Trajectories of recurring victimization among people with major mental disorders.
J Interpers Violence. 2014 Apr;29(6):987-1005
Authors: Teasdale B, Daigle LE, Ballard E
Relatively little is known about the violent victimization experiences of people with major mental disorders. Moreover, to date, no studies have examined recurring violent victimization experiences of people with major mental disorders. Using a risk heterogeneity framework commonly used in the study of recurring victimization, the current study examines the extent of recurring victimization among people with Diagnostic and Statistical Manual of Mental Disorders (DSM) Axis I mental disorders and trajectories of recurring violent victimization (n = 262), across four waves of data collected during a 1-year longitudinal study. Multilevel logistic regression analyses tested disorder, time, and time by disorder cross-level interactions predicting recurring victimization. Results suggest that recurring violent victimization is not uncommon among mentally disordered victims of violence, with 64% of victims experiencing a recurring victimization at a later point in time. However, trajectories of recurring violent victimization are not uniform across types of mental illness. Indeed, individuals diagnosed with a substance abuse disorder or major depression show significantly declining trajectories across the follow-up period whereas individuals diagnosed with a manic disorder or a schizophrenia spectrum disorder have flat trajectories of recurring violent victimization across the study period. Results of tests for cross-level interactions between disorder type and time demonstrate that individuals with a major depression or substance abuse/dependence diagnosis are significantly different from those with a schizophrenia spectrum diagnosis in their trajectories of recurring victimization.
PMID: 24255064 [PubMed - indexed for MEDLINE]
Psychopharmacology of bipolar I disorder during lactation: a case report of the use of lithium and aripiprazole in a nursing mother.
Arch Womens Ment Health. 2014 Oct 29;
Authors: Frew JR
PMID: 25352315 [PubMed - as supplied by publisher]
A Preliminary Observation of Increased Glial Cell Line-Derived Neurotrophic Factor in Manic Switch due to Electroconvulsive Treatment in Depressive Patients.
J ECT. 2014 Oct 28;
Authors: Tunca Z, Bayn M, Alkn T, Ozerdem A, Resmi H, Akan P
OBJECTIVE: Neurotrophic factors are known to be involved in the pathogenesis of mood disorders. However, the precise neurobiology underlying relapse into depression or switch to mania under antidepressant treatment is not fully understood. Evidence suggests the role of neuroplasticity in these processes.
METHOD: Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor (GDNF) serum levels were measured concomitantly during electroconvulsive treatment (ECT) in 30 depressive patients (25 patients with unipolar, 5 with bipolar depression), including those who relapsed into depression (n = 6) or switched to mania (n = 3) within 1 to 4 weeks after the end of the ECT, and in 33 healthy volunteers.
RESULTS: Despite significant decrease in depression scores, the levels of brain-derived neurotrophic factor did not significantly change during the ECT, also in the patients who relapsed into depression or switched to mania. However, GDNF levels were lower in the ECT responders compared with pre-ECT levels (z = -2.203; P = 0.01) and increased in manic switch compared with the ECT responders (z = -2.761; P = 0.001) (Cohen d = -1.75; effect size r = -0.66) and healthy controls as well (P = 0.044).
CONCLUSIONS: Our data suggest the role of GDNF in manic switch and the involvement of glial system in the pathogenesis of mood disorders.
PMID: 25354171 [PubMed - as supplied by publisher]
Lifetime autism spectrum features in a patient with a psychotic mixed episode who attempted suicide.
Case Rep Psychiatry. 2014;2014:459524
Authors: Simoncini M, Miniati M, Vanelli F, Callari A, Vannucchi G, Mauri M, Dell'Osso L
We present a case report of a young man who attempted suicide during a mixed episode with psychotic symptoms. The patient's history revealed the lifetime presence of signs and features belonging to the autism spectrum realm that had been completely overlooked. We believe that this case is representative of an important and barely researched topic: what happens to children with nondiagnosed and nontreated subthreshold forms of autism when they grow old. The issue of early recognition of autism spectrum signs and symptoms is discussed, raising questions on the diagnostic boundaries between autism and childhood onset psychotic spectrums among patients who subsequently develop a full-blown psychotic disorder.
