18 voxels, p=0.04). Finally, in antipsychotic-naive SCZ, NAA was reduced in right frontal gyri (19 voxels, p=0.05) and myo-inositol was reduced in the left cerebellum (34 voxels, p=0.02). SBP subjects had no significant differences from HC in any area of the brain for any of the metabolites at a voxel-wise p-threshold of 0.001. A cluster of reduced Glx was found at in the right cuneus and precuneus (276 voxels, p=0.05) using a less stringent voxel-wise p-threshold of p< 0.05.DiscussionData-driven spectroscopic brain examination supports the presence of reductions in Glx in the left STG early in the course of schizophrenia; this was not seen in individuals with bipolar symptoms. A trend toward decreased Glx in the right cuneus and pre-cuneus in bipolar and schizoaffective patients is consistent with previous findings of abnormal function in this area. The left STG may be a critical target for postmortem and neuromodulation studies in schizophrenia studies.