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International Review of Psychosis & Bipolarity

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Chair: Prof Maria Luisa Figueira (PT)

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9 January 2015

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26 January 2015

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Most Recent Articles Published on Psychosis and Bipolarity:

Substance use disorders and psychotic disorders in epilepsy: A population-based registry study.

Epilepsy Res. 2014 Jul 7;

Authors: Bakken IJ, Revdal E, Nesvåg R, Brenner E, Knudsen GP, Surén P, Ghaderi S, Gunnes N, Magnus P, Reichborn-Kjennerud T, Camilla Stoltenberg, Trogstad LI, Håberg SE, Brodtkorb E

Abstract
BACKGROUND: Epilepsy affects around 70 million people worldwide. Psychiatric comorbidity may add to the burden of the disease. We studied substance use disorders and psychotic disorders among people with epilepsy from a population-based perspective.
METHODS: Norwegian specialist health services (hospitals and outpatient clinics) report diagnoses for individual patients to the Norwegian Patient Register. We used information on subjects born in 1930-1994 who were registered with a diagnosis of epilepsy at least once during the five-year period of 2008-2012. We compared the proportion of people with epilepsy registered with substance use disorders (alcohol use disorders or non-alcohol drug use disorders) and psychotic disorders (schizophrenia spectrum disorders or bipolar disorder) with similar figures in the population without epilepsy. We applied chi-square tests and log-binomial regression for analysis.
RESULTS: Overall, 0.90% of the Norwegian adult population was registered with epilepsy in somatic hospitals during 2008-2012. The total proportion registered with alcohol use disorder was 5.74% among people with epilepsy and 1.29% in the population without epilepsy (age- and sex-adjusted relative risk [RR]: 4.42, 95% confidence interval [CI]: 4.22-4.62). The corresponding figures were 4.32% and 1.22% (RR 3.86 [95% CI: 3.67-4.06] for drug use disorder, 1.72% and 0.60% (RR 2.94 [95% CI: 2.71-3.19]) for schizophrenia spectrum disorders, and 1.50% and 0.68% (RR 2.29 [95% CI: 2.10-2.49]) for bipolar disorder.
CONCLUSION: People with epilepsy were more often registered with substance use disorders and psychotic disorders than people without epilepsy. Psychiatric comorbidity requires particular attention in both diagnostic work-up and management of epilepsy, and creates complex medical challenges that require close cooperation between neurologists and psychiatrists. These findings may have implications for the organization and further development of comprehensive epilepsy care.

PMID: 25062893 [PubMed - as supplied by publisher]



Commingling analysis of age-of-onset in bipolar I disorder and the morbid risk for major psychoses in first degree relatives of bipolar I probands.

J Affect Disord. 2014 Jul 9;168C:197-204

Authors: Grigoroiu-Serbanescu M, Rietschel M, Hauser J, Czerski PM, Herms S, Sun X, Wickramaratne P, Elston RC

Abstract
BACKGROUND: Age-of-onset (AO) is increasingly used in molecular genetics of bipolar I disorder (BP-I) as a phenotypic specifier with the goal of reducing genetic heterogeneity. However, questions regarding the cut-off age for defining early onset (EO), as well as the number of onset groups characterizing BP-I have emerged over the last decade with no definite conclusion. The aims of this paper are: 1) to see whether a mixture of three distributions better describes the AO of BP-I than a mixture of two distributions in different independent samples; 2) to compare the morbid risk (MR) for BP-I and for major affective disorders and schizophrenia in first degree relatives of BP-I probands by proband onset group derived from commingling analysis, since the MR to relatives is a trait with strong genetic background.
METHODS: We applied commingling (admixture) analysis to the AO of three BP-I samples from Romania (n=621), Germany (n=882), and Poland (n=354). Subsequently, the morbid risk (MR) for BP-I and for major psychoses (BP-I, BP-II, Mdd-UP, schizoaffective disorders, schizophrenia) was estimated in first degree relatives by proband AO-group derived from admixture analysis in the Romanian sample.
RESULTS: In the three independent samples and in the combined sample two- and three-AO-group distributions fitted the empirical data equally well. The upper EO limit varied between 21 and 25 years from sample to sample. The MR for both BP-I and for all major psychoses was similar in first degree relatives of EO probands (AO?21) and in relatives of intermediate-onset probands (AO=22-34). Significant MR differences appeared only when comparing the EO group to the late-onset (LO) group (AO>34). Similar to Mdd-UP and schizophrenia, a significant MR decrease in proband first degree relatives was visible after proband AO of 34 years. Under the three-AO-group classification the MR for both BP-I and all major psychoses in first degree relatives did not differ by relative sex in any proband AO-group. Under the two-AO-group classification female relatives of LO probands (AO>24) had a significantly higher MR for all major psychoses than male relatives, while there was no sex difference for the relatives of EO probands.
LIMITATIONS: MR was not computed in the German and Polish samples because family data were not available and 34% of the relatives of the Romanian probands were not available for direct interview.
CONCLUSION: Similar to other clinical traits, the MR for major psychoses to relatives failed to support a three-AO-group classification in BP-I suggesting that this is not more useful for the molecular analysis than a two-AO-group classification.

PMID: 25063958 [PubMed - as supplied by publisher]



Seasonality and bipolar disorder: A systematic review, from admission rates to seasonality of symptoms.

J Affect Disord. 2014 Jul 10;168C:210-223

Authors: Geoffroy PA, Bellivier F, Scott J, Etain B

Abstract
INTRODUCTION: Bipolar disorder (BD) is a severe mental disorder affecting 1-4% of the population worldwide. It is characterized by periods of (hypo)manic and depressive episodes. Seasonal patterns (SP) may be observed in admission rates, mood relapses and symptom fluctuations.
METHODS: We conducted a systematic review of seasonality in BD, classifying studies based on seasonal admission rates to seasonality of symptoms assessments.
RESULTS: Fifty-one papers were identified of which 32 addressed hospitalization rates by season, 6 addressed categorical diagnoses, and 13 explored symptom dimensions. Seasonal peaks for different BD mood episodes are observed worldwide and widely replicated. Manic episodes peak during spring/summer and, to a lesser extent, in autumn, depressive episodes peak in early winter and, to a lesser extent, summer, and mixed episodes peak in early spring or mid/late summer. There was a high frequency of SP for manic episodes (15%) and depressive episodes (25%), the latter being associated with a more complex clinical profile (BD II subtype, comorbid eating disorders, more relapses and rapid cycling). Finally, there was evidence for greater seasonal fluctuations in mood and behavior in individuals with BD than in those with unipolar depression or 'healthy' controls.
LIMITATIONS: Sample size, gender distribution, methodological quality and sophistication of the analytical approaches employed varied considerably.
CONCLUSIONS: There is evidence of seasonality in BD, with emerging evidence that climatic conditions may trigger BD symptoms or episodes. A better understanding of the underlying mechanisms would facilitate the development of personalized chronobiological therapeutic and preventive strategies.

