A. González-Pinto

Staging systems in bipolar disorder: an International Society for Bipolar Disorders Task Force Report.

We discuss the rationale behind staging systems described specifically for bipolar disorders. Current applications, future directions and research gaps in clinical staging models for bipolar disorders are outlined.

Principal components of mania

OBJECTIVE An alternative to the categorical classification of psychiatric diseases is the dimensional study of the signs and symptoms of psychiatric syndromes. To date, there have been few reports about the dimensions of mania, and the existence of a depressive dimension in mania remains controversial. The aim of this study was to investigate the dimensions of manic disorder by using classical scales to study the signs and symptoms of affective disorders. METHODS One-hundred and three consecutively admitted inpatients who met DSM IV criteria for bipolar disorder, manic or mixed were rated with the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HDRS-21). A principal components factor analysis of the HDRS-21 and the YMRS was carried out. RESULTS Factor analysis showed five independent and clinically interpretable factors corresponding to depression, dysphoria, hedonism, psychosis and activation. The distribution of factor scores on the depressive factor was bimodal, whereas it was unimodal on the dysphoric, hedonism and activation factors. Finally, the psychosis factor was not normally distributed. LIMITATIONS Patients of the sample were all medicated inpatients. CONCLUSIONS Mania seems to be composed of three core dimensions, i.e. hedonism, dysphoria and activation, and is frequently accompanied by a psychotic and a depressive factor. The existence of a depressive factor suggests that it is essential to evaluate depression during mania, and the distribution of the depressive factor supports the existence of two different states in mania.

Peripheral brain-derived neurotrophic factor in schizophrenia and the role of antipsychotics: meta-analysis and implications

It has been postulated that schizophrenia (SZ) is related to a lower expression of brain-derived neurotrophic factor (BDNF). In the past few years, an increasing number of divergent clinical studies assessing BDNF in serum and plasma have been published. It is now possible to verify the relationship between BDNF levels and severity of symptoms in SZ as well as the effects of antipsychotic drugs on BDNF using meta-analysis. The aims of this study were to verify if peripheral BDNF is decreased in SZ, whether its levels are correlated with positive and negative symptomatology and if BDNF levels change after antipsychotic treatment. This report consists of two distinct meta-analyses of peripheral BDNF in SZ including a total of 41 studies and more than 7000 participants: (1) peripheral BDNF levels in serum and plasma were moderately reduced in SZ compared with controls. Notably, this decrease was accentuated with the disease duration. However, the extent of peripheral BDNF level decrease did not correlate with the severity of positive and negative symptoms. (2) In plasma, but not serum, peripheral BDNF levels are consistently increased after antipsychotic treatment irrespective of the patient’s response to medication. In conclusion, there is compelling evidence that there are decreased levels of peripheral BDNF in SZ, in parallel to previously described reduced cerebral BDNF expression. It remains unclear whether these systemic changes are causally related to the development of SZ or if they are merely a pathologic epiphenomenon.

Psychoeducation and cognitive-behavioral therapy in bipolar disorder: an update

Objective:  To review the available literature on psychoeducation and cognitive‐behavioral therapy (CBT) in bipolar disorder (BD) and to give an integral view of these therapies.

Tardive dyskinesia associated with higher mortality in psychiatric patients: results of a meta-analysis of seven independent studies.

This article reports a meta-analysis of seven independent studies on the association of tardive dyskinesia with all-cause mortality in psychiatric patients. Most of the studies included provide either small sample sizes or follow-up periods too short to reach a substantive conclusion on their own. In the meta-analysis, the overall odds ratio (OR) was significant when calculated either by the fixed-effects model (OR = 1.4, 95% confidence interval [CI] = 1.2-1.7, p < 0.005) or the random-effects model (OR = 1.4, 95% CI = 1.1-1.8, p < 0.005). There was no overall heterogeneity (Q test = 8.1, df = 7,p = 0.32). The overall estimate changed within study designs (OR = 1.4,p = 0.002 in three prospective controlled studies; OR = 2.2, p = 0.02 in two prospective uncontrolled studies; and OR = 0.9, p = 0.80 in two retrospective controlled studies). It was modified upward when the two most influential studies (one prospective and one retrospective) were removed from the overview (OR = 2.2, 95% CI = 1.4-3.5,p = 0.001; Q test = 0.81, df = 4,p = 0.94). The conclusion of the meta-analysis was that tardive dyskinesia must be considered a weak risk factor in terms of mortality. It remains to be elucidated whether it is a risk factor on its own or just a surrogate for any unknown organic liability.

