Bipolar Disorder type 1 (BP-1) is a severe and common psychiatric disorder with a strong genetic contribution to increased disease risk. Heritability is around 60% and at least a dozen different genes seems to be involved in the etiology. The DAOA-G72/G30) locus on chromosome 13p22-34 has been associated with BP-1 in at least six independent datasets, although there are different SNPs and haplotypes associated with increased disease risk in these studies.

276 Swedish patients with BP-1, diagnosed according to DSM-IV, and 940 controls were analyzed with 36 SNPs from eight previously reported candidate genes for bipolar disorder (DAOA-G72/G30, P2RX7, COMT, BDNF, CAMKK2, GRK3, SLC6A4 and S100A10). Genotyping was carried out with Applied Biosystems TaqMan® using ABI PRISM® 7900HT Sequence Detecting System. Statistical analysis was performed with the Unphased program.

None of the SNPs showed a significant association by itself. However, three SNPs in different haplotype blocks in the DAOA-G72/G30 genes were together associated to bipolar disorder (p=0.0009). The association remained when different SNPs in each haplotype block were analyzed.

This is the first study of the G72/30 gene in a homogeneous Swedish BP-1 sample. We found a strong association, which required SNPs from three different haplotype blocks. Thus, the association between the DAOA-G72/G30 genes and Swedish patients with BP-1 disorder was more complex than previous findings.

Traditionally, health researcher has focused on negative states, their determinants and consequences.Until relatively recently, few studies have been conducted on subjective moods or feelings of well-being and their determinants. The purpose of the present study was to examine the relationship between general health and psychological well-being.

Participants were 145 undergraduate students of Islamic Azad university of Azadshahr. The mean age of the participants was 24.7 years (SD = 4.52) and ages ranged from 18 to 40 years old. They were 49 men and 96 women.

All participants completed a questionnaire booklet containing two self- report measures: The Scales of Psychological Well-Being (Ryff, 1995) and General Health Questionnaire (GHQ-28).

The results of the present study demonstrate that: Correlation between psychological well-being and student's general health is meaningful and positive.

Combined data are presented from two long-term, phase III studies (D1447C00126; D1447C00127) that examined the efficacy and safety of quetiapine in combination with lithium/divalproex in the prevention of mood events (manic, mixed, or depressed) in bipolar I disorder.

During a stabilization phase (12–36 weeks), patients received quetiapine (400–800 mg/day; open-label; flexible, divided doses) with lithium or divalproex (target serum concentrations 0.5–1.2 mEq/L and 50–125 μg/mL). Thereafter, patients were randomized to double-blind treatment with quetiapine (400–800 mg/day)+lithium/divalproex or placebo+lithium/divalproex for up to 104 weeks. The primary endpoint was time to the first mood event, defined by medication initiation, hospitalization for a mood event, YMRS or MADRS scores ≥20 at 2 consecutive assessments, or discontinuation due to a mood event.

In total, 3414 patients entered the stabilization phase and 1326 were randomized and received ≥1 dose of study medication. Rates of recurrence were 19.3% vs 50.4% for quetiapine and placebo groups, respectively. The risk of recurrence of a mood event was significantly reduced in the quetiapine group relative to the placebo group (HR=0.30, P<0.0001). HRs for the risk of recurrence of manic and depressed events were both 0.30 (P<0.0001). Long-term treatment with quetiapine was generally well tolerated; safety data including glucose changes will also be presented.

Quetiapine in combination with lithium/divalproex is significantly more effective than lithium/divalproex alone in the prevention of mood episodes associated with bipolar I disorder, irrespective of the index episode.

Supported by funding from AstraZeneca Pharmaceuticals LP.

Bipolar disorder (BD) is chronic psychiatric disorder characterized by remission and exacerbations of mood disturbances. Treatment of BD is often complicated and includes in the first step treatment with lithium, after with other ”mood stabilizers“, antipsychotics, antidepressants.

1. - To assess the changse of treatment with lithium over the period of time

2. - The number of hospitalizations in the patients with BD and differences in using of lithium, age and type of first episode

1. - Retrospective survey of in-patient's files(1997 - 2007) with typical limitations for restrospective case survey:

2. - BD, n = 125 (67% women with BD, DSM-IV)

3. - Number of hospitalizations, average number hospitalizations/year, type of treatment, using of lithium

1. - The first episode was depressive in 62% of patients and average number of episodes: 6,2

2. - There was a steady decrease in use of mood stabilizers medication over the time(68% vs 82%)

3. - We observed increase in prescription of atypical antipsychotics (in 80% of patients; last 6 years = 93%)

4. - The using of lithium was in 52% of patients (in 41% patients during first hospitalization) with average dose 1250mg of lithium and average surface of lithium in blood: 0,64mmol/l

We find out trend in using of lithium in 52% patients with BD last time again with average dose 1250mg per day and average surface of lithium in blood 0,64mmol/l and increasing of prescription of atypical antipsychotics (last 6 years = 93%).

