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.

Metabolic Syndrome (MS) is constituted by a set of specific metabolic alterations being postulated that the main dysfunction is insulin resistance. Estimates point to higher prevalence of MS in bipolar patients, between 30 to 35%. Cost-effective screening methods, not recurring to blood test, have been researched.

Analyse knowledge and importance given to MS in bipolar patients. Test the viability of MS screening without blood tests.

Observational, cross-sectional study. Random sample of 15 adult bipolar patients, in euthymic phase. Semi-structured interview, YMRS, HAMD were applied. MS diagnosis investigated according to the International Diabetes Federation (IDF) criteria. MS screening was defined positive if blood pressure ≥ 130/85 or anti-hypertensive medication and abdominal perimeter > 90 in males or > 80 in females. A questionnaire about knowledge, attitudes and concerns on MS was applied.

14 patients completed the investigation protocol. Five (36%) met IDF criteria for metabolic syndrome. Screening sensitivity was 80% and specificity 78%. Twelve patients (80%) were overweigh or obese. Mean IMC in patients that met IDF criteria for MS was 30 while in the other group mean IMC was 26. Only 3 (20%) have ever heard about MS, but the majority of the patients were concerned, in decreasing order, about weight gain, blood pressure cholesterol and hyperglycemia control.

Although limited by small sample size, this study strengthens the idea that MS screening can be effective in clinical practice, it also indicates the need to educate BP patients about MS and to prevent overweight.

Decision making, as well as working memory and executive functions are among the most significant cognitive processes, associated with prefrontal cortex function. Decision making is associated with the orbitofrontal cortex function. Working memory and executive functions are dependent on the dorsolateral prefrontal cortex. Orbitofrontal, as well as dorsolateral prefrontal cortex dysfunction in bipolar disorder has been reported. The aim of the study was to assess decision making and executive functions in euthymic bipolar patients.

The study included 13 euthymic bipolar patients (6 female, 7 male), aged 43±11 years and 11 age, sex and education years matched healthy controls. Decision making was assessed with Iowa Gambling Task (IGT). Working memory and executive functions were assessed with Wisconsin Card Sorting Test (WCST) and Trail Making Test (TMT). Depressive and/ or manic symptoms were measured with Hamilton Depression Scale (HAM-D) and Young Mania Rating Scale (YMRS).

Euthymic bipolar patients made more nonperseverative errors (t=2,53, p=0,01), gave less conceptual level responses (t=-2,33, p=0,03), completed less categories (t=-1,66, p=0,005) and used more cards to complete first category (t=1,49, p=0,003) in WCST. They also gained less money in IGT (t=-1,34, p=0,03).

Bipolar patients performed significantly worse on several measures of WCST. Euthymic bipolar patients gained less money in IGT compared to healthy controls, although no significant differences in responding style in IGT were found.

Bipolar patients show a significant degree of psychosocial disfunction even in euthymia. Recent studies have reported deficits in Theory of Mind and emotion recognition in BD. Our hypothesis is that social cognition deficit could be associated with a poor general functioning and psychosocial disadvantage in BD.

A sample of 27 euthymic bipolar patients were recluted. Based on Global Assessment of Functioning, they were divided into two groups: good or low general functioning. Euthymia was defined as YMRS < 6 and HDRS < 8, during a 3-month period. Patients with high (n 18) and low (n 9) functioning were compared on several clinical variables and on social / general cognitive measures. Both verbal and non verbal Theory of Mind capacities were assesed (faux pas test and face emotion recognition test). Finally, sustained attention and executive functions were evaluated (Asarnow Test and WSCT).

High- and low-functioning groups did not differ with respect to demographic and clinical variables (age, sex, age at onset, years of evolution of illness, history of prior psychotic symptoms; p = n.s.). However, low-functioning group showed poorer performance than high-functioning group both in faux pas test (U Mann Whitney; p=0.035) and face emotion recognition (U; p = 0.021). In addition, low-functioning group also showed a significant impairment in general cognitive funtions such as sustained attention (U, p = 0.007) and executive funtions (U, p = 0.046).

Social cognition deficit is associated with a poorer general functioning and psychosocial disadvantage.

