Pregnancy and the postpartum are times of increased risk for women with bipolar disorder to develop new episodes.

To evaluate factors that are supposed to be associated with recurrence of bipolar I disorder among euthymic women with a history of bipolar I disorder, which could be used as a predictors of bipolar I disorder in that period.

Eighty-three pregnant women with history of bipolar I disorder were followed through pregnancy and post-partum periods for possible recurrence of a new episode. All women were assessed using the MINI International Neuropsychiatric Interview. Factors that may contribute to recurrence were assessed prospectively; these included age of patients, age of onset of bipolar disorder, duration of illness, number of previous attacks, number of previous pregnancies, prior episodes in pregnancy or postpartum, complications during pregnancy and labor, pregnancy type, prior hospitalization, prior suicidal attempts, time since last episode in months, and continuation of medications.

Sixty five % of euthymic bipolar females had recurrence of a new episode, either during pregnancy (33.73%) or 4 weeks postpartum (31.32%). Discontinuation of medications, longer duration of illness, more number of previous attacks, more number of previous pregnancies, more prior episodes in pregnancy, more complication during pregnancy, more complication during labor, unplanned pregnancy type, prior hospitalization, were associated with recurrence of bipolar disorder during pregnancy and postpartum.

Multiple factors were associated with risk of recurrence of bipolar I disorder during pregnancy and postpartum, which should be while planning treatment for such women.

Kraepelin described in “manic-depressive insanity” (1899/1913) co-ocurrence of opposite polarity symptoms in mania, hypomania, and depression. A full opposite polarity syndrome was not required to diagnose mixed state(s). Actually, mixed state(s) in the official nosology - ICD-1o and DSM-IV - is essentially limited to fullblown mixed state(s) with concomitant syndromal mania and depression. Nevertheless in the past 35 years contributions of Akiskal, Benazzi, and others followed a time of opposition to Krapelin's concept of mixed states - on the part of proeminent psychiatrists, namely: Karl Jaspers and Kurt Scheneider.

To review knowledge about depressive mixed state(s) and its importance in clinical practice.

To emphasize recent evidence supporting clinical and treatment implications of depressive mixed state(s) in both unipolar and bipolar depressed patients.

Sciencedirect and Pubmed search of English-language papers published between January 2000 e September 2010 using and cross-listing key words: bipolar mixed states, depressive mixed state/s, mixed depression, excited depression, agitated depression and suicide.

Recently depressive mixed state(s) was “redefined” and validated as a major depressive episode with some concurrent hypomanic symptoms, its diagnostic validity supported by familiar history and its utility supported by treatment response (negative effects of antidepressants).

No response, worsening and suicidality observed in some depressed patients on antidepressants may reflect the inadequacy of our current oficial nosology which fails to recognize patients for whom antidepressant therapy unprotected by mood stabilizing agents and/or atypical antipsychotics appears to be inappropriate.

There are manic disorders with depressive symptoms in mixed mania that do not reach the threshold for the diagnosis of mixed episode.Mania and hypomania are evaluated with scales that do not detect the depressive symptoms of patients in manic episode.

To determine the usefulness of HAMD-5 and MES depression scales in patients with bipolar disorder type I and II who have a manic or hypomanic episode with depressive symptoms. These scales were compared with the HAMD-21 and the MADRS scales respectively.

100 subjects between 18 and 65 years old were included. All patients met the DSM-IV-TR criteria for bipolar disorder with manic or hypomanic symptoms and major depression.All patients were evaluated at baseline and at 3 and 4 weeks during the follow-up.

At baseline the HAMD-5 and the MES had high reliability (α = 0.88 and α = 0,74 respectively)The test-retest reliability between the 3rd and the 4th week was great for both scales (HAMD-5: r = 0,89; p < 0,001; MES: r = 0,77; p < 0,001).The convergent validity had an acceptable level for the HAMD-5 (HAMD-21/HAMD-5 = 0,73; 95% CI 0,599–0,873) and for the MES (MADRS/MES = 0,79; 95% CI 0,766–0,894)Regarding the discriminant validity, the values for the HAMD-5 and MES were higher than for the HAMD-21 and MADRS respectively (HAM-5: AUC = 0,92, 95% CI: 0,892–0,980; MES: AUC = 0,86, 95% CI: 0,786–0,934).

