To evaluate insulin resistance (IR) among outpatients with bipolar disorder (BD) in order to determine clinical correlates of IR in this patient population.

We performed a cross-sectional study in sixty-five DSM-IV-TR BD patients consecutively assessed from January to August 2007 at the Bipolar Disorder Program, Hospital de Clínicas de Porto Alegre, Brazil. IR was diagnosed using the homeostatic model assessment - insulin resistance (HOMA-IR). Metabolic syndrome (MS) diagnosis and metabolic variables were assessed using three definitions: National Cholesterol Educational Program - Adult Treatment Panel III (NCEP-ATP III); NCEP-ATP III modified criteria and International Diabetes Federation (IDF).

IR was present in 43.1% of the sample (women 40%, men 44.4%). The prevalence of MS defined by the NCEP-ATP III criteria was 32.3%, NCEP-ATP III modified was 40% and IDF was 41.5%. NCEP-ATP III modified criteria showed the best trade-off between sensitivity (78.6%) and specificity (89.2%) to detect insulin resistance. Waist circumference was the best clinical parameter associated with IR in the linear regression model (B=0.014, SE 0.002, t=6.18, p< 0.001). Areas under ROC curves were similar for waist circumference and different MS definitions (chi2=2.98, df=3, p=0.39).

Currently MS criteria may provide reasonable sensitivity and specificity for the detection of insulin resistance in patients with bipolar disorder. Waist circumference may be a simple and inexpensive means to predict insulin resistance in this population.

To document the phenotypic and genotypic characteristics of a three generational large family loaded with affective disorders.

Linkage analysis is done in a large three generational Turkish family loaded with affective disorders. 8 patients and 17 relatives are examined with SCID-I and the clinical characteristics of the patients are documented. Blood is drawn from all family members to isolate DNA but only the patients DNA are included in the molecular analysis and these patients are screened for five susceptibility regions implicated for both schizophrenia and bipolar disorder (10p12, 13q32, 18p11.2, 22q11 ve 20 p12-q12).

Clinical assesment of the patients revealed that, the depressive episodes of the patients are likely to be melancoholic and suicidal in nature and the manic episodes are usually associated with mood-congruent psychotic symptoms. No linkage could be detected for the screened regions in molecular analysis. Only a loss of heterozygosity could be detected in 18p11.2 region.

The allelic loss from the maternal allele in this region did not seem to segregate with the disorder and this maternal allele loss could not be explained by an imprinting mechanism, since there was no parental transmission of the disorder in this pedigree. This region must be screened with multiple markers and sitogenetic analysis should be done in order to be able to understand whether there is a real loss of in this part of the chromosome.

Several MRI studies have identified structural abnormalities in association with bipolar disorder. The literature is however heterogeneous and there is remaining uncertainty about the brain areas pivotal to the pathogenesis of the condition. The aim of this study was to identify, appraise and summarise volumetric MRI studies of brain regions comparing bipolar disorder with an unrelated control group and/or patients with schizophrenia.

A systematic review and random-effects meta-analysis was carried out to identify key areas of structural abnormality in bipolar disorder and whether the pattern of affected areas separated bipolar disorder from schizophrenia. Excessive variability was explored using meta-regression analyses.

Seventy two reports met inclusion criteria. Subjects with bipolar disorder showed significant whole brain and prefrontal lobe volume reductions, and also increases in the volume of the globus pallidus. Enlargement of the lateral ventricles in bipolar disorder was confirmed, although the magnitude of enlargement was smaller than in schizophrenia. Subjects with schizophrenia, but not bipolar disorder, showed significant reductions in right amygdala volumes. Heterogeneity was statistically significant for many of the analyses and could amongst others be explained by age, duration of illness and year of publication.

There appear to be robust changes in brain volume in bipolar disorder compared with healthy volunteers. Age and duration of illness appear to be key issues in determining the magnitude of observed effect sizes.

We aimed to explore the expert perspective on relevant issues of individuals with bipolar disorder. The specific aims are to identify problems in functioning important to individuals with BD and to quantify these using the ICF.

An online survey on functioning in BD was conduced. For each ICF domain one question was presented. Recruited participants were psychiatrists, general physicians, psychologists, nurses and social workers worldwide. Answers were linked to the ICF according to predefined rules (Cieza, 2001). Data analyses include frequencies of ICF categories named by experts.