To study Body Mass Index (BMI) and Blood Pressure (BP) in bipolar patients.

Retrospective study in bipolar inpatients of an acute psychiatric Portuguese department during a two years period. Of the 60 bipolar inpatients, 31 were selected. The patients without height or weight data were excluded.

The mean age was 48.5 years. 66.7% of the patients were women. The most frequent pharmacological association (13.3%) was sodium valproate and olanzapine. Using INE´s (National Statistic Institute, 2007) criteria, 25.8% of these patients were overweight and 16.13% obese. Approximately 50% of the patients over 45 years were overweight or obese. Approximately 50% of the patients on sodium valproate were overweight or obese, although there was no statistically significant correlation between psychopharmacological treatment and BMI. Only 3.6% of the patients had systolic blood pressure above 140mmHg or diastolic blood pressure above 90mmHg.

The studied population has a frequency of overweight superior to the general portuguese population (25.8% vs 18.6%). The percentage of patients with hypertension is inferior comparatively to the general population (3.6% vs 20%). The results of the study show the importance of monitoring and controlling metabolic risk factors in bipolar patients. Attending to the specificities of bipolar patients it is important to study prospectively metabolic syndrome in this population.

bipolar disorder or manic-depressive psychosis is a serious chronic disease and frequent, as it affects about 5% of the population, regardless of culture or of the human race. The socio-economic cost it engenders is considerable.

Bipolar disorders are defined by criteria set in the latest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). There are several types of bipolar disorder, that all involve episodes of depression and mania to a degree, bipolar disorder is a lifelong illness. There are currently several subtypes of bipolar disorder (bipolar disorder, type I), (bipolar disorder, type II), (bipolar disorder, Type III). Different subtypes of the disease bipolar belong to what is now called bipolar spectrum. This distinction is important clinically, because it is necessary for the therapeutic choice.

Newer anticonvulsant medications, including lamotrigine, gabapentin, and topiramate are being studied to determine how well they work in stabilizing mood cycle. Four major mechanisms of action underlying the pharmacological effects of anticonvulsants:

Several anticonvulsant of the last generation are currently being evaluated in the treatment of bipolar disorder. So far, the Lamotrigine is studied as a mood stabilizer and antidepressant. These new treatments may represent a promising alternative for patients resistant to the former mood stabilizer, such as lithium and valproic acid. However, many studies are still needed to determine their effectiveness and their indications.

To study the changes in plasma concentration of homovanillic acid (pHVA) and its relation with clinical outcome during treatment of Bipolar I patients with olanzapine plus lithium.

Fifty six (33 women and 23 men) Bipoar I patients, age 35.1±9.4 (SD) years, diagnosed according to DSM-IV, were treated initially with 10mg/day of olanzapine for 4 days and subsequently with 20 mg/day. On the 8th day lithium was added until a concentration of 0.6 to 1.2 mEq/L was reached in plasma. Patients were, at least, a week without neuroleptic or mood stabilizer medication.

Their clinical state was evaluated before and during 28 days of treatment with the Young scale and with the Clinical Global Impression.

Morning fasting levels of pHVA were analyzed the same days that scales were passed.

Plasma HVA after 28 days of treatment does not decline as habitually happens with neuroleptic treatment alone. Moreover, there was a trend toward significance of a Positive Correlation between pHVA and clinical improvement.

The addition of Lithium to Olanzapine altered the pattern of pHVA response from the first days of treatment up to day 28, suppressing the habitual decline in pHVA concentration. These results are similar to those observed by Bowers et al. (1992) when lithium was combined with perphenazine. The correlation between changes in pHVA concentration during 28 days of treatment and clinical outcome was the opposite to that found in schizophrenic patients treated with neuroleptics alone.

In bipolar disorder, hospital treatment is generally required in acute manic episodes, due to lack of compliance and adherence to treatment, and in episodes with marked depressive symptoms, especially suicidal ideation. Analyzing patterns of hospital admission rates is important in order to estimate treatment outcomes in both the acute and remitting phases of the disease. The aim of this study was to analyze secular trends in admissions and re-admissions for bipolar disorder in Sweden.

