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International Review of Psychosis & Bipolarity

Join us in Rome, Italy, 22-24 May 2016


Chair: Professor Paulo Girardi (IT)

Co-Chair: Dr Giulio Perugi (IT)

The ONLY speciality International Conference in Schizophrenia & Bipolar Disorders in Europe in 2016

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Most Recent Articles Published on Psychosis and Bipolarity:

Related Articles

Magnetic seizure therapy-induced mania: a report of 2 cases.

J ECT. 2015 Mar;31(1):e4-6

Authors: Noda Y, Daskalakis ZJ, Fitzgerald PB, Downar J, Rajji TK, Blumberger DM

Abstract
BACKGROUND: Magnetic seizure therapy (MST) is a novel brain stimulation modality used to treat refractory depression through the induction of seizures. It is currently being investigated as a potential alternative treatment to electroconvulsive therapy. To our knowledge, there have not been any previous reports of MST-induced mania.
OBJECTIVE: We aim to describe 2 cases of patients with a major depressive episode who developed acute symptoms of mania during a course of MST.
METHODS: The current report describes 2 cases of mania that occurred in the context of an ongoing open-label study of MST in treatment-resistant depression. The MST was administered 2 or 3 times per week and applied directly over the left and right dorsolateral prefrontal cortex. Treatment is administered until patients achieve remission or a maximum of 24 treatments. A MagVenture Twin coil and MST stimulator were used for treatment. The center of each coil was placed over F3 and F4 according to the 10-20 electroencephalography system.
RESULTS: Patient 1 had developed manic symptoms precipitously after the sixth MST treatment, and patient 2 developed manic symptoms after the 23rd MST treatment. In both patients, the MST treatment course was stopped. Their manic symptoms resolved rapidly with pharmacotherapy after cessation of MST treatments.
CONCLUSIONS: As with electroconvulsive therapy, switches to mania or hypomania should be considered as potential adverse effects of MST.

PMID: 24839980 [PubMed - indexed for MEDLINE]



Related Articles

Rivaroxaban for thromboprophylaxis in a patient receiving electroconvulsive therapy.

J ECT. 2015 Mar;31(1):e19-20

Authors: Shuman M, Hieber R, Moss L, Patel D

PMID: 25587812 [PubMed - indexed for MEDLINE]



Related Articles

Oral acetylcysteine for neuropsychiatric disorders.

Am J Health Syst Pharm. 2015 Jun 1;72(11):923-6, 928-9

Authors: Racz R, Sweet BV, Sohoni P

PMID: 25987686 [PubMed - indexed for MEDLINE]



Related Articles

Inappropriate Antibiotic Therapy in a Patient With Heart Failure and Prolonged QT Interval: A Teachable Moment.

JAMA Intern Med. 2015 Nov;175(11):1748-9

Authors: Gupta A, Mody P, Pandey A

PMID: 26389523 [PubMed - indexed for MEDLINE]



Related Articles

Model Development of Mothering by Women with Bipolar Illness.

Issues Ment Health Nurs. 2016 Feb;37(2):75-82

Authors: Lewin LC, Templin TN

Abstract
A sensitive, secure, and consistent relationship with their mother is critical for young children. There is a dearth of knowledge about the quality of mothering of young children by women with bipolar disorder. These mothers are frequently challenged, unable to provide consistency, and are at risk for loss of child custody. The model described in this article reflects a critical analysis of conceptual and empirical literature regarding mothering quality, resourcefulness, disorder severity, medication adherence, social supports, and child-rearing beliefs. The model can provide a conceptual framework for research, direct the selection of research instruments, and hypothesize the relationships among constructs.

PMID: 26864837 [PubMed - in process]



Related Articles

Task sharing for the care of severe mental disorders in a low-income country (TaSCS): study protocol for a randomised, controlled, non-inferiority trial.

Trials. 2016;17(1):76

Authors: Hanlon C, Alem A, Medhin G, Shibre T, Ejigu DA, Negussie H, Dewey M, Wissow L, Prince M, Susser E, Lund C, Fekadu A

Abstract
BACKGROUND: Task sharing mental health care through integration into primary health care (PHC) is advocated as a means of narrowing the treatment gap for mental disorders in low-income countries. However, the effectiveness, acceptability, feasibility and sustainability of this service model for people with a severe mental disorder (SMD) have not been evaluated in a low-income country.
METHODS/DESIGN: A randomised, controlled, non-inferiority trial will be carried out in a predominantly rural area of Ethiopia. A sample of 324 people with SMD (diagnoses of schizophrenia, schizoaffective disorder, bipolar disorder or major depressive disorder) with an ongoing need for mental health care will be recruited from 1) participants in a population-based cohort study and 2) people attending a psychiatric nurse-led out-patient clinic. The intervention is a task-sharing model of locally delivered mental health care for people with SMD integrated into PHC delivered over 18 months. Participants in the active control arm will receive the established and effective model of specialist mental health care delivered by psychiatric nurses at an out-patient clinic within a centrally located general hospital. The hypothesis is that people with SMD who receive mental health care integrated into PHC will have a non-inferior clinical outcome, defined as a mean symptom score on the Brief Psychiatric Rating Scale, expanded version, of no more than six points higher, compared to participants who receive the psychiatric nurse-led service, after 12 months. The primary outcome is change in symptom severity. Secondary outcomes are functional status, relapse, service use costs, service satisfaction, drop-out and medication adherence, nutritional status, physical health care, quality of care, medication side effects, stigma, adverse events and cost-effectiveness. Sustainability and cost-effectiveness will be further evaluated at 18 months. Randomisation will be stratified by health centre catchment area using random permuted blocks. The outcome assessors and investigators will be masked to allocation status.
DISCUSSION: Evidence about the effectiveness of task sharing mental health care for people with SMD in a rural, low-income African country will inform the World Health Organisation's mental health Gap Action Programme to scale-up mental health care globally.
TRIAL REGISTRATION: NCT02308956 (ClinicalTrials.gov). Date of registration: 3 December 2014.

