Showing papers in "Bipolar Disorders in 2013"

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013.

Abstract: The Canadian Network for Mood and Anxiety Treatments published guidelines for the management of bipolar disorder in 2005, with updates in 2007 and 2009. This third update, in conjunction with the International Society for Bipolar Disorders, reviews new evidence and is designed to be used in conjunction with the previous publications.The recommendations for the management of acute mania remain largely unchanged. Lithium, valproate, and several atypical antipsychotic agents continue to be first-line treatments for acute mania. Monotherapy with asenapine, paliperidone extended release (ER), and divalproex ER, as well as adjunctive asenapine, have been added as first-line options.For the management of bipolar depression, lithium, lamotrigine, and quetiapine monotherapy, as well as olanzapine plus selective serotonin reuptake inhibitor (SSRI), and lithium or divalproex plus SSRI/bupropion remain first-line options. Lurasidone monotherapy and the combination of lurasidone or lamotrigine plus lithium or divalproex have been added as a second-line options. Ziprasidone alone or as adjunctive therapy, and adjunctive levetiracetam have been added as not-recommended options for the treatment of bipolar depression. Lithium, lamotrigine, valproate, olanzapine, quetiapine, aripiprazole, risperidone long-acting injection, and adjunctive ziprasidone continue to be first-line options for maintenance treatment of bipolar disorder. Asenapine alone or as adjunctive therapy have been added as third-line options.

Epidemiology of suicide in bipolar disorders: a systematic review of the literature.

Abstract: OBJECTIVE: Suicidal behavior is a major public health problem worldwide, and its prediction and prevention represent a challenge for everyone, including clinicians. The aim of the present paper is to provide a systematic review of the existing literature on the epidemiology of completed suicides in adult patients with bipolar disorder (BD). METHODS: We performed a Pubmed/Medline, Scopus, PsycLit, PsycInfo, and Cochrane database search to identify all relevant papers published between 1980 and 2011. A total of 34 articles meeting our inclusion criteria were included in the present review. RESULTS: Several prospective follow-up contributions, many retrospective analyses, and a few psychological autopsy studies and review articles investigated the epidemiology of completed suicides in patients with BD. The main finding of the present review was that the risk for suicide among BD patients was up to 20-30 times greater than that for the general population. CONCLUSION: Special attention should be given to the characteristics of suicides in patients with BD. Better insight and understanding of suicide and suicidal risk in this very disabling illness should ultimately help clinicians to adequately detect, and thus prevent, suicidal acts in patients with BD. Language: en

Biological basis of suicide and suicidal behavior.

Abstract: Objective Suicide is a major public health concern as each year 30,000 people die by suicide in the US alone. In the teenage population, it is the second leading cause of death. There have been extensive studies of psychosocial factors associated with suicide and suicidal behavior. However, very little is known about the neurobiology of suicide. Recent research has provided some understanding of the neurobiology of suicide, which is the topic of this review.

Dissociable patterns of abnormal frontal cortical activation during anticipation of an uncertain reward or loss in bipolar versus major depression

Abstract: OBJECTIVES: Recent research has found abnormalities in reward-related neural activation in bipolar disorder (BD), during both manic and euthymic phases. However, reward-related neural activation in currently depressed individuals with BD and that in currently depressed individuals with major depressive disorder (MDD) have yet to be directly compared. Here, we studied these groups, examining the neural activation elicited during a guessing task in fronto-striatal regions identified by previous studies. METHODS: We evaluated neural activation during a reward task using fMRI in two groups of depressed individuals, one with bipolar I disorder (BD-I) (n = 23) and one with MDD (n = 40), with similar levels of illness severity, and a group of healthy individuals (n = 37). RESULTS: Reward expectancy-related activation in the anterior cingulate cortex was observed in the healthy individuals, but was significantly reduced in depressed patients (BD-I and MDD together). Anticipation-related activation was increased in the left ventrolateral prefrontal cortex in the BD-I depressed group compared with the other two groups. There were no significant differences in prediction error-related activation in the ventral striatum across the three groups. CONCLUSIONS: The findings extend previous research which has identified dysfunction within the ventrolateral prefrontal cortex in BD, and show that abnormally elevated activity in this region during anticipation of either reward or loss may distinguish depressed individuals with BD-I from those with MDD. Altered activation of the anterior cingulate cortex during reward expectancy characterizes both types of depression. These findings have important implications for identifying both common and distinct properties of the neural circuitry underlying BD-I and MDD.

Suicidal ideation and suicide attempts in children and adolescents with bipolar disorder: a systematic review of prevalence and incidence rates, correlates, and targeted interventions.

Abstract: OBJECTIVE: Pediatric bipolar disorder (PBD) is associated with poor outcomes, including suicidal ideation (SI) and suicide attempt (SA). However, frequencies and risk factors of SI/SA and targeted intervention trials for SI/SA in PBD have not been reviewed systematically. METHODS: We conducted a systematic PubMed review, searching for articles reporting on prevalences/incidences, correlates and intervention studies targeting SI/SA in PBD. Weighted means were calculated, followed by an exploratory meta-regression of SI and SA correlates. RESULTS: Fourteen studies (n = 1595), in which 52.1% of patients were male and the mean age was 14.4 years, reported data on SI/SA prevalence (N = 13, n = 1508) and/or correlates (N = 10, n = 1348) in PBD. Weighted mean prevalences were: past SI = 57.4%, past SA = 21.3%, current SI = 50.4%, and current SA = 25.5%; incidences (mean 42 months of follow-up) were: SI = 14.6% and SA = 14.7%. Regarding significant correlates, SI (N = 3) was associated with a higher percentage of Caucasian race, narrow (as opposed to broad) PBD phenotype, younger age, and higher quality of life than SA. Significant correlates of SA (N = 10) included female sex, older age, earlier illness onset, more severe/episodic PBD, mixed episodes, comorbid disorders, past self-injurious behavior/SI/SA, physical/sexual abuse, parental depression, family history of suicidality, and poor family functioning. Race, socioeconomic status, living situation, and life events were not clearly associated with SA. In a meta-regression analysis, bipolar I disorder and comorbid attention-deficit hyperactivity disorder were significantly associated with SA. Only one open label study targeting the reduction of SI/SA in PBD was identified. CONCLUSIONS: SI and SA are very common but under-investigated in PBD. Exploration of predictors and protective factors is imperative for the establishment of effective preventive and intervention strategies, which are urgently needed. Language: en

Differences in resting corticolimbic functional connectivity in bipolar I euthymia.