PMID: 25063960 [PubMed - as supplied by publisher]



Differential hippocampal gene expression and pathway analysis in an etiology-based mouse model of major depressive disorder.

Am J Med Genet B Neuropsychiatr Genet. 2014 Jul 25;

Authors: Zubenko GS, Hughes HB, Jordan RM, Lyons-Weiler J, Cohen BM

Abstract
We have recently reported the creation and initial characterization of an etiology-based recombinant mouse model of a severe and inherited form of Major Depressive Disorder (MDD). This was achieved by replacing the corresponding mouse DNA sequence with a 6-base DNA sequence from the human CREB1 promoter that is associated with MDD in individuals from families with recurrent, early-onset MDD (RE-MDD). In the current study, we explored the effect of the pathogenic Creb1 allele on gene expression in the mouse hippocampus, a brain region that is altered in structure and function in MDD. Mouse whole-genome profiling was performed using the Illumina MouseWG-6 v2.0 Expression BeadChip microarray. Univariate analysis identified 269 differentially-expressed genes in the hippocampus of the mutant mouse. Pathway analyses highlighted 11 KEGG pathways: the phosphatidylinositol signaling system, which has been widely implicated in MDD, Bipolar Disorder, and the action of mood stabilizers; gap junction and long-term potentiation, which mediate cognition and memory functions often impaired in MDD; cardiac muscle contraction, insulin signaling pathway, and three neurodegenerative brain disorders (Alzheimer's, Parkinson's, and Huntington's Diseases) that are associated with MDD; ribosome and proteasome pathways affecting protein synthesis/degradation; and the oxidative phosphorylation pathway that is key to energy production. These findings illustrate the merit of this congenic C57BL/6 recombinant mouse as a model of RE-MDD, and demonstrate its potential for highlighting molecular and cellular pathways that contribute to the biology of MDD. The results also inform our understanding of the mechanisms that underlie the comorbidity of MDD with other disorders. © 2014 Wiley Periodicals, Inc.

PMID: 25059218 [PubMed - as supplied by publisher]



Sleep-wake disturbance in interepisode bipolar disorder and high-risk individuals: A systematic review and meta-analysis.

Sleep Med Rev. 2014 Jun 26;

Authors: Ng TH, Chung KF, Ho FY, Yeung WF, Yung KP, Lam TH

Abstract
Over the past decade, researchers have shifted focus from the manic and depressive episodes to the interepisode period in the study of sleep-wake disturbance in bipolar disorder. The objective of this systematic review was to compile and synthesize studies that employed sleep diary, actigraphy, polysomnography, and questionnaires to compare sleep-wake patterns in people with interepisode bipolar disorder or high-risk individuals vs. normal controls and/or people with primary insomnia. We searched key databases until June 2013. Our search identified 21 eligible studies, yielding 24 sleep-wake variables. A total of 531 people with interepisode bipolar disorder, 157 high-risk individuals, 678 normal controls and 67 adults with primary insomnia were evaluated. Using a random-effects model, our analyses suggest that adults with interepisode bipolar disorder appear worse than normal controls in most variables and comparable to adults with primary insomnia in certain aspects. Sleep onset latency, wake after sleep onset, and variability of sleep-wake variables were most consistently impaired in interepisode bipolar disorder. In comparison with controls, high-risk individuals were found to have higher variability in sleep efficiency and lower relative amplitude. The findings provide a foundation for the search for candidate endophenotypes and the development of novel interventions for bipolar disorder.

PMID: 25060968 [PubMed - as supplied by publisher]



Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World

Book. 2001

Authors: Institute of Medicine (US) Committee on Nervous System Disorders in Developing Countries

Abstract
Brain disorders?neurological, psychiatric, and developmental?now affect at least 250 million people in the developing world, and this number is expected to rise as life expectancy increases. Yet public and private health systems in developing countries have paid relatively little attention to brain disorders. The negative attitudes, prejudice, and stigma that often surround many of these disorders have contributed to this neglect. Lacking proper diagnosis and treatment, millions of individual lives are lost to disability and death. Such conditions exact both personal and economic costs on families, communities, and nations. The report describes the causes and risk factors associated with brain disorders. It focuses on six representative brain disorders that are prevalent in developing countries: developmental disabilities, epilepsy, schizophrenia, bipolar disorder, depression, and stroke. The report makes detailed recommendations of ways to reduce the toll exacted by these six disorders. In broader strokes, the report also proposes six major strategies toward reducing the overall burden of brain disorders in the developing world.


PMID: 25057559



Cost-Effectiveness of Asenapine in the Treatment of Patients with Bipolar I Disorder with Mixed Episodes in an Italian Context.

Adv Ther. 2014 Jul 24;

Authors: Caresano C, Di Sciascio G, Fagiolini A, Maina G, Perugi G, Ripellino C, Vampini C

Abstract
INTRODUCTION: Bipolar disorder is a chronic disease characterized by periods of mania or hypomania, depression, or a combination of both (mixed state). Because bipolar disorder is one of the leading causes of disability, it represents an important economic burden on society. Asenapine (ASE) is a new second-generation antipsychotic developed and approved for the treatment of manic or mixed episodes associated with bipolar disorder. The objective of the present study was to assess the cost-effectiveness of ASE compared to olanzapine (OLA) in the treatment of patients experiencing mixed episodes associated with bipolar I disorder in the context of the Italian National Health Service (NHS).
METHODS: A pharmacoeconomic model was developed to simulate the management of Italian bipolar I patients with mixed episodes over a 5-year time horizon by combining clinical parameters with resource utilization. An expert panel of Italian psychiatrists and health economists was responsible for adapting a UK model to the Italian context. The primary outcome measure of the economic evaluation was the incremental cost effectiveness ratio, where effectiveness is measured in terms of quality adjusted life-years gained. Scenario analyses, sensitivity analyses, and a probabilistic sensitivity analysis were performed to test the robustness of the model.
RESULTS: This pharmacoeconomic model showed that ASE resulted to be dominant over OLA; in fact, ASE was associated with lower direct costs (derived largely by the savings from hospitalizations avoided) and also generated a better quality of life. Results were robust to changes in key parameters; both scenario analyses and sensitivity analyses demonstrated model reliability.
CONCLUSIONS: Results from this study suggest that the management of bipolar I patients with mixed episodes using ASE as alternative to OLA can lead to cost saving for the Italian NHS and improve patients quality of life.

PMID: 25055791 [PubMed - as supplied by publisher]



De novo CNVs in Bipolar Affective Disorder and Schizophrenia.

