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International Review of Psychosis & Bipolarity

Join us in Lisbon, Portugal, 26-28 April 2015

Chair: Prof Maria Luisa Figueira (PT)



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27 October 2014

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19 December 2014

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9 January 2015

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26 January 2015

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13 February 2015

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27 February 2015

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23 March 2015

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Most Recent Articles Published on Psychosis and Bipolarity:

Temperamental differences between bipolar disorder, borderline personality disorder, and attention deficit/hyperactivity disorder: Some implications for their diagnostic validity.

J Affect Disord. 2014 May 29;169C:101-104

Authors: Eich D, Gamma A, Malti T, Vogt Wehrli M, Liebrenz M, Seifritz E, Modestin J

BACKGROUND: The relationship between borderline personality disorder (BPD), bipolar disorder (BD), and attention deficit/hyperactivity disorder (ADHD) requires further elucidation.
METHODS: Seventy-four adult psychiatric in- and out-patients, each of them having received one of these diagnoses on clinical assessment, were interviewed and compared in terms of diagnostic overlap, age and sex distribution, comorbid substance, anxiety and eating disorders, and affective temperament.
RESULTS: Diagnostic overlap within the three disorders was 54%. Comorbidity patterns and gender ratio did not differ. The disorders showed very similar levels of cyclothymia.
LIMITATIONS: Sample size was small and only a limited number of validators were tested.
CONCLUSIONS: The similar extent of cyclothymic temperament suggests mood lability as a common denominator of BPD, BD, and ADHD.

PMID: 25173432 [PubMed - as supplied by publisher]

Thalamocortical abnormalities in auditory brainstem response patterns distinguish DSM-IV bipolar disorder type I from schizophrenia.

J Affect Disord. 2014 Aug 13;169C:105-111

Authors: Sköld M, Källstrand J, Nehlstedt S, Nordin A, Nielzén S, Holmberg J, Adolfsson R

BACKGROUND: Bipolar disorder type I (BP-I) belongs to a spectrum of affective disorders that are expressed in many different ways and therefore can be difficult to distinguish from other conditions, especially unipolar depression, schizoaffective disorder, schizophrenia (SZ), but also anxiety and personality disorders. Since early diagnosis and treatment have shown to improve the long-term prognosis, complementary specific biomarkers are of great value. The auditory brainstem response (ABR) has previously been applied successfully to identify specific abnormal ABR patterns in SZ and Asperger syndrome.
METHODS: The current study investigated the early auditory processing of complex sound stimuli e.g. forward masking, in BP-I compared to SZ patients. The ABR curves of BP-I patients (n=23) and SZ patients (n=20) were analyzed in terms of peak amplitudes and correlation with an ABR norm curve based on a non-psychiatric control group (n=20).
RESULTS: BP-I patients had significantly higher wave III (p=0.0062) and wave VII (p=0.0472) amplitudes compared with SZ patients. Furthermore, BP-I patients, and to a lesser extent SZ patients, showed low correlation with the norm ABR curve in the part of the curve comprising waves VI-VII.
LIMITATIONS: Sample size was relatively small and study groups were not matched for age and gender.
CONCLUSIONS: BP-I patients showed specific aberrances, specifically in the latter part of the ABR curve, implicating abnormalities in thalamocortical circuitry. The abnormal ABR wave patterns significantly separated BP-I patients from SZ patients suggesting that ABR might serve as a biomarker for BP-I.

PMID: 25173433 [PubMed - as supplied by publisher]

B vitamin polymorphisms and behavior: Evidence of associations with neurodevelopment, depression, schizophrenia, bipolar disorder and cognitive decline.

Neurosci Biobehav Rev. 2014 Aug 27;

Authors: Mitchell ES, Conus N, Kaput J

The B vitamins folic acid, vitamin B12 and B6 are essential for neuronal function, and severe deficiencies have been linked to increased risk of neurodevelopmental disorders, psychiatric disease and dementia. Polymorphisms of genes involved in B vitamin absorption, metabolism and function, such as methylene tetrahydrofolate reductase (MTHFR), cystathionine ? synthase (C?S), transcobalamin 2 receptor (TCN2) and methionine synthase reductase (MTRR), have also been linked to increased incidence of psychiatric and cognitive disorders. However, the effects of these polymorphisms are often quite small and many studies failed to show any meaningful or consistent associations. This review discusses previous findings from clinical studies and highlights gaps in knowledge. Future studies assessing B vitamin-associated polymorphisms must take into account not just traditional demographics, but subjects' overall diet, relevant biomarkers of nutritional status and also analyze related genetic factors that may exacerbate behavioral effects or nutritional status.

PMID: 25173634 [PubMed - as supplied by publisher]

Applications of blood-based protein biomarker strategies in the study of psychiatric disorders.

Prog Neurobiol. 2014 Aug 27;

Authors: Chan MK, Gottschalk MG, Haenisch F, Tomasik J, Ruland T, Rahmoune H, Guest PC, Bahn S

Major psychiatric disorders such as schizophrenia, major depressive and bipolar disorders are severe, chronic and debilitating, and are associated with high disease burden and healthcare costs. Currently, diagnoses of these disorders rely on interview-based assessments of subjective self-reported symptoms. Early diagnosis is difficult, misdiagnosis is a frequent occurrence and there are no objective tests that aid in the prediction of individual responses to treatment. Consequently, validated biomarkers are urgently needed to help address these unmet clinical needs. Historically, psychiatric disorders are viewed as brain disorders and consequently only a few researchers have as yet evaluated systemic changes in psychiatric patients. However, promising research has begun to challenge this concept and there is an increasing awareness that disease-related changes can be traced in the peripheral system which may even be involved in the precipitation of disease onset and course. Converging evidence from molecular profiling analysis of blood serum/plasma have revealed robust molecular changes in psychiatric patients, suggesting that these disorders may be detectable in other systems of the body such as the circulating blood. In this review, we discuss the current clinical needs in psychiatry, highlight the importance of biomarkers in the field, and review a representative selection of biomarker studies to highlight opportunities for the implementation of personalized medicine approaches in the field of psychiatry. It is anticipated that the implementation of validated biomarker tests will not only improve the diagnosis and more effective treatment of psychiatric patients, but also improve prognosis and disease outcome.