Abstract: Bipolar disorder is a serious psychiatric illness thought to involve deficits in the neural substrates for emotion regulation because of its characteristic profile of lifetime depressed and manic mood episodes (1, 2). Neuroimaging research in healthy subjects has revealed a number of brain areas involved in emotional regulation, including subcortical (e.g., amygdala) and ventrolateral prefrontal cortical (vlPFC) regions (3, 4). Research in both humans and primates has additionally demonstrated strong anatomical projections between these areas, forming the substrate for which functional coupling (connectivity) is possible (5, 6). The amygdala, for example, is functionally responsive to emotional stimuli, while the vlPFC is instrumental in the regulation of that response. In healthy subjects, during down-regulation of emotion, the functional connectivity between these areas has been observed to increase (7, 8). The above-referenced functional magnetic resonance imaging (fMRI) studies of emotion regulation involve observation of brain activity while subjects perform a task. Recent studies that have evaluated subjects while not performing any cognitive tasks–e.g., resting state studies–have also revealed intrinsic activation patterns in the brain. Resting state fMRI provides complementary information to task-based fMRI in that both provide a platform for examining functional brain networks. Spatially distributed large-scale brain networks can be reliably derived and interrogated by either kind of fMRI experiment (9–11) and one could argue that both contribute different dimensions to a full characterization of brain activity. A variety of methods have been used to analyze such data (12) and have been applied to diverse clinical populations in the effort to delineate disease-related dysfunctions in connectivity (13). While there are a handful of studies that have investigated functional connectivity in bipolar disorder, few are resting state studies (Table 1). Of these, there is some overlap with the regions used as seeds, such as the medial prefrontal cortex (14, 15) or amygdala (16, 17) but the findings show differences in connectivity in lateralization (left or right hemisphere), sign (positive or negative coupling), and between-group differences (healthy subjects > bipolar disorder or bipolar disorder > healthy subjects). Three of these studies investigated bipolar mania and/or depression (14, 15, 17); however, one combined several mood states into its bipolar disorder sample (16) while another combined bipolar I and II disorder subjects (14). This latter issue is particularly problematic as there is evidence to suggest that patterns of activation and connectivity change with different mood state and subtype of bipolar disorder (17–19). For a clearer picture of the underlying pathophysiology of bipolar disorder, further research that investigates common regions in both hemispheres in single mood states and in single bipolar disorder subtypes is necessary. Table 1 A selection of functional magnetic resonance imaging (fMRI)connectivity studies in bipolar disorder The goal of the present resting state study was to elucidate differences in intrinsic functional connectivity that might contribute to mood lability in bipolar I disorder. We therefore took a focused approach to assessing connectivity in two bilateral brain regions strongly implicated in emotion regulation (four regions in total: right and left amygdalae and right and left vlPFC) in a group of euthymic bipolar I disorder subjects. We hypothesized that subjects with bipolar I disorder would demonstrate aberrant functional connectivity relative to healthy subjects between amygdalae and lateral vlPFC–regions that subserve emotion regulation. Furthermore, observed alterations of brain connectivity during the euthymic state may be considered a potential biomarker of trait aspects of the disease.

Evidence‐based treatment strategies for treatment‐resistant bipolar depression: a systematic review

Abstract: Sienaert P, Lambrichts L, Dols A, De Fruyt J. Evidence-based treatment strategies for treatment-resistant bipolar depression: a systematic review. Bipolar Disord 2012: 00: 000–000. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objectives: Treatment resistance in bipolar depression is a common clinical problem that constitutes a major challenge for the treating clinician as there is a paucity of treatment options. The objective of this paper was to review the evidence for treatment options in treatment-resistant bipolar depression, as found in randomized controlled trials and with special attention to the definition and assessment of treatment resistance. Methods: A Medline search (from database inception to May 2012) was performed using the search terms treatment resistance or treatment refractory, and bipolar depression or bipolar disorder, supplemented with 43 separate searches using the various pharmacologic agents or technical interventions as search terms. Results: Only seven studies met our inclusion criteria. These studies examined the effects of ketamine (n = 1), (ar)modafinil (n = 2), pramipexole (n = 1), lamotrigine (n = 1), inositol (n = 1), risperidone (n = 1), and electroconvulsive therapy (ECT) (n = 2). Conclusions: The available level I evidence for treatment strategies in resistant bipolar depression is extremely scarce, and although the response rates reported are reassuring, most of the strategies remain experimental. There is an urgent need for further study in homogeneous patient samples using a clear concept of treatment resistance.

Reproductive outcomes and risk of subsequent illness in women diagnosed with postpartum psychosis.

Abstract: Objectives: Women who experience postpartum psychosis (PP) seek guidance on further pregnancies and risk of illness; however, empirical data are limited. This study describes reproductive and mental health outcomes in women diagnosed with PP and examines clinical risk factors as predictors of further illness. Methods: A retrospective cohort design was used; 116 women who experienced episodes of mania or depression with psychotic features within six weeks of childbirth were recruited. All subjects underwent clinical diagnostic interviews and medical case notes were reviewed. Results: Only 33% of women had an antecedent history, of which 34% had bipolar disorder and 55% unipolar depression. Only 58% of those with PP in their first pregnancy had a subsequent pregnancy, and 18% of marriages ended following the PP episode. Clinical presentation at the time of initial episode did not influence the timing of the onset of symptoms, treatment, or recovery. Although 86% of patients received treatment within 30 days of onset, 26% of women reported ongoing symptoms at a year after delivery. The recurrence rate of PP was 54.4%; a longer duration of the index episode (p < 0.05) and longer latency between the index PP and next pregnancy predicted a subsequent PP. The rate of subsequent non-puerperal episodes was 69%, and all these episodes were bipolar. Conclusions: Postpartum psychosis is difficult to predict in women with no antecedent history and is associated with a high rate of subsequent puerperal and non-puerperal illness. Risk of further illness needs to be conveyed in order to allow fully informed decisions to be made regarding future pregnancies.

A quantitative review of neurocognition in euthymic late-life bipolar disorder.