PMID: 26865254 [PubMed - in process]



Related Articles

The differential levels of inflammatory cytokines and BDNF among bipolar spectrum disorders.

Int J Neuropsychopharmacol. 2016 Feb 10;

Authors: Wang TY, Lee SY, Chen SL, Chang YH, Wang LJ, Chen PS, Chen SH, Chu CH, Huang SY, Tzeng NS, Li CL, Chung YL, Hsieh TH, Chiu YC, Lee IH, Chen KC, Yang YK, Hong JS, Lu RB

Abstract
OBJECTIVE: Emerging evidence suggests that inflammation and neurodegeneration underlies bipolar disorder (BP). To investigate biological markers of cytokines and brain-derived neurotrophic factor (BDNF) between bipolar I (BP-I), bipolar II (BP-II), and other specified bipolar disorder with short duration hypomania (SBP) may support the association with inflammatory dysregulation and BP, and more specifically, provide evidence for SBP patients were similar to BP-II patients from a biological marker perspective.
METHODS: We enrolled patients with BP-I (n=234), BP-II (n=260), SBP (n=243), and healthy controls (n=140). Their clinical symptoms were rated using the Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS). Inflammatory cytokine (TNF-?, CRP, TGF-?1, and IL-8) and BDNF levels were measured in each group. Multivariate analysis of covariance (MANCOVA) and linear regression controlled for possible confounders were used to compare cytokine and BDNF levels among the groups.
RESULTS: MANCOVA adjusted for age and sex and a main effect of diagnosis was significant (p<0.001). Three of the 5 measured biomarkers (TNF-?, TGF-?1 and IL-8) were significantly (P=0.006, 0.01, and <0.001) higher in all BP patients than in Controls. Moreover, covarying for multiple associated confounders showed that BP-I patients had significantly higher IL-8 levels than did BP-II and SBP patients in MANCOVA (P=0.03) and linear regression (P=0.02) analyses. Biomarkers differences between BP-II and SBP patients were nonsignificant.
CONCLUSION: The immunological disturbance along the bipolar spectrum, was most severe in BP-I patients. SBP patients and BP-II patients did not differ in these biological markers.

PMID: 26865313 [PubMed - as supplied by publisher]



Related Articles

The Bidirectional Relation Between Emotional Reactivity and Sleep: From Disruption to Recovery.

Behav Neurosci. 2016 Feb 11;

Authors: Altena E, Micoulaud-Franchi JA, Geoffroy PA, Sanz-Arigita E, Bioulac S, Philip P

Abstract
Sleep disturbances are highly prevalent and greatly affect consecutive emotional reactivity, while sleep quality itself can be strongly affected by reactions to previous emotional events. In this review, we shed light on this bidirectional relation through examples of pathology: insomnia and bipolar disorder. We show that both experimental sleep deprivation and insomnia are related to increased emotional reactivity and increased amygdala activation upon emotional stimuli presentation, and that particularly Rapid Eye Movement (REM) sleep is important for emotional processing and reorganization of emotion-specific brain activity. Increased emotional reactivity affects REM sleep quality and sleep spindles, while REM sleep is particularly affected in insomnia, possibly related to condition-specific hyperarousal levels. Normal sleep onset deactivation of brain regions important for emotional processing (amygdala, anterior cingulate cortex (ACC)) is further affected in insomnia. In bipolar disorder, sleep disturbances are common in both symptomatic and nonsymptomatic phases. Both amygdala and ACC volume and function are affected in bipolar disorder, with the ACC showing phase-dependent resting state activity differences. Deficient Gamma-aminobutyric acid (GABA) GABA-ergic activity of this region might play a role in sleep disturbances and their influence on emotional reactivity, given the inhibitory role of GABA on brain activity during sleep and its deficiency in both bipolar disorder and insomnia. Promising findings of normalizing brain activity in both insomnia and bipolar disorder upon treatment may inspire a focus on treatment studies investigating the normalization of sleep, emotional reactivity, and their corresponding brain activity patterns. (PsycINFO Database Record

PMID: 26866361 [PubMed - as supplied by publisher]



Related Articles

A comprehensive meta-analysis of ZNF804A SNPs in the risk of schizophrenia among Asian populations.

Am J Med Genet B Neuropsychiatr Genet. 2016 Feb 11;

Authors: Huang L, Ohi K, Chang H, Yu H, Wu L, Yue W, Zhang D, Gao L, Li M

Abstract
Common variants in ZNF804A increased the risk of schizophrenia (and bipolar disorder), with low effect sizes in Europeans, which is in line with the polygenic nature of the illnesses, and implies that genetic analyses in small samples may not be sufficient to detect stable results. This notion is supported by the inconsistent replications of ZNF804A variations among individual small Asian samples, indicating the absence of definitive conclusions in this population. We collected psychiatric phenotypic and genetic data from Asian genome-wide association (GWA) and individual replication studies, which include up to 13,452 cases, 17,826 healthy controls, and 680 families, that is, the largest-scale study on ZNF804A in Asian populations to date. The European GWAS risk single nucleotide polymorphism (SNP) rs1344706 was nominally associated with schizophrenia in these Asian samples (one-tailed P?=?4.26?×?10(-2) , odds ratio [OR]?=?1.048), and the association was further strengthened when bipolar disorder data was also included (one-tailed P?=?1.85?×?10(-2) , OR?=?1.057). Besides, a non-synonymous SNP rs1366842 in the exon 4 of ZNF804A was also associated with schizophrenia (P?=?9.96?×?10(-3) , OR?=?1.095). We additionally analyzed other 163 SNPs covering ZNF804A region, but none of them showed any evidence of association. Though the two SNPs did not remain significant if we applied multiple corrections, our analysis should be interpreted as a primary replication study with in prior hypothesis, and rs1344706 and rs1366842 might confer a small but detectable risk of schizophrenia (and bipolar disorder) in Asians. Moreover, the current data suggest the necessity of replication analyses in a large enough scale samples. © 2016 Wiley Periodicals, Inc.