PMID: 25173695 [PubMed - as supplied by publisher]

Effect of acute asenapine treatment on Fos expression in the forebrain structures under normal conditions and mild stress preconditioning in the rat.

Brain Res Bull. 2014 Aug 26;

Authors: Majercikova Z, Cernackova A, Horvathova L, Osacka J, Pecenak J, Kiss A

Asenapine (ASE) is an novel atypical antipsychotic drug approved for the treatment of schizophrenia and bipolar disorder. Stress is an inseparable part of the human life, which may interfere with the therapeutic effect of different drugs. The aim of the present study was: 1) to delineate the quantitative and qualitative profiles of the ASE effect on Fos expression in the striatum, septum, nucleus accumbens, and the prefrontal cortex and 2) to find out whether a chronic unpredictable variable mild stress (CMS) preconditioning may modify the effect of acute ASE treatment. Stress paradigms included restrain, social isolation, crowding, swimming, and cold. The animals were exposed to CMS for 21 days and on the day 22(nd) received an injection of vehicle (saline 300?l/rat s.c.) or ASE (0.3mg/kg s.c.). They were sacrificed 90min after the treatments. Fos protein was visualized by avidin biotin peroxidase (ABC). Four groups of animals were investigated: controls+vehicle, controls+ASE, CMS+vehicle, and CMS+ASE. The number of Fos labeled neurons was calculated per total investigated area, which was selective for each structure, and also recalculated per a unified sector. ASE treatment induced significant and very similar increase of the Fos expression in both ASE control and ASE CMS animals in comparison with saline control and CMS ones. Moreover, ASE induced regional differences in the number of Fos-positive neurons. In both ASE groups most pronounced response in the number of Fos profiles occurred in the dorsolateral striatum, ventrolateral septum, shell of the nucleus accumbens, and the medial prefrontal cortex. Mild Fos response was seen in the dorsomedial and ventromedial striatum and core of the nucleus accumbens. No response was seen in the dorsolateral septum. The present paper demonstrate for the first time the character of the Fos distribution in the forebrain structures induced by acute ASE treatment as well as ASE response to 21 days CMS preconditioning. The study provides an important comparative background that may help in the further understanding of the effect of ASE on the brain activation as well as its responsiveness to CMS challenges.

PMID: 25171958 [PubMed - as supplied by publisher]

An fMRI study of emotional face encoding in youth at risk for bipolar disorder.

Eur Psychiatry. 2014 Aug 26;

Authors: Tseng WL, Bones BL, Kayser RR, Olsavsky AK, Fromm SJ, Pine DS, Leibenluft E, Brotman MA

Face memory deficits may be a bipolar disorder (BD) endophenotype. BD (n=27) and unaffected youth at risk (n=13) exhibited middle frontal gyrus hypoactivation during successful vs. unsuccessful encoding. Parahippocampal gyrus dysfunction was found in BD and at-risk youth (vs. low-risk, n=37). Middle occipital gyrus hypoactivation was only present in BD.

PMID: 25172156 [PubMed - as supplied by publisher]

The influence of cognitive reserve on psychosocial and neuropsychological functioning in bipolar disorder.

Eur Neuropsychopharmacol. 2014 Aug 15;

Authors: Forcada I, Mur M, Mora E, Vieta E, Bartrés-Faz D, Portella MJ

Cognitive reserve (CR) refers to the hypothesized capacity of an adult brain to cope with brain pathology in order to minimize symptomatology. CR was initially investigated in dementia and acute brain damage, but it is being applied to other neuropsychiatric conditions. The present study aims at examining the fit of this concept to a sample of euthymic bipolar patients compared with healthy controls in order to investigate the role of CR in predicting psychosocial and cognitive outcome in bipolar disorder (BD). The sample included 101 subjects: 52 patients meeting DSM-IV-TR criteria for BD type I or II and 49 healthy controls (HC) matched for age and gender. They were all assessed with a cognitive battery tapping into executive and memory functioning. CR was obtained using three different proxies: education-occupation, leisure activities and premorbid IQ. Psychosocial functioning was evaluated by means of the Functioning Assessment Short Test (FAST). MANCOVAs were performed to determine differences in cognitive and functioning variables. Linear regression analyses were carried out to predict neuropsychological and psychosocial outcomes. Euthymic bipolar patients showed worse neuropsychological performance and psychosocial functioning than HC. The linear regression models revealed that CR was significantly predictive of FAST score (?=-0.47, p<0.0001), Executive Index (?=0.62, p<0.0001) and Visual Memory Index (?=0.44, p=0.0004), indicating that CR is a significant predictor of cognitive and psychosocial functioning in euthymic bipolar outpatients. Therefore, CR may contribute to functional outcome in BD and may be applied in research and clinical interventions to prevent cognitive and functional impairment.

PMID: 25172270 [PubMed - as supplied by publisher]

Repetitive Elements and Epigenetic Marks in Behavior and Psychiatric Disease.