Abstract: Fil: Samame, Cecilia. Universidad Favaloro. Facultad de Medicina. Instituto de Neurociencias; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas; Argentina

Brain gamma-aminobutyric acid (GABA) abnormalities in bipolar disorder

Abstract: Objectives Gamma-aminobutyric acid (GABA) abnormalities have been implicated in bipolar disorder. However, due to discrepant studies measuring postmortem, cerebrospinal fluid, plasma, and in vivo brain levels of GABA, the nature of these abnormalities is unclear. Using proton magnetic resonance spectroscopy, we investigated tissue levels of GABA in the anterior cingulate cortex and parieto-occipital cortex of participants with bipolar disorder and healthy controls. Methods Fourteen stably medicated euthymic outpatients with bipolar disorder type I (mean age 32.6 years, eight male) and 14 healthy control participants (mean age 36.9 years, 10 male) completed a proton magnetic resonance spectroscopy scan at 4-Tesla after providing informed consent. We collected data from two 16.7-mL voxels using MEGAPRESS, and they were analyzed using LCModel. Results GABA/creatine ratios were elevated in bipolar disorder participants compared to healthy controls [F(1,21) = 4.4, p = 0.048] in the anterior cingulate cortex (25.1% elevation) and the parieto-occipital cortex (14.6% elevation). Bipolar disorder participants not taking GABA-modulating medications demonstrated greater GABA/creatine elevations than patients taking GABA-modulating medications. Conclusions We found higher GABA/creatine levels in euthymic bipolar disorder outpatients compared to healthy controls, and the extent of this elevation may be affected by the use of GABA-modulating medications. Our findings suggest that elevated brain GABA levels in bipolar disorder may be associated with GABAergic dysfunction and that GABA-modulating medications reduce GABA levels in this condition.

Incidence rates and risk factors of bipolar disorder in the general population: a population-based cohort study

Abstract: Objective To estimate the incidence rates (IRs) of bipolar I and bipolar II disorders in the general population according to sociodemographic population characteristics. Methods A cohort study (during the years 1996–2007) was conducted in a general practitioners research database with a longitudinal electronic record of 800000 patients throughout the Netherlands [the Integrated Primary Care Information (IPCI) database]. Cases of bipolar disorder were identified and classified by systematic review of medical records. Age- and gender-specific IRs were calculated per calendar year, degree of urbanization, and degree of deprivation. Results The overall IR of bipolar disorder was 0.70/10000 person-years (PY) [95% confidence interval (CI): 0.57–0.83]; the IR of bipolar I disorder was 0.43/10000 PY (95% CI: 0.34–0.55) and the IR of bipolar II disorder was 0.19/10000 PY (95% CI: 0.13–0.27). Two peaks in the age at onset of the disorder were noticed: one in early adulthood (15–24 years; 0.68/10000 PY) and a larger peak in later life (45–54 years; 1.2/10000 PY). In bipolar II disorder, only one peak, in the 45–54 year age category (IR 0.42/10000 PY), was found. The IRs of bipolar disorder were significantly higher in deprived areas. Similar rates were found for men compared to women and in urban compared to rural areas. No association was found between the onset of first (hypo)manic episode and month or season of birth. Conclusions We found two peaks in the age at onset of bipolar disorder, one in early adulthood and one in later life, the former consisting mainly of bipolar I disorder subjects. The incidence of bipolar disorder is higher in deprived areas. The onset of bipolar disorder is not associated with gender, urbanization, or month or season of birth.

Increased risk of developing dementia in patients with bipolar disorder: a nested matched case–control study

Abstract: Wu K-Y, Chang C-M, Liang H-Y, Wu C-S, Wu EC-H, Chen C-H,Chau Y-L, Tsai H-J. Increased risk of developing dementia in patientswith bipolar disorder: a nested matched case–control study.Bipolar Disord 2013: 15: 787–794. © 2013 John Wiley & Sons A/S.Published by John Wiley & Sons Ltd.Objective: The association between bipolar disorder and subsequentdementia risk is not well established. The objective of this study was toinvestigate whether patients with bipolar disorder were at an increasedrisk for developing dementia.Methods: A conditional logistic regression model was performed usingdata from the National Health Insurance Research Database, anationwide dataset in Taiwan. The study sample included 9,304 patientswith incident dementia first diagnosed between 2000 and 2009, and55,500 gender-, age-, and index date-matched subjects without dementia.Cerebrovascular disease, diabetes, hypertension, head injury, chronicpulmonary disease, alcohol-related disorders, substance use disorders,and health system utilization were treated as covariates in the analyses.Results: After controlling for the covariates, bipolar disorder wassignificantly associated with an increased risk of subsequent dementia[adjusted odds ratio (aOR) = 4.32, 95% confidence interval (CI):3.21–5.82]. An increased risk of developing dementia was observed inmales and females alike (aOR = 4.01, 95% CI: 2.53–6.35 in males;aOR = 4.55, 95% CI: 3.07–6.73 in females). Moreover, a significantlyincreased risk was observed in subjects diagnosed with dementia beforethe age of 65 years (aOR = 3.77, 95% CI: 1.78–8.01).Conclusions: Findings from this study suggest a positive associationbetween the presence of a lifetime history of bipolar disorder and anincreased risk of developing dementia. Furthermore, our results alsosuggest that subjects with bipolar disorder tend to develop dementia inmiddle age. Going forward, it will be of importance to confirm ourfindings in different populations.

Prenatal stress and affective disorders in a population birth cohort

Abstract: Kleinhaus K, Harlap S, Perrin M, Manor O, Margalit-Calderon R, Opler M, Friedlander Y, Malaspina D. Prenatal stress and affective disorders in a population birth cohort. Bipolar Disord 2012: 00: 000–000. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objectives: Pregnant women exposed to an acute traumatic event are thought to produce offspring with an increased incidence of affective disorders. It is not known whether there are specific times in pregnancy which confer increased vulnerability, or if psychosocial stress alone can increase the incidence of affective disorders in offspring. We examined the relationship of the timing of an acute psychosocial threat during pregnancy to the incidence of affective disorders in offspring using data from a large birth cohort. Methods: Using data on 90079 offspring born in Jerusalem in 1964–1976 and linked to Israel’s psychiatric registry, we constructed proportional hazards models to evaluate the link between gestational age during the Arab–Israeli war of June 1967 and incidence of mood disorders. Results: Those in their first trimester of fetal development during the war were more likely to be admitted to hospitals for any mood disorders [relative risk (RR) = 3.01, 95% confidence interval (CI): 1.68–5.39, p = 0.0002]; for bipolar disorder the risk was doubled (RR = 2.44, 95% CI: 0.996–5.99, p = 0.054) and for all ‘other’ mood disorders the risk was tripled (RR = 3.61, 95% CI: 1.68–7.80, p = 0.001). Mood disorders were also increased in offspring whose mothers had been in the third month of pregnancy in June of 1967 (RR = 5.54, 95% CI: 2.73–11.24, p < 0.0001). Conclusions: A time-limited exposure to a severe threat during early gestation may be associated with an increased incidence of affective disorders in offspring. The third month of fetal development was a moment of special vulnerability.