Hum Mol Genet. 2014 Jul 23;

Authors: Georgieva L, Rees E, Moran JL, Chambert KD, Milanova V, Craddock N, Purcell S, Sklar P, McCarroll S, Holmans P, O'Donovan MC, Owen MJ, Kirov G

Abstract
An increased rate of de novo copy number variants (CNVs) has been found in schizophrenia (SZ), autism and developmental delay. An increased rate has also been reported in bipolar affective disorder (BD). Here, in a larger BD sample, we aimed to replicate these findings and compare de novo CNVs between SZ and BD. We used Illumina microarrays to genotype 368 BD probands, 76 SZ probands and all their parents. CNVs were called by PennCNV and filtered for frequency (<1%) and size (>10kb). Putative de novo CNVs were validated with the z-score algorithm, manual inspection of log R ratios, and qPCR probes. We found 15 de novo CNVs in BD (4.1% rate) and six in SZ (7.9% rate). Combining results with previous studies and using a cut-off of >100kb, the rate of de novo CNVs in BD was intermediate between controls and SZ: 1.5% in controls, 2.2% in BD and 4.3% in SZ. Only the differences between SZ and BD and SZ and controls were significant. The median size of de novo CNVs in BD (448kb) was also intermediate between SZ (613kb) and controls (338kb), but only the comparison between SZ and controls was significant. Only one de novo CNV in BD was in a confirmed SZ locus (16p11.2). Sporadic or early onset cases were not more likely to have de novo CNVs. We conclude that de novo CNVs play a smaller role in BD compared to SZ. Patients with a positive family history can also harbour de novo mutations.

PMID: 25055870 [PubMed - as supplied by publisher]



Population study of disease burden, management, and treatment of bipolar disorder in Sweden: a retrospective observational registry study.

Bipolar Disord. 2014 Jul 24;

Authors: Carlborg A, Ferntoft L, Thuresson M, Bodegard J

Abstract
OBJECTIVES: The aim of the study was to describe temporal changes in bipolar disorder during 20 years within the Swedish population and to investigate clinical and socioeconomic characteristics, drug treatment, and mortality among patients with bipolar disorder.
METHODS: We conducted a retrospective, nationwide registry study (the Swedish Population Register) that included all patients diagnosed with bipolar disorder (1991-2010) and linked individual data from the Swedish National Patient Register, the National Prescribed Drug Register, and the Population Register (NCT01455961). A cross-sectional cohort analysis was performed for years 2006 versus 2009. Data were analyzed using descriptive statistics.
RESULTS: During the study period, the annual incidence of diagnosed bipolar disorder increased 3.5-fold, and patients were diagnosed at a younger age. Mortality among patients with bipolar disorder was twice that of the general population. Compared to an age-standardized population, 30% fewer patients with bipolar disorder were available for work. Among the 40% employed, 64% reported sick leave (46% >100 days/year). Despite similar education levels, disposable income was lower compared to the general population. The most commonly preceding psychiatric diagnoses were depressive or anxiety disorders. Comparing the data for 2006 and 2009 demonstrated similar somatic comorbidity burdens and socioeconomic levels. There was also a decrease in dispensed antipsychotic medications and lithium, while antiepileptic prescriptions increased slightly. Antidepressant dispenses remained virtually unchanged.
CONCLUSIONS: In Sweden, the incidence and prevalence of diagnosed bipolar disorder have increased during the last 20 years. Compared to the general population, these patients had similar education levels, lower employment levels, less disposable income, more sick leave, and twice the mortality. A trend towards earlier diagnosis, more use of antidepressants, and less use of lithium was seen.

PMID: 25056132 [PubMed - as supplied by publisher]



Near-infrared spectroscopic study of frontopolar activation during face-to-face conversation in major depressive disorder and bipolar disorder.

J Psychiatr Res. 2014 Jun 26;

Authors: Takei Y, Suda M, Aoyama Y, Sakurai N, Tagawa M, Motegi T, Yamaguchi M, Narita K, Fukuda M

Abstract
Major depressive disorder (MDD) and bipolar disorder (BD) patients show speech characteristics that vary greatly according to mood state. In a previous study, we found impaired temporal and right inferior frontal gyrus (IFG) activation in schizophrenia during face-to-face conversation; no study had, however, previously investigated mood disorders during face-to-face conversation. Here, we investigated frontal and temporal lobe activation during conversation in patients with MDD and BD. Frontal and temporal lobe activation was measured using near-infrared spectroscopy (NIRS) in 29 patients with MDD, 31 patients with BD, and 31 normal controls (NC). We compared continuous activation and rapid change of activation with talk/listen phase changes during the conversation and analyzed the correlation between these indices and clinical variables. Both the MDD and BD groups showed decreased continuous activation in the left dorsolateral prefrontal (DLPFC) and left frontopolar cortices (FPCs); they also showed decreased rapid change in bilateral FPC activation. In the MDD group, the rapid change of activation was positively correlated with Global Assessment of Functioning (GAF) scores. In the BD group, continuous activation was negatively correlated with age of onset. These results indicate that frontal activation during conversation decreases in both MDD and BD. However, both continuous activation and rapid change may reflect the pathophysiological character of MDD and BD; in particular, the reduced amount of rapid change in the right FPC may be related to impaired adaptive ability in MDD.

PMID: 25056175 [PubMed - as supplied by publisher]



Myelination, oligodendrocytes, and serious mental illness.

Glia. 2014 Jul 23;

Authors: Haroutunian V, Katsel P, Roussos P, Davis KL, Altshuler LL, Bartzokis G

Abstract
Historically, the human brain has been conceptually segregated from the periphery and further dichotomized into gray matter (GM) and white matter (WM) based on the whitish appearance of the exceptionally high lipid content of the myelin sheaths encasing neuronal axons. These simplistic dichotomies were unfortunately extended to conceptually segregate neurons from glia, cognition from behavior, and have been codified in the separation of clinical and scientific fields into medicine, psychiatry, neurology, pathology, etc. The discrete classifications have helped obscure the importance of continual dynamic communication between all brain cell types (neurons, astrocytes, microglia, oligodendrocytes, and precursor (NG2) cells) as well as between brain and periphery through multiple signaling systems. The signaling systems range from neurotransmitters to insulin, angiotensin, and multiple kinases such a glycogen synthase kinase 3 (GSK-3) that together help integrate metabolism, inflammation, and myelination processes and orchestrate the development, plasticity, maintenance, and repair that continually optimize function of neural networks. A more comprehensive, evolution-based, systems biology approach that integrates brain, body, and environmental interactions may ultimately prove more fruitful in elucidating the complexities of human brain function. The historic focus on neurons/GM is rebalanced herein by highlighting the importance of a systems-level understanding of the interdependent age-related shifts in both central and peripheral homeostatic mechanisms that can lead to remarkably prevalent and devastating neuropsychiatric diseases. Herein we highlight the role of glia, especially the most recently evolved oligodendrocytes and the myelin they produce, in achieving and maintaining optimal brain function. The human brain undergoes exceptionally protracted and pervasive myelination (even throughout its GM) and can thus achieve and maintain the rapid conduction and synchronous timing of neural networks on which optimal function depends. The continuum of increasing myelin vulnerability resulting from the human brain's protracted myelination underlies underappreciated communalities between different disease phenotypes ranging from developmental ones such as schizophrenia (SZ) and bipolar disorder (BD) to degenerative ones such as Alzheimer's disease (AD). These shared vulnerabilities also expose significant yet underexplored opportunities for novel treatment and prevention approaches that have the potential to considerably reduce the tremendous burden of neuropsychiatric disease. GLIA 2014.