PMID: 26866941 [PubMed - as supplied by publisher]



Related Articles

Impaired glucose metabolism moderates the course of illness in bipolar disorder.

J Affect Disord. 2016 Feb 4;195:57-62

Authors: Mansur RB, Rizzo LB, Santos CM, Asevedo E, Cunha GR, Noto MN, Pedrini M, Zeni M, Cordeiro Q, McIntyre RS, Brietzke E

Abstract
BACKGROUND: The longitudinal course of bipolar disorder (BD) is highly heterogeneous, and is moderated by the presence of general medical comorbidities. This study aimed to investigate the moderating effects of impaired glucose metabolism (IGM) on variables of illness course and severity in a BD population.
METHODS: Fifty-five patients with BD were evaluated. All subjects were evaluated with respect to current and past psychiatric and medical disorders, as well as lifetime use of any medication. Body mass index (BMI) and metabolic parameters were obtained. IGM was operationalized as pre-diabetes or type 2 diabetes mellitus.
RESULTS: Thirty (54.5%) individuals had IGM. After adjustment for age, gender, ethnicity, alcohol use, smoking, BMI and past and current exposure to psychotropic medications, individuals with IGM, when compared to euglycemic participants, had an earlier age of onset (RR: 0.835, p=0.024), longer illness duration (RR: 1.754, p=0.007), a higher number of previous manic/hypomanic episodes (RR: 1.483, p=0.002) and a higher ratio of manic/hypomanic to depressive episodes (RR: 1.753, p=0.028). Moreover, we observed a moderating effect of IGM on the association between number of mood episodes and other variables of illness course, with the correlation between lifetime mood episodes and frequency of episodes being significantly greater in the IGM subgroup (RR: 1.027, p=0.029). All associations observed herein remained significant after adjusting for relevant confounding factors (e.g. age, alcohol and tobacco use, exposure to psychotropic agents, BMI).
LIMITATIONS: Cross-sectional design, small sample size.
CONCLUSIONS: Comorbid IGM may be a key moderator of illness progression in BD.

PMID: 26866976 [PubMed - as supplied by publisher]



Single-dose infusion ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories.

Psychol Med. 2016 Feb 12;:1-14

Authors: Kishimoto T, Chawla JM, Hagi K, Zarate CA, Kane JM, Bauer M, Correll CU

Abstract
BACKGROUND: Ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists (NMDAR antagonists) recently demonstrated antidepressant efficacy for the treatment of refractory depression, but effect sizes, trajectories and possible class effects are unclear.
METHOD: We searched PubMed/PsycINFO/Web of Science/clinicaltrials.gov until 25 August 2015. Parallel-group or cross-over randomized controlled trials (RCTs) comparing single intravenous infusion of ketamine or a non-ketamine NMDAR antagonist v. placebo/pseudo-placebo in patients with major depressive disorder (MDD) and/or bipolar depression (BD) were included in the analyses. Hedges' g and risk ratios and their 95% confidence intervals (CIs) were calculated using a random-effects model. The primary outcome was depressive symptom change. Secondary outcomes included response, remission, all-cause discontinuation and adverse effects.
RESULTS: A total of 14 RCTs (nine ketamine studies: n = 234; five non-ketamine NMDAR antagonist studies: n = 354; MDD = 554, BD = 34), lasting 10.0 ± 8.8 days, were meta-analysed. Ketamine reduced depression significantly more than placebo/pseudo-placebo beginning at 40 min, peaking at day 1 (Hedges' g = -1.00, 95% CI -1.28 to -0.73, p < 0.001), and loosing superiority by days 10-12. Non-ketamine NMDAR antagonists were superior to placebo only on days 5-8 (Hedges' g = -0.37, 95% CI -0.66 to -0.09, p = 0.01). Compared with placebo/pseudo-placebo, ketamine led to significantly greater response (40 min to day 7) and remission (80 min to days 3-5). Non-ketamine NMDAR antagonists achieved greater response at day 2 and days 3-5. All-cause discontinuation was similar between ketamine (p = 0.34) or non-ketamine NMDAR antagonists (p = 0.94) and placebo. Although some adverse effects were more common with ketamine/NMDAR antagonists than placebo, these were transient and clinically insignificant.
CONCLUSIONS: A single infusion of ketamine, but less so of non-ketamine NMDAR antagonists, has ultra-rapid efficacy for MDD and BD, lasting for up to 1 week. Development of easy-to-administer, repeatedly given NMDAR antagonists without risk of brain toxicity is of critical importance.

PMID: 26867988 [PubMed - as supplied by publisher]



Full-field electroretinogram in autism spectrum disorder.

Doc Ophthalmol. 2016 Feb 11;