Adv Genet. 2014;86C:185-252

Authors: Darby MM, Sabunciyan S

Repetitive elements, which are relics of previous transposition events, constitute a large proportion of the human genome. The ability of transposons to gives rise to new DNA combinations has clearly provided an evolutionary advantage to their hosts. Transposons have shaped our genomes by giving rise to novel coding sequences, alternative gene promoters, conserved noncoding elements, and gene networks. Despite its benefits, the process of transposition can also create deleterious DNA combinations, and a growing number of human diseases are being linked to abnormal repetitive element activity. To limit transposition, cells tightly regulate and immobilize repetitive elements using DNA methylation and other epigenetic marks. Recent findings in neuropsychiatric disorders implicate both repetitive elements and epigenetic marks as potential etiological factors. It is possible that these observations are linked and that the reported alterations in epigenetic marks may create a permissive state enabling transposons to mobilize. In this work, we provide a detailed description of repetitive element biology and epigenetics to familiarize the readers with the subject matter and to illustrate how their disruption can result in pathology. We also review the evidence for the involvement of these two factors in neuropsychiatric disorders and discuss the need for replication studies to confirm these initial findings. We are cautiously optimistic that further characterization of epigenetic mark and repetitive element activity in the brain will reveal the underlying causes of schizophrenia, bipolar disorder, and major depression.

PMID: 25172351 [PubMed - as supplied by publisher]

Correlations of inflammatory gene pathways, corticolimbic functional activities, and aggression in pediatric bipolar disorder: A preliminary study.

Psychiatry Res. 2014 Aug 15;

Authors: Barzman D, Eliassen J, McNamara R, Abonia P, Mossman D, Durling M, Adler C, DelBello M, Lin PI

The mechanisms underlying aggression in adolescents with bipolar disorder have been poorly understood. The present study has investigated the associations among TNF gene expressions, functional brain activations under the frustrative non-reward task, and aggression in adolescents with bipolar disorder. Baseline gene expressions and aggressive tendencies were measured with the RNA-sequencing and Brief Rating of Aggression by Children and Adolescents (BRACHA), respectively. Our results show that activity levels of left subgenual anterior cingulate gyrus (ACG), right amygdala, left Brodmann area 10 (orbitofrontal cortex), and right thalamus were inversely correlated with BRACHA scores and were activated with frustrative non-reward during the affective Posner Task. In addition, 11 TNF related gene expressions were significantly correlated with activation of amygdala or ACG during the affective Posner Task. Three TNF gene expressions were inversely correlated with BRACHA score while one TNF gene (TNFAIP3) expression was positively correlated with BRACHA score. Therefore, TNF-related inflammatory cytokine genes may play a role in neural activity associated with frustrative non-reward and aggressive behaviors in pediatric bipolar disorder.

PMID: 25172408 [PubMed - as supplied by publisher]

Related Articles

Restless legs syndrome associated with the combined use of quetiapine and venlafaxine.

J Clin Psychopharmacol. 2014 Feb;34(1):159-61

Authors: Michopoulos I, Ferentinos P, Oulis P, Gournellis R

PMID: 24135842 [PubMed - indexed for MEDLINE]

Related Articles

Delirium caused by a drug-drug interaction between bupropion and risperidone.

J Clin Psychopharmacol. 2014 Feb;34(1):161-2

Authors: Lu YY, Hsueh JH, Wei IH, Huang CC

PMID: 24346746 [PubMed - indexed for MEDLINE]

Diagnostic Stability of Psychiatric Disorders in Re-Admitted Psychiatric Patients in Kerman, Iran.

Glob J Health Sci. 2014;6(5):34966

Authors: Alavi F, Nakhaee N, Sabahi A

BACKGROUND: Several studies have evaluated the stability of psychiatric diagnosis follow in readmission of patients in psychiatric hospitals. However, there is little data concerning this matter from Iran. This study is designed to evaluate this diagnostic stability of the commonest psychiatric disorders in Iran.
OBJECTIVES: The objective of this study was to determine the long-term diagnostic stability of the most prevalent psychiatric disorders among re-admitted patients at the Shahid Beheshti teaching hospital in Kerman, Iran.
PATIENTS &METHODS: This study was based on 485 adult patients re-admitted at the Shahid Beheshti hospital between July and November 2012.All of the diagnoses were made according to DSM IV TR.Prospective and retrospective consistency and the ratio of patients who were obtained a diagnosis in at least 75%, 100% of the admissions were calculated.
RESULTS: The most frequent diagnoses at the first admission were bipolar disorder (48.5%) and Major depressive disorder (18.8%). The most stable diagnosis was bipolar disorder (71% prospective consistency, 69.4% retrospective consistency). Schizoaffective disorder had the greatest diagnostic instability (28.5% prospective consistency, 16.6% retrospective consistency).
CONCLUSIONS: Among the cases evaluated, bipolar disorder had the most stability in diagnosis and the stability of schizoaffective disorder was poor.

PMID: 25168983 [PubMed - as supplied by publisher]

Comorbidity of Stevens-Johnson syndrome and neutropenia associated with lamotrigine: a case report.

Gen Hosp Psychiatry. 2014 Jul 27;

Authors: Yasui-Furukori N, Hashimoto K, Tsuruga K, Nakamura K

A 19-year-old woman with a medical history of depressive mood arrived and was treated with lamotrigine at 25 mg/day. On day 10, a high fever of 39.3°C and a diffuse, erythematous, pruritic full-body rash involving the palms of her hands and the soles of her feet developed, and she was diagnosed with Stevens-Johnson syndrome (SJS). On day 17, white blood cell count (WBC) result was 1,240/?l with 54.1% neutrophils (670/?l), and the WBC decreased to 840/?l with 60.7% neutrophils (510/?l) on day 18. The trend toward improvement included skin symptoms after steroid pulse therapy using 1000 mg/day. Based on the clinical course, we concluded that the SJS and leukopenia and/or neutropenia are associated with lamotrigine. Monitoring of WBC should be kept in mind when administering lamotrigine.