PMID: 25056210 [PubMed - as supplied by publisher]



Post-discharge suicides of inpatients with bipolar disorder in Finland.

Bipolar Disord. 2014 Jul 24;

Authors: Isometsä E, Sund R, Pirkola S

Abstract
OBJECTIVES: Suicide risk in psychiatric inpatients is known to be remarkably high after discharge. However, temporal patterns and risk factors among patients with bipolar disorder remain obscure. We investigated post-discharge temporal patterns of hazard and risk factors by type of illness phase among patients with bipolar disorder.
METHODS: Based on national registers, all discharges of patients with bipolar disorder from a psychiatric ward in Finland in 1987-2003 (n = 52,747) were identified, and each patient was followed up to post-index discharge or to suicide (n = 466). For discharges occurring in 1995-2003 (n = 35,946), factors modifying hazard of suicide during the first 120 days (n = 129) were investigated.
RESULTS: The temporal pattern of suicide risk depended on the type of illness phase, being highest but steeply declining after discharge with depression; less high and declining in mixed states; lower and relatively stable after mania. In Cox models, for post-discharge suicides (n = 65) after hospitalizations for bipolar depression (n = 9,635), the hazard ratio was 8.05 (p = 0.001) after hospitalization with a suicide attempt and 3.63 (p < 0.001) for male patients, but 0.186 (p = 0.001) for patients taking lithium. Suicides after mania (n = 28) or mixed episodes (n = 20) were predicted by male sex and preceding suicide attempts, respectively.
CONCLUSIONS: Among inpatients with bipolar disorder, suicide risk is high and related strongly to the time elapsed from discharge after hospitalizations for depressive episodes, and less strongly after hospitalizations for mixed episodes. Intra-episodic suicide attempts and male sex powerfully predict suicide risk. Lower suicide rate after hospitalizations for depression among patients prescribed lithium is consistent with a preventive effect.

PMID: 25056223 [PubMed - as supplied by publisher]



The efficacy and tolerability of cariprazine in acute mania associated with bipolar I disorder: a phase II trial.

Bipolar Disord. 2014 Jul 24;

Authors: Durgam S, Starace A, Li D, Migliore R, Ruth A, Németh G, Laszlovszky I

Abstract
OBJECTIVES: Cariprazine, an orally active and potent dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors, is being developed for the treatment of schizophrenia and bipolar mania. This Phase II trial evaluated the efficacy, safety, and tolerability of cariprazine versus placebo in the treatment of acute manic or mixed episodes associated with bipolar I disorder.
METHODS: This was a multinational, randomized, double-blind, placebo-controlled, flexible-dose study of cariprazine 3-12 mg/day in patients with acute manic or mixed episodes associated with bipolar I disorder. Following washout, patients received three weeks of double-blind treatment. The primary and secondary efficacy parameters were change from baseline to Week 3 in Young Mania Rating Scale (YMRS) and Clinical Global Impressions-Severity (CGI-S) scores, respectively. Post-hoc analysis evaluated changes on YMRS single items.
RESULTS: In each group, 118 patients received double-blind treatment; 61.9% of placebo and 63.6% of cariprazine patients completed the study. The overall mean daily dose of cariprazine was 8.8 mg/day. At Week 3, cariprazine significantly reduced YMRS and CGI-S scores versus placebo, with least square mean differences of -6.1 (p < 0.001) and -0.6 (p < 0.001), respectively. On each YMRS item, change from baseline to Week 3 was significantly greater for cariprazine versus placebo (all, p < 0.05). A significantly greater percentage of cariprazine patients than placebo patients met YMRS response (48% versus 25%; p < 0.001) and remission (42% versus 23%; p = 0.002) criteria at Week 3. Adverse events (AEs) led to discontinuation of 12 (10%) placebo and 17 (14%) cariprazine patients. The most common AEs (> 10% for cariprazine) were extrapyramidal disorder, headache, akathisia, constipation, nausea, and dyspepsia. Changes in metabolic parameters were similar between groups, with the exception of fasting glucose; increases in glucose were significantly greater for cariprazine versus placebo (p < 0.05). Based on Barnes Akathisia Rating Scale and Simpson-Angus Scale scores, more cariprazine than placebo patients experienced treatment-emergent akathisia (cariprazine: 22%; placebo: 6%) or extrapyramidal symptoms (parkinsonism) (cariprazine: 16%; placebo: 1%).
CONCLUSION: Cariprazine demonstrated superior efficacy versus placebo and was generally well tolerated in patients experiencing acute manic or mixed episodes associated with bipolar I disorder.

PMID: 25056368 [PubMed - as supplied by publisher]



Targeting mitochondrially mediated plasticity to develop improved therapeutics for bipolar disorder.

Expert Opin Ther Targets. 2014 Jul 24;:1-17

Authors: de Sousa RT, Machado-Vieira R, Zarate CA, Manji HK

Abstract
Introduction: Bipolar disorder (BPD) is a severe illness with few treatments available. Understanding BPD pathophysiology and identifying potential relevant targets could prove useful for developing new treatments. Remarkably, subtle impairments of mitochondrial function may play an important role in BPD pathophysiology. Areas covered: This article focuses on human studies and reviews evidence of mitochondrial dysfunction in BPD as a promising target for the development of new, improved treatments. Mitochondria are crucial for energy production, generated mainly through the electron transport chain (ETC) and play an important role in regulating apoptosis and calcium (Ca(2+)) signaling as well as synaptic plasticity. Mitochondria move throughout the neurons to provide energy for intracellular signaling. Studies showed polymorphisms of mitochondria-related genes as risk factors for BPD. Postmortem studies in BPD also show decreased ETC activity/expression and increased nitrosative and oxidative stress (OxS) in patient brains. BPD has been also associated with increased OxS, Ca(2+) dysregulation and increased proapoptotic signaling in peripheral blood. Neuroimaging studies consistently show decreased energy levels and pH in brains of BPD patients. Expert opinion: Targeting mitochondrial function, and their role in energy metabolism, synaptic plasticity and cell survival, may be an important avenue for development of new mood-stabilizing agents.