Authors: Constable PA, Gaigg SB, Bowler DM, Jägle H, Thompson DA

Abstract
PURPOSE: To explore early findings that individuals with autism spectrum disorder (ASD) have reduced scotopic ERG b-wave amplitudes.
METHODS: Light-adapted (LA) and dark-adapted (DA) ERGs were produced by a range of flash strengths that included and extended the ISCEV standard from two subject groups: a high-functioning ASD group N = 11 and a Control group N = 15 for DA and N = 14 for LA ERGs who were matched for mean age and range. Flash strengths ranged from DA -4.0 to 2.3 log phot cd s m(-2) and LA -0.5 to 1.0 log phot cd s m(-2), and Naka-Rushton curves were fitted to DA b-wave amplitude over the first growth limb (-4.0 to -1.0 log phot cd s m(-2)). The derived parameters (V max, K m and n) were compared between groups. Scotopic 15-Hz flicker ERGs (14.93 Hz) were recorded to 10 flash strengths presented in ascending order from -3.0 to 0.5 log Td s to assess the slow and fast rod pathways, respectively. LA 30-Hz flicker ERGs, oscillatory potentials (OPs) and the responses to prolonged 120-ms ON-OFF stimuli were also recorded.
RESULTS: The ISCEV LA b-wave amplitude produced by 0.5 log phot cd s m(-2) was lower in the ASD group (p < 0.001). Repeated measures ANOVA for the LA b-wave amplitude series forming the photopic hill was significantly (p = 0.01) different between groups. No group differences were observed for the distributions of the time to peaks of LA a-wave, b-wave or the photopic negative responses (phNR) (p > 0.08) to the single flash stimuli, but there was a significant difference in the distribution for the LA b-wave amplitudes (corrected p = 0.006). The prolonged 120-ms ON responses were smaller in the ASD group (corrected p = 0.003), but the OFF response amplitude (p > 0.6) and ON and OFF times to peaks (p > 0.4) were similar between groups. The LA OPs showed an earlier bifurcation of OP2 in the younger ASD participants; however, no other differences were apparent in the OPs or 30-Hz flicker waveforms. DA b-wave amplitudes fell below the control 5th centile of the controls for some individuals including four ASD participants (36 %) at the 1.5 log phot cd s m(-2) flash strength and two (18 %) ASD participants at the lower -2 log phot cd s m(-2) flash strength. However, across the 13 flash strengths, there were no significant group differences for b-wave amplitude's growth (repeated measures ANOVA p = 0.83). Nor were there any significant differences between the groups for the Naka-Rushton parameters (p > 0.09). No group differences were observed in the 15-Hz scotopic flicker phase or amplitude (p > 0.1), DA ERG a-wave amplitude or time to peak (p > 26). The DA b-wave time to peak at 0.5 log phot cd s m(-2) was longer in the ASD group (p = 0.04).
CONCLUSION: Under LA conditions, the b-wave is reduced across the ASD group, along with the ON response of the prolonged flash ERG. Some ASD individuals also show subnormal DA ERG b-wave amplitudes. These exploratory findings suggest there is altered cone-ON bipolar signalling in ASD.

PMID: 26868825 [PubMed - as supplied by publisher]



Effects of short-term quetiapine treatment on emotional processing, sleep and circadian rhythms.

J Psychopharmacol. 2016 Feb 11;

Authors: Rock PL, Goodwin GM, Wulff K, McTavish SF, Harmer CJ

Abstract
BACKGROUND: Quetiapine is an atypical antipsychotic that can stabilise mood from any index episode of bipolar disorder. This study investigated the effects of seven-day quetiapine administration on sleep, circadian rhythms and emotional processing in healthy volunteers.
METHODS: Twenty healthy volunteers received 150 mg quetiapine XL for seven nights and 20 matched controls received placebo. Sleep-wake actigraphy was completed for one week both pre-dose and during drug treatment. On Day 8, participants completed emotional processing tasks.
RESULTS: Actigraphy revealed that quetiapine treatment increased sleep duration and efficiency, delayed final wake time and had a tendency to reduce within-day variability. There were no effects of quetiapine on subjective ratings of mood or energy. Quetiapine-treated participants showed diminished bias towards positive words and away from negative words during recognition memory. Quetiapine did not significantly affect facial expression recognition, emotional word categorisation, emotion-potentiated startle or emotional word/faces dot-probe vigilance reaction times.
CONCLUSIONS: These changes in sleep timing and circadian rhythmicity in healthy volunteers may be relevant to quetiapine's therapeutic actions. Effects on emotional processing did not emulate the effects of antidepressants. The effects of quetiapine on sleep and circadian rhythms in patients with bipolar disorder merit further investigation to elucidate its mechanisms of action.

PMID: 26869012 [PubMed - as supplied by publisher]



Cognition and functioning in bipolar depression.

Rev Bras Psiquiatr. 2016 Feb 5;

Authors: Kapczinski NS, Narvaez JC, Magalhães PV, Bücker J, Peuker AC, Loredo AC, Troiano F, Czepielewski L, Rosa A, Fries G, Gama CS

Abstract
OBJECTIVES: Depressive symptoms are associated with worse outcomes in patients with bipolar disorder (BD). However, scarce data are available regarding neurocognitive profiles across different areas of functioning among BD patients with moderate and severe depression. Our objective was to assess cognition and global functioning in a group of patients with bipolar depression.
METHODS: Data were available for 100 patients with bipolar depression (78% female) and 70 controls (64% female) paired by age and education level. Cognitive function was assessed with a neuropsychological test battery. Functioning was assessed with the Functioning Assessment Short Test.
RESULTS: In patients, severe depression was associated with poorer cognitive performance on measures of executive function. Patients with severe depression showed worse global functioning than those with moderate depression (z = 2.54, p = 0.011). In patients with severe depression, lower global functioning was associated with lower scores in working memory (r = -0.200, p = 0.010), and executive function (r = -0.210, p = 0.007; and r = 0.293, p < 0.001).
CONCLUSION: Our findings suggest cognitive impairment and global functioning impairment are associated with the severity of depressive symptoms in bipolar depression. Intensive treatment of depressive symptoms in patients with BD is crucial to improve cognitive functioning and, consequently, functional outcomes.

PMID: 26870909 [PubMed - as supplied by publisher]



Serum BDNF levels in unaffected first-degree relatives of patients with bipolar disorder.

Rev Bras Psiquiatr. 2016 Feb 5;

Authors: Nery FG, Gigante AD, Amaral JA, Fernandes FB, Berutti M, Almeida KM, Stertz L, Bristot G, Kapczinski F, Lafer B

Abstract
OBJECTIVE: Unaffected relatives of bipolar disorder (BD) patients have been investigated for the identification of endophenotypes in an attempt to further elucidate the pathophysiology of the disease. Brain-derived neurotrophic factor (BDNF) is considered to be implicated in the pathophysiology of BD, but its role as an endophenotype has been poorly studied. We investigated abnormal serum BDNF levels in BD patients, in their unaffected relatives, and in healthy controls.
METHODS: BDNF levels were obtained from 25 DSM-IV bipolar I disorder patients, 23 unaffected relatives, and 27 healthy controls. All BD patients were in remission. The unaffected subjects were first-degree relatives of the proband who had no lifetime DSM-IV diagnosis of axis I disorder. BDNF serum levels were determined by sandwich ELISA using monoclonal BDNF-specific antibodies.
RESULTS: There were no statistical differences in BDNF levels among BD patients, relatives, and healthy controls.
CONCLUSION: Serum BDNF levels may not indicate high genetic risk for BD, possibly acting as state markers rather than trait markers of the disease.