Obesity and the three-year longitudinal course of bipolar disorder.

Abstract: Bipolar disorder (BD) is a neuropsychiatric disorder that is characterized by a high degree of symptom severity and episode recurrence, and by its frequent association with psychiatric and medical comorbidities (1–3). One comorbidity that has generated substantial interest is obesity. In recent years, clinical and epidemiologic studies have yielded several convergent findings regarding the association between BD and obesity. First, the prevalence of obesity is significantly increased in BD, whether subjects are ascertained from community samples or treatment-seeking samples (4–6). Explanations for this association are numerous, and include the effect of psychotropic medications, excessive carbohydrate consumption, low rate and intensity of exercise, reduced fat oxidation, substance misuse, and maladaptive efforts at self-modulation of mood by over eating (7–13). Second, it appears that obesity is associated with several proxies for illness severity in BD, including increased number of manic and depressive episodes, increased depressive symptom severity, treatment-resistance, suicidality, and treatment utilization (14–21). A natural question that emerges from these cross-sectional associations is whether obesity is a predictor of prospective illness course in BD. Recently, we examined the prevalence and correlates of obesity in Wave 1 (2001–2002) of the National Survey on Alcohol and Related Conditions (NESARC), a large representative sample of the United States population (4). We found that obesity is significantly more prevalent among adults with BD as compared to the general population. We also found that obesity is associated with greater depressive severity and increased prevalence of anxiety disorders, but decreased prevalence of past-year substance use disorder (SUD). However, by virtue of the cross-sectional methodology employed, the direction of the observed associations is uncertain. We therefore set out to examine the hypothesis that obesity at baseline is associated with a more severe longitudinal course of BD, determined prospectively, as defined by greater burden of mood symptoms, new-onset psychiatric and medical comorbidity, and increased functional impairment. We hypothesized that obese subjects with BD, as compared to non-obese subjects with BD, would experience more mood episodes, have higher rates of psychiatric treatment utilization, would more frequently develop comorbid conditions, and would experience greater increases in functional impairment during the three years between Wave 1 and Wave 2 (2004–2005) of the NESARC.

The impact of child sexual abuse on the course of bipolar disorder: a systematic review

Abstract: Maniglio R. The impact of child sexual abuse on the course of bipolar disorder: a systematic review. Bipolar Disord 2013: 00: 000-000. © 2013 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objectives: The aim of this review was to elucidate the impact of child sexual abuse on all clinical phenomena that occur after the onset of bipolar disorder, including associated clinical features that are not part of the diagnostic criteria for the disorder. Methods: Five databases were searched and supplemented with a hand search of reference lists from retrieved papers. Study quality was assessed using a validated quality assessment tool. Blind assessments of study eligibility and quality were conducted by two independent researchers to reduce bias, minimize errors, and enhance the reliability of findings. Disagreements were resolved by consensus. Results: Eighteen studies that included a total of 2996 adults and youths with bipolar disorder and met the minimum quality criteria necessary to ensure objectivity and not invalidate results were analyzed. Across studies, child sexual abuse was strongly (and perhaps directly) associated with posttraumatic stress disorder; whereas it was less strongly (and perhaps indirectly) related to suicide attempts, alcohol and/or drug abuse or dependence, psychotic symptoms, and an early age of illness onset. In regard to the association between child sexual abuse and other clinical variables concerning the course of bipolar disorder, evidence was scant or conflicting. Conclusions: Child sexual abuse is associated (either directly or indirectly) with some clinical phenomena that represent a more severe form of bipolar disorder. Although such a traumatic experience may directly affect the development of posttraumatic stress disorder, the effects of early sexual abuse on later suicidal behavior, substance abuse, and psychotic symptoms may operate through the mediating influences of certain psychopathological or neurobiological variables. Language: en

A systematic review of the evidence on the treatment of rapid cycling bipolar disorder.

Abstract: Fountoulakis KN, Kontis D, Gonda X, Yatham LN. A systematic review of the evidence on the treatment of rapid cycling bipolar disorder. Bipolar Disord 2013: 15: 115–137. © 2013 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objective: Rapid cycling is associated with longer illness duration and greater illness severity in bipolar disorder. The aim of the present study was to review the existing published randomized trials investigating the effect of treatment on patients with rapid cycling bipolar disorder. Methods: A MEDLINE search was conducted using combinations of the following key words: bipolar and rapid or rapid-cycling or rapid cycling and randomized. The search was conducted through July 16, 2011, and no conference proceedings were included. Results: The search returned 206 papers and ultimately 25 papers were selected for review. Only six randomized, controlled trials specifically designed to study a rapid cycling population were found. Most data were derived from post hoc analyses of trials that had included rapid cyclers. The literature suggested that: (i) rapid cycling patients perform worse in the follow-up period; (ii) lithium and anticonvulsants have comparable efficacies; (iii) there is inconclusive evidence on the comparative acute or prophylactic efficacy of the combination of anticonvulsants versus anticonvulsant monotherapy; (iv) aripiprazole, olanzapine, and quetiapine are effective against acute bipolar episodes; (v) olanzapine and quetiapine appear to be equally effective to anticonvulsants during acute treatment; (vi) aripiprazole and olanzapine appear promising for the maintenance of response of rapid cyclers; and (vii) there might be an association between antidepressant use and the presence of rapid cycling. Conclusion: The literature examining the pharmacological treatment of rapid cycling is still sparse and therefore there is no clear consensus with respect to its optimal pharmacological management. Clinical trials specifically studying rapid cycling are needed in order to unravel the appropriate management of rapid cycling bipolar disorder.

Bipolar II disorder is associated with thinning of prefrontal and temporal cortices involved in affect regulation

Abstract: Objectives The neurobiological substrate of bipolar II disorder (BD-II) remains largely unknown. A few previous studies have found evidence for cerebral cortical thinning in mixed samples of BD-II and bipolar I disorder patients; however, no study of cortical thickness or surface area has been limited to BD-II. In the present study, we compared magnetic resonance imaging (MRI)-based indices of cortical thickness and surface area between individuals with BD-II and healthy controls. Methods Thirty-six individuals with a DSM-IV diagnosis of BD-II and 42 controls underwent 3T MRI. Comparisons of thickness and relative surface areal expansion across the cerebral cortical mantle were performed using Freesurfer. Results Individuals with BD-II showed significant thinning in two prefrontal clusters primarily comprising the left subgenual anterior cingulate cortex, left perigenual ventromedial prefrontal cortex (PFC), bilateral dorsomedial PFC, and bilateral dorsolateral PFC (p < 0.0002 for both clusters, cluster size corrected) and in a left temporal cluster involving the superior, middle, and inferior temporal gyrus (p = 0.006, cluster size corrected). No group differences in cortical surface area were found. No significant effect of medication, mood state, illness duration, or family history of bipolar disorders on cortical thinning was observed. Conclusions These results indicate that BD-II is associated with thinning of prefrontal and temporal cortices implicated in the expression and regulation of negative and positive affect. Longitudinal studies are needed to clarify whether cortical thinning is a stable trait of BD-II, an illness effect that might progress during the course of the disease, or a combination of the two.