Health professionals from all WHO-world regions and from different professional backgrounds accepted our invitation to participate. The Americas was the highest represented region (36%) and a significant part of the professionals involved were psychiatrists. From all the concepts contained in the answers, body functions categories with highest frequency of appearance were emotional functions (3,5%), mentioned by 62% of the experts and sleep functions (2,4%) mentioned by 58%. The body structure brain corresponds to 2% of the total categories obtained and was included by 56% of the experts. Maintaining one's health was the most mentioned activity and participation (2,8%), referred by 36% of the participants and important environmental factors include health services (4,8%) and immediate family(3,8%), which appeared in 82% of the questionnaires.

The present study is an important step in applying of the ICF to BD. It also shows an important level of agreement between experts around the world regarding central issues of the disorder.

Funded by MURINET-MRTN-CT-2006-035794

Bipolar disorder diagnoses in youth have significantly increased in the past decade. To help establish proper diagnostic practices, four different phenotypes have been proposed, ranging from meeting full DSM-IV criteria to “severely mood disordered” conditions (Leibenluft et al, 2003). So far, not much is known about these phenotypes and their response to treatment in the community.

To identify youth diagnosed with bipolar disorder versus mood disorder NOS and evaluate their response to treatment in a community clinic.

A retrospective chart review identified 19 children with bipolar disorder and 22 with mood disorder NOS and “followed back” these patients for eight months. Pre- and post-treatment Global Assessment of Functioning (GAF) and Clinical Global Improvement (CGI) scales were collected.

There were no differences between the two groups in terms of gender, number of diagnoses, family history of bipolar disorder, initial GAF, level of care needed, or number of medications needed. Youth with bipolar disorder were older, had more risk factors for suicidality, more past medication trials, and more hospitalizations. Severely mood disordered patients had more ADHD.

After eight months, bipolar disorder youth improved significantly more than severely mood disordered patients: Change in GAF (+10.4 vs +5.3), endpoint GAF (56.9 vs 50.3), and CGI (2.6 vs 3.1).

Even though bipolar disorder youth look more like adults with bipolar disorder (older age, more suicidality, more hospitalizations), severely mood disordered youth respond much less to treatment in a community clinic.

Bipolar disorder (BD) is chronic psychiatric disorder by mood swings, symptoms of BD are serious and life-threating. Suicide risk in patients with BD is 25-50%, more frequent during depressive episode (Compton,2000) but with adequate treatment suicide risk can be presented in nearby 50% of patients only (Goodwin, Jamison,2006). Despite these facts data about the changes of treatment habits over the longer period of time under naturalistic condition are lacking.

To assess presence of suicidal thoughts and attempts in inpatients with BD and follow-up changes of treatment with lithium over the period of time.

It was retrospective survey of in-patient's files hospitalized at the 1st Dept. of Psychiatry, UPJS, Kosice (1997-2007) with typical limitations for retrospective case survey. All patients had diagnosis of BD (DSM-IV), n=125 (67% of women and 33% of men). We discovered changes in suicidal behaviour with/without treatment of lithium.

The first episode was depressive in 62% of patients, average number of episodes: 8,2. There was trend of decrease in use of lithium over the time (68% vs 84% in men, 29% vs 60% in women). The suicidal thoughts were more frequent during depressive episode (in 50% of women and 18% of men). Suicidal thoughts and attempts were 3 times more frequent in women vs men with BD. Suicidal attempts were 4 times more frequent in women with treatment with lithium vs without lithium.

Geriatric bipolar disorder is associated with a significant morbidity, mortality and poor psychosocial outcomes. Bipolar affective disorder contributes substantially to geriatric mood disorders and to geriatric hospitalizations. Mania in late-life is often a tremendous treatment challenge because of frequent medical co-morbidity and age-related variations in response to therapeutics.

To report a case of mania in late-life, in order to discuss the impact of bipolar disorder in the elderly, underlining treatment difficulties in the geriatric population.

Case study and review of the literature.

A 70 year old woman was hospitalized in a geriatric service of a psychiatric hospital with a maniac episode. She had a history of bipolar disorder diagnosed during her adult life. She had several co-morbid medical conditions, including diabetes, hypertension, dyslipidemia and psoriasis. There was a successful multidisciplinary approach and intervention, allowing a significant improvement and reintegration in the community.

Geriatric patients with bipolar disorder carry a substantial burden of general medical conditions. There are few studies and a lack of specific algorithms concerning bipolar management in the elderly. It is urgent the development of specific interventions that target medical burden in patients with bipolar disorder and further research on the treatment of bipolar disorder in old age. A multidisciplinary approach is essential to allow a holistic treatment and improvement of quality of life parameters in this population.