PMID: 26870912 [PubMed - as supplied by publisher]



Lithium Ameliorates LPS-Induced Astrocytes Activation Partly via Inhibition of Toll-Like Receptor 4 Expression.

Cell Physiol Biochem. 2016 Feb 15;38(2):714-725

Authors: Li N, Zhang X, Dong H, Zhang S, Sun J, Qian Y

Abstract
BACKGROUND/AIMS: Astrocytes are critical for the development of postoperative cognitive dysfunction (POCD). In addition, astrocytes express toll-like receptors 4 (TLR4) and build up responses to innate immune triggers by releasing pro-inflammatory molecules. The pathogenesis of neurological disorders often involves the activation of astrocytes and associated inflammatory processes. Lithium, a primary drug for the treatment of bipolar disorder, has recently been suggested to have a role in neuroprotection during neurodegenerative diseases. In this study, we aimed to investigate whether lithium can ameliorate LPS-induced astrocytes activation via inhibition of TLR4 expression.
METHODS: Primary astrocytes cells were pretreated with lithium and stimulated with lipopolysaccharide (LPS). Cellular activation, cytokine production, and TLR4 expression, were assessed.
RESULTS: Lithium significantly inhibited LPS-induced astrocytes activation and pro-inflammatory cytokine production, as well as LPS-induced TLR4 expression.
CONCLUSIONS: Lithium can inhibit LPS-induced TLR4 expression and astrocytes activation. These results indicate that lithium plays an important role in astrocytes activation and neuroinflammation-related diseases, which may open new avenues for neuroscience and biomedical research, and also offers new insight into the treatment of POCD.

PMID: 26870942 [PubMed - as supplied by publisher]



Treatment of suicidal depression with ketamine in rapid cycling bipolar disorder.

Asia Pac Psychiatry. 2016 Mar;8(1):98-101

Authors: Sampath H, Sharma I, Dutta S

PMID: 26871425 [PubMed - as supplied by publisher]



Antioxidant effect of simvastatin throught oxidative imbalance caused by lisdexamfetamine dimesylate.

An Acad Bras Cienc. 2016 Feb 5;

Authors: Eger GA, Ferreira VV, Batista CR, Bonde H, Lima DD, Wyse AT, Cruz JN, Rodrigues AF, Magro DD, Cruz JG

Abstract
The present study aims to directly investigate the behavioral and antioxidant effects of simvastatin in a model of bipolar mania induced by lisdexamfetamine dimesylate. Wistar rats were treated for 30 days with simvastatin. On the 24th day after the start of treatment, each rat was administered lisdexamfetamine dimesylate for 7 days. The results suggest that simvastatin combined with lisdexamfetamine dimesylate induced a significant increased locomotion and lisdexamfetamine dimesylate administration causes an oxidative imbalance determined by an increment in lipid peroxidation, protein oxidation and alterations in the activities of antioxidant enzymes in brain areas; moreover, in the presence of simvastatin, most of these effects were prevented. These findings contribute to a better understanding of the critical roles of lisdexamfetamine dimesylate in the treatment of neuropsychiatric disorders, associated with increased oxidative stress and changes in antioxidant enzymatic defense. In view of the central role played by lisdexamfetamine dimesylate, the established antioxidant effect of simvastatin therapy is of major interest.

PMID: 26871491 [PubMed - as supplied by publisher]



Treatment patterns and characteristics of older antipsychotic users in Germany.

Int Clin Psychopharmacol. 2016 Feb 11;

Authors: Schmedt N, Jobski K, Kollhorst B, Krappweis J, Rüther E, Schink T, Garbe E

Abstract
The aim of this study was to investigate the characteristics and treatment patterns of older antipsychotic (AP) users in Germany. We carried out a cohort study in the German Pharmacoepidemiological Research Database and identified new AP users aged at least 65 years between 2005 and 2011. Possible indications, comedication, and information on persistence and adherence, concurrent multiple use, and switch of APs were assessed. Overall, 298?847 individuals were included in the cohort. Almost 70% entered the cohort with a typical antipsychotic (TAP). Melperone (23.4%) was used most frequently, followed by promethazine (18.3%), sulpiride (11.0%), and risperidone (10.3%). AP users had a low prevalence of schizophrenia and bipolar disorders in contrast to dementia. Initiators of atypical antipsychotics had more treatment episodes compared with TAPs (median 3 vs. 2), but lower median persistence (14 vs. 22 days). Persistence was also lower in patients with, rather than without, dementia. The overall percentage of concurrent multiple use and switch to other APs was low with 5.6%, but higher in patients with, rather than without, dementia. In conclusion, APs were used for a broad range of indications, mostly other than schizophrenia and bipolar disorders. Low persistence and a high number of treatment episodes suggest frequent 'as-needed' treatment, especially in dementia patients.

PMID: 26871678 [PubMed - as supplied by publisher]



Role of Pharmacogenetics in Improving the Safety of Psychiatric Care by Predicting the Potential Risks of Mania in CYP2D6 Poor Metabolizers Diagnosed With Bipolar Disorder.

Medicine (Baltimore). 2016 Feb;95(6):e2473

Authors: Sánchez-Iglesias S, García-Solaesa V, García-Berrocal B, Sanchez-Martín A, Lorenzo-Romo C, Martín-Pinto T, Gaedigk A, González-Buitrago JM, Isidoro-García M

Abstract
One of the main concerns in psychiatric care is safety related to drug management. Pharmacogenetics provides an important tool to assess causes that may have contributed the adverse events during psychiatric therapy. This study illustrates the potential of pharmacogenetics to identify those patients for which pharmacogenetic-guided therapy could be appropriate. It aimed to investigate CYP2D6 genotype in our psychiatric population to assess the value of introducing pharmacogenetics as a primary improvement for predicting side effects.A broad series of 224 psychiatric patients comprising psychotic disorders, depressive disturbances, bipolar disorders, and anxiety disorders was included. The patients were genotyped with the AmpliChip CYP450 Test to analyzing 33 allelic variants of the CYP2D6 gene.All bipolar patients with poor metabolizer status showed maniac switching when CYP2D6 substrates such as selective serotonin reuptake inhibitors were prescribed. No specific patterns were identified for adverse events for other disorders.We propose to utilize pharmacogenetic testing as an intervention to aid in the identification of patients who are at risk of developing affective switching in bipolar disorder treated with selective serotonin reuptake inhibitors, CYP2D6 substrates, and inhibitors.