PMID: 25349762 [PubMed]
An important role for cholecystokinin, a CLOCK target gene, in the development and treatment of manic-like behaviors.
Mol Psychiatry. 2014 Mar;19(3):342-50
Authors: Arey RN, Enwright JF, Spencer SM, Falcon E, Ozburn AR, Ghose S, Tamminga C, McClung CA
Mice with a mutation in the Clock gene (Clock?19) have been identified as a model of mania; however, the mechanisms that underlie this phenotype, and the changes in the brain that are necessary for lithium's effectiveness on these mice remain unclear. Here, we find that cholecystokinin (Cck) is a direct transcriptional target of CLOCK and levels of Cck are reduced in the ventral tegmental area (VTA) of Clock?19 mice. Selective knockdown of Cck expression via RNA interference in the VTA of wild-type mice produces a manic-like phenotype. Moreover, chronic treatment with lithium restores Cck expression to near wild-type and this increase is necessary for the therapeutic actions of lithium. The decrease in Cck expression in the Clock?19 mice appears to be due to a lack of interaction with the histone methyltransferase, MLL1, resulting in decreased histone H3K4me3 and gene transcription, an effect reversed by lithium. Human postmortem tissue from bipolar subjects reveals a similar increase in Cck expression in the VTA with mood stabilizer treatment. These studies identify a key role for Cck in the development and treatment of mania, and describe some of the molecular mechanisms by which lithium may act as an effective antimanic agent.
PMID: 23399917 [PubMed - indexed for MEDLINE]
Functional SNPs are enriched for schizophrenia association signals.
Mol Psychiatry. 2014 Mar;19(3):276-7
Authors: Bacanu SA, Chen J, Sun J, Richardson K, Lai CQ, Zhao Z, O'Donovan MC, Kendler KS, Chen X
PMID: 23546170 [PubMed - indexed for MEDLINE]
Inositol synthesis regulates activation of GSK-3? in neuronal cells.
J Neurochem. 2014 Oct 26;
Authors: Ye C, Greenberg ML
The synthesis of inositol provides precursors of inositol lipids and inositol phosphates that are pivotal for cell signaling. Mood-stabilizers lithium and valproic acid (VPA), used for treating bipolar disorder, cause cellular inositol depletion, which has been proposed as a therapeutic mechanism of action of both drugs. Despite the importance of inositol, the requirement for inositol synthesis in neuronal cells is not well understood. Here, we examined inositol effects on proliferation of SK-N-SH neuroblastoma cells. The essential role of inositol synthesis in proliferation is underscored by the findings that exogenous inositol was dispensable for proliferation, and inhibition of inositol synthesis decreased proliferation. Interestingly, the inhibition of inositol synthesis by knocking down INO1, which encodes inositol-3-phosphate synthase, the rate-limiting enzyme of inositol synthesis, led to inactivation of GSK-3? by increasing the inhibitory phosphorylation of this kinase. Similarly, the mood-stabilizer VPA effected transient decreases in intracellular inositol, leading to inactivation of GSK-3?. As GSK-3 inhibition has been proposed as a likely therapeutic mechanism of action, the finding that inhibition of inositol synthesis results in inactivation of GSK-3? suggests a unifying hypothesis for mechanism of mood-stabilizing drugs. This article is protected by copyright. All rights reserved.
PMID: 25345501 [PubMed - as supplied by publisher]
Lithium and GSK-3? promoter gene variants influence cortical gray matter volumes in bipolar disorder.