For bipolar disorder and its subdiagnoses, the number of admissions, length of stay and days in hospital during 1997-2005 was calculated. Readmission rates over five years were calculated for patients discharged for the first and the second time during 2000.

The number of admissions for patients with bipolar disorder in Sweden increased from around 3,500 to more than 4,000, partly explained by increasing rates of first admissions. Three fourths were readmissions. Hospital days increased, since the length of stay was not reduced. Manic episodes represented half the hospitalizations, depressive a quarter, and mixed ten percent. Patients with their second admission had 1.9 readmissions during five years, compared to 1.2 for patients with their first admission in 2000.

Physicians should consider early and effective treatment with long term outcomes in mind. The progressive course is clearly shown by the increasing rates of readmissions after the second admission compared to the first. The increasing number of first admissions is an indication that more patients have received a bipolar disorder diagnosis.

To examine efficacy and tolerability of topiramate as an adjunctive treatment for overweight refractory bipolar patients.

Patients (n=30) with Bipolar I or II, were provided with an open label treatment with topiramate as an add-on therapy. All patients deemed refractory to at least one mood stabilizer, were overweight, and were treated with topiramate as an adjuvant to existing medication for at least 12 weeks. The primary effectiveness measure was the Clinical Global Impression Scale (CGI). Other scales included the Young's Mania Rating Scale (YMRS), and the Hamilton Depression scale (HAMD21). Measures prior to adding topiramate were compared to those repeated at 4, 8 and 12 weeks. Tolerance, and weight changes were monitored.

There was significant reduction in both depressive and manic symptoms with adjunctive treatment. The mean BMI at 12 weeks of topiramate treatment dropped by 2 points (p<0.0001).

Topiramate is an effective adjunctive treatment in bipolar refractory patients and the significant weight reduction effects may result in important medical risk reductions, and make topiramate attractive for some obese bipolar patients.

Psychiatric manifestations are very common in Connective Tissue Disorders as a manifestation of the disease process itself and not exclusively related to medication but are frequently overlooked by Psychiatrists and not taken into account by non-psychiatric Physicians.

A brief summary of literature on the topic and presentation of clinical cases in which psychotic manic-like or depressive-like episodes are the first manifestation of Connective Tissue Disorders and how these cases evolve resembling Bipolar Disorder.

Atypical clinical presentations and other clinical signs and symptoms may lead to further diagnostic testing with positive Anti-nuclear and other auto-antibodies and the possible diagnosis of Connective Tissue Disorders.

Psychotic manic-like and depressive-like episodes may be the initial presentation of Connective Tissue Disorders. Screening of ANA and anti-DNAds may eventually be warranted on a routine basis.

Recent studies found an association between the psychotic phenotype of bipolar (BP) disorder and the G72/G30 gene. As the psychotic features are considered a promissing phenotypic trait that might enhance the chance of identifying the genes underlying the BP, we tried to estimate the heritability of psychotic features in connection with the parent-of-origin and proband /affected relative gender.

244 unilineally affected families in which the proband had relatives diagnosed with BP, schizoaffective disorders, schizophrenia, recurrent MDD-UP were selected from our sample of 376 families ascertained through a BP-I proband from consecutive hospital admissions without regard to familial psychopathology. The data were analysed with SAGE 5.4-software (ASSOC and FCORR) (Elston et al, 2007).

In the total familial sample the sex of the affected individuals significantly influenced the total variance of the PSYCHOSIS-liability. Females were more prone to PSYCHOSIS (OR=1.64, 95%CI=1.47-1.65) being 2-times more frequently psychotic than males. The parent-of-origin did not influence the variance of PSYCHOSIS-liability (p=0.75). Nevertheless in families with paternal (PAT) transmission (N=133) the heritability of PSYCHOSIS was higher than in maternal (MAT) families (N=111) . (11.56% versus 6.86%). In PAT families the parent-offspring transmission was significant (p=0.046), while the sibling effect (that includes parent-offspring correlation and environmental influences) was not significant (p=0.22). In MAT families the parent-offspring transmission was not significant (p=0.41), while the sibling effect was significant (p=0.0022).

Our data show that sex and parent-of-origin may modify the liability to psychotic BP. Genetic factors seem to be stronger in PAT families.

Risk of suicide in bipolar disorder (BP) patients is one of the highest in psychiatric disorders. It is stated that long term treatment with lithium, selectively, can reduce the risk of suicide commitments and attempts. In our study, rates of suicide attempts of BP patients before and after treatment with a mood stabilizer (MS) and the relationship between suicide and other risk factors are investigated in a specialized tertiary outpatient mood disorder clinic in Istanbul, Turkey.