The close anatomical and functional connection between the orbitofrontal cortex and olfactory processing suggests that emotion regulation and olfactory identification could be associated. Smell identification deficit (SID) is common in adult schizophrenia, but it has been less studied in bipolar patients, who also show a significant degree of social disadvantage.

A sample of 27 euthymic bipolar patients were recluted. Euthymia was defined as YMRS < 6 and HDRS < 8, during a 3-month period. Patients were assessed with the University of Pennsylvania Smell Identification Test (UPSIT), Face Recognition Test and a verbal Theory of Mind test (Faux Pas Test), in order to examine the association between olfactory identification ability and social cognition domains.

According to the hypothesis, olfactory identification was positively correlated with Face Emotion Recognition (Pearson, p = 0.007) and verbal Theory of Mind (Pearson, p=0.030). Smell identification was similar in smoker (15/27) and non-smoker subgroup of the sample (U Mann Whitney; p = n.s). No differences were neither found between male (14/27) and female subgroup (U; p = n.s).

Olfactory identification and social cognition (specially, face emotion recognition) appear to represent two correlated traits in bipolar disorder, suggesting a possible common neural substrate.

Under-recognised bipolar spectrum disorder is going to be one of the most important debates in new articles and researches. Recent data, enlarging bipolar criteria to temperament, family history and more, try to help clinicians in the recognition of the broader spectrum of bipolarity and so getting the most adequate therapeutic attitude.

Consecutive 86 Tunisian patients who meet the DSM IV criteria for major depressive episode (MDE) were interviewed with the temperament evaluation of Memphis,Pisa,Paris and San Diego in order to assess the frequency of cyclothymic temperament (CT).Then we compared the distribution of bipolar criteria, as defined by Akiskal between cyclothymic depressive patients and non cyclothymic ones.Finally the evolution under antidepressants was studied using the GFE:the global functioning evaluation.

34.9% of patients meet the criteria of cyclothymic temperament and compared to the 65.1% who did not, they had significantly lower age of onset, higher recurrence of MDE, more atypical features and more suicidal attempts and comorbidities (anxious disorders and drug abuse).Family history of bipolar disorder was more frequently found within the cyclothymic group as well as psychotic symptoms but not with a significant difference. Finally 71.4% of the non cyclothymic patients improved under antidepressants (GFE score >= 70) compared to only 26.6% in the group of cyclothymic ones.

If we consider the large criteria of bipolarity and the concept of an affective spectrum, the prevalence of bipolar disorder become higher than previously believed, making clinicians reconsider the relevance of the diagnostic of unipolar trouble and the pertinence of the antidepressant treatment.

The catecholamine hypothesis of affective disorders suggests that depression is associated with a functional decrease of catecholamines. There is consistent evidence that COMT gene would be a candidate gene for studies of bipolar disorder.

The study was performed on patients with bipolar disorder n=298 (male n=126, female n=172). Control subjects were blood donors n=336 (male n=130, female n=206), who were not psychiatrically assessed. The subgroup of patients with psychotic features not congruent with mood contained n=88 patients, males n=41, females n=47. The subgroup of patients with psychotic features congruent with mood contained n=89 patients, males n=47, females n=42. The subgroup of patients with melancholic depression contained n=197 patients, males n=76, females n= 121. A polymorphism was analysed by PCR-RFLP method.

There were no differences in the frequency of genotypes, alleles between patients and controls in the whole group (p=0,286 for genotypes, p= 0,652 for alleles). Dividing the patients according to the gender, no differences in the frequency of either genotypes or alleles were found (p=0,298 for genotype males, p=0,456 for genotypes females). We did not find the association in the subgroup of patients with psychotic features congruent (p=0,828 for genotypes, p= 0,866 for alleles), or not congruent with mood (p=0,116 for genotypes, p= 0,673 for alleles) and with the subgroup of patients with depression with melancholic features (p= 0,758 for genotypes, p= 0,849 for alleles).

Results of our study suggest that the polymorphism of COMT gene is not associated with the susceptibility to bipolar disorder.

Our study represents a pilot evaluation about how the MOOD-SR recognizes subthreshold manifestations that may be associated with clinical symptomatology in a group of bipolar patients.