Psychopharmacology (Berl). 2014 Oct 28;
Authors: Benedetti F, Poletti S, Radaelli D, Locatelli C, Pirovano A, Lorenzi C, Vai B, Bollettini I, Falini A, Smeraldi E, Colombo C
RATIONALE: Lithium is the mainstay for the treatment of bipolar disorder (BD) and inhibits glycogen synthase kinase-3? (GSK-3?). The less active GSK-3? promoter gene variants have been associated with less detrimental clinical features of BD. GSK-3? gene variants and lithium can influence brain gray and white matter structure in psychiatric conditions, so we studied their combined effect in BD.
OBJECTIVES: The aim of this study is to investigate the effects of ongoing long-term lithium treatment and GSK-3? promoter rs334558 polymorphism on regional gray matter (GM) volumes of patients with BD.
MATERIALS AND METHODS: GM volumes were estimated with 3.0 Tesla MRI in 150 patients affected by a major depressive episode in course of BD. Duration of lifetime lithium treatment was retrospectively assessed. Analyses were performed by searching for significant effects of lithium and rs334558 in the whole brain.
RESULTS: The less active GSK-3? rs334558*G gene promoter variant and the long-term administration of lithium were synergistically associated with increased GM volumes in the right frontal lobe, in a large cluster encompassing the boundaries of subgenual and orbitofrontal cortex (including Brodmann areas 25, 11, and 47). Effects of lithium on GM revealed in rs334558*G carriers only, consistent with previously reported clinical effects in these genotype groups, and were proportional to the duration of treatment.
CONCLUSIONS: Lithium and rs334558 influenced GM volumes in areas critical for the generation and control of affect, which have been widely implicated in the process of BD pathophysiology. In the light of the protective effects of lithium on white matter integrity, our results suggest that the clinical effects of lithium associate with a neurotrophic effect on the whole brain, probably mediated by GSK-3? inhibition.
PMID: 25345732 [PubMed - as supplied by publisher]
Effect of lithium on behavioral disinhibition induced by electrolytic lesion of the median raphe nucleus.
Psychopharmacology (Berl). 2014 Oct 28;
Authors: Pezzato FA, Can A, Hoshino K, Horta JD, Mijares MG, Gould TD
RATIONALE: Alterations in brainstem circuits have been proposed as a possible mechanism underlying the etiology of mood disorders. Projections from the median raphe nucleus (MnR) modulate dopaminergic activity in the forebrain and are also part of a behavioral disinhibition/inhibition system that produces phenotypes resembling behavioral variations manifested during manic and depressive phases of bipolar disorder.
OBJECTIVE: The aim of this study is to assess the effect of chronic lithium treatment on behavioral disinhibition induced by MnR lesions.
METHODS: MnR electrolytic lesions were performed in C57BL/6J mice, with sham-operated and intact animals as control groups. Following recovery, mice were chronically treated with lithium (LiCl, added in chow) followed by behavioral testing.
RESULTS: MnR lesion induced manic-like behavioral alterations including hyperactivity in the open field (OF), stereotyped circling, anxiolytic/risk taking in the elevated plus maze (EPM) and light/dark box (LDB) tests, and increased basal body temperature. Lithium was specifically effective in reducing OF hyperactivity and stereotypy but did not reverse (EPM) or had a nonspecific effect (LDB) on anxiety/risk-taking measures. Additionally, lithium decreased saccharin preference and prevented weight loss during single housing.
CONCLUSIONS: Our data support electrolytic lesions of the MnR as an experimental model of a hyper-excitable/disinhibited phenotype consistent with some aspects of mania that are attenuated by the mood stabilizer lithium. Given lithium's relatively specific efficacy in treating mania, these data support the hypothesis that manic symptoms derive not only from the stimulation of excitatory systems but also from inactivation or decreased activity of inhibitory mechanisms.
PMID: 25345734 [PubMed - as supplied by publisher]
Psychiatric factors do not affect recurrence risk of hyperemesis gravidarum.
J Obstet Gynaecol Res. 2014 Oct 27;
Authors: Magtira A, Paik Schoenberg F, MacGibbon K, Tabsh K, Fejzo MS
AIM: The aim of this study is to determine whether psychiatric symptoms affect recurrence risk of hyperemesis gravidarum (HG).