There is little data to indicate whether or not patients with chronic mental illness can provide self-report QOL data or if informant reports can substitute the patients’ ratings. We evaluated patient-proxy agreement in patients with schizophrenia and bipolar disorder and compared levels of agreement according to the relationship between patient-proxies.

WHOQOL-BREF and SF-36, two of the most popular quality of life instrument were administered to 82 schizophrenia-proxy and 50 bipolar disorder patient-proxy pairs.

Proxies of schizophrenia patients rated patients’ QOL lower than the patients themselves. Agreement between patients and proxies on the four main domains of QOL was moderate to good. Moreover, the agreement between patients’ and proxies’ ratings was higher when the proxy was a mother or spouse compared to father.

These findings suggest that proxy rating of QOL can be used as a reasonable estimate of the patients’ rating of QOL in schizophrenia and bipolar patients, at least in Korea. Knowing which domains of QoL are affected in specific psychiatric disorders can help clinicians focus on particular QoL domains during the diagnostic process and to define adequate treatment goals. Therefore, the assessment of QoL may be an important part of the diagnostic process because it can give insight into the areas of functioning in which a patient is suffering the most.

We describe a 15-year-old African American female with a family history positive for Bipolar I disorder and schizophrenia who presented with symptoms consistent with an affective disorder. The patient was diagnosed with Bipolar I disorder with catatonic features and required multiple hospitalizations for mood disturbance. Two years after her initial presentation, the patient was noted to have a malar rash and subsequently underwent a full rheumatologic workup, which revealed cerebral vasculitis. Neuropsychiatric lupus (NPSLE) was diagnosed and, following treatment with steroids, the patient improved substantially and no longer required further psychiatric medication or therapy.

Neuropsychiatric manifestations of lupus (NPSLE) have been shown to occur in 80-91% of adults and up to 95% of pediatric patients with SLE. In the case we described, diagnosis was hindered by the patient's presentation of what appeared to be isolated psychiatric symptoms and her strong family history of psychiatric disease. Thus, given the especially high prevalence of NPSLE in pediatric patients with lupus, it is important for clinicians to recognize that neuropsychiatric symptoms in an adolescent may indeed be the initial manifestations of SLE.

Self-administered questionnaires were given to 152 nurses employed in three Portuguese public hospitals. The questionnaire items included socio demographic and job-related data and two scales: the Portuguese version of TEMPS-A Scale (Akiskal, 2005) and the Personal Self-esteem Scale (Ribeiro, J.L.P 2006). For statistical analysis besides descriptive statistics, a correlation model was used.

Hyperthimic Temperament was the more prevalent subtype. Women presented a higher Self-esteem positively correlated with Ciclothymic and Anxious temperaments. The results also show that there is a correlation between marital status and Irritable Temperament, and between the years of professional experience and the Cyclothymic and Hyperthymic Temperaments.

An interaction between temperament subtypes, self-esteem and professional experience was observed. Gender differences are also significant. Further study is needed to investigate the potential relationship between temperament, self-esteem and professional satisfaction and resilience to job-related stress factors in Psychiatric Departments.

Several reports indicate that Bipolar Disorder (BD) is frequently underdiagnosed

leading to overuse of antidepressants and underuse of mood stabilizers.

The aim is to review literature concerning this subject published since 2000.

BD seems to be frequently underdiagnosed. Several studies, as EPIDEP and NEMESIS, reveal insufficiencies on the diagnosis of this disorder, suggesting that clinicians miss this diagnosis about half of the times, and that about three quarters of these patients are not receiving appropriate treatment, respectively.

BD is often misdiagnosed as Major Depression Disorder (MDD), with approximately 40% of BD patients being initially diagnosed as MDD. On the other hand, a large fraction of patients initially diagnosed as MDD will change diagnosis to BD during follow-up, with some authors presenting values as high as 67%. Studies comparing the depressive features of MDD and BD point to some strong clinical indicators of bipolarity in patients presenting with depression, such as family history, seasonal pattern, postpartum onset, psychotic symptoms, younger age, suicidal behaviours, among others.

To a lesser extent, BD can also be misdiagnosed as: substance abuse, borderline personality, obsessive-compulsive disorder, among others.

It is also important to consider that a large fraction of patients with BD diagnosis will change diagnosis during the follow-up period.

BD patients with the diagnosis may represent only a fraction of the subjects with this disorder, and the true epidemiological extent of this problem needs further investigation.