PMID: 25169759 [PubMed - as supplied by publisher]

Improvement in suicidal ideation after ketamine infusion: Relationship to reductions in depression and anxiety.

J Psychiatr Res. 2014 Aug 12;

Authors: Ballard ED, Ionescu DF, Vande Voort JL, Niciu MJ, Richards EM, Luckenbaugh DA, Brutsché NE, Ameli R, Furey ML, Zarate CA

OBJECTIVE: Suicide is a psychiatric emergency. Currently, there are no approved pharmacologic treatments for suicidal ideation. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that rapidly reduces suicidal ideation as well as depression and anxiety, but the dynamic between these symptoms is not known. The aim of this analysis was to evaluate whether ketamine has an impact on suicidal thoughts, independent of depressive and anxiety symptoms.
METHODS: 133 patients with treatment-resistant depression (major depressive disorder or bipolar I/II disorder) received a single subanesthetic infusion of ketamine (0.5 mg/kg over 40 min). Post-hoc correlations and linear mixed models evaluated the relationship between suicidal ideation and depression and anxiety symptoms using the Hamilton Depression Rating Scale (HAMD), Scale for Suicidal Ideation (SSI), Beck Depression Inventory (BDI), and Hamilton Anxiety Rating Scale (HAMA) focusing on 230 min post-infusion.
RESULTS: At 230 min post-infusion, correlations between changes in suicidal ideation and depression ranged from 0.23 to 0.44 (p < .05), accounting for up to 19% in the variance of ideation change. Correlations with anxiety ranged from 0.23 to 0.40 (p < .05), accounting for similar levels of variance. Ketamine infusion was associated with significant reductions in suicidal ideation compared to placebo, when controlling for the effects of ketamine on depression (F1,587 = 10.31, p = .001) and anxiety (F1,567 = 8.54, p = .004).
CONCLUSIONS: Improvements in suicidal ideation after ketamine infusion are related to, but not completely driven by, improvements in depression and anxiety. Investigation of the specific effects of ketamine on suicidal thoughts is warranted.

PMID: 25169854 [PubMed - as supplied by publisher]

Atypical right hemispheric functioning in the euthymic state of bipolar affective disorder.

Psychiatry Res. 2014 Aug 15;

Authors: Najt P, Hausmann M

Bipolar disorder (BD) has been associated with right hemisphere dysfunction. These findings usually come from studies that have not distinguished between symptomatic and euthymic states of BD. The present study aims to investigate atypical right (and left) hemispheric functioning in euthymic BD patients. We evaluated 40 participants (18 healthy controls and 22 euthymic BD patients) using an emotional prosody dichotic listening task and a linguistic dichotic listening task which have been shown to produce a strong left ear advantage (LEA) and right ear advantage (REA), indicating a right and left hemisphere superiority, respectively. The results replicate the well-known LEA in emotional prosody for healthy controls. In contrast, no ear advantage was found for emotional prosody in euthymic BD patients. Both groups revealed the well-established REA in the linguistic dichotic listening task. The patient group was heterogeneous with regard to medication, as it consisted of patients with a variety of pharmacological treatments. The results are in line with previous studies in symptomatic BD patients, and suggest that atypical LEA in emotional prosody can be interpreted as a neurobehavioral vulnerability marker of emotional dysregulation and dysfunction in the right hemispheric fronto-temporal network in both symptomatic and euthymic BD patients.

PMID: 25169888 [PubMed - as supplied by publisher]

Oral Loading of Sodium Valproate Compared to Intravenous Loading and Oral Maintenance in Acutely Manic Bipolar Patients.

Neuropsychobiology. 2014 Aug 21;70(1):29-35

Authors: Ghaleiha A, Haghighi M, Sharifmehr M, Jahangard L, Ahmadpanah M, Bajoghli H, Holsboer-Trachsler E, Brand S

Background: In patients suffering from bipolar disorders (BPD), we explored to what extent oral loading of sodium valproate (SV) leads to more rapid symptom improvement compared to intravenous loading and oral maintenance administration. Methods: Ninety patients (mean age: 35.00 years) with BPD and currently in an acute manic state were randomly assigned to one of three study conditions: oral loading (20 mg/kg oral single-dose SV on the first day, then 10-15 mg/kg SV daily, divided dose), intravenous loading (20 mg/kg SV intravenous injection on the first day, then 10-15 mg/kg orally, divided dose), or oral maintenance administration (15-20 mg/kg SV daily from the beginning) over the first 7 days of treatment. SV plasma levels, side effects and symptoms were evaluated at baseline and on days 1, 3, and 7 after commencing treatment. Results: There were significant Time-by-Group interactions for symptom improvements, symptom severity, and SV plasma levels, with positive values in the oral and intravenous loading conditions, compared to the oral maintenance condition. Post hoc analyses showed that oral and intravenous conditions led to similar improvements. Conclusions: Both oral and intravenous loading of SV led to quicker and more efficient improvement and SV plasma levels as compared to an oral maintenance regimen. © 2014 S. Karger AG, Basel.

PMID: 25171133 [PubMed - as supplied by publisher]

Depression and cardiovascular disease: an update on how course of illness may influence risk.