METHODS: The study sample included 108 women with HG treated with i.v. fluids in their first pregnancy. Women were divided into two groups based on recurrence of HG in their second pregnancy. Participants submitted medical records and completed a survey regarding pregnancy characteristics and psychiatric symptoms. The ?(2) -test and Student's t-test were performed to compare the two groups.
RESULTS: Eighty-four women (71%) had a recurrence of HG requiring i.v. fluid for dehydration, and were compared with 34 women (29%) who did not have a recurrence. There were no significant differences in obstetric history, although there was a trend toward greater time between first and second pregnancy in the recurrence group (P?=?0.08). There were no differences in pre-existing psychiatric diagnoses including anxiety, depression, bipolar disorder, panic or eating disorders. Following the first HG pregnancy, participants in both groups were well matched for all post-traumatic stress symptoms.
CONCLUSION: This study is the first to analyze the relationship of psychiatric factors to risk of recurrence of HG. No factors were identified that increase the risk of recurrence including stress symptoms following a HG pregnancy. Psychological sequelae associated with HG are probably a result of the physical symptoms of prolonged severe nausea and vomiting, medication and/or hospitalization, and likely play no role in disease etiology.
PMID: 25345812 [PubMed - as supplied by publisher]
A randomized controlled pilot trial of lithium in spinocerebellar ataxia type 2.
J Neurol. 2014 Oct 28;
Authors: Saccà F, Puorro G, Brunetti A, Capasso G, Cervo A, Cocozza S, de Leva M, Marsili A, Pane C, Quarantelli M, Russo CV, Trepiccione F, De Michele G, Filla A, Morra VB
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant disorder. Lithium is able to stimulate autophagy, and to reduce Ca(2+) efflux from the inositol-1,4,5-triphosphate receptor. We designed a phase II, randomized, placebo-controlled, double-blind, 48-week trial with lithium carbonate in 20 patients with SCA2. The primary objective was to determine safety and tolerability of lithium. The secondary objectives were to determine disease progression, quality of life, mood, and brain volume change. Sixteen patients completed the trial, 8 randomized to lithium, 8 to placebo. Forty adverse events (AEs) were reported during the trial, twenty-eight in the lithium and 12 in the placebo group (p = 0.11). Mean AE duration was 57.4 ± 60.8 and 77.4 ± 68.5 days (p = 0.37). Non-significant differences were observed for the SARA and for brain volume change, whereas a significant reduction in the BDI-II was observed for lithium group (p < 0.05). Lithium was well tolerated and reported AEs were similar to those previously described for bipolar disorder patients. A correctly powered phase III trial is needed to assess if lithium may slow disease progression in SCA2.
PMID: 25346067 [PubMed - as supplied by publisher]
A bold meta-analysis on suicidality in bipolar disorder.
Bipolar Disord. 2014 Oct 24;
Authors: Baethge C
PMID: 25346160 [PubMed - as supplied by publisher]
Identification of suicide risk in bipolar disorder.
Bipolar Disord. 2014 Oct 24;
Authors: Lopez-Castroman J, Courtet P, Baca-Garcia E, Oquendo MA
PMID: 25346206 [PubMed - as supplied by publisher]
Suicidal behaviour in bipolar disorder: understanding the role of affective states.
Bipolar Disord. 2014 Oct 24;
Authors: Saunders KE, Hawton K
PMID: 25346260 [PubMed - as supplied by publisher]
Clozapine for treatment-resistant bipolar disorder: a systematic review.
Bipolar Disord. 2014 Oct 27;
Authors: Li XB, Tang YL, Wang CY, de Leon J
OBJECTIVE: To evaluate the efficacy and safety of clozapine for treatment-resistant bipolar disorder (TRBD).