Risk factors for suicide in schizophrenia: systematic review and clinical recommendations.

To identify risk factors associated with suicide of patients with schizophrenia and provide clinical recommendations, which integrate research findings into a consensus based on clinical experience and evidence.

Clinical implications of predominant polarity and the polarity index in bipolar disorder: a naturalistic study

Predominant polarity (PP) is an important variable in maintenance treatment of bipolar disorder (BD). This study aimed at determining the role of polarity index (PI), a metric indicating antimanic versus antidepressive prophylactic potential of drugs, in clinical decision‐making.

Assessment of Medication Adherence in a Cohort of Patients with Bipolar Disorder

INTRODUCTION This study aimed to identify factors associated with medication adherence in bipolar disorder (BPD) patients. METHODS EMBLEM is a 2-year, prospective, observational study on the outcomes of BPD patients initiating or changing treatment for a manic/mixed episode. Data were collected at baseline, during the first 12 weeks of treatment (acute phase) and up to 24 months of follow-up (maintenance phase). Adherence was assessed by investigators at every visit. Repeated measures logistic regression analyses identified variables associated with adherence. RESULTS Of 1,831 patients included in the analysis, 76.6% were adherent and 23.4% were non-adherent with their BPD medication during the maintenance phase. Patients were more likely to be adherent if they had insight into their illness at week 12. Patients were less likely to be adherent if they had cannabis abuse/dependence during the acute phase, work impairment or higher CGI hallucinations/delusions at baseline DISCUSSION Psychotic symptoms, poor insight, cannabis abuse/dependence and work impairment are negatively related to medication adherence during maintenance therapy of bipolar disorder. Patients with these characteristics may need a different therapeutic approach.

Age-dependence of Schneiderian psychotic symptoms in bipolar patients.

Psychotic symptoms frequently occur in bipolar disorder, especially in younger patients. However, whether the association with younger age also extends to psychotic symptoms that have traditionally been associated with schizophrenia, such as Schneiderian first-rank symptoms (FRSs), is unclear. This study examined FRSs in bipolar I patients and their relationship to age and gender. The sample comprised 103 consecutive inpatients who met DSM IV criteria for bipolar disorder, manic or mixed. FRSs were rated with the Scale for the Assessment of Positive Symptoms (SAPS). Interaction between FRSs and gender and FRSs and age was assessed using logistic regression. A high rate of FRSs in manic and mixed patients was found with a higher frequency in men (31%) than in women (14%; P=0.038). A monotonic increase in the association between FRSs and younger age was apparent (odds ratios (OR) over five levels: 1.42; 1.00-2.01). These results confirm previous findings that FRSs are not specific to schizophrenia and suggest in addition that a dimension of nuclear psychotic experiences of developmental origin extends across categorically defined psychotic disorders.

Working memory as a predictor of negative symptoms and functional outcome in first episode psychosis

The relationship of neurocognitive course with clinical and functional outcomes in psychosis is not well known, especially in the long term. The aim of the study was to examine the clinical and neuropsychological course of first-episode psychosis patients at 5-year follow-up and analyze the relationship of cognitive performance with clinical and functional outcome. The 5-year follow-up was conducted with 26 first-episode psychosis patients. Psychotic symptoms were measured by the Positive and Negative Syndrome Scale, manic and depressive symptoms by the Young Mania Rating Scale and Hamilton Depression Rating Scale respectively, and psychosocial functioning by the Functioning Assessment Short Test. The cognitive domains were assessed by the Wechsler Adult Intelligence Scale, the Wisconsin Card Sorting Test, the Trail Making Test, the Verbal Fluency Test, the Stroop Colour-Word Test and the Wechsler Memory Scale. Patients showed symptomatic improvement in the follow-up except in negative psychotic symptoms. There was also improvement in most cognitive domains except in working memory and processing speed in the follow-up. Working memory impairment was associated to negative psychotic symptoms and poor functional outcomes. Negative symptoms mediated the relationship between working memory and outcome. Therefore, negative symptoms should be a primary target of treatment to improve functional outcomes.