Both scales showed an adequate correlation with the HAMD-21 and MADRS and a high capacity of detection of mixed, pure and other symptoms as their remission.

Non-adherence of medication still is a major problem among patients suffering from bipolar disorders.

Previous studies focused mainly on possible side-effects, attitudes and subjective well-being. Most scales concerning this issue have been developed by psychiatric experts and based on their knowledge not on the patients points of view.

The purpose of this study was to find out what kind of drug effects the patients themselves want.

2 focus-groups with 13 patients and In-depth interviews with 15 mania patients were conducted to collect information about subjective burden and symptoms of the illness. Content analyses of the transcriptions were performed and the results were used to develop a first draft of the questionnaire.

The final German test version consists of 32 items and is called “The Subjective Mania Scale”. The study of content-validity showed that all SMS items were considered to be important by more than 50% of the sample. Test-retest reliability and sensitivity to change were evaluated. All SMS-items showed a significant change between time-point 1 and 3.

The SMS-rating scale is a feasible, reliable and valid instrument for clinical trials among mania patients.

Recent epidemiological studies suggest that the prevalence of bipolar disorder might be misdiagnosed initially as unipolar depression due to the difficulty to detect episodes of hypomania. The Hypomania Checklist (HCL-32), validated in Spanish, is a self-report questionnaire with 32 hypomania items designed to screen for hypomanic episodes.

To examine the prevalence of hypomania in patients with unipolar depression. Corroborate the efficacy of the HCL-32 to detect symptoms of hypomania.

The presence of hypomanic symptoms was assessed by the HCL-32 in a sample of 128 subjects diagnosed with bipolar I disorder (n = 30), bipolar II disorder (n = 1), unipolar depression (n = 57), and anxiety disorder (n = 15) according to DSM-IV-TR criteria. A control group of healthy subjects was selected (n = 25).

The discriminative capacity was analyzed by the ROC curve. The AUC was 0.65 which did not indicate a good capacity. The sensitivity (S), specificity (E) and prevalence (P) of hypomania in unipolar patients for the following cut-off points were :14: S = 81.6%,95%CI(69.8, 93.5); E = 30.1%,95%CI(19.7,40.6); P = 74.1%; 15: S = 77.6%,95%CI(64.9,90.3); E = 37.4%,95%CI(26.3,48.4); P = 67.2%; 16: S = 59.2%,95%CI(44.4,73.9); E = 55.4%,95%CI(44.1,74.0); P = 51.7%; 17: S = 55.1%,95%CI(40.2,70.1); E = 57.8%,95%CI(46.6,69.1); P = 48.3%.

The HCL-32 has a high sensitivity but a low specificity as screening instrument. This might explain the high proportion of hypomania found in this study. The difference with previous studies is that our sample was heterogeneous, unstable and serious. This suggests that the HCL-32 is not valid for any psychiatric sample. Future research should develop more specific instruments with better external validity.

According to recent findings, certain clinical symptoms of the patients suffering from affective and anxiety disorder can be related to dissociation. The aim of our study is to examine if the level of dissociation in bipolar affective disorder differ from the level of dissociation in healthy volunteers.

41 patients suffering from bipolar disorder (51.2% females), and 198 healthy controls (71.2% females) were included in the study. The patients with bipolar affective disorder in remission of the illness were recruited from the Outpatient psychiatric department of Psychiatry Clinic of University hospital Olomouc. Patients were psychiatrically assessed and the state of the disorder was evaluated by experienced psychiatrist. Only patients in remission of the disorder, evaluated as 1 or 2 points of clinical global impression - severity scale, were included into the study. All participants were assessed with the Dissociative Experiences Scale (DES).

The groups didn’t differ in demographic variables like age, gender and education. Patients had significantly higher mean score on the DES and pathological DES than healthy controls.

Our results suggest that the level of psychological dissociation in bipolar affective patients is higher than in healthy controls.

Supported by grant IGA MZ ČR NT11047

The study investigated the effect of the parental age on the age-of-onset (AO) in bipolar I disorder (BPI) in connection with proband gender and family history for major psychoses in a directly interviewed sample of 530 BPI probands.