At Day Hospital of Psychiatry, Policlinico “A. Gemelli”, Bipolar Disorders Unit, it has been conducted an experimental study on a heterogeneous sample of 24 patients with a diagnosis of Bipolar Disorder type I. Patients have been assessed with the MOOD-SR, a clinical self-reported interview, that is specific for the spectrum of subthreshold pathology, and with the Quality of Life (QoL), that investigates the patient's quality of life.

We have found that 16 patients on 24 report a score higher than 60 (68,4%). Among these, 10 female patients on 15 have a total score higer than 61 (68.75%) while 6 male patients on 9 obtain a total score higher than 60 (62,5%). However, these results have only preliminary value, further studies are needed in order to obtain a deeper evaluation.

Spectrum manifestations are both indicator of course and response to treatment and predictive for relapse. This finding may represent an important preventive instrument for maniacal relapse in patients with Bipolar Disorder, that is often underdiagnosed or confused for Unipolar Depression. By adequately recognizing the problem we will be able to refine diagnosis and individualize therapy.

To compare the effectiveness of a manualised group cognitive behaviour therapy (CBT) programme for people with bipolar disorder (BPD) and major depressive disorder (MDD).

In addition to treatment as usual (TAU), 17 people with BPD and 17 matched controls with MDD completed 8 or 12 sessions of twice weekly group CBT, followed by 6 booster sessions, held at monthly intervals. Participants completed the Structured Clinical Interview for DSM-IV Axis 1 Disorders, Clinician Version (SCID-1) and the University of Rhode Island Change Assessment (URICA) prior to therapy. They completed the Beck Depression Inventory - II (BDI), the Beck Anxiety Inventory (BAI), the Clinical Outcomes in Routine Evaluation (CORE), the World Health Organisation Quality of Life Brief Version (WHOQoL - BREF) and the Dysfunctional Attitudes Scale (DAS) before and after therapy and at the final follow-up session. The BDI and BAI were also completed at each group session.

Both groups showed statistically and clinically significant improvement on the BDI and BAI after treatment and at follow-up. Both groups showed a significant improvement on the psychological health sub-scale on the WHOQoL-BREF.

Manualised group CBT leads to a reduction in the symptoms of depression and anxiety in people with both BPD and MDD and helps improve their perceived quality of life.

None.

To synthesize the available knowledge on cardiovascular and respiratory comorbidities in patients with bipolar disorder (BD).

Relevant studies were identified by a MEDLINE search from 1966 to January 2008, and supplemented by a manual review of reference lists of the articles identified and previous review articles. When available, priority was given to comparative studies.

We identified 21 studies, 15 (71%) comparative. As compared to the general population, two studies reported higher point-prevalence rates of hypertension (28-60.8% vs 11.9-43%), two studies lower point-prevalence rates (10.4-34.8% vs 14.9-36.8%), one study a higher lifetime-prevalence rate (28.7% vs 14.8%), and one study a significantly increased incidence rate ratio (1.24 females and 1.34 for males). In addition, two studies reported higher point-prevalence rates of hypertension than in medical samples (4.6-18.1% vs 2.2-9.2%) and one study reported a higher risk than in patients with schizophrenia (OR 1.13, 95%CI 1.01-1.26). Point-prevalence rate of stroke was not different than in the general population (n=1, 1.7 vs 2.1, p=0.063); four studies evaluating the risk of stroke as compared to clinical samples provide contradictory results. Point-prevalence rates (n=2, 15.9-17% vs 8.3-10%) and lifetime-prevalence rate (n=1, 16.7% vs 9.7%) of asthma were higher than in the general population. Point-prevalence rates of COPD were also higher than in the general population (n=1, 10.6% vs 9.4%) and in clinical samples (n=3, 1-12.9% vs 0.6-3.6%).

BD seems to be associated with increased rates of hypertension, asthma and COPD. Available data do not support the association between BD and stroke.

To evaluate the frequency of nutritional, metabolic and endocrine disorders in patients with bipolar disorder (BD).

A Medline search (up to January 2008) in and manual review of reference lists of relevant primary articles and review articles. All studies in Spanish or English, all study designs, BD diagnosis by any criteria, with a sample size of ≥ 30 patients, and which reported any measure of frequency measure or association.