Curr Psychiatry Rep. 2014 Oct;16(10):492

Authors: Fiedorowicz JG

Depression constitutes a novel and independent risk factor for cardiovascular disease, which despite extensive support in the literature has been underappreciated. While much of the evidence for depression as a risk factor for cardiovascular disease is based on studies following myocardial infarction, the elevated vascular risk conveyed by depression is not confined to periods following acute coronary syndromes. For that matter, the risk appears across mood disorders with evidence for even greater risk in bipolar disorder. This review summarizes the literature linking depressive disorders to cardiovascular mortality with a focus on how the course of illness of mood disorders may influence this risk. Mood disorders may influence risk over decades of illness in a dose-response to symptom burden, or the persistence of affective symptomatology. This may be mediated through changes in the activity of the autonomic nervous system, the hypothalamic-pituitary-adrenal axis, and inflammatory cytokines. Whether treatment of depression can mitigate this risk is not established although there are suggestions to support this contention, which could be better studied with more effective treatments of depression and larger standardized samples. Directions for future study of mechanisms and treatment are discussed. Regardless of causal mechanisms, persons with depressive disorders and other risk factors for vascular disease represent a neglected, high-risk group for cardiovascular events. In addition to the appropriate treatment for depression, screening and optimized management of traditional risk factors for cardiovascular diseases is necessary.

PMID: 25163592 [PubMed - in process]

Pathological gambling treated with lithium: The role of assessing temperament.

Addict Behav. 2014 Jun 5;39(12):1911-1913

Authors: Chaim CH, Nazar BP, Hollander E, Lessa JL

BACKGROUND AND AIMS: Pathological gambling is a condition for which there is still no FDA-approved treatment although some medications seem to be effective at reducing its symptoms. In DSM-V, it is now classified as an addiction disorder. Data show that baseline comorbidities in patients with gambling and substance misuse behavior are frequent. These might include not only major syndromes but also subclinical ones. Bipolar spectrum conditions are often among these comorbidities. Lithium has been showed to be effective in PG subjects with bipolar spectrum comorbidity, and we present a case where assessment of temperament was helpful in treatment selection.
CONCLUSIONS: This case illustrates the clinical benefits of how the assessment of temperament and comorbidities in pathological gambling patients may guide the clinician to a successful treatment choice. The case presented also corroborates previous evidence on the efficacy of lithium in patients with pathological gambling and comorbid bipolar spectrum conditions and euphoric temperament. Future clinical trials on pathological gambling pharmacotherapy should include temperament assessment to evaluate its influence on different outcomes.

PMID: 25163751 [PubMed - as supplied by publisher]

Inter-episode affective intensity and instability: Predictors of depression and functional impairment in bipolar disorder.

J Behav Ther Exp Psychiatry. 2014 Aug 7;46C:14-18

Authors: Gershon A, Eidelman P

BACKGROUND AND OBJECTIVES: Dysregulated affect is a hallmark feature of acute episodes of bipolar disorder (BD) and persists during inter-episode periods. Its contribution to course of illness is not yet known. The present report examines the prospective influence of inter-episode affect dysregulation on symptoms and functional impairment in BD.
METHODS: Twenty-seven participants diagnosed with inter-episode bipolar I disorder completed daily measures of negative and positive affect for 49 days (±8 days) while they remained inter-episode. One month following this daily assessment period, symptom severity interviews and a measure of functional impairment were administered by telephone.
RESULTS: More intense negative affect and positive affect during the inter-episode period were associated with higher depressive, but not manic, symptoms at the one-month follow-up assessment. More intense and unstable negative affect, and more unstable positive affect, during the inter-episode period were associated with greater impairment in home and work functioning at the follow-up assessment. All associations remained significant after controlling for concurrent symptom levels.
LIMITATIONS: The findings need to be confirmed in larger samples with longer follow-up periods. A more comprehensive assessment of functional impairment is also warranted.
CONCLUSIONS: The findings suggest that a persistent affective dysregulation between episodes of BD may be an important predictor of depression and functional impairment. Monitoring daily affect during inter-episode periods could allow for a more timely application of interventions that aim to prevent or reduce depressive symptoms and improve functioning for individuals with BD.

PMID: 25164093 [PubMed - as supplied by publisher]

Episodic memory impairments in bipolar disorder are associated with functional and structural brain changes.

Bipolar Disord. 2014 Aug 27;

Authors: Oertel-Knöchel V, Reinke B, Feddern R, Knake A, Knöchel C, Prvulovic D, Pantel J, Linden DE

OBJECTIVES: We combined multimodal functional magnetic resonance imaging (fMRI) and structural magnetic resonance imaging to probe abnormalities in brain circuits underpinning episodic memory performance deficits in patients with bipolar disorder (BD).
METHODS: We acquired whole-brain fMRI data in 21 patients with BD and a matched group of 20 healthy controls during a non-verbal episodic memory task, using abstract shapes. We also examined density of gray matter, using voxel-based morphometry (VBM), and integrity of connecting fiber tracts, using diffusion tensor imaging (DTI) and tract-based spatial statistics, for areas with significant activation differences.
RESULTS: Patients with BD remembered less well than controls which shapes they had seen and had lower activation levels during the encoding stage of the task in the anterior cingulate gyrus, the precuneus/cuneus bilaterally, and the left lingual gyrus, and higher activation levels during the retrieval stage in the left temporo-parietal junction. Patients with BD showed reduced gray matter volumes in the left anterior cingulate, the precuneus/cuneus bilaterally, and the left temporo-parietal region in comparison with controls. DTI revealed reduced radial, axial, and mean diffusivity in the left superior longitudinal fascicle in patients with BD compared with controls.
CONCLUSIONS: Changes in task-related activation in frontal and parietal areas were associated with poorer episodic memory in patients with BD. Compared with data from single imaging modalities, integration of multimodal neuroimaging data enables the building of more complete neuropsychological models of mental disorders.

PMID: 25164120 [PubMed - as supplied by publisher]

Corpus callosal morphology in youth with bipolar depression.