All 530 probands, 73.0% of their first-degree and 22.62% of their second-degree relatives were administered the DIGS and FIGS interviews. The family history (FH) method was used for unavailable relatives. The impact of parental age on proband early/late AO was evaluted through logistic regressions. The commingling analysis (SAGEv6.1-software) was used to determine the cut-off age separating the early/late AO.

We evidenced a significant influence of the paternal age ≥ 35 years on AO in BPI disorder in the total sample (p = 0.023) and in some subgroups defined by positive/negative FH for major psychoses: the sporadic group (p = 0.035) and the group with FH of recurrent unipolar major depression (Mdd-RUP) (p = 0.041). No effect of the paternal/maternal age on disease AO was found in patients with FH of bipolar/schizoaffective disorders/schizoprenia (BP/SA/SCZ). The global significant effect of the advancing paternal age on the decreasing proband AO was generated by female patients (p = 0.022). No effect of the paternal/maternal age on disease AO was found in male patients. Paternal age was older in fathers of sporadic cases and of cases with FH of Mdd-RUP than in cases with FH of BP/SA/SCZ (p = 0.011).

We evidenced a selective effect of the advancing paternal age on bipolar onset depending on offspring gender and type of FH for major psychoses.

Phenotype homogeneity and heritability are important conditions for identifying the genetic basis of bipolar I disorder (BPI) in association studies. Our objective was to study the heritability of mood-incongruent psychosis (MIP) in BPI in a sample of 504 families ascertained through BPI probands (294 females; 210 males) recruited from consecutive hospital admissions.

There were 402 families with a psychotic proband and 275 families with a proband with MIP. All probands were directly interviewed as well as 79.55% first-degree and 22.59% second-degree relatives. The narrow and the broad sense heritability (h2) of MIP and the effect of sex and age were estimated using S.A.G.E.v.6.01-software (2009).

There was no sex difference for the psychosis prevalence in probands but MIP was two times more frequent in females than in males. In families with MIP probands the narrow-sense h2 for MIP was 0.14 (SE = 0.02, P = 0.002) and the broad-sense h2 was 0.20 (SE = 0.014, P = 0.0000). Significant but lower heritabilities were found in families with a psychotic proband (narrow-sense h2 = 0.12; broad-sense h2 = 0.13). In the total sample the narrow-sense h2 was 0.06 (P < 0.005) and the broad-sense h2 was 0.10 (P < 0.00001). The female sex was more prone to incongruency (χ2 = 33.32, P = 0.0000).

The heritability of MIP was significant but not high in families ascertained through BPI probands regardless of familial psychopathology. These finding is in line with GWAS-studies showing that the polygenic score fails to differentiate psychotic BPI from non-psychotic BPI. Is therefore incongruent psychosis a useful dimension for association studies?

The aim of our study is the investigation of burn-out indexes in public mental health services employees (psychiatrists, psychologists, nursing staff, care providers) working with patients affected by Bipolar Disorder in order to correlate them with patients’ indexes of satisfaction about received treatment and care.

A sample of 20 employees of mental health services (psychiatrists, psychologists, nurses) and one consisting of 22 patients with a diagnosis of Bipolar Disorder have been recruited at the Bipolar Disorders Unit of the Day Hospital of Psychiatry of the A. Gemelli Hospital in Rome. Operators have been submitted the Maslach Burnout Inventory (Emotional distress, Depersonalization, Personal satisfaction/achievement/fulfilment) while patients have been submitted the Questionnaire on Satisfaction of patient (QS)

By calculating the Spearman Correlation Coefficient the Depersonalization dimension proves highly correlated with the three subscales of QS: Doctor-Patient relationship quality (-.51); Information Quality and Doctor's therapeutic competence (-.48); Efficiency of service organization (-.58)

In our sample high levels of Depersonalization are correlated to a low satisfaction of patients. We therefore expect low levels of Depersonalization to be correlated with a higher satisfaction of the patient. Although it is not possible to generalize these results we can hypothesize that burn out negatively influences patients’ satisfaction.

Temperament represents one of the basic elements of bipolar spectrum.

A systematic search was undertaken in MEDLINE (from 1977 to 2007) to obtain articles published in English regarding the association of temperament and bipolar disorder. Keywords used were “temperament”, “bipolar disorder”, “assessment”, “bipolar spectrum”, “subthreshold”.