METHODS: A systematic review of randomized controlled studies, open-label prospective studies, and retrospective studies of patients with TRBD was carried out. Interventions included clozapine monotherapy or clozapine combined with other medications. Outcome measures were efficacy and adverse drug reactions (ADRs).
RESULTS: Fifteen clinical trials with a total sample of 1,044 patients met the inclusion criteria. Clozapine monotherapy or clozapine combined with other treatments for TRBD was associated with improvement in: (i) symptoms of mania, depression, rapid cycling, and psychotic symptoms, with many patients with TRBD achieving a remission or response; (ii) the number and duration of hospitalizations, the number of psychotropic co-medications, and the number of hospital visits for somatic reasons for intentional self-harm/overdose; (iii) suicidal ideation and aggressive behavior; and (iv) social functioning. In addition, patients with TRBD showed greater clinical improvement in long-term follow-up when compared with published schizophrenia data. Sedation (12%), constipation (5.0%), sialorrhea (5.2%), weight gain (4%), and body ache/pain (2%) were the commonly reported ADRs; however, these symptoms but did not usually require drug discontinuation. The percentage of severe ADRs reported, such as leukopenia (2%), agranulocytosis (0.3%), and seizure (0.5%), appeared to be lower than those reported in the published schizophrenia literature.
CONCLUSION: The limited current evidence supports the concept that clozapine may be both an effective and a relatively safe medication for TRBD.
PMID: 25346322 [PubMed - as supplied by publisher]
Randomized, controlled trial of Interpersonal and Social Rhythm Therapy for young people with bipolar disorder.
Bipolar Disord. 2014 Oct 24;
Authors: Inder ML, Crowe MT, Luty SE, Carter JD, Moor S, Frampton CM, Joyce PR
OBJECTIVE: This randomized, controlled clinical trial compared the effect of interpersonal and social rhythm therapy (IPSRT) to that of specialist supportive care (SSC) on depressive outcomes (primary), social functioning, and mania outcomes over 26-78 weeks in young people with bipolar disorder receiving psychopharmacological treatment.
METHODS: Subjects were aged 15-36 years, recruited from a range of sources, and the patient groups included bipolar I disorder, bipolar II disorder, and bipolar disorder not otherwise specified. Exclusion criteria were minimal. Outcome measures were the Longitudinal Interval Follow-up Evaluation and the Social Adjustment Scale. Paired-sample t-tests were used to determine the significance of change from baseline to outcome period. Analyses of covariance were used to determine the impact of therapy, impact of lifetime and current comorbidity, interaction between comorbidity and therapy, and impact of age at study entry on depression.
RESULTS: A group of 100 participants were randomized to IPSRT (n = 49) or SSC (n = 51). The majority had bipolar I disorder (78%) and were female (76%), with high levels of comorbidity. After treatment, both groups had improved depressive symptoms, social functioning, and manic symptoms. Contrary to our hypothesis, there was no significant difference between therapies. There was no impact of lifetime or current Axis I comorbidity or age at study entry. There was a relative impact of SSC for patients with current substance use disorder.
CONCLUSIONS: IPSRT and SSC used as an adjunct to pharmacotherapy appear to be effective in reducing depressive and manic symptoms and improving social functioning in adolescents and young adults with bipolar disorder and high rates of comorbidity. Identifying effective treatments that particularly address depressive symptoms is important in reducing the burden of bipolar disorder.
PMID: 25346391 [PubMed - as supplied by publisher]
Vitamin B12 level may be related to the efficacy of single ketamine infusion in bipolar depression.