Charts of 608 bipolar disorder patients (DSM-IV) followed in our outpatient mood disorder clinic were evaluated retrospectively and 89 containing incomplete or unreliable data about the suicide history were excluded.

Lifetime rates of suicide attempts were 19,9% for BP-I patients (n=95), 50% for BP-II patients (n=8), 8,3% for BP-NOS patients (n=2) respectively. The rate of suicide was higher in BP-II patients. Duration of illness and onset as depressive episode were found as significant predictors of suicide attempt in logistic regression analysis. The rate of suicide attempt before treatment with MS was higher than the rate after treatment with MS (15,6% vs. 6,2%; p<0,001). Our findings suggest that the risk of suicide attempts in bipolar patients and especially in BP-II is highly increased, predicting the factors of suicide earlier and treating patients adequately could prevent this risk efficiently.

To evaluate the efficacy and safety of aripiprazole monotherapy as acute and continuation therapy for acute bipolar I mania.

Patients with acute bipolar I mania were randomized (1:1:1) to double-blind aripiprazole (15–30 mg/day; n=155), placebo (n=165) or lithium (900–1500 mg/day; n=160) for 3 weeks. At the end of Week 3, patients randomized to placebo were blindly switched to aripiprazole. Key efficacy outcome measures were mean change from baseline in YMRS Total score at Week 3 (LOCF; primary endpoint) and Week 12.

Improvements in YMRS Total scores from baseline were significantly greater versus placebo as early as Day 2 with aripiprazole (p=0.003) and Day 7 with lithium (p=0.040; LOCF). At Week 3, improvements from baseline in mean YMRS Total scores were significantly greater with aripiprazole (–12.96; p<0.001) and lithium (–12.03; p=0.005) versus placebo (–9.01; LOCF). These improvements were maintained to Week 12 (LOCF) with both aripiprazole (–14.48) and lithium (–12.71). Response rate was significantly greater versus placebo as early as Day 2 with aripiprazole (p=0.026), and Day 10 with lithium (p=0.006; LOCF). Response rates continued to increase over the study period and at Week 12 were 56.5% with aripiprazole and 49.0% with lithium.

Aripiprazole significantly improved symptoms as early as Day 2 and throughout the 3-week, placebo-controlled portion of this study in acutely manic patients. The beneficial effects of aripiprazole were sustained through Week 12 and were similar to lithium, confirming the robust efficacy of aripiprazole in these patients.

Risperidone has shown to be effective and generally well tolerated in the treatment of patients with acute manic episodes in bipolar disorder when given as monotherapy or in combination in randomized-controlled-trials. This non-interventional study served to add evidence for therapeutic benefit of risperidone in this indication in a clinical routine-setting.

Prospective, multi-center non-interventional trial (RIS-BIM-4001) performed in Germany. Inpatients with a baseline score ≥20 in the Young-Mania-Rating-Scale (YMRS) were eligible for enrollment. All patients were evaluated based on intent-to-treat-analysis (ITT).

251 patients were evaluated (54% female, median age 46 years). The most frequent concomitant medications during the study were valproic acid (40%), lorazepam (36%), diazepam (33%) and lithium (24%). The mean daily dose of risperidone at endpoint was 4.5±1.5mg/day. Mean YMRS total score improved significantly from baseline to endpoint (33.6±8.5 to 14.6±8.8; p<0.0001), also mean MADRS total score (13.14±5.83 to 7.18±5.8; p<0.0001) and mean BPRS total score (13.5±5.1 to 7.4±3.6; p<0.0001). A total of 185 AEs was documented in 100 (39.84% out of the total ITT-patients), thereof 102 AEs (55,1%) in 59 patients (23.51%) were evaluated by the physicians an at least possible causal relationship to risperidone. Most frequent were EPS (6.4%).

In this non-interventional trial oral risperidone treatment was associated with a significant and clinically relevant improvement of psychopathology. These data are in line with the results of previous randomized controlled trials and support the good tolerability and safety of risperidone in the treatment of bipolar inpatients with acute moderate to severe manic symptoms.

Recent research indicates intramuscular ziprasidone produces a significant, early (within 24 hours) improvement in psychotic symptoms. In this analysis, we evaluated the potential for an early antipsychotic response to oral ziprasidone in subjects with acute bipolar mania.