In opposition to the dichotomic conception which up to the end of XIX century considered mania and depression as two distinct and separate categories, Kraepelin has postulated a psychopathological “continuum” between temperament and affective disorders called “bipolar spectrum”. This concept has been reintroduced in contemporary psychiatry by Akiskal's works. By rebuilding the history of patients affected by bipolar disorder, temperamental traits can be already observed in the pre-morbid period and can also persist during disorder-free intervals.

By interpreting and diagnosing multiple expressions of bipolar spectrum, psychiatrists today are facing one of the most important challenges in everyday clinical practice. The temperamental “dysregulation” is the pathological basis of mood disorders and some temperamental traits in individuals can reflect a predisposition to develop a mood disorder.

Previous studies have provided evidence for Theory of Mind (ToM) impairment in bipolar disorder (BD). The aim of the study was to determine whether ToM impairment can be considered as a trait- marker or a state characteristic of BD.

ToM was assessed in 29 patients with bipolar-I during an episode and in remission as well as in 29 pair-matched for age, gender and education level healthy controls. Three different ToM tests were used (multilevel assessment): First Order False Belief Stories, Hinting Test, Faux Pas Recognition Test. Attention, memory, verbal learning ability, visuospatial ability, executive functions were also assessed using WAIS – Vocabulary, Block design, and Digit span, Stroop Test, Rey Auditory Verbal Learning Test, Trail Making Test, Wisconsin Card Sorting Test. Paired t-test was used to compare patients’ neuropsychological performance in episode and euthimic states and one-way ANOVA with post hoc Bonferroni corrections for the between groups comparisons.

Patients showed significant impairments on ToM tasks in the acute phase compared to the control group. ToM deficits did not persist beyond mood episode, except patients’ poor performance on Faux Pas. Dysfunction in verbal learning, working memory, visospatial ability was found during both the acute and the euthymic phases in relation to the comparison group. Poorer performance in attention, immediate verbal memory and executive function tasks was observed only in the acute phase of the illness.

Impairments in social cognition might reflect underlying general cognitive deficits and residual symptoms rather than representing a specific trait-marker in BD.

Emotional dysregulation in Bipolar Disorder (BD) is thought to be linked with prefrontal cortex (PFC) dysfunction associated with cognitive control coupled with increased or aberrant activation within regions associated with emotional processing.

To determine the common and distinct patterns of functional brain abnormalities during affective and emotionally neutral cognitive processing in BD.

Current models of BD emphasise the relationship between mood dysregulation and fronto-limbic dysfunction during affective or “hot” processing. However, they do not account for deficits in emotionally neutral or “cold” tasks of memory and executive function which are also present in BD. Therefore the purpose of this study was to examine the neural correlates of affective decision making and working memory in BD.

Participants were 36 euthymic BD patients and 37 healthy controls matched for age, gender and IQ. FMRI was conducted during the Iowa Gambling Task (IGT) and the n-back working memory task as respective exemplars of “hot” and “cold” processing.

There were no group differences in performance on either task. BD patients demonstrated a pattern of inefficient engagement within the ventral frontopolar PFC in both the IGT and n-back. These abnormalities showed task-related segregation along the medial-lateral dimension for “hot” and “cold” processing respectively. Patients also showed greater activation in the anterior cingulate cortex during the IGT and in the insula during the n-back. These regions are thought to respond to markers of autonomic arousal.

These data demonstrate ventral frontopolar PFC inefficiency as a shared abnormality underpinning both “hot” and “cold” processing deficits in BD.

Bipolar I Disorder (BID) might be diagnosed primarily as schizophrenia or major depressive disorder in children and adolescents due to unstable or vague symptoms. The depressive phase not yet followed by a manic or mixed episode in either adults or adolescents may lead to an early misdiagnosis. The concept of mixed episode as a manic episode intruding on previous depressive traits puts emphasis on early managements that may lead to a mixed episode.

Assess of changes in clinical features of BID.

To determine the frequency of mixed and manic phase of BID and assess change in rate of mixed versus manic episode on a year-over-year basis.