Bipolar Disord. 2014 Aug 28;

Authors: MacMaster FP, Langevin LM, Jaworska N, Kemp A, Sembo M

OBJECTIVES: Recent evidence has demonstrated that corpus callosum maturation follows a similar developmental timeline to cognitive processes. Bipolar disorder (BD) has been associated with disruptions in error processing, response inhibition, and motor functioning, which are mediated by underlying white matter structures, including the corpus callosum. Disruptions in white matter integrity have been demonstrated in BD. However, it is unknown whether alterations in the developmental trajectory of the corpus callosum may contribute to cognitive impairments in the disorder.
METHODS: We assessed the area of the corpus callosum and its subregions (the genu, rostral body, anterior and posterior bodies, isthmus, and splenium) in 14 treatment-naïve adolescents with BD (<21 years of age and in the depressed phase) and 18 healthy adolescent controls.
RESULTS: In comparison with healthy controls, participants with BD demonstrated a significantly reduced overall corpus callosum area. We also noted smaller areas in the anterior and posterior mid-body of the corpus callosum in adolescents with BD.
CONCLUSIONS: Our results suggest that commissural fibers of the corpus callosum are disrupted in early-onset BD. Specific decreases in the anterior and posterior mid-body callosal aspects may contribute to motor organization and inhibition deficits seen in BD. These findings are consistent with the involvement of inter-hemispheric tracts in early-onset BD, which may reflect an early deviation in white matter development.

PMID: 25164210 [PubMed - as supplied by publisher]

Intracerebral Administration of BDNF Protects Rat Brain Against Oxidative Stress Induced by Ouabain in an Animal Model of Mania.

Mol Neurobiol. 2014 Aug 28;

Authors: Valvassori SS, Arent CO, Steckert AV, Varela RB, Jornada LK, Tonin PT, Budni J, Mariot E, Kapczinski F, Quevedo J

Several studies have suggested that alterations in brain-derived neurotrophic factor (BDNF) and increased oxidative stress have a central role in bipolar disorder (BD). Intracerebroventricular (ICV) injection of ouabain (OUA) in rats alters oxidative stress parameters and decreases BDNF levels in the brain. In this context, the present study aims to investigate the effects of BDNF ICV administration on BDNF levels and oxidative stress parameters in brains of rats submitted to animal model of mania induced by OUA. Wistar rats received an ICV injection of OUA, artificial cerebrospinal fluid (ACSF), OUA plus BDNF, or ACSF plus BDNF. Locomotor activity and risk-taking behavior in the rats were measured using the open-field test. In addition, we analyzed the BDNF levels and oxidative stress parameters (TBARS, Carbonyl, CAT, SOD, GR, and GPx) in the frontal cortex and hippocampus of rats. The BDNF was unable to reverse the ouabain-induced hyperactivity and risk-taking behavior. Nevertheless, BDNF treatment increased BDNF levels, modulated the antioxidant enzymes, and protected the OUA-induced oxidative damage in the brain of rats. These results suggest that BDNF alteration observed in BD patients may be associated with oxidative damage, both seen in this disorder.

PMID: 25164569 [PubMed - as supplied by publisher]

Maintaining mood stability in bipolar disorder: a clinical perspective on pharmacotherapy.

Evid Based Ment Health. 2014 Aug 27;

Authors: Malhi GS, McAulay C, Das P, Fritz K

PMID: 25165167 [PubMed - as supplied by publisher]

Mixed, melancholic, and anxious features in depression: A cross-sectional study of sociodemographic and clinical correlates.

Ann Clin Psychiatry. 2014 Aug 1;26(3):E3-E13

Authors: Zaninotto L, Souery D, Calati R, Scudellari P, Janiri L, Montgomery S, Kasper S, Zohar J, Mendlewicz J, Serretti A

BACKGROUND: Major depression (MD) is currently viewed as a heterogeneous condition, characterized by different psychopathological dimensions.
METHODS: Our sample was composed of 1,289 nonpsychotic bipolar/unipolar depressed patients. Participants were divided into mixed (MXD), melancholic (MEL), and anxious (ANX) depressed, according to a hierarchical functional model. Sociodemographic and clinical variables were compared across depressive subtypes by ?2 test and analysis of variance. The Young Mania Rating Scale (YMRS) and 2 subscales (melancholic [MEL-S] and psychic-somatic anxiety [PSOM-ANX]) from the Hamilton Depression Rating Scale also served as continuous outcome measures.
RESULTS: MXD patients more frequently had bipolar I disorder (BD I), younger age of onset, and a higher familial load for mood disorders. MEL and ANX patients were more frequently diagnosed with major depressive disorder and reported a higher suicide risk. YMRS scores in depression was associated with BD I diagnosis (P < .0001) and manic polarity of the last episode (P < .0001), while a depressive polarity of the last episode (P < .0001) was associated with higher MEL-S score. No specific predictor was associated with PSOM-ANX score.
CONCLUSIONS: Overall, our findings suggest that mixed depressive features are associated with significant hallmarks of bipolarity, and melancholic features may be influenced by previous depressive polarity. The symptom domain of anxiety appears to have no specific predictor.

PMID: 25166487 [PubMed - as supplied by publisher]

Childhood Trauma, Temperament, and Character in Subjects With Major Depressive Disorder and Bipolar Disorder.