The immature dentate gyrus represents a shared phenotype of mouse models of epilepsy and psychiatric disease.

Abstract: Shin R, Kobayashi K, Hagihara H, Kogan JH, Miyake S, Tajinda K,Walton NM, Gross AK, Heusner CL, Chen Q, Tamura K, Miyakawa T,Matsumoto M. The immature dentate gyrus represents a sharedphenotype of mouse models of epilepsy and psychiatric disease.Bipolar Disord 2013: 15: 405–421. © 2013 John Wiley & Sons A/S.Published by John Wiley & Sons Ltd.Objectives: There is accumulating evidence to suggest psychiatricdisorders, such as bipolar disorder and schizophrenia, share commonetiologies, pathophysiologies, genetics, and drug responses with many ofthe epilepsies. Here, we explored overlaps in cellular/molecular,electrophysiological, and behavioral phenotypes between putative mousemodels of bipolar disorder/schizophrenia and epilepsy. We tested thehypothesis that an immature dentate gyrus (iDG), whose associationwith psychosis in patients has recently been reported, represents acommon phenotype of both diseases.Methods: Behaviors of calcium/calmodulin-dependent protein kinase IIalpha (a-CaMKII) heterozygous knock-out (KO) mice, which are arepresentative bipolar disorder/schizophrenia model displaying iDG, andpilocarpine-treated mice, which are a representative epilepsy model, weretested followed by quantitative polymerase chain reaction (qPCR)/immunohistochemistry for mRNA/protein expression associated with aniDG phenotype. In vitro electrophysiology of dentate gyrus granule cells(DG GCs) was examined in pilocarpine-treated epileptic mice.Results: The two disease models demonstrated similar behavioraldeficits, such as hyperactivity, poor working memory performance, andsocial withdrawal. Significant reductions in mRNA expression andimmunoreactivity of the mature neuronal marker calbindin andconcomitant increases in mRNA expression and immunoreactivity of theimmature neuronal marker calretinin represent iDG signatures that arepresent in both mice models. Electrophysiologically, we have confirmedthat DG GCs from pilocarpine-treated mice represent an immature state.A significant decrease in hippocampal a-CaMKII protein levels was alsofound in both models.Conclusions: Our data have shown iDG signatures from mouse modelsof both bipolar disorder/schizophrenia and epilepsy. The evidencesuggests that the iDG may, in part, be responsible for the abnormalbehavioral phenotype, and that the underlying pathophysiologies inepilepsy and bipolar disorder/schizophrenia are strikingly similar.

Immunosenescence is associated with human cytomegalovirus and shortened telomeres in type I bipolar disorder.

Abstract: Rizzo LB, Do Prado CH, Grassi-Oliveira R, Wieck A, Correa BL,Teixeira AL, Bauer ME Immunosenescence is associated with humancytomegalovirus and shortened telomeres in type I bipolar disorderBipolar Disord 2013: 15: 832–838 © 2013 John Wiley & Sons A/SPublished by John Wiley & Sons LtdObjective: Bipolar disorder (BD) has been associated with persistentlow-grade inflammation and premature cell senescence, as shown byreduced telomere length (TL) The human cytomegalovirus (CMV) hasincreasingly been implicated in accelerated immunosenescence in agingstudies Here, we compared CMV serology and its relationships with cellsenescence markers, including TL and lymphocyte subsets, in patientswith type I BD and healthy controlsMethods: Twenty-two euthymic female patients with BD type I and 17age-matched healthy controls were selected for the study A sample ofblood was collected and mononuclear cells and DNA were isolated andTL measured CMV immunoglobulin M (IgM) and IgG titers weremeasured using chemiluminescent assays Lymphocyte subsets[T, natural killer (NK) and NKT] were phenotyped by flow cytometryResults: Individuals with BD had shorter TLs but higher CMV IgGlevels than controls (both p < 001) CMV IgG level was inverselycorrelated with TL None of the subjects showed IgM reactivity forCMV, excluding acute viral infection CMV IgG level was associatedwith expansion of senescent CD8+CD28 T cells and NK cells, whichare involved in viral controlConclusions: These data support the hypothesis of accelerated aging inBD, as shown by shortened telomeres, higher seropositivity for CMV,and expansion of senescent T cells

Aripiprazole for the treatment of pediatric bipolar I disorder: a 30‐week, randomized, placebo‐controlled study

Abstract: Objective: To evaluate the long-term efficacy, safety, and tolerability of aripiprazole in pediatric subjects with bipolar I disorder. Methods: A randomized, double-blind, 30-week, placebo-controlled study of aripiprazole (10 or 30 mg/day) in youths (10–17 years) with bipolar I disorder (manic or mixed) ± psychotic features (n = 296) was performed. After four weeks, acute treatment completers continued receiving ≤26 weeks of double-blind treatment (n = 210). The primary outcome was Young Mania Rating Scale (YMRS) total score change. Results: Of the 210 subjects who entered the 26-week extension phase, 32.4% completed the study (45.3% for aripiprazole 10 mg/day, 31.0% for aripiprazole 30 mg/day, and 18.8% for placebo). Both aripiprazole doses demonstrated significantly (p < 0.001) greater improvements in YMRS total score at endpoint compared with placebo in protocol-specified last observation carried forward analyses, but not in observed case or mixed-model repeated measures at week 30. Overall time to all-cause discontinuation was longer for aripiprazole 10 mg/day (15.6 weeks) and aripiprazole 30 mg/day (9.5 weeks) compared with placebo (5.3 weeks; both p < 0.05 versus placebo). Both aripiprazole doses were significantly superior to placebo regarding response rates, Children’s Global Assessment of Functioning and Clinical Global Impressions-Bipolar severity of overall and mania scores at endpoint in all analyses. Commonly reported adverse events included headache, somnolence, and extrapyramidal disorder. Conclusions: Aripiprazole 10 mg/day and 30 mg/day were superior to placebo and generally well tolerated in pediatric subjects with bipolar I disorder up to 30 weeks. Despite the benefits of treatment, completion rates were low in all treatment arms.