Pharmacopsychiatry. 2013 Sep;46(6):227-8
Authors: Permoda-Osip A, Dorszewska J, Bartkowska-Sniatkowska A, Chlopocka-Wozniak M, Rybakowski JK
The single infusion of ketamine, an N-methyl-d-aspartic acid (NMDA) glutamate receptor antagonist, exerts a therapeutic effect in both unipolar and bipolar depression. Homocysteine (HCY) acts agonistically on the NMDA receptor, hyperhomocysteinemia is related to depression, and folic acid and vitamin B12 are associated with HCY system. We estimated the serum levels of these substances in 20 bipolar depressed patients before ketamine infusion. 10 patients responded favorably to this procedure, as their score on the Hamilton depression rating scale, compared to baseline, was reduced by more than 50%, after 7 days. The vitamin B12 level was significantly higher in "responders" compared to the remaining patients. No differences between the 2 groups were found with regard to HCY, folic acid levels and such clinical factors as age, duration of illness and duration of current episode. These preliminary data suggest that the vitamin B12 level may be connected with the efficacy of ketamine infusion in bipolar depression.
PMID: 23846402 [PubMed - indexed for MEDLINE]
A novel cognitive behaviour therapy for bipolar disorders (Think Effectively About Mood Swings or TEAMS): study protocol for a randomized controlled trial.
Trials. 2014 Oct 24;15(1):405
Authors: Mansell W, Tai S, Clark A, Akgonul S, Dunn G, Davies L, Law H, Morriss R, Tinning N, Morrison AP
BACKGROUND: Existing psychological therapies for bipolar disorders have been found to have mixed results, with a consensus that they provide a significant, but modest, effect on clinical outcomes. Typically, these approaches have focused on promoting strategies to prevent future relapse. An alternative treatment approach, termed 'Think Effectively About Mood Swings' (TEAMS) addresses current symptoms, including subclinical hypomania, depression and anxiety, and promotes long-term recovery. Following the publication of a theoretical model, a range of research studies testing the model and a case series have demonstrated positive results. The current study reports the protocol of a feasibility randomized controlled trial to inform a future multi-centre trial.
METHODS: A target number of 84 patients with a diagnosis of bipolar I or II disorder, or bipolar disorder not-otherwise-specified are screened, allocated to a baseline assessment and randomized to either 16 sessions of TEAMS therapy plus treatment-as-usual (TAU) or TAU. Patients complete self-report inventories of depression, anxiety, recovery status and bipolar cognitions targeted by TEAMS. Assessments of diagnosis, bipolar symptoms, medication, access to services and quality of life are conducted by assessors blind to treatment condition at 3, 6, 12 and 18 months post-randomization. The main aim is to evaluate recruitment and retention of participants into both arms of the study, as well as adherence to therapy, to determine feasibility and acceptability. It is predicted that TEAMS plus TAU will reduce self-reported depression in comparison to TAU alone at six months post-randomization. The secondary hypotheses are that TEAMS will reduce the severity of hypomanic symptoms and anxiety, reduce bipolar cognitions, improve social functioning and promote recovery compared to TAU alone at post-treatment and follow-up. The study also incorporates semi-structured interviews about the experiences of previous treatment and the experience of TEAMS therapy that will be subject to qualitative analyses to inform future developments of the approach.
DISCUSSION: The design will provide preliminary evidence of efficacy, feasibility, acceptability, uptake, attrition and barriers to treatment to design a definitive trial of this novel intervention compared to treatment as usual.Trial registration: This trial was registered with Current Controlled Trials (ISRCTN83928726) on registered 25 July 2014.
PMID: 25344393 [PubMed - as supplied by publisher]
Unreasonable adjustments: medical education, mental disorder, disability discrimination and public safety.
J Law Med. 2014 Sep;22(1):31-53
Authors: Parker M
Recently the Civil and Administrative Tribunal of New South Wales found that the, University of Newcastle had discriminated against a medical student with borderline personality disorder and bipolar disorder on the grounds of her disability. This column summarises the case, and integrates a psychodynamic account of borderline personality disorder with Fulford's conceptual analysis of mental disorder as action failure, that is no different in principle from physical illnesses, some instances of which appear to uncontroversially rule out of contention some applicants for medical training. It is argued that some applicants for medical and health care programs with mental disorders should not be selected, because their disabilities are not amenable to satisfactory accommodation in the university training period, and they are incompatible with clinical training and practice. Universities should develop "Inherent Requirement" policies that better integrate their responsibility to support disabled students with the responsibility, currently reserved entirely to regulators, to ensure safe practice by their graduates.