PMID: 25056514 [PubMed - as supplied by publisher]



Frontal cortical and subcortical projections provide a basis for segmenting the cingulum bundle: implications for neuroimaging and psychiatric disorders.

J Neurosci. 2014 Jul 23;34(30):10041-54

Authors: Heilbronner SR, Haber SN

Abstract
The cingulum bundle (CB) is one of the brain's major white matter pathways, linking regions associated with executive function, decision-making, and emotion. Neuroimaging has revealed that abnormalities in particular locations within the CB are associated with specific psychiatric disorders, including depression and bipolar disorder. However, the fibers using each portion of the CB remain unknown. In this study, we used anatomical tract-tracing in nonhuman primates (Macaca nemestrina, Macaca fascicularis, Macaca mulatta) to examine the organization of specific cingulate, noncingulate frontal, and subcortical pathways through the CB. The goals were as follows: (1) to determine connections that use the CB, (2) to establish through which parts of the CB these fibers travel, and (3) to relate the CB fiber pathways to the portions of the CB identified in humans as neurosurgical targets for amelioration of psychiatric disorders. Results indicate that cingulate, noncingulate frontal, and subcortical fibers all travel through the CB to reach both cingulate and noncingulate targets. However, many brain regions send projections through only part, not all, of the CB. For example, amygdala fibers are not present in the caudal portion of the dorsal CB. These results allow segmentation of the CB into four unique zones. We identify the specific connections that are abnormal in psychiatric disorders and affected by neurosurgical interventions, such as deep brain stimulation and cingulotomy.

PMID: 25057206 [PubMed - in process]



The role of F-actin in modulating Clathrin-mediated endocytosis: Lessons from neurons in health and neuropsychiatric disorder.

Commun Integr Biol. 2014;7:e28740

Authors: Loebrich S

Abstract
Clathrin-mediated endocytosis is one of several mechanisms for retrieving transmembrane proteins from the cell surface. This key mechanism is highly conserved in evolution and is found in any eukaryotic cell from yeast to mammals. Studies from several model organisms have revealed that filamentous actin (F-actin) plays multiple distinct roles in shaping Clathrin-mediated endocytosis. Yet, despite the identification of numerous molecules at the interface between endocytic machinery and the cytoskeleton, our mechanistic understanding of how F-actin regulates endocytosis remains limited. Key insights come from neurons where vesicular release and internalization are critical to pre- and postsynaptic function. Recent evidence from human genetics puts postsynaptic organization, glutamate receptor trafficking, and F-actin remodeling in the spotlight as candidate mechanisms underlying neuropsychiatric disorders. Here I review recent findings that connect the F-actin cytoskeleton mechanistically to Clathrin-mediated endocytosis in the central nervous system, and discuss their potential involvement in conferring risk for neuropsychiatric disorder.

PMID: 25053985 [PubMed]



Emotion recognition deficits in schizophrenia-spectrum disorders and psychotic bipolar disorder: Findings from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study.

Schizophr Res. 2014 Jul 19;

Authors: Ruocco AC, Reilly JL, Rubin LH, Daros AR, Gershon ES, Tamminga CA, Pearlson GD, Hill SK, Keshavan MS, Gur RC, Sweeney JA

Abstract
BACKGROUND: Difficulty recognizing facial emotions is an important social-cognitive deficit associated with psychotic disorders. It also may reflect a familial risk for psychosis in schizophrenia-spectrum disorders and bipolar disorder.
OBJECTIVE: The objectives of this study from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium were to: 1) compare emotion recognition deficits in schizophrenia, schizoaffective disorder and bipolar disorder with psychosis, 2) determine the familiality of emotion recognition deficits across these disorders, and 3) evaluate emotion recognition deficits in nonpsychotic relatives with and without elevated Cluster A and Cluster B personality disorder traits.
METHOD: Participants included probands with schizophrenia (n=297), schizoaffective disorder (depressed type, n=61; bipolar type, n=69), bipolar disorder with psychosis (n=248), their first-degree relatives (n=332, n=69, n=154, and n=286, respectively) and healthy controls (n=380). All participants completed the Penn Emotion Recognition Test, a standardized measure of facial emotion recognition assessing four basic emotions (happiness, sadness, anger and fear) and neutral expressions (no emotion).
RESULTS: Compared to controls, emotion recognition deficits among probands increased progressively from bipolar disorder to schizoaffective disorder to schizophrenia. Proband and relative groups showed similar deficits perceiving angry and neutral faces, whereas deficits on fearful, happy and sad faces were primarily isolated to schizophrenia probands. Even non-psychotic relatives without elevated Cluster A or Cluster B personality disorder traits showed deficits on neutral and angry faces. Emotion recognition ability was moderately familial only in schizophrenia families.
CONCLUSIONS: Emotion recognition deficits are prominent but somewhat different across psychotic disorders. These deficits are reflected to a lesser extent in relatives, particularly on angry and neutral faces. Deficits were evident in non-psychotic relatives even without elevated personality disorder traits. Deficits in facial emotion recognition may reflect an important social-cognitive deficit in patients with psychotic disorders.

PMID: 25052782 [PubMed - as supplied by publisher]



Folate Augmentation of Treatment - Evaluation for Depression (FolATED): randomised trial and economic evaluation.

Health Technol Assess. 2014 Jul;18(48):1-160

Authors: Bedson E, Bell D, Carr D, Carter B, Hughes D, Jorgensen A, Lewis H, Lloyd K, McCaddon A, Moat S, Pink J, Pirmohamed M, Roberts S, Russell I, Sylvestre Y, Tranter R, Whitaker R, Wilkinson C, Williams N