Characteristics of patients diagnosed with schizoaffective disorder compared with schizophrenia and bipolar disorder

Abstract: Objectives Information on basic demographic and clinical characteristics of schizoaffective disorder is sparse and subject to sampling bias and low diagnostic reliability. In the present study we aimed to: (i) estimate the demographic and clinical descriptors in schizoaffective disorder patients and (ii) compare the findings with those with schizophrenia and bipolar disorder. Methods To minimize sampling bias and low reliability, we systematically reviewed studies that simultaneously compared schizoaffective, schizophrenia, and bipolar disorder patients. We estimated demographic, clinical, and psychometric characteristics based on weighted pooling, and compared disorders by meta-analysis. We also estimated whether schizoaffective disorder is closer to schizophrenia or to bipolar disorder. Results We identified 50 studies that included 18312 patients. Most characteristics of the 2684 schizoaffective disorder patients fell between those of 4814 diagnosed with bipolar disorder and 10814 with schizophrenia. However, the schizoaffective group had the highest proportion of women (52%), had the youngest age at illness onset (23.3 ± 3.8 years), and had the highest standardized ratings of psychosis and depression. Differences in pooled parameters between schizoaffective versus schizophrenia and versus bipolar disorder subjects were similar. Values for patients with schizoaffective disorders mostly were intermediate between schizophrenia and bipolar disorder. However, the majority of studies showed schizoaffective patients to be more like schizophrenia than bipolar disorder patients in seven out of nine demographic and clinical categories as well as in five out of eight psychometric measures. These results remained similar when we restricted the analyses to studies with psychotic bipolar disorder patients only or to studies using the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IIIR and DSM-IV only. Conclusions The present study provided estimates of important characteristics of schizoaffective disorder – as balanced as possible in summarizing the findings from observational studies as unbiased as possible. The results did not support the hypothesis that schizoaffective disorder is primarily an affective disorder. The stronger resemblance of schizoaffective disorder to schizophrenia than to bipolar disorder needs further investigation.

Amygdala and whole-brain activity to emotional faces distinguishes major depressive disorder and bipolar disorder.

Abstract: Objectives It can be clinically difficult to distinguish depressed individuals with bipolar disorder (BD) and major depressive disorder (MDD). To examine potential biomarkers of difference between the two disorders, the current study examined differences in the functioning of emotion-processing neural regions during a dynamic emotional faces task. Methods During functional magnetic resonance imaging, healthy control adults (HC) (n = 29) and depressed adults with MDD (n = 30) and BD (n = 22) performed an implicit emotional-faces task in which they identified a color label superimposed on neutral faces that dynamically morphed into one of four emotional faces (angry, fearful, sad, happy). We compared neural activation between the groups in an amygdala region-of-interest and at the whole-brain level. Results Adults with MDD showed significantly greater activity than adults with BD in the left amygdala to the anger condition (p = 0.01). Results of whole-brain analyses (at p < 0.005, k ≥ 20) revealed that adults with BD showed greater activity to sad faces in temporoparietal regions, primarily in the left hemisphere, whereas individuals with MDD demonstrated greater activity than those with BD to displays of anger, fear, and happiness. Many of the observed BD–MDD differences represented abnormalities in functioning compared to HC. Conclusions We observed a dissociation between depressed adults with BD and MDD in the processing of emerging emotional faces. Those with BD showed greater activity during mood-congruent (i.e., sad) faces, whereas those with MDD showed greater activity for mood-incongruent (i.e., fear, anger, and happy) faces. Such findings may reflect markers of differences between BD and MDD depression in underlying pathophysiological processes.

C9ORF72 expansion in a family with bipolar disorder

Abstract: Objective To investigate the role in bipolar disorder of the C9ORF72 hexanucleotide repeat expansion responsible for frontotemporal lobe dementia and amyotrophic lateral sclerosis Methods Eighty-nine subjects from a previously described panel of individuals with bipolar disorder ascertained for genetic studies were screened to detect expansion of the C9ORF72 repeat One two-generation family with bipolar disorder and an expanded repeat was characterized in depth using molecular diagnostics, imaging, histopathology, and neurological and neuropsychological evaluation Results One proband, with the typical clinical presentation of bipolar disorder, carried an expanded C9ORF72 allele of heterogeneous length between 14 and 20 kilobases (kb) as assessed by Southern blot The expanded allele was inherited from a parent with atypical, late onset clinical features of bipolar disorder, who subsequently progressed to frontotemporal lobe dementia The expansion in peripheral blood of the parent ranged from 85 to 20 kb Cultured lymphoblastoid cells from this parent exhibited a homogeneous expansion of only 85 kb Conclusions The disease course in the two generations described here demonstrates that expansion of the C9ORF72 may be associated with a form of bipolar disorder that presents clinically with classic phenomenology and progression to neurodegenerative disease The frequency in our bipolar disorder cohort was only 1%, indicating that C9ORF72 is not a major contributor to bipolar disorder DNA from cultured cells may be biased towards shorter repeats and nonrepresentative of the endogenous C9ORF72 expansion

Overlapping and distinct gray and white matter abnormalities in schizophrenia and bipolar I disorder

Abstract: Objectives Schizophrenia and bipolar disorder may share common neurobiological mechanisms, but few studies have directly compared gray and white matter structure in these disorders We used diffusion-weighted magnetic resonance imaging and a region of interest based analysis to identify overlapping and distinct gray and white matter abnormalities in 35 patients with schizophrenia and 20 patients with bipolar I disorder in comparison to 56 healthy volunteers Methods We examined fractional anisotropy within the white matter and mean diffusivity within the gray matter in 42 regions of interest defined on a probabilistic atlas following non-linear registration of the images to atlas space Results Patients with schizophrenia had significantly lower fractional anisotropy in temporal (superior temporal and parahippocampal) and occipital (superior and middle occipital) white matter compared to patients with bipolar disorder and healthy volunteers By contrast, both patient groups demonstrated significantly higher mean diffusivity in frontal (inferior frontal and lateral orbitofrontal) and temporal (superior temporal and parahippocampal) gray matter compared to healthy volunteers, but did not differ from each other Conclusions Our study implicates overlapping gray matter frontal and temporal lobe structural alterations in the neurobiology of schizophrenia and bipolar I disorder, but suggests that temporal and occipital lobe white matter deficits may be an additional risk factor for schizophrenia Our findings may have relevance for future diagnostic classification systems and the identification of susceptibility genes for these disorders

Mood lability among offspring of parents with bipolar disorder and community controls