PMID: 26871771 [PubMed - as supplied by publisher]



Risk of Psychiatric Disorders Following Symptomatic Menopausal Transition: A Nationwide Population-Based Retrospective Cohort Study.

Medicine (Baltimore). 2016 Feb;95(6):e2800

Authors: Hu LY, Shen CC, Hung JH, Chen PM, Wen CH, Chiang YY, Lu T

Abstract
Menopausal transition is highly symptomatic in at least 20% of women. A higher prevalence of psychiatric symptoms, including depression, anxiety, and sleep disturbance, has been shown in women with symptomatic menopausal transition. However, a clear correlation between symptomatic menopausal transition and psychiatric disorders has not been established.We explored the association between symptomatic menopausal transition and subsequent newly diagnosed psychiatric disorders, including schizophrenia as well as bipolar, depressive, anxiety, and sleep disorders.We investigated women who were diagnosed with symptomatic menopausal transition by an obstetrician-gynecologist according to the data in the Taiwan National Health Insurance Research Database. A comparison cohort comprised age-matched women without symptomatic menopausal transition. The incidence rate and the hazard ratios of subsequent newly diagnosed psychiatric disorders were evaluated in both cohorts, based on the diagnoses of psychiatrists.The symptomatic menopausal transition and control cohorts each consisted of 19,028 women. The incidences of bipolar disorders (hazard ratio [HR]?=?1.69, 95% confidence interval [CI]?=?1.01-2.80), depressive disorders (HR?=?2.17, 95% CI?=?1.93-2.45), anxiety disorders (HR?=?2.11, 95% CI?=?1.84-2.41), and sleep disorders (HR?=?2.01, 95% CI?=?1.73-2.34) were higher among the symptomatic menopausal transition women than in the comparison cohort. After stratifying for follow-up duration, the incidence of newly diagnosed bipolar disorders, depressive disorders, anxiety disorders, and sleep disorders following a diagnosis of symptomatic menopausal transition remained significantly increased in the longer follow-up groups (1-5 and ? 5 years).Symptomatic menopausal transition might increase the risk of subsequent newly onset bipolar disorders, depressive disorders, anxiety disorders, and sleep disorders. A prospective study is necessary to confirm these findings.

PMID: 26871843 [PubMed - as supplied by publisher]



Utilisation of extended release quetiapine (Seroquel XL?): Results from an observational cohort study in England.

Eur Psychiatry. 2016 Feb 9;33:61-67

Authors: Osborne V, Davies M, Layton D, Shakir SA

Abstract
BACKGROUND: A post-authorisation safety study was carried out as part of the EU Risk Management Plan to examine the long-term (up to 12 months) use of quetiapine XL as prescribed in general practice in England.
AIM: To present a description of the drug utilisation characteristics of quetiapine XL.
METHODS: An observational, population-based cohort design using the technique of Modified Prescription-Event Monitoring (M-PEM). Patients were identified from dispensed prescriptions issued by general practitioners (GPs) for quetiapine XL between September 2008 and February 2013. Questionnaires were sent to GPs 12 months following the 1st prescription for each individual patient, requesting drug utilisation information. Cohort accrual was extended to recruit additional elderly patients (special population of interest). Summary descriptive statistics were calculated.
RESULTS: The final M-PEM cohort consisted of 13,276 patients; median age 43 years (IQR: 33, 55) and 59.0% females. Indications for prescribing included bipolar disorder (n=3820), MDD (n=2844), schizophrenia (n=2373) and other (non-licensed) indications (n=3750). Where specified, 59.3% (7869/13,276) were reported to have used quetiapine IR (immediate release formulation) previously at any time. The median start dose was highest for patients with schizophrenia (300mg/day [IQR 150, 450]). The final elderly cohort consisted of 3127 patients and 28.5% had indications associated with dementia. The median start dose for elderly patients was highest for patients with schizophrenia or BD (both 100mg/day [IQR 50, 300]).
CONCLUSIONS: The prevalence of off-label prescribing in terms of indication and high doses was common, as was use in special populations such as the very elderly. Whilst off-label use may be unavoidable in certain situations, GPs may need to re-evaluate prescribing in circumstances where there may be safety concerns. This study demonstrates the ongoing importance of observational studies such as M-PEM to gather real-world clinical data to support the post-marketing benefit:risk management of new medications, or existing medications for which license extensions have been approved.

PMID: 26872067 [PubMed - as supplied by publisher]



A Naturalistic Randomized Placebo-Controlled Trial of Extended-Release Metformin to Prevent Weight Gain Associated With Olanzapine in a US Community-Dwelling Population.