J Nerv Ment Dis. 2014 Sep;202(9):695-698

Authors: Perna G, Vanni G, Di Chiaro NV, Cavedini P, Caldirola D

In nonclinical samples, childhood trauma (CT) has been found to negatively affect temperament/character traits. In major depressive disorder (MDD) and bipolar disorder (BD), abnormal personality traits have been found to impair clinical course/treatment outcome. Although a link between CT and MDD/BD is firmly established, no previous studies explored the relationship between CT and temperament/character in these populations. We investigated this issue in a preliminary sample of inpatients with MDD (n = 29) or BD (n = 50). We assessed CT (sexual/physical/emotional abuse, physical/emotional neglect) (Childhood Trauma Questionnaire), personality traits (Temperament and Character Inventory-Revised version), and illness severity (Brief Psychiatric Rating Scale). We found significant (p < 0.01) associations between emotional neglect, emotional abuse, physical neglect, and low self-directedness (SD). Potential underlying mechanisms are discussed. Because low SD has been previously associated with illness severity and poor outcome, the relationship between CT and low SD might partly explain the well-known negative impact of CT on course and outcome of MDD/BD.

PMID: 25167131 [PubMed - as supplied by publisher]

'Emerging Biology of PDE10A'

Curr Pharm Des. 2014 Aug 26;

Authors: S Wilson L, Brandon NJ

Cyclic AMP and cyclic GMP are essential second messengers that regulate multiple signaling pathways in virtually all cell types. Their accumulation in cells is finely regulated by cyclic nucleotide phosphodiesterases (PDEs), the only enzymes that can degrade these signaling molecules and thus provide exquisite control over intracellular signaling processes. One PDE family, PDE10A, is highly enriched in the brain and its unique expression profile in specific brain regions of interest, in particular to antipsychotic treatment, has made it an attractive therapeutic target for the treatment of schizophrenia. However, after a Phase II trial failure of a selective PDE10A inhibitor for the treatment of schizophrenia, it has encouraged the field to reexamine the role of this enzyme in the brain, and the possible CNS disorders in which PDE10A inhibition could be therapeutic. We will review the localization of PDE10A, both within the brain and the neuron and discuss how its role in regulating cAMP and cGMP accumulation modulates intracellular signaling pathways. Since this cellular signaling has best been documented in the striatum, we will focus our discussion of PDE10A in the context of disorders that affect the basal ganglia, including psychiatric disorders such as bipolar disorder and autism spectrum disorders and the movement disorders, including Parkinson's disease and Huntington's disease.

PMID: 25159072 [PubMed - as supplied by publisher]

Mood Stabilizers and Antipsychotics for Acute Mania: A Systematic Review and Meta-Analysis of Combination/Augmentation Therapy Versus Monotherapy.

CNS Drugs. 2014 Aug 27;

Authors: Ogawa Y, Tajika A, Takeshima N, Hayasaka Y, Furukawa TA

BACKGROUND: Pharmacotherapy remains the mainstay of treatment for acute bipolar mania, but there are many choices, including mood stabilizers (MSs) and antipsychotics (APs).
OBJECTIVE: To provide an up-to-date and comprehensive review of the efficacy, acceptability and adverse effects of MSs and APs as combination or augmentation therapy versus monotherapy with either drug class for the treatment of acute mania.
DATA SOURCES: The Cochrane Central Register of Controlled Trials, MEDLINE, PsycINFO, Scopus, and clinical trial databases were searched for articles published between the inception of the databases and July 1, 2014. The following keywords were used: [bipolar disorder, mania, manic, mixed bipolar, schizoaffective] combined with the names of MSs and APs. The reference lists of all the identified randomized controlled trials (RCTs), articles that cited the identified trials, and recent systematic reviews were also checked.
STUDY SELECTION: Double-blind RCTs comparing MS and AP as combination or augmentation therapy with either monotherapy during the acute phase treatment of mania were included in the present study. The electronic search yielded 6,445 potential articles in September 2013 and 264 new references in an updated search performed in July 2014. Finally, 19 RCTs were considered eligible for our meta-analyses: MS plus AP combination or augmentation therapy was compared with MS monotherapy in 14 trials (n = 3,651) and with AP monotherapy in 6 trials (n = 606) [one study compared combination therapy versus both MS monotherapy and AP monotherapy].
DATA EXTRACTION: The primary outcomes were the mean change scores on validated rating scales for mania and all-cause discontinuation at 3 weeks. The secondary outcomes included response, remission, the mean change scores for depression, dropouts due to adverse events and to inefficacy, and adverse events at 3 weeks and mean change scores on validated rating scales at 1 week. Using random-effects models, standardized mean difference (SMD), risk ratio (RR) and numbers needed to treat with their 95 % confidence intervals (CIs) were calculated.
RESULTS: Most patients included in trials comparing combination/augmentation therapy versus MS monotherapy had prior treatment with an MS, while more than 70 % of participants in trials comparing combination/augmentation therapy versus AP monotherapy had not been on medications or were washed out from their previous medication before randomization. MS plus AP combination/augmentation therapy was more effective than MS monotherapy in terms of change in scores on mania rating scales at 3 weeks (SMD -0.26; 95 % CI -0.36 to -0.15) and at 1 week (SMD -0.17, -0.29 to -0.04). MS plus AP combination/augmentation therapy was more effective than AP monotherapy at 3 weeks (SMD -0.31, -0.50 to -0.12), but not at 1 week (SMD -0.22, -0.84 to 0.40). No significant differences were seen between the combination/augmentation therapy and either monotherapy group in study withdrawal for any reason (MS + AP vs. MS monotherapy: RR 0.99, 0.88-1.12; MS + AP vs. AP monotherapy: RR 0.70, 0.47-1.04) or adverse events (MS + AP vs. MS monotherapy: RR 1.39, 0.97-1.99; MS + AP vs. AP monotherapy: RR 0.62, 0.27-1.40). The combination/augmentation therapy was associated with more side effects, especially with somnolence, while it did not increase treatment-emergent depression.
CONCLUSIONS: Combining MS and AP is more efficacious and more burdensome than, but overall as acceptable as, the continuation of MS or AP monotherapy, when either monotherapy has not been successful. There is currently no robust evidence to judge whether MS and AP combination therapy is more efficacious than MS monotherapy as the initial therapy for acutely manic patients without prior medication.