Abstract: Bipolar disorder (BP) is a recurrent illness that usually has its onset during adolescence and is associated with substantial morbidity and impairment (1). Nonetheless, there is often a delay of up to a decade from the onset of the mood symptoms until proper diagnosis and treatment of BP (1, 2) increasing the risk of worse outcomes (2–4). Therefore, identification of early BP symptomatology could aid in earlier treatment and better psychosocial outcome. Retrospective studies of youth and adults with BP consistently indicate increased irritability, mood lability, subclinical mood and anxiety symptomatology, and behavior and sleep problems may be potential prodromal symptoms of BP (5–12). Of these symptoms, mood lability, defined as sudden, exaggerated, unpredictable and developmentally inappropriate changes in mood, is one of the strongest potential prodromal symptoms for BP. However, it is important to note that as used in the literature, mood lability is an umbrella term that captures pathological changes across several mood states including irritability. Among the studies that reported mood lability (or irritability) as a prodromal for BP, Angst and colleagues (7) in a large prospective adult community study reported that, independent of family history, unstable mood regulation was the strongest risk factor for BP. Also, Egeland and colleagues (13) in a well-characterized sample of 58 Amish bipolar I disorder (BP-I) adults whose medical records from childhood were available, reported that the most frequently symptoms included episodic changes in depressed, irritable, anger, and increased energy. In this study, there was a 9–12-year time interval between appearance of the first symptoms and the onset of the BP-I. Finally, Correll and colleagues (14) also reported a long symptomatic prodromal phase prior to the first manic episode manifested by mood lability (including anger outbursts), subclinical manic and depressed symptoms, anxiety, and social isolation. To obviate the biases encountered with retrospective investigations, and since the single most significant vulnerability factor for the development of BP is a family history of BP, studies have evaluated the prevalence of psychopathology in child and adolescent offspring of parents with BP. Using categorical as well as dimensional measurements, cross-sectional studies have reported higher levels of mood lability (including irritability and other rapid mood fluctuations), negative affect, depressed mood, anxiety, aggressive behaviors, and attention and sleep problems in offspring of parents with BP when compared with offspring of controls (8, 9, 12, 15–22). In the Pittsburgh Bipolar Offspring Study (BIOS) (18), from which the sample for the present study is derived, the offspring of parents with BP, particularly those offspring who already developed BP, had higher scores in the Total, Internalizing, Anxious/Depressed, Withdrawn/Depressed, and Aggressive Behavior scales of the Children Behavior Checklist (CBCL), the CBCL–Dysregulation Profile (CBCL-DP), and a sum of CBCL items associated with mood lability than the offspring of the control parents (17), independent of child and parental non-BP psychopathology. Using the Child Hostility Inventory, Farchione and colleagues (23) also reported high levels of irritability and hostility in the BIOS offspring of parents with BP when compared with offspring of the controls. The above literature suggest that mood lability and its components (e.g., irritability) as well the presence of subclinical mood and anxiety symptoms are a potential prodromal phenotype for BP. However, these symptoms, and in particular mood lability, are ubiquitous among psychiatric disorders (24–28). In fact, whereas some have found mood lability to be associated with the development of BP (5, 11, 14, 29–32), others have reported that it increases the risk for anxiety and depressive disorders, antisocial behaviors, and suicidality, but not BP (33–38). Thus, further investigations with more clear definitions or instruments to ascertain mood lability and its components are warranted to clarify the association of these symptoms with pediatric BP in high-risk populations without full-blown BP. Different methods have been used to ascertain mood lability such as single items and a composite of symptoms derived from instruments not specifically designed to ascertain mood lability, like the CBCL (e.g., 24, 26, 39–41). We therefore decided to use a parent-report (about their children) scale specifically developed to assess mood lability in youth, the Children’s Affective Lability Scale (CALS) (42). To compare and expand the original factor analysis of the CALS which was carried out with school children among whom there is less likelihood of mood symptomatology, and because the primary aim of our study was to identify prodromal symptoms of mania, a new factor analysis was performed. In this study, we sought to investigate the prevalence of mood lability and its components in non-BP offspring of BP parents, BP offspring of BP parents, and offspring of community control parents. These comparisons will help to clarify whether excessive mood lability only exists in the BP offspring of BP parents or is also increased in the non-BP offspring of parents with BP. Moreover, since some control parents are healthy whereas others have non-BP psychopathology, we will be able to evaluate if excessive mood lability is associated with having a parent with BP or is non-specifically associated parental overall psychopathology. Based on the literature and prior BIOS results it was hypothesized that after adjusting for confounding factors (e.g., effect of parental and offspring non-BP psychopathology) non-BP offspring of BP parents will have significantly higher scores on the parent and child CALS and its subscales than the offspring of community control parents. In addition, after adjusting for confounding factors, BP offspring of BP parents will show higher CALS scores than the non-BP offspring of BP parents and the offspring of the control parents.

Aspirin for treatment of lithium-associated sexual dysfunction in men: randomized double-blind placebo-controlled study.

Abstract: Objectives The aim of the present study was to assess the effect of aspirin on lithium-related sexual dysfunction in men with stable bipolar affective disorder (BAD). Methods In a randomized, double-blind, placebo-controlled study, 32 men with stable BAD who had been on lithium maintenance therapy randomly received aspirin (240 mg/day) or placebo for six weeks. The International Index for Erectile Function (IIEF) was used to assess sexual symptoms at baseline, Week 3, and Week 6. Depressive and mania symptoms and plasma lithium concentrations were assessed at baseline and Week 6. Side effects were assessed using a checklist. Results Thirty patients (15/group) completed the study. Baseline and endpoint lithium concentrations and mania and depressive symptoms did not differ significantly between the two groups. Significant effects of time × treatment interaction were observed for total score [Greenhouse–Geisser: F(1.410,39.466) = 6.084, p = 0.010] and erectile function [Greenhouse–Geisser: F(1.629,45.602) = 7.250, p = 0.003]. By Week 6, patients in the aspirin group showed significantly greater improvement in the total (63.9% improvement from the baseline) and erectile function domain (85.4% improvement from the baseline) scores than the placebo group (14.4% and 19.7% improvement from the baseline, p-values = 0.002 and 0.001, respectively). By Week 6, 12 (80%) patients in the aspirin group and three (20%) patients in the placebo group met the criteria of minimal clinically important change [χ2(1) = 10.800, p = 0.001]. Other IIEF domains also showed significant improvement at the end of the trial. The frequency of side effects was similar between the two groups. Conclusion Aspirin effectively improves lithium-related sexual dysfunction in men with stable BAD.

White matter differences in euthymic bipolar I disorder: a combined magnetic resonance imaging and diffusion tensor imaging voxel-based study.