PMID: 25341318 [PubMed - in process]
Altered Functional Connectivity between Emotional and Cognitive Resting State Networks in Euthymic Bipolar I Disorder Patients.
PLoS One. 2014;9(10):e107829
Authors: Lois G, Linke J, Wessa M
Bipolar disorder is characterized by a functional imbalance between hyperactive ventral/limbic areas and hypoactive dorsal/cognitive brain regions potentially contributing to affective and cognitive symptoms. Resting-state studies in bipolar disorder have identified abnormal functional connectivity between these brain regions. However, most of these studies used a seed-based approach, thus restricting the number of regions that were analyzed. Using data-driven approaches, researchers identified resting state networks whose spatial maps overlap with frontolimbic areas such as the default mode network, the frontoparietal networks, the salient network, and the meso/paralimbic network. These networks are specifically engaged during affective and cognitive tasks and preliminary evidence suggests that functional connectivity within and between some of these networks is impaired in bipolar disorder. The present study used independent component analysis and functional network connectivity approaches to investigate functional connectivity within and between these resting state networks in bipolar disorder. We compared 30 euthymic bipolar I disorder patients and 35 age- and gender-matched healthy controls. Inter-network connectivity analysis revealed increased functional connectivity between the meso/paralimbic and the right frontoparietal network in bipolar disorder. This abnormal connectivity pattern did not correlate with variables related to the clinical course of the disease. The present finding may reflect abnormal integration of affective and cognitive information in ventral-emotional and dorsal-cognitive networks in euthymic bipolar patients. Furthermore, the results provide novel insights into the role of the meso/paralimbic network in bipolar disorder.
PMID: 25343370 [PubMed - as supplied by publisher]
Homocysteine levels in schizophrenia and affective disorders-focus on cognition.
Front Behav Neurosci. 2014;8:343
Authors: Moustafa AA, Hewedi DH, Eissa AM, Frydecka D, Misiak B
Although homocysteine (Hcy) has been widely implicated in the etiology of various physical health impairments, especially cardiovascular diseases, overwhelming evidence indicates that Hcy is also involved in the pathophysiology of schizophrenia and affective disorders. There are several mechanisms linking Hcy to biological underpinnings of psychiatric disorders. It has been found that Hcy interacts with NMDA receptors, initiates oxidative stress, induces apoptosis, triggers mitochondrial dysfunction and leads to vascular damage. Elevated Hcy levels might also contribute to cognitive impairment that is widely observed among patients with affective disorders and schizophrenia. Supplementation of vitamins B and folic acid has been proved to be effective in lowering Hcy levels. There are also studies showing that this supplementation strategy might be beneficial for schizophrenia patients with respect to alleviating negative symptoms. However, there are no studies addressing the influence of add-on therapies with folate and vitamins B on cognitive performance of patients with schizophrenia and affective disorders. In this article, we provide an overview of Hcy metabolism in psychiatric disorders focusing on cognitive correlates and indicating future directions and perspectives.
PMID: 25339876 [PubMed]
Adjunctive lisdexamfetamine in bipolar depression: a preliminary randomized, placebo-controlled trial.