PMID: 25160685 [PubMed - as supplied by publisher]

The Impact of Psychopharmacology on Contemporary Psychiatry.

Can J Psychiatry. 2014 Aug 1;59(8):401-405

Authors: Baldessarini RJ

PMID: 25161063 [PubMed - as supplied by publisher]

Expression of ZNF804A in Human Brain and Alterations in Schizophrenia, Bipolar Disorder, and Major Depressive Disorder: A Novel Transcript Fetally Regulated by the Psychosis Risk Variant rs1344706.

JAMA Psychiatry. 2014 Aug 27;

Authors: Tao R, Cousijn H, Jaffe AE, Burnet PW, Edwards F, Eastwood SL, Shin JH, Lane TA, Walker MA, Maher BJ, Weinberger DR, Harrison PJ, Hyde TM, Kleinman JE

Importance: The single-nucleotide polymorphism rs1344706 in the zinc finger protein 804A gene (ZNF804A) shows genome-wide association with schizophrenia and bipolar disorder. Little is known regarding the expression of ZNF804A and the functionality of rs1344706.
Objectives: To characterize ZNF804A expression in human brain and to investigate how it changes across the life span and how it is affected by rs1344706, schizophrenia, bipolar disorder, and major depressive disorder.
Design, Setting, and Participants: Molecular and immunochemical methods were used to study ZNF804A messenger RNA (mRNA) and ZNF804A protein, respectively. ZNF804A transcripts were investigated using next-generation sequencing and polymerase chain reaction-based methods, and ZNF804A protein was investigated using Western blots and immunohistochemistry. Samples of dorsolateral prefrontal cortex and inferior parietal lobe tissue were interrogated from 697 participants between 14 weeks' gestational age and age 85 years, including patients with schizophrenia, bipolar disorder, or major depressive disorder.
Main Outcomes and Measures: Quantitative measurements of ZNF804A mRNA and immunoreactivity, and the effect of diagnosis and rs1344706 genotype.
Results: ZNF804A was expressed across the life span, with highest expression prenatally. An abundant and developmentally regulated truncated ZNF804A transcript was identified, missing exons 1 and 2 (ZNF804AE3E4) and predicted to encode a protein lacking the zinc finger domain. rs1344706 influenced expression of ZNF804AE3E4 mRNA in fetal brain (P?=?.02). In contrast, full-length ZNF804A showed no association with genotype (P?>?.05). ZNF804AE3E4 mRNA expression was decreased in patients with schizophrenia (P?=?.006) and increased in those with major depressive disorder (P?<?.001), and there was a genotype-by-diagnosis interaction in bipolar disorder (P?=?.002). ZNF804A immunoreactivity was detected in fetal and adult human cerebral cortex. It was localized primarily to pyramidal neurons, with cytoplasmic as well as dendritic and nuclear staining. No differences in ZNF804A-immunoreactive neurons were seen in schizophrenia or related to rs1344706 (P?>?.05).
Conclusions and Relevance: rs1344706 influences the expression of ZNF804AE3E4, a novel splice variant. The effect is limited to fetal brain and to this isoform. It may be part of the mechanism by which allelic variation in ZNF804A affects risk of psychosis. ZNF804A is translated in human brain, where its functions may extend beyond its predicted role as a transcription factor.

PMID: 25162540 [PubMed - as supplied by publisher]

Related Articles

MAOA and mechanisms of panic disorder revisited: from bench to molecular psychotherapy.

Mol Psychiatry. 2014 Jan;19(1):122-8

Authors: Reif A, Richter J, Straube B, Höfler M, Lueken U, Gloster AT, Weber H, Domschke K, Fehm L, Ströhle A, Jansen A, Gerlach A, Pyka M, Reinhardt I, Konrad C, Wittmann A, Pfleiderer B, Alpers GW, Pauli P, Lang T, Arolt V, Wittchen HU, Hamm A, Kircher T, Deckert J

Panic disorder with agoraphobia (PD/AG) is a prevalent mental disorder featuring a substantial complex genetic component. At present, only a few established risk genes exist. Among these, the gene encoding monoamine oxidase A (MAOA) is noteworthy given that genetic variation has been demonstrated to influence gene expression and monoamine levels. Long alleles of the MAOA-uVNTR promoter polymorphism are associated with PD/AG and correspond with increased enzyme activity. Here, we have thus investigated the impact of MAOA-uVNTR on therapy response, behavioral avoidance and brain activity in fear conditioning in a large controlled and randomized multicenter study on cognitive behavioral therapy (CBT) in PD/AG. The study consisted of 369 PD/AG patients, and genetic information was available for 283 patients. Carriers of the risk allele had significantly worse outcome as measured by the Hamilton Anxiety scale (46% responders vs 67%, P=0.017). This was accompanied by elevated heart rate and increased fear during an anxiety-provoking situation, that is, the behavioral avoidance task. All but one panic attack that happened during this task occurred in risk allele carriers and, furthermore, risk allele carriers did not habituate to the situation during repetitive exposure. Finally, functional neuroimaging during a classical fear conditioning paradigm evidenced that the protective allele is associated with increased activation of the anterior cingulate cortex upon presentation of the CS+ during acquisition of fear. Further differentiation between high- and low-risk subjects after treatment was observed in the inferior parietal lobes, suggesting differential brain activation patterns upon CBT. Taken together, we established that a genetic risk factor for PD/AG is associated with worse response to CBT and identify potential underlying neural mechanisms. These findings might govern how psychotherapy can include genetic information to tailor individualized treatment approaches.

PMID: 23319006 [PubMed - indexed for MEDLINE]

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