Abstract: Emsell L, Langan C, Van Hecke W, Barker GJ, Leemans A, Sunaert S,McCarthy P, Nolan R, Cannon DM, McDonald C. White matterdifferences in euthymic bipolar I disorder: a combined magneticresonance imaging and diffusion tensor imaging voxel-based study.Bipolar Disord 2013: 15: 365–376. © 2013 John Wiley & Sons A/S.Published by John Wiley & Sons Ltd.Objectives: A broad range of subtle and markedly heterogenousneuroanatomical abnormalities of grey matter and white matter havebeen reported in bipolar disorder. Euthymic bipolar disorder patientsrepresent a clinically homogenous group in which to identify trait-basedbiomarkers of bipolar disorder. In this study, we sought to clarify thenature and extent of neuroanatomical differences in a large, clinicallyhomogeneous group of euthymic bipolar disorder patients.Methods: Structural magnetic resonance imaging (sMRI) was obtainedfor 60 patients with prospectively confirmed euthymic bipolar I disorderand 60 individually age- and gender-matched healthy volunteers. Highangular resolution diffusion tensor imaging (DTI) scans were obtainedfor a subset of this sample comprising 35 patients and 43 controls. Voxel-based analysis of both sMRI and DTI data sets was performed.Results: Bipolar disorder patients displayed global reductions in whitematter volume and fractional anisotropy reductions in the corpuscallosum, posterior cingulum, and prefrontal white matter comparedwith controls. There were corresponding increases in radial diffusivity inthe callosal splenium in patients compared with controls. No significantgroup differences were detected in grey matter. In patients, lithium wasassociated with a bilateral increase in grey matter volume in the temporallobes, but not with any DTI parameter.Conclusions: Euthymic bipolar I disorder is characterized by both diffuseglobal white matter deficits and potential regional disorganization ininterhemispheric and longitudinal tracts, while grey matter appears to bepreserved.

The association of the effect of lithium in the maintenance treatment of bipolar disorder with lithium plasma levels: a post hoc analysis of a double-blind study comparing switching to lithium or placebo in patients who responded to quetiapine (Trial 144).

Abstract: Nolen WA, Weisler RH. The association of the effect of lithium in the maintenance treatment of bipolar disorder with lithium plasma levels: a post hoc analysis of a double-blind study comparing switching to lithium or placebo in patients who responded to quetiapine (Trial 144). Bipolar Disord 2012: 15: 100-109. (C) 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objectives: There is no robust proof that the efficacy of lithium in the prevention of manic and depressive episodes in bipolar disorder depends on its plasma level. This analysis aimed to compare the effect of lithium within the presumed therapeutic range of 0.61.2 mEq/L and below 0.6 mEq/L with that of placebo. Methods: We carried out a post hoc analysis of a double-blind trial in which patients aged >= 18 years with bipolar I disorder (DSM-IV) who had achieved stabilization from a manic, depressive, or mixed episode during open-label treatment with quetiapine were randomized to continue quetiapine or to switch to lithium or placebo for up to 104 weeks. Of patients randomized to lithium, 201 obtained median lithium levels between 0.6 and 1.2 mEq/L, and 137 obtained median lithium levels

Religiosity, mood symptoms, and quality of life in bipolar disorder.

Abstract: Objectives The aim of the present study was to investigate the relationship between religiosity and mood, quality of life, number of hospitalizations, and number of severe suicide attempts among bipolar disorder patients. Methods In a cross-sectional study of bipolar disorder outpatients (N = 168), we assessed symptoms of mania [Young Mania Rating Scale (YMRS)], depression [Montgomery–Asberg Depression Rating Scale (MADRS)], religiosity (Duke Religious Index), religious coping (Brief RCOPE), and quality of life [World Health Organization Quality of Life–Brief Version (WHOQOL-BREF)]. Sociodemographic data, number of suicide attempts, and number of hospitalizations were obtained through an interview with the individual and analysis of the patient's medical records. Logistical and linear regressions of the association between the religious indicators and clinical variables were conducted, controlling for sociodemographic variables. Results A total of 148 (88.1%) individuals reported some type of religious affiliation. Intrinsic religiosity [odds ratio (OR) = 0.19, 95% confidence interval (CI): 0.06–0.57, p = 0.003] and positive religious coping strategies (OR = 0.25, CI: 0.09–0.71, p = 0.01) were associated with fewer depressive symptoms. All four domains of quality of life were directly and significantly correlated with intrinsic religiosity. Positive religious coping was correlated with higher levels of the psychological (β = 0.216, p = 0.002) and environmental (β = 0.178, p = 0.028) quality-of-life domains. Negative religious coping was associated with lower scores on the psychological domain of quality of life (β = −0.182, p = 0.025). Conclusions Intrinsic religiosity and positive religious coping are strongly associated with fewer depressive symptoms and improved quality of life. Negative religious coping is associated with worse quality of life. Religiosity is a relevant aspect of patients' lives and should be taken into consideration by physicians when assessing and managing bipolar disorder patients. Further longitudinal studies are needed to determine the causality and therapeutic implications of our findings.

Impact of psychotropic drugs on suicide and suicidal behaviors

Abstract: OBJECTIVE: To examine the impact of psychotropic drugs on suicide and suicidal behaviors in bipolar disorders. METHODS: A Medline search of articles published from January 1960 to January 2013 was performed using relevant keywords to identify studies examining the relationship of psychotropic drugs to suicidal behaviors. The publications were further reviewed for relevant references and information. Additionally, the US Food and Drug Administration Center for Drug Evaluation Research website was searched. RESULTS: The available studies used differing methodologies, making interpretation of the findings difficult. Studies suggest that antidepressants may increase suicidal risk in bipolar disorder, this possibly being related to the induction of broadly defined mixed states. There is no evidence that antiepileptic drugs as a class increase suicidal risk in patients with bipolar disorder. Only lithium provides convincing data that it reduces the risk of suicide over the long term. There is little known regarding the effects of antipsychotics, as well as anti-anxiety and hypnotic drugs, on suicidal behavior. CONCLUSIONS: The available evidence for the impact of psychotropics on suicidal risk in patients with bipolar disorder is largely methodologically flawed and, except for a few instances, clinically not useful at this point. Adequately powered, prospective randomized controlled studies are needed to assess the impact of each class of psychotropic and each psychotropic as well as common combination therapies. Until such studies have been carried out, clinicians are urged to exercise caution in using these drugs and rely on the traditional means of carefully assessing and monitoring patients with bipolar disorder who are at high risk for suicide. Language: en