J Clin Psychopharmacol. 2016 Feb 11;

Authors: Rado J, von Ammon Cavanaugh S

Abstract
OBJECTIVE: This 24-week pilot study assessed the efficacy, tolerability, and safety of adjunctive metformin versus placebo for the prevention of olanzapine-associated weight gain in community-dwelling adult patients with schizophrenia, schizoaffective disorder, bipolar disorder, or major depression with psychotic features.
METHODS: In a double-blind study, 25 patients were randomly assigned to receive 24 weeks of either olanzapine plus metformin or olanzapine plus placebo. Metformin extended release was titrated to 2000 mg daily as tolerated. No other antipsychotics were allowed, whereas psychotropic medications including antidepressants and mood stabilizers were permitted. The primary outcome measures were change in body weight and homeostatic model assessment for insulin resistance from baseline to week 24.
RESULTS: The intent-to-treat population comprised patients who had 1 or more post-baseline visit. Mean change in body weight for the olanzapine plus metformin (O/M) group was 5.5 lb, which was less than the 12.8 lb gain for the olanzapine plus placebo (O/P) group (P < 0.05). Compared with O/P group who gained 7% of their body weight, patients in the O/M group gained 3% (P < 0.037). Body mass index change in the O/M group was 0.85 versus 2.02 in the O/P group (P < 0.045). There was a trend for a greater increase in baseline to end point homeostatic model assessment for insulin resistance and waist circumference in the O/P group versus the O/M group.
CONCLUSIONS: In this naturalistic sample of typical US community-dwelling patients, metformin was effective and well tolerated for the prevention of olanzapine-associated weight gain. Adjunctive metformin should be studied in a similar but larger population to determine its role in the prevention of olanzapine-associated weight gain.

PMID: 26872112 [PubMed - as supplied by publisher]



DARPP-32: from neurotransmission to cancer.

Oncotarget. 2016 Feb 8;

Authors: Belkhiri A, Zhu S, El-Rifai W

Abstract
Dopamine and cAMP-regulated phosphoprotein Mr 32,000 (DARPP-32), also known as phosphoprotein phosphatase-1 regulatory subunit 1B (PPP1R1B), was initially discovered as a substrate of dopamine-activated protein kinase A (PKA) in the neostriatum in the brain. While phosphorylation at Thr-34 by PKA converts DARPP-32 into a potent inhibitor of protein phosphatase 1 (PP1), phosphorylation at Thr-75 transforms DARPP-32 into an inhibitor of PKA. Through regulation of DARPP-32 phosphorylation and modulation of protein phosphatase and kinase activities, DARPP-32 plays a critical role in mediating the biochemical, electrophysiological, and behavioral effects controlled by dopamine and other neurotransmitters in response to drugs of abuse and psychostimulants. Altered expression of DARPP-32 and its truncated isoform (t-DARPP), specifically in the prefrontal cortex, has been associated with schizophrenia and bipolar disorder. Moreover, cleavage of DARPP-32 by calpain has been implicated in Alzheimer's disease. Amplification of the genomic locus of DARPP-32 at 17q12 has been described in several cancers. DARPP-32 and t-DARPP are frequently overexpressed at the mRNA and protein levels in adenocarcinomas of the breast, prostate, colon, and stomach. Several studies demonstrated the pro-survival, pro-invasion, and pro-angiogenic functions of DARPP-32 in cancer. Overexpression of DARPP-32 and t-DARPP also promotes chemotherapeutic drug resistance and cell proliferation in gastric and breast cancers through regulation of pro-oncogenic signal transduction pathways. The expansion of DARPP-32 research from neurotransmission to cancer underscores the broad scope and implication of this protein in disparate human diseases.

PMID: 26872373 [PubMed - as supplied by publisher]



Related Articles

Manic psychosis associated with ginseng: a report of two cases and discussion of the literature.

J Diet Suppl. 2015 Jun;12(2):119-25

Authors: Norelli LJ, Xu C

Abstract
BACKGROUND: Herbal medicine use, highly prevalent in the general population, is often a neglected component of the medical history. Herbs are presumed safe because they are "natural" self-care products. We call attention to the following issues: Panax ginseng, one of the most frequently used herbal medicines, has complex pharmacological activity, and can be associated with severe psychiatric symptoms. Physicians may be unfamiliar with herbal therapy risks, and the need for further education and systematic research is highlighted.
OBJECTIVE: To describe two cases of new onset manic psychoses associated with high dose, chronic ginseng use, and review the relevant literature.
CASE REPORTS: A 23-year-old man developed acute mania after one month of daily ginseng use and intermittent cannabis use. A 79-year-old man developed hypomania while using ginseng and yohimbine for erectile dysfunction, and had a recurrence of mania after stopping yohimbine but increasing his daily intake of ginseng.
CONCLUSIONS/SUMMARY: Symptoms of mania fully remitted within days upon discontinuation of ginseng and supportive treatment. Available data prevent a clear determination of causation; however, ginseng-induced mania in the these and previous case reports is suggested by the following: patients had no prior psychiatric history, daily use of ginseng was temporally associated with mania onset, patients ingested much higher doses for a longer duration than recommended in Traditional Chinese Medicine (TCM), and withdrawal of ginseng led to rapid remission. Generally well tolerated, many physicians are unaware that ginseng may be associated with acute and significant psychiatric disturbances for certain at-risk individuals.

PMID: 24689505 [PubMed - indexed for MEDLINE]



Related Articles

A Pilot Study of Safety and Efficacy of Cranial Electrotherapy Stimulation in Treatment of Bipolar II Depression.

J Nerv Ment Dis. 2015 Nov;203(11):827-35

Authors: McClure D, Greenman SC, Koppolu SS, Varvara M, Yaseen ZS, Galynker II

Abstract
This double-blind, sham-controlled study sought to investigate the effectiveness of cranial electrotherapy stimulation (CES) for the treatment of bipolar II depression (BD II). After randomization, the active group participants (n = 7) received 2 mA CES treatment for 20 minutes five days a week for 2 weeks, whereas the sham group (n = 9) had the CES device turned on and off. Symptom non-remitters from both groups received an additional 2 weeks of open-label active treatment. Active CES treatment but not sham treatment was associated with a significant decrease in the Beck Depression Inventory (BDI) scores from baseline to the second week (p = 0.003) maintaining significance until week 4 (p = 0.002). There was no difference between the groups in side effects frequency. The results of this small study indicate that CES may be a safe and effective treatment for BD II suggesting that further studies on safety and efficacy of CES may be warranted.

PMID: 26414234 [PubMed - indexed for MEDLINE]



Lithium in Medicine: Mechanisms of Action.