Abstract
BACKGROUND: Folate deficiency is associated with depression. Despite the biological plausibility of a causal link, the evidence that adding folate enhances antidepressant treatment is weak.
OBJECTIVES: (1) Estimate the clinical effectiveness and cost-effectiveness of folic acid as adjunct to antidepressant medication (ADM). (2) Explore whether baseline folate and homocysteine predict response to treatment. (3) Investigate whether response to treatment depends on genetic polymorphisms related to folate metabolism.
DESIGN: FolATED (Folate Augmentation of Treatment - Evaluation for Depression) was a double-blind and placebo-controlled, but otherwise pragmatic, randomised trial including cost-utility analysis. To yield 80% power of detecting standardised difference on the Beck Depression Inventory version 2 (BDI-II) of 0.3 between groups (a 'small' effect), FolATED trialists sought to analyse 358 participants. To allow for an estimated loss of 21% of participants over three time points, we planned to randomise 453.
SETTINGS: Clinical - Three centres in Wales - North East Wales, North West Wales and Swansea. Trial management - North Wales Organisation for Randomised Trials in Health in Bangor University. Biochemical analysis - University Hospital of Wales, Cardiff. Genetic analysis - University of Liverpool.
PARTICIPANTS: Four hundred and seventy-five adult patients presenting to primary or secondary care with confirmed moderate to severe depression for which they were taking or about to start ADM, and able to consent and complete assessments, but not (1) folate deficient, vitamin B12 deficient, or taking folic acid or anticonvulsants; (2) misusing drugs or alcohol, or suffering from psychosis, bipolar disorder, malignancy or other unstable or terminal illness; (3) (planning to become) pregnant; or (4) participating in other clinical research.
INTERVENTIONS: Once a day for 12 weeks experimental participants added 5?mg of folic acid to their ADM, and control participants added an indistinguishable placebo. All participants followed pragmatic management plans initiated by a trial psychiatrist and maintained by their general medical practitioners.
MAIN OUTCOME MEASURES: Assessed at baseline, and 4, 12 and 25 weeks thereafter, and analysed by 'area under curve' (main); by analysis of covariance at each time point (secondary); and by multi-level repeated measures (sensitivity analysis): Mental health - BDI-II (primary), Clinical Global Impression (CGI), Montgomery-Åsberg Depression Rating Scale (MADRS), UKU side effects scale, and Mini International Neuropsychiatric Interview (MINI) suicidality subscale; General health - UK 12-item Short Form Health Survey (SF-12), European Quality of Life scale - 5 Dimensions (EQ-5D); Biochemistry - serum folate, B12, homocysteine; Adherence - Morisky Questionnaire; Economics - resource use.
RESULTS: Folic acid did not significantly improve any of these measures. For example it gained a mean of just 2.9 quality-adjusted life-days [95% confidence interval (CI) from -12.7 to 7.0 days] and saved a mean of just £48 (95% CI from -£292 to £389). In contrast it significantly reduced mental health scores on the SF-12 by 3.0% (95% CI from -5.2% to -0.8%).
CONCLUSIONS: The FolATED trial generated no evidence that folic acid was clinically effective or cost-effective in augmenting ADM. This negative finding is consistent with improving understanding of the one-carbon folate pathway suggesting that methylfolate is a better candidate for augmenting ADM. Hence the findings of FolATED undermine treatment guidelines that advocate folic acid for treating depression, and suggest future trials of methylfolate to augment ADM.
TRIAL REGISTRATION: Current Controlled Trials ISRCTN37558856.
FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 48. See the HTA programme website for further project information.

PMID: 25052890 [PubMed - in process]



Genetic association between a 'standing' variant of NOD2 and bipolar disorder.

Immunobiology. 2014 Jul 9;

Authors: Oliveira J, Hamdani N, Etain B, Bennabi M, Boukouaci W, Amokrane K, Fortier C, Marzais F, Bengoufa D, Bellivier F, Henry C, Kahn JP, Charron D, Krishnamoorthy R, Leboyer M, Tamouza R

Abstract
Bipolar disorders (BD) are chronic, multisystem and multifactorial disorders with significant lifetime morbidity, mortality and socio-economic burden. Understanding the underlying genetic and disease triggering environmental factors should improve diagnosis, prognosis, prevention and therapeutic management of the disease. Since intestinal innate dysimmunity seems to play a significant role in the etiopathogeny of BD, we explored in a sample of French Caucasian BD patients, the genetic polymorphisms of NOD2 (nucleotide-binding oligomerization domain containing 2) gene, a key player in such immunity. We found a Caucasian-specific 'standing' variation to be associated with BD. The significance of this finding is discussed in the context of Crohn's disease as well as the complex function of NOD2 in innate immunity.

PMID: 25053139 [PubMed - as supplied by publisher]



Analysis of t(9;17)(q33.2;q25.3) chromosomal breakpoint regions and genetic association reveals novel candidate genes for bipolar disorder.

Bipolar Disord. 2014 Jul 23;

Authors: Rajkumar AP, Christensen JH, Mattheisen M, Jacobsen I, Bache I, Pallesen J, Grove J, Qvist P, McQuillin A, Gurling HM, Tümer Z, Mors O, Børglum AD

Abstract
OBJECTIVES: Breakpoints of chromosomal abnormalities facilitate identification of novel candidate genes for psychiatric disorders. Genome-wide significant evidence supports the linkage between chromosome 17q25.3 and bipolar disorder (BD). Co-segregation of translocation t(9;17)(q33.2;q25.3) with psychiatric disorders has been reported. We aimed to narrow down these chromosomal breakpoint regions and to investigate the associations between single nucleotide polymorphisms within these regions and BD as well as schizophrenia (SZ) in large genome-wide association study samples.
METHODS: We cross-linked Danish psychiatric and cytogenetic case registers to identify an individual with both t(9;17)(q33.2;q25.3) and BD. Fluorescent in situ hybridization was employed to map the chromosomal breakpoint regions of this proband. We accessed the Psychiatric Genomics Consortium BD (n = 16,731) and SZ (n = 21,856) data. Genetic associations between these disorders and single nucleotide polymorphisms within these breakpoint regions were analysed by BioQ, FORGE, and RegulomeDB programmes.
RESULTS: Four protein-coding genes [coding for (endonuclease V (ENDOV), neuronal pentraxin I (NPTX1), ring finger protein 213 (RNF213), and regulatory-associated protein of mammalian target of rapamycin (mTOR) (RPTOR)] were found to be located within the 17q25.3 breakpoint region. NPTX1 was significantly associated with BD (p = 0.004), while ENDOV was significantly associated with SZ (p = 0.0075) after Bonferroni correction.
CONCLUSIONS: Prior linkage evidence and our findings suggest NPTX1 as a novel candidate gene for BD.

PMID: 25053281 [PubMed - as supplied by publisher]



Combined Ketamine/Transcranial Magnetic Stimulation Treatment of Severe Depression in Bipolar I Disorder.

J ECT. 2014 Jul 22;

Authors: Best SR

PMID: 25054363 [PubMed - as supplied by publisher]



Evaluation of the Potential for a Pharmacokinetic Drug-Drug Interaction Between Armodafinil and Ziprasidone in Healthy Adults.