We conducted a pooled analysis of two 3-week, randomized, double-blind, placebo-controlled trials of ziprasidone (40-160 mg/d) in hospitalized patients (N=415) with bipolar I disorder, and a current manic (N=257) or mixed episode (N=158), with (N=151) or without (N=245) psychotic features. Efficacy assessments included the Mania Rating Scale (MRS, derived from the SADS-C). Remission was defined as achieving a MRS score <= 12. Improvement in psychosis was evaluated by a sum of the three SADS-C psychosis items (delusions, hallucinations, and suspiciousness). MMRM and logistic regression analyses were applied to estimate the time course of response.

Significantly greater response rate (>50% decrease from baseline) and improvement in the SADS-C psychosis score were observed in the ziprasidone group (versus placebo) as early as Day 4 (p<0.01), and the magnitude of improvement increased with time (p<0.003). At Day 21, remission rate with ziprasidone monotherapy was 49% versus 36% in the placebo group (p=0.02). Early antipsychotic response at Day 4 was an accurate predictor of remission at Day 21 (p<0.01, ROC=0.76).

Ziprasidone was associated with a rapid onset of response in psychotic symptoms in patients with acute bipolar mania. This early reduction in psychotic symptoms was found to mediate overall improvement in manic symptoms and predict remission at endpoint.

To investigate the prevalence of mixed episodes during the course of illness in bipolar disorder.

A total of 1620 patients with an ICD-10 diagnosis of bipolar affective disorder at the first psychiatric contact were identified in a period from 1994 to 2003 in Denmark and the prevalence of mixed, depressive and hypomanic/manic episodes were calculated at each episode.

The prevalence of mixed episodes increased from the first episode to the tenth episode, however, only for women (6.7 % of the first episodes leading to psychiatric care compared to 18.2 % of the tenth episodes). For men, the prevalence of mixed episodes was constantly low. At all episodes, the presence of a current mixed episode increased the risk substantially of getting a future mixed episode.

Clinicians should pay more attention to mixed episodes, especially among women, as they may represent an increasing treatment challenge as the illness progress.

To describe 12 month outcomes of French patients enrolled in EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication).

EMBLEM is a prospective, observational study on outcomes of manic/mixed episode. Adult patients were enrolled within the standard course of care if they initiated/changed oral medication for treatment of acute mania. All treatment decisions were at the discretion of the treating psychiatrist. 530 psychiatrists (126 French) enrolled 3459 eligible patients (771 French). 12 months results of the French cohort will be presented.

At baseline, mean age was 45.5 years (sd 13.6) and 59% were female. 68% were outpatients and 34% had a mixed episode. 76% of French patients were eligible for follow-up at 12 months. 80% improved (CGI-BP overall decrease >2) during follow-up whereas 47% patients never achieved recovery (two consecutive CGI-BP overall <2). 37% of patients presented with no medication at baseline. 41.6% were started on monotherapy and 58.4% on combination therapy; of those 54% and 28% respectively remained on their initial medication throughout the 12 months. 25% were treated with antidepressants in addition to their new oral medication, which increased to 35% at 12 months.

In this naturalistic study, less than half of French patients achieved recovery during 12 months follow-up. Antidepressant was frequent at baseline and use increased during follow-up. Twice as many patients remained on the same monotherapy as those on the same combination therapy

Low serum total cholesterol has been reported to be assotiated with risk of suicidal, violent and impulsive behaviours. To date there are no laboratory tests for diagnosing bipolar disorder (BD). Case vignette to illustrate the clinical observation of changes of serum total cholesterol (STChol) and mood disturbaces of patient with bipolar disorder (BD) at admission and in remission was used.

A 23- years old, healthy and drug-free female met the ICD-10 criteria for bipolar disorder. She was assesed during two mixed episodes to explore change in serum cholesterol (Chol) levels at admission (A) of first (1e) episode and after remission (R), one month later. The readmission due to second consecutive mixed episode (2e) was 19 months later. MADRS scale for depression and YMRS scale for mania were applied, and body mass index (BMI) was assessed.

Chol-1eA 2,50 mmol/l (normal range 3,63-6,20 mmol/l), Chol-1eR 3,90 mmol/l; Chol- 2eA 3,05 mmol/l. BMI-1e 20,5 BMI-2e 21,0. YMRS-1eA score 27, YMRS-1eR score 4, MADRS-1eA score 23, MADRS-1eR score 3, YMRS-2eA score 23, MADRS-2eA score 21. The patient did not change her diet during the course of illness.

In this case low STChol was assotiated with the oncet of mixed episodes of BD and normalised after remmision of episode. Low STChol could be a state marker or risk factor for mixed episode of BD. Further investigations are need to explore the possible relationship between STChol and course of different episodes of BD.