Int Clin Psychopharmacol. 2014 Oct 21;
Authors: McElroy SL, Martens BE, Mori N, Blom TJ, Casuto LS, Hawkins JM, Keck PE
This study evaluated the efficacy and tolerability of lisdexamfetamine (LDX) in the treatment of bipolar depression. Twenty-five outpatients with bipolar I or II disorder and syndromal depression despite at least 4 weeks of stable mood stabilizer and/or antipsychotic therapy were randomized to receive LDX (N=11) or placebo (N=14) in an 8-week, prospective, parallel-group, double-blind study. In the primary longitudinal analysis, LDX and placebo produced similar rates of improvement in depressive symptoms as assessed by the Montgomery-Asberg Depression Scale. However, LDX was associated with a statistically significantly greater rate of improvement in self-reported depressive symptoms and daytime sleepiness, and with greater reductions in fasting levels of low-density lipoprotein and total cholesterol. In the secondary baseline-to-endpoint analysis, LDX was associated with statistically significant improvements in self-reported measures of depression, daytime sleepiness, fatigue, and binge eating, as well as with improvements in fasting levels of triglycerides and low-density lipoprotein and total cholesterol. LDX was well tolerated and was not associated with any serious adverse events, but there was one case of suspected misuse. The small sample size (because of premature study termination by the funding sponsor) may have limited the detection of important drug-placebo differences. Larger studies on the use of psychostimulants for treatment of bipolar depression seem warranted.
PMID: 25340384 [PubMed - as supplied by publisher]
Repeated positive fighting experience in male inbred mice.
Nat Protoc. 2014 Nov;9(11):2705-2717
Authors: Kudryavtseva NN, Smagin DA, Kovalenko IL, Vishnivetskaya GB
Repeated aggression is a frequent symptom of many psychiatric and neurological disorders, including obsessive-compulsive and attention deficit hyperactivity disorders, bipolar and post-traumatic stress disorders, epilepsy, autism, schizophrenia and drug abuse. However, repeated aggression is insufficiently studied because there is a lack of adequate models in animals. The sensory contact model (SCM), widely used to study the effects of chronic social defeat stress, can also be used to investigate the effects of repeated aggression. Mice with repeated positive fighting experience in daily agonistic interactions in this model develop pronounced aggressiveness, anxiety and impulsivity, disturbances in motivated and cognitive behaviors, and impairments of sociability; they also demonstrate hyperactivity, attention-deficit behavior, motor dysfunctions and repetitive stereotyped behaviors, such as jerks, rotations and head twitches. In this protocol, we describe how to apply the SCM to study repeated aggression in mice. Severe neuropathology develops in male mice after 20-21 d of agonistic interactions.
PMID: 25340443 [PubMed - as supplied by publisher]
SULT4A1 haplotype: conflicting results on its role as a biomarker of antipsychotic response.
Pharmacogenomics. 2014 Sep;15(12):1557-1564
Authors: Wang D, Li Q, Favis R, Jadwin A, Chung H, Fu DJ, Savitz A, Gopal S, Cohen N
Aim: Based on previous pharmacogenetic findings, we investigated the possible association between SULT4A1-1 haplotype and antipsychotic treatment response. Materials & methods: Using Mixed Model Repeated Measures, we tested the relationship between SULT4A1-1 status (+ carrier, - noncarrier) and clinical improvement (in Positive and Negative Syndrome Scale total score) among European ancestry patients treated with paliperidone extended release (n = 937), paliperidone palmitate (n = 990), risperidone (n = 507) and olanzapine (n = 381) in 12 schizophrenia, two schizoaffective disorder and three bipolar I disorder trials. SULT4A1-1 haplotype was determined using tagging SNP rs763120. Results: There was no significant difference between SULT4A1-1(+) and SULT4A1-1(-) patients for treatment response to paliperidone or olanzapine. SULT4A1-1(-) patients had better treatment response to risperidone in one schizophrenia trial, but not in another schizophrenia trial or bipolar mania trial. Conclusion: Across three psychiatric disorders (n = 2815 patients), we observed no consistent association between SULT4A1-1 status and atypical antipsychotic effect. Original submitted 11 February 2014; Revision submitted 2 July 2014.
PMID: 25340730 [PubMed - as supplied by publisher]
Violent victimization of adult patients with severe mental illness: a systematic review.
Neuropsychiatr Dis Treat. 2014;10:1925-39
Authors: Latalova K, Kamaradova D, Prasko J
The aims of this paper are to review data on the prevalence and correlates of violent victimization of persons with severe mental illness, to critically