Thirty studies were identified: 18 (60%) cross-sectional and 12 (40%) retrospective cohort; 2 (6.7%) population- based; and 2 (6.7%) random sampling. The frequency of obesity in patients with BD was higher than that of the general population (n=4, 19-53% vs 9-14%), of other medical populations (n=1, 4.6% vs 1.1%) and of patients with schizophrenia (n=1, 11.6% vs 9.9%). The frequency of diabetes in patients with BD was higher than (n=5, 6-26% vs 2-16%) or similar to (n=2, 3.5-4.3% vs 3.4-4.8%) that of the general population; higher than that of other medical samples (n=2, 1.8-4.4% vs 0.6-2.2%) and similar to that in of patients with schizophrenia (n=1, 17.7% vs 17.6%). The frequency of dyslipidaemia was higher than that found in a medical sample (n=1, 0.9% vs 0.3%) and in patients with schizophrenia (n=1, 27% vs 23%). The frequency of hypothyroidism was higher than that of a medical sample (n=1, 10% vs 3%).

BD appears to be associated with obesity. It may also be associated with dyslipidaemia and hypothyroidism. Data on the association between BD and diabetes are inconclusive.

To synthesize the available knowledge on gynaecological and obstetric comorbidities in patients with bipolar disorder (BD).

Relevant studies were identified by a MEDLINE search from 1966 to January 2008, and supplemented by a manual review of reference lists of the articles identified and previous review articles. We included studies with any design, in patients with BD as diagnosed by any criteria, with sample size ≥30 patients, and reporting any measure of frequency or association as regards the comorbidities. When available, priority was given to comparative studies.

We identified 4 studies: 3 were comparative; 1 was cross-sectional and 3 were retrospective cohort studies; 1 was population-based study; and 4 used a convenience sample. A retrospective study reported an increased risk of pregnancy complications in patients with BD (OR1.23, 95%CI 1.06-1.44) but not of labor/delivery or neonatal complications; as compared to controls, patients with BD had an increased risk of placenta previa (OR2.04, 95% CI 1.11-3.73), antepartum hemorrhage (OR 1.66, 95%CI 1.15-2.39), and drug side-effects (OR 3.94, 95%CI 1.46-10.62). In another retrospective study, patients with BD had an increased risk of endometriosis (OR: 1.93, 95%CI 1.37-2.70), inflammatory disease of ovary (OR 2.17, 95%CI 1.84-2.57), and disorders of menstruation (OR 1.79, 95%CI 1.56-2.05). In a cross-sectional study, gynaecological disorders were more common in patients with BD than in patients with schizophrenia (4% vs 1.3%).

Although the information is scanty, available data suggest that patients with BD might have an increased risk of gynaecological and obstetric comorbidities/complications.

Bipolar disorder is a serious mental illness which may affect between 2% and 5% of the population. These patients present much higher morbidity and mortality rates than the general population. In addition to a higher mortality rate from suicide, they also have a higher prevalence of other physical disorders.

The purpose of this consensus is to establish recommendations for diagnostic procedures and clinical interventions in order to control the risk factors which have repercussions on the physical health of the patients.

After carrying out a systematic review of medical co-morbidity and mortality rates in bipolar disorder, two multidisciplinary consensus meetings were held in which 31 psychiatrists and 11 experts from other medical specialities participated.

Working groups were formed for each speciality for the purposes of adapting the guidelines applied in the general population to these patients.

The bibliographical review revealed an increased risk of hypertension, obesity, smoking, pulmonary diseases, migraine and HIV infection. There is evidence of higher mortality rates from cardiovascular and respiratory diseases and infections, as well as from suicide. The expert group reached consensus on a series of basic measures for detecting medical co-morbidity. The resulting recommendations will be validated by Spanish Psychiatry and General Medicine Associations.

The physical health of patients with bipolar disorder could be improved. It is hoped that the publication of this consensus will have an impact in terms of better psychosocial functioning, quality of life and life expectancy for these patients in Spain.