Clin Drug Investig. 2014 Jul 22;

Authors: Darwish M, Bond M, Yang R, Hellriegel ET, Robertson P

Abstract
BACKGROUND: Armodafinil has been studied as adjunctive therapy for major depressive episodes associated with bipolar I disorder. This open-label, single-centre, 2-period study evaluated the effect of armodafinil, a moderate inducer of cytochrome-P450 (CYP) isoenzyme CYP3A4, on the pharmacokinetics and safety of ziprasidone, an atypical antipsychotic used to treat bipolar I disorder and metabolized in part by CYP3A4.
METHODS: Thirty-five healthy subjects received ziprasidone (20 mg) alone and after armodafinil pretreatment (titrated to 250 mg/day); of those, 25 were evaluable for pharmacokinetics. Pharmacokinetic parameters were derived from plasma concentrations of ziprasidone collected prior to and over the 48 h after each ziprasidone administration. Plasma concentrations of armodafinil and its circulating metabolites, R-modafinil acid and modafinil sulfone, were also obtained after repeated daily dosing of armodafinil alone. Safety and tolerability were assessed.
RESULTS: Systemic exposure to ziprasidone was similar following administration alone or after pretreatment with armodafinil, as assessed by mean peak plasma concentration (C max, 52.1 vs 50.4 ng/mL) and area under the plasma concentration-time curve from time 0 to infinity (AUC0-?, 544.6 vs 469.1 ng·h/mL). Geometric mean ratios of systemic exposure (ziprasidone alone: ziprasidone after pretreatment with armodafinil) were close to unity, with associated 90 % confidence intervals (CIs) within the range of 0.80-1.25 (C max, 0.97; 90 % CI, 0.87-1.08; AUC0-?, 0.86; 90 % CI, 0.82-0.91). Adverse events were consistent with the known safety profiles of each agent.
CONCLUSION: Systemic exposure to ziprasidone was not affected by pretreatment with armodafinil. Both drugs were generally safe and well tolerated under the conditions studied.

PMID: 25047407 [PubMed - as supplied by publisher]



All the world's a (clinical) stage: rethinking bipolar disorder from a longitudinal perspective.

Mol Psychiatry. 2014 Jul 22;

Authors: Frank E, Nimgaonkar VL, Phillips ML, Kupfer DJ

Abstract
Psychiatric disorders have traditionally been classified using a static, categorical approach. However, this approach falls short in facilitating understanding of the development, common comorbid diagnoses, prognosis and treatment of these disorders. We propose a 'staging' model of bipolar disorder that integrates genetic and neural information with mood and activity symptoms to describe how the disease progresses over time. From an early, asymptomatic, but 'at-risk' stage to severe, chronic illness, each stage is described with associated neuroimaging findings as well as strategies for mapping genetic risk factors. Integrating more biologic information relating to cardiovascular and endocrine systems, refining methodology for modeling dimensional approaches to disease and developing outcome measures will all be crucial in examining the validity of this model. Ultimately, this approach should aid in developing targeted interventions for each group that will reduce the significant morbidity and mortality associated with bipolar disorder.Molecular Psychiatry advance online publication, 22 July 2014; doi:10.1038/mp.2014.71.

PMID: 25048003 [PubMed - as supplied by publisher]



Neuropsychological performance of patients with soft bipolar spectrum disorders.

Bipolar Disord. 2014 Jul 22;

Authors: Lin K, Xu G, Lu W, Ouyang H, Dang Y, Guo Y, So KF, Lee TM

Abstract
OBJECTIVES: There is much evidence that shows that a substantial number of individuals with DSM-IV-defined unipolar depression (UP) manifest hypomanic sub-syndrome and bipolar diathesis. Other definitions have conceptualized the term soft bipolar spectrum (SBP) for these individuals. Little is known about the cognitive profiles of individuals with SBP. We hypothesized that they are representative of individuals with bipolar II disorder and are different from that of 'strict' UP.
METHODS: Consecutive referrals suffering major depressive episodes were categorically assigned to groups of either bipolar I disorder (n = 98), bipolar II disorder (n = 138), or UP (n = 300). Based on the SBP criteria by Akiskal and Pinto (17), patients with UP were subdivided into 81 SBP and 219 strict UP. We administered self- and clinician-administered scales to evaluate affective temperaments, and neuropsychological tests to assess seven cognitive domains.
RESULTS: Patients with SBP performed significantly better than strict UP patients in the domains of processing speed (p = 0.002), visual-spatial memory (p = 0.017), and verbal working memory (p = 0.017). Compared to patients with bipolar I disorder, patients with SBP were significantly better in set shifting (p < 0.001) and visual-spatial memory (p = 0.042). Patients with SBP performed similarly to patients with bipolar II disorder in all of the cognitive domains tested (p > 0.05). There was a group × cognitive domain interaction effect between bipolar I disorder, bipolar II disorder, SBP, and strict UP groups [Pillai's F = 2.231, df = (18,1437), p = 0.002].
CONCLUSIONS: Our data suggest that patients with SBP differ from patients with UP not only in external validators (e.g., family history of bipolar disorder) and hypomanic symptoms, but also in neuropsychological performance and that the profiles of cognitive functioning were different across bipolar I disorder and 'bipolar II spectrum' that subsumes bipolar II disorder and SBP.

PMID: 25048414 [PubMed - as supplied by publisher]



Are 'buy-polar' forces and 'try-polar' thinking expanding bipolarity?

Aust N Z J Psychiatry. 2014 Jul 21;48(8):697-700

Authors: Malhi GS, Porter RJ

PMID: 25048651 [PubMed - as supplied by publisher]



Comorbidity between attention deficit hyperactivity disorder (ADHD) and bipolar disorder in a specialized mood disorders outpatient clinic.

J Affect Disord. 2014 Jul 9;168C:161-166

Authors: Perroud N, Cordera P, Zimmermann J, Michalopoulos G, Bancila V, Prada P, Dayer A, Aubry JM

Abstract
BACKGROUND: Comorbidity between ADHD and Bipolar Disorder (BD) is associated with greater severity of BD. The current study aims at investigating, in a specialized mood disorders clinic, the percentage of comorbid ADHD-BD subjects and assessing the impact of ADHD on the severity of BD.
METHODS: Out of 539 mood disorders subjects, the medical records of 138 BD subjects were scrutinized in terms of their clinical and demographic characteristics, and their scores at the Adult ADHD Self-Report Scale (ASRS-v1.1) Symptom Checklist were logged. Those positively scoring at the ASRS-v1.1 underwent clinical assessment by a senior psychiatrist specialized in ADHD. Comorbid ADHD-BD subjects were then compared with BD sufferers without ADHD.
RESULTS: Sixty-three (45.65%) of the participants were screened positive at the ASRS-v1.1. 49 were clinically assessed for the presence of ADHD. Only 27 (55%) received a diagnosis of ADHD. Comorbid ADHD-BD subjects were found to be younger at the onset of BD, showed higher numbers of depressive episodes, more anxiety and substance use disorders, more borderline personality traits and greater cyclothymic temperament. Comorbid BD-ADHD subjects reported more childhood emotional abuse.
LIMITATIONS: Some subjects were unreachable and thus not clinically assessed for ADHD.
CONCLUSIONS: More than 20% of BD subjects were suffering from ADHD. The comorbidity of the two disorders was associated with worse outcomes, possibly resulting from stressful early-life events. More than 40% of the subjects who scored positively at the ASRS-v1.1 did not suffer from ADHD, which suggests that this scale should be used with caution in BD subjects.