Study is a cross sectional study performed on 322 patients diagnosed with BID hospitalized in the psychiatric ward of Imam Hossein Hospital during the years of 1991 to 2006. Each episode was considered as an individual case. A single psychiatrist used DSM IV-TR criteria to differentiate a mixed episode from a manic one.

Among 322 patients, 117 were cases of mixed episode and 205 patients were diagnosed as manic episode. Year-over-year comparisons showed an increasing rate of the diagnosis of mixed episode during the course of the study.

The increased rate of the diagnosis of the mixed episode during the period of the study drives attention to all the probable factors that might have a role on the subsequent changes of the clinical feature of BID toward mixed episode.

There are major health care implications of quality of life (QOL) in longstanding disorders such as Bipolar affective disorder (BD) for the patients and their caregivers.

The aim of the present study is to compare quality of life among bipolar disorder patients, their caregivers and to assess whether the level of depression correlates with the scores of quality of life in Bipolar Disorder patients.

We compared bipolar disorder (N = 40), their caregivers (N = 40) and no psychiatric illnesses (N = 150) on health related quality of life (HRQOL) which was assessed using the 26-item World Health Organization QOL instrument (WHOQOL-BREF Hindi version). All patients were diagnosed using the Structured Clinical Interview for DSM IV. Within the group with bipolar disorder, we examined the relationship between HRQOL using WHOQOL BREF Hindi version and depression assessed using the 17-item Hamilton Depression Rating Scale (HDRS).

Patients in bipolar disorder group had lower QOL on all the four domains compared to healthy controls, caregivers. The four domains of the WHOQOL scale correlated negatively with the HDRS.

Our findings suggest that bipolar depression and residual symptoms of depression are negatively correlated with QOL in BD patients.

Agitation and aggressive behavior are common symptoms in patients with an acute relapse of bipolar mania.

Quetiapine XR is an effective treatment in agitated patients with an acute relapse of bipolar disorder.

The aim of this study was to assess the efficacy and tolerability of Quetiapine XR in patients with manic episode.

This naturalistic, observational study evaluated 45 patients diagnosed with manic episode, bipolar disorder I (DSM IV-TR) for a period of 4 weeks, during which the patients received Quetiapine XR, in doses between 800 mg and 1000 mg per day, using a rapid titration scheme.

Efficacy of the treatment was measured using Young Mania Rating Scale (YMRS) and Clinical Global Impression Scale (CGI), performed at baseline, and then weekly. The Overt Aggression Scale-Modified (OAS-M) was used daily until day 4 and then once per week. Extrapyramidal symptoms were assessed with Barnes Akathisia Rating Scale and Abnormal Involuntary Movement Scale.

Important improvement of OAS-M total score was observed from the second day of treatment. After 4 weeks, more than a half of the patients presented a decrease of YMRS score with more than 50%. The CGI score also significantly improved. The treatment was well tolerated, mild to moderated adverse reactions being registered, without extrapyramidal symptoms.

These results confirm that Quetiapine XR is an effective and safe treatment for patients with an acute relapse of bipolar disorder I, the rapid titration scheme of the doses leading to a good control of aggressive behavior.

Autonomic nervous system (ANS) dysfunction and reduced heart rate variability (HRV) have been reported in a wide variety of psychiatric disorders, but have not been well characterized in bipolar patiens in remission. We recorded cardiac activity and assessed HRV in bipolar outpatients in remission.

Ascertain if ANS decrease with the age of the patient; ascertain relation between activity of ANS and level of dissociation, and other components (age of patients, and age of disorder, dosage of psychotropic medication)

Autonomic nervous system (ANS) has been evaluated during orthostatic change in three positions (1- lie down 5 minutes, 2 – stand up 5 minutes, 3 – lie down 5 minutes). The functioning of the ANS has been measured by the diagnostic systems that are using the power spectral analysis which quantifies the heart rate variability (HRV) was assessed using time domain, frequency domain, and nonlinear analyses in 23 bipolar patients in remission.

We found highly statistically significant negative correlations between level of dissociation measured by DES and most of parameters of ANS. We found negative correlations between the age of the patient and activity of ANS, and negative correlations between activity of ANS and duration and onset of disorder.

Autonomic dysregulation is associated with bipolar disorder in remission and has relation to level of dissociation and probably to age of patiens and age of onset and duration of disorder.

Supported by grant IGA MZ ČR NT11047