Met Ions Life Sci. 2016;16:557-84

Authors: Mota de Freitas D, Leverson BD, Goossens JL

Abstract
In this chapter, we review the mechanism of action of lithium salts from a chemical perspective. A description on how lithium salts are used to treat mental illnesses, in particular bipolar disorder, and other disease states is provided. Emphasis is not placed on the genetics and the psychopharmacology of the ailments for which lithium salts have proven to be beneficial. Rather we highlight the application of chemical methodologies for the characterization of the cellular targets of lithium salts and their distribution in tissues.

PMID: 26860311 [PubMed - in process]



Detection and treatment of omega-3 fatty acid deficiency in psychiatric practice: Rationale and implementation.

Lipids Health Dis. 2016;15(1):25

Authors: Messamore E, McNamara RK

Abstract
A body of translational evidence has implicated dietary deficiency in long-chain omega-3 (LCn-3) fatty acids, including eicosapenaenoic acid (EPA) and docosahexaenoic acid (DHA), in the pathophysiology and potentially etiology of different psychiatric disorders. Case-control studies have consistently observed low erythrocyte (red blood cell) EPA and/or DHA levels in patients with major depressive disorder, bipolar disorder, schizophrenia, and attention deficit hyperactivity disorder. Low erythrocyte EPA?+?DHA biostatus can be treated with fish oil-based formulations containing preformed EPA?+?DHA, and extant evidence suggests that fish oil supplementation is safe and well-tolerated and may have therapeutic benefits. These and other data provide a rationale for screening for and treating LCn-3 fatty acid deficiency in patients with psychiatric illness. To this end, we have implemented a pilot program that routinely measures blood fatty acid levels in psychiatric patients entering a residential inpatient clinic. To date over 130 blood samples, primarily from patients with treatment-refractory mood or anxiety disorders, have been collected and analyzed. Our initial results indicate that the majority (75 %) of patients exhibit whole blood EPA?+?DHA levels at ?4 percent of total fatty acid composition, a rate that is significantly higher than general population norms (25 %). In a sub-set of cases, corrective treatment with fish oil-based products has resulted in improvements in psychiatric symptoms without notable side effects. In view of the urgent need for improvements in conventional treatment algorithms, these preliminary findings provide important support for expanding this approach in routine psychiatric practice.

PMID: 26860589 [PubMed - in process]



Cigarette and waterpipe smoking among adult patients with severe and persistent mental illness in Bahrain: a comparison with the National Non-communicable Diseases Risk Factors Survey.

BMC Res Notes. 2016;9(1):77

Authors: Hamadeh RR, Ansari AA, Jahrami H, Offi AA

Abstract
BACKGROUND: Smoking has been associated with several types of mental illness namely schizophrenia, depression, bipolar disorders with a prevalence of smoking twice that of the general population. The study objective was to ascertain whether waterpipe tobacco smoking (WTS), cigarette smoking and all types of tobacco smoking are more common among Bahraini patients with severe and persistent mental illness (SPMI) than the general population.
METHODS: A cross-sectional study was conducted on 222 adult SPMI both in- and out- patients who attended the Psychiatric Hospital in Bahrain. A 29-item questionnaire, which included sociodemographic variables, pattern and history of psychiatric illness and a comprehensive smoking history, was used. Comparative smoking data were obtained from the Bahraini National Non-communicable Diseases Risk Factors Survey.
RESULTS: The prevalence of smoking of tobacco among SPMI patients was 30.2 % compared to 19.9 % in the general population. The corresponding values for cigarette smoking were 25.2, 13.8 %, respectively and for WTS, 11.3, 8.4 %, respectively. SPMI patients were 1.7 (95 % CI 1.3, 2.4 %) times more likely to be smokers, 2.1 (95 % CI 1.5, 2.9 %) times, cigarette smokers and 1.4 (95 % CI 0.9, 1.9 %) times WTS than the general population. SPMI patients smoked at a younger age and consumed more cigarettes than the general population. The mean age started smoking was lower among men than women, similar for cigarettes, and higher for WTS.
CONCLUSIONS: The prevalence of smoking among patients with SPMI in Bahrain is twice that of the general population. The findings of the study have implications on the provision of healthcare to mentally ill patients in the country.

PMID: 26861042 [PubMed - in process]



A functional vesicular monoamine transporter 1 (VMAT1) gene variant is associated with affect and the prevalence of anxiety, affective and alcohol use disorders in a longitudinal population-representative birth cohort study.

Int J Neuropsychopharmacol. 2016 Feb 9;

Authors: Vaht M, Kiive E, Veidebaum T, Harro J

Abstract
Background Inter-individual differences in the monoaminergic systems have been shown to moderate the risk for a lifetime history of anxiety, affective and alcohol use disorders. A common single nucleotide polymorphism in the vesicular monoamine transporter 1 gene (VMAT1 rs1390938 G/A; Thr136Ile) has been reported as functional in vitro and associated with bipolar disorder and anxiety. We aimed at assessing the association between the VMAT1 genotype, affect, and affect-related psychiatric disorders in a longitudinal population-representative study.Methods We used the database of the Estonian Children Personality Behaviour and Health Study (beginning in 1998). Cohorts of initially 9 (recalled at ages 15 and 18, n=579) and 15 (recalled at ages 18 and 25; n=654) years old children provided self-reports on impulsivity, anxiety, depressiveness, neuroticism, and alcohol use. In addition, psychiatric assessment based on DSM-IV was carried out in the older cohort at age 25.Results Subjects homozygous for the less prevalent A (136Ile) allele reported lower maladaptive impulsivity, state and trait anxiety, depressiveness, and neuroticism, and were less likely to have been diagnosed with an affective, anxiety, and/or alcohol use disorder by young adulthood. While in the younger cohort alcohol use started at younger age, this birth cohort effect was dependent on genotype: only G allele carriers and in particular the GG homozygotes started alcohol use earlier.Conclusions VMAT1 rs1390938/Thr136Ile is associated with mood, personality, and alcohol use in general population. Subjects homozygous for the 'hyperfunction' allele (AA; Ile/Ile) appear to be more resilient to these disorders.

PMID: 26861143 [PubMed - as supplied by publisher]





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