To evaluate the effectiveness of extended release quetiapine fumarate (quetiapine XR) as once-daily monotherapy for manic symptoms in bipolar I disorder.

In this 3-week, randomized, parallel-group, double-blind study, adults with bipolar I disorder (most recent episode manic or mixed; with or without rapid cycling) were randomized to once-daily treatment with either quetiapine XR (n=149; Day 1, 300 mg; Day 2, 600 mg; Day 3 through Week 3, 400-800 mg flexibly dosed) or placebo (n=159). Primary outcome measure was change from baseline to Week 3 in Young Mania Rating Scale (YMRS) total score. Secondary outcome measures included YMRS response and remission and change in Clinical Global Impression-Bipolar (CGI-BP)-Severity of Illness and -Change scales. Change from baseline was compared between groups with analysis of covariance, using the last observation carried forward approach for missing data.

Once-daily quetiapine XR was associated with significant, sustained improvement in manic symptoms compared with placebo, beginning on Day 4 (P< 0.001) and continuing through Week 3 (mean change: -14.34 versus -10.52; P< 0.001). At Week 3, quetiapine XR-treated patients showed significantly greater response (P< 0.01) and remission (P< 0.01) rates and improvement in CGI-BP-associated scores than placebo-treated patients. Adverse events were mild to moderate in intensity, the most common being sedation, dry mouth, and somnolence for quetiapine XR.

Once-daily quetiapine XR monotherapy (400-800 mg) was efficacious (from Day 4 through Week 3) and generally well tolerated in the treatment of manic episodes associated with bipolar I disorder.

Supported by funding from AstraZeneca Pharmaceuticals LP.

To evaluate the effectiveness of extended-release quetiapine fumarate (quetiapine XR) as once-daily monotherapy for bipolar depression.

Patients in this double-blind, placebo-controlled study were acutely depressed adults with bipolar I or II disorder (with or without rapid cycling), and were randomized to 8 weeks of once-daily treatment with quetiapine XR 300 mg (n=133) or placebo (n=137). The primary outcome measure was change from baseline to endpoint (Week 8) in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary outcome measures included response (MADRS total score reduction ≥50%) and remission (MADRS total score ≤12) rates at endpoint, changes from baseline to endpoint in MADRS item scores, and Clinical Global Impressions-Bipolar (CGI-BP) severity of illness and change. Change from baseline was compared between groups with analysis of covariance using last observation carried forward approach.

Quetiapine XR 300 mg/d was significantly more effective than placebo in improving depressive symptoms, from first assessment (Week 1; P< 0.001) to endpoint (P< 0.001). Compared with placebo, quetiapine XR was associated with higher response (P< 0.001) and remission (P< 0.05) rates and greater improvements from baseline to endpoint in MADRS total score (-17.43 vs -11.92; P< 0.001), MADRS item scores for core symptoms of depression, and CGI-BP-related outcomes at Week 8. Most common adverse events with quetiapine XR were dry mouth, somnolence, and sedation.

Quetiapine XR (300 mg) once-daily monotherapy was efficacious (from Weeks 1 through 8) compared with placebo and generally well tolerated in bipolar depression.

Supported by funding from AstraZeneca Pharmaceuticals LP.

This unique study of treatment of the mixed state of bipolar I disorder using simultaneous depression and mania response criteria compared divalproex monotherapy versus olanzapine augmentation in a 6-week, randomized, double-blind trial.

Patients (age 18-60 years) with 14-28 days of divalproex monotherapy (blood levels of 75-125 μg/mL) were randomized to augmentation with olanzapine 5-20 mg/day or placebo. Data collected included: Hamilton Depression Rating Scale (HDRS), Young Mania Rating Scale (YMRS), Clinical Global Impression for Bipolar Illness (CGI-BP), hospitalizations, concomitant medications, and adverse events (AEs). Primary co-objectives were comparisons of baseline to endpoint changes in HDRS and YMRS. Secondary objectives included comparisons of times to onset (25% reduction) and response (50% reduction) in both HDRS and YMRS, change in CGI-BP, hospitalizations, and safety.