The objective of this study was to evaluate the efficacy and safety of ziprasidone adjunctive to a mood stabilizer for the maintenance treatment of bipolar mania.

Male and female subjects with bipolar I disorder with MRS 3 14 were enrolled. Subjects achieving ≥ 8 consecutive weeks of stability with open-label ziprasidone (80-160 mg/d) and lithium or divalproex were randomized into the 6-month double-blind maintenance period, to ziprasidone + mood stabilizer or placebo + mood stabilizer. The primary and key secondary end points were the time to intervention for a mood episode, and time to discontinuation for any reason, respectively. Inferential analysis was performed using a Kaplan-Meier product-limit estimator (Log-rank test).

127 and 112 subjects were randomized to and treated in the ziprasidone and placebo groups, respectively. The time to intervention for a mood episode was significantly different, favoring ziprasidone (p = 0.0104). 19.7% and 32.4% of ziprasidone and placebo subjects, respectively, required intervention for a mood episode. Time to discontinuation for any reason was significantly different (p = 0.0047), favoring ziprasidone. Among treatment-emergent adverse events occurring in the double-blind period, the only event occurring more frequently in the ziprasidone group than in the placebo group (≥ 5%) was tremor (6.3% vs 3.6%, respectively).

These results demonstrate that ziprasidone is an effective, safe, and well-tolerated adjunctive treatment with a mood stabilizer for long-term maintenance treatment of bipolar mania.

Quetiapine combined with lithium or divalproex is an effective maintenance treatment for bipolar I disorder.1,2 This double-blind, randomized trial (D1447C00144) investigated quetiapine monotherapy as maintenance treatment.

Adults experiencing manic, depressed, or mixed episodes of bipolar disorder received open-label quetiapine. Patients achieving stabilization (YMRS ≤12 and MADRS ≤12, 4 consecutive weeks) were randomized to continue quetiapine (300-800 mg/d) or to switch to placebo or lithium (target serum 0.6-1.2 mEq/L) for up to 104 weeks or recurrent mood event. The primary endpoint was time to recurrence of any mood event. The study was terminated when interim analysis provided positive results.

Of 2438 patients starting open-label quetiapine, 1226 (50.3%) were randomized to study medication with 1172 in the ITT population. Mean median quetiapine dose was 546 mg/d; mean median lithium serum level was 0.63 mEq/L. Time to recurrence of any mood event was longer for continued quetiapine versus switching to placebo (HR, 0.29; 95% CI, 0.23-0.38; P< 0.0001), for switching to lithium versus switching to placebo (HR, 0.46; 95% CI, 0.36-0.59; P< 0.0001), and for continued quetiapine versus switching to lithium (HR, 0.66; 95% CI, 0.49-0.88; P=0.005). Safety findings were consistent with known profiles.

In patients stabilized on quetiapine, continued quetiapine significantly decreased time to recurrence of any mood event versus switching to placebo. Switching to lithium was also more effective than switching to placebo and conferred no additional benefit versus continuing quetiapine.Supported by funding from AstraZeneca Pharmaceuticals LP.

Protocadherins (PCHD) are cell adhesion proteins with an important role in neuronal migration, differentiation and synaptogenesis. The linkage studies suggest that the 5q31-linked protocadherin family locus should be considered as potential candidate locus in schizophrenia and bipolar disorder. In this study, we focused particularly on single-nucleotide polymorphisms (SNPs) located in PCHDα enhancer. Results from the Czech cohort of patients with bipolar disorder (BD) will be presented.

Unrelated inpatients and outpatients with BD based on Schedule for Affective Disorders and Schizophrenia - Lifetime (n=167) and blood bank donors as control subjects (n=211) were recruited in the study. Four SNPs posted in dbSNP (rs31745, rs10036519, rs3756337 and rs59497) in the PCDHα gene enhancer were analyzed. The data sets were analysed using a case control design.

In case of SNP, rs31745, a significant increase in homozygosity for the minor allele (T) was detected in patients with BD; 5% had this genotype, but no controls (p=0.001). The distribution of allels did not differ between patients and controls. No significant differences were found in allele or genotype distribution for three other SNPs.

The findings suggest that the PCHDα is an interesting gene family to consider in BD susceptibility.