PMID: 25051093 [PubMed - as supplied by publisher]



Illness-course modulates suicidality-related prefrontal gray matter reduction in women with bipolar disorder.

Acta Psychiatr Scand. 2014 Jul 9;

Authors: Lijffijt M, Rourke ED, Swann AC, Zunta-Soares GB, Soares JC

Abstract
OBJECTIVE: Explore interrelationships between suicide attempt history (Objective 1) or suicide attempt severity (Objective 2) with prefrontal cortex gray matter (PFCGM ) volume and illness-course in patients with bipolar disorder (BD).
METHOD: Ninety-three women with BD-I or -II diagnosis (51 with and 42 without suicide attempt history) underwent structural MRI and filled out questionnaires. Measured were GM volumes of 11 PFC regions, BD illness-course, and attempt history and severity. Effects were examined with repeated measures GLM or logit analyses.
RESULTS: Objective 1: Attempt history was associated with increased trait impulsivity and aggression, and higher prevalence of BD-I, past drug use disorder, and past psychiatric hospitalization. PFCGM volume was lower in patients with than without attempt history in those with past psychiatric hospitalization. PFCGM volume was higher in patients with than without attempt history in those without hospitalization. Higher trait aggression predicted attempt history. Objective 2: Increased frontal pole volume and younger age at first hospitalization predicted many suicide attempts.
CONCLUSION: Attempt history in patients with BD related to PFCGM volume reduction or increase. Volume modulation by psychiatric hospitalization could reflect effects of illness-course or care. Attempt severity was not related to volume reduction. Research on suicidality-brain relationships should include illness-course and attempt severity measures.

PMID: 25039251 [PubMed - as supplied by publisher]



Monocyte activation, brain-derived neurotrophic factor (BDNF), and S100B in bipolar offspring: a follow-up study from adolescence into adulthood.

Bipolar Disord. 2014 Jul 17;

Authors: Mesman E, Hillegers MH, Ambree O, Arolt V, Nolen WA, Drexhage HA

Abstract
OBJECTIVES: There is increasing evidence that both immune and neurochemical alterations are involved in the pathogenesis of bipolar disorder; however, their precise role remains unclear. In this study, we aimed to evaluate neuro-immune changes in a prospective study on children of patients with bipolar disorder.
METHODS: Bipolar offspring, from the prospective Dutch bipolar offspring study (n = 140), were evaluated cross-sectionally within a longitudinal context at adolescence, young adulthood, and adulthood. We examined the expression of 44 inflammation-related genes in monocytes, the cytokines pentraxin 3 (PTX3), chemokine ligand 2 (CCL2), and interleukin-1? (IL-1?), and brain-derived neurotrophic factor (BDNF) and S100 calcium binding protein B (S100B) in the serum of bipolar offspring and healthy controls.
RESULTS: During adolescence, bipolar offspring showed increased inflammatory gene expression in monocytes, high serum PTX3 levels, but normal CCL2 levels. BDNF levels were decreased, while S100B levels were normal. During young adulthood, monocyte activation remained, although to a lesser degree. Serum PTX3 levels remained high, and signs of monocyte migration became apparent through increased CCL2 levels. BDNF and S100B levels were not measured. At adulthood, circulating monocytes had lost their activation state, but CCL2 levels remained increased. Both BDNF and S100B were now increased. Abnormalities were independent of psychopathology state at all stages.
CONCLUSIONS: This study suggests an aberrant neuro-immune state in bipolar offspring, which followed a dynamic course from adolescence into adulthood and was present irrespective of lifetime or future mood disorders. We therefore assumed that the aberrant neuro-immune state reflects a general state of vulnerability for mood disorders rather than being of direct predictive value.

PMID: 25039314 [PubMed - as supplied by publisher]



Impulsivity predicts time to reach euthymia in adults with bipolar disorder.

Bipolar Disord. 2014 Jul 16;

Authors: Dawson EL, Shear PK, Howe SR, Adler CM, DelBello MP, Fleck DE, Strakowski SM

Abstract
OBJECTIVES: Specific demographic and illness characteristics have been identified as predictors of overall morbidity and treatment course among individuals with bipolar disorder. However, the role of specific cognitive limitations on disease severity and treatment response is unclear. The present study evaluated whether impulsiveness during acute mania was a significant predictor of achieving euthymia within one year following psychiatric hospitalization.
METHODS: Participants were 94 adult inpatients (60 manic) with bipolar I disorder. Baseline symptom severity was assessed using the Young Mania Rating Scale and the Montgomery-Åsberg Depression Rating Scale. Impulsivity was measured with the Stop Signal Task, Degraded Stimulus Continuous Performance Task, Delayed Response Task, and Barratt Impulsiveness Scale-11.
RESULTS: Individual predictors of time to reach euthymia included fewer depressive symptoms and better impulse control at baseline, later age at illness onset, shorter illness duration, and the absence of comorbid attention-deficit hyperactivity disorder. Self-reported impulsivity was a significant independent predictor of time to euthymia, even after accounting for relevant clinical variables.
CONCLUSIONS: Better trait impulse control may be associated with better treatment responsiveness among adults with bipolar disorder.

PMID: 25039396 [PubMed - as supplied by publisher]



Personal view: hormones and depression in women.

Climacteric. 2014 Jul 21;:1-3

Authors: Studd J

Abstract
Depression is more common in women, occurring at times of hormonal fluctuations as premenstrual depression, postnatal depression and perimenopausal depression. These are all related to changes in hormone levels and constitute the diagnosis of reproductive depression. There is a risk that severe premenstrual depression can be misdiagnosed as bipolar disorder and that women will be started on inappropriate antidepressants or mood-stabilizing therapy. The most effective treatment for severe premenstrual syndrome is by suppression of ovulation and suppression of the cyclical hormonal changes by transdermal estrogens or by GnRH analogs. Postnatal depression is more common in women with a history of premenstrual depression and also responds to transdermal estrogens. Transdermal testosterone gel can be also used in women who suffer loss of energy and loss of libido which may be due to the inappropriate prescription of antidepressants. There is also a role for the Mirena IUS and laparoscopic hysterectomy and oophorectomy in women who are progestogen-intolerant. The hormonal causation of certain common types of depression in women and the successful treatment by estrogens should be understood by psychiatrists and gynecologists.

PMID: 25040604 [PubMed - as supplied by publisher]





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