Patients were 59% female, 51% Caucasian, 33% African American, and 14% Hispanic with mean standard deviation (SD) HDRS and YMRS scores of 22.2 (4.5) and 20.9 (4.4). Mean standard error (SE) score changes for the olanzapine (n=100) or placebo (n=101) arms, respectively, were: HDRS, -9.37 (.55) and -7.69 (.54), p=.022; YMRS, -10.15 (.44) and -7.68 (.44), p< .001; and CGI-BP, -1.34 (.11) and -1.06 (.11), p=.056. Times-to-onset (median 7 vs 14 days) and response (median 25 vs 49 days) were significantly shorter for olanzapine augmentation. One olanzapine patient required hospitalization (p=1.0). Treatment-emergent AEs were consistent with previously-published rates.

Six-week olanzapine treatment augmentation was associated with greater and earlier reduction of manic and depressive symptoms in mixed episode patients on divalproex treatment.

To date, little is known about the impact of substance use on physical health of patients with bipolar disorder. This study provides data on the impact of tobacco, alcohol and cannabis upon weight, metabolic profile and cardiovascular risk in these patients.

Naturalistic, cross-sectional, multicenter study conducted in Spain. Current use of tobacco, alcohol and cannabis was registered based on patient’ self-reports. Patients were evaluated for presence of metabolic syndrome (MetS) according to modified NCEP ATP III criteria, for cardiovascular risk using the Framinghan function (CHD) and the Systematic COronary Risk Evaluation (SCORE) function (CMR).

The mean age was 46.6 years and 49% were male. Fitty-one percent used tobacco, 13% alcohol and 12.5% cannabis. Mean body mass index (BMI) was 27.9 kg/m2, 22.4% had MetS and ten-year CHD and CMR risks were 7.6% and 1.8% respectively. Patients who used tobacco had significantly higher CHD risk (8.82 versus 5.74, p < 0.01), and used more antipsychotic (1.23 versus 1.04, p 0.002) and overall (3.18 versus 2.71, p 0.01) drugs for the treatment of their bipolar disorder. Patients who used cannabis had significantly lower BMI (26.0 versus 28.2, p < 0.05) and lower CMR (0.37 versus 1.99, p < 0.001), however, when controlling by age, severity of mania and presence of metabolic syndrome these associations disappear.

Substance use, mainly tobacco, is high in patients with bipolar disorder. Use of tobacco is associated with higher cardiovascular risk and greater number of antipsychotic and overall drugs for the bipolar disorder.

From 35% to 60% of cases the initial presentation of illness in bipolar disorder is different from mania or hypomania. So far the studies that have investigated predictors of (hypo)mania have been concentrated on samples suffering from depression. On one hand is well known that antidepressant drugs are commonly prescribed in a broad spectrum of disorders other than depression. On the other hand there are strong connections within bipolar disorder and anxiety disorders that have been reported to be a possible clinical onset of a subsequent bipolar disorder.In all these cases patients are likely to be treated with antidepressants drugs, the effects of which has been associated with a worsened course of bipolar illness, from switching to mania to a rapid cycling course. This is the reason that led to perform a research on predictors of bipolar evolution on an antidepressant treated sample of outpatients irrespective of the diagnosis.This study examines clinical features at the first presentation of the illness that can be considered predictive of the subsequent bipolar course of illness.

A sample of outpatients treated for the first time in their life with antidepressant drugs has been prospectively evaluated in order to assess the clinical features associated with the later onset of bipolar disorder.

Since the discovery of the tryptophan hydroxylase 2 gene (TPH2) several studies reported association of TPH2 genetic variation with bipolar I disorder (BPI). Our objectives were to replicate in the Romanian population the recently described association of a rare functional SNP (rs17110563) and of a haplotype covering the 5′ region of TPH2 with BPI (Cichon et al., 2008) and to investigate the influence of the phenotypic traits age-of-onset, family history and parent-of-origin”, defined according to clinical criteria, on the degree of association between TPH2 and BPI.

Sixteen TPH2 SNPs were genotyped in a Romanian sample of 198 BPI patients and 180 controls screened for psychiatric disorders. Statistical analysis of the data was performed with Haploview3.32 and FAMHAP.

The functional SNP rs17110563 (encoding a Pro206Ser substitution) was present in Romanian BPI patients and absent in controls. SNPs located in the 5′-region (rs11178997, rs11178998, rs7954758), significantly associated with BPI in German patients were not associated with BPI in Romanian patients at single-marker level, but gave evidence for association at haplotypic level in a subgroup of patients with paternal transmission of BPI. Evidence for association was identified between haplotypes located in the 3′-region of TPH2 and BPI in the overall sample as well as in the subgroups of familial cases, the subgroup with paternal transmission, and the subgroup with AO≤25 years.

Our data provide support for the involvement of TPH2 in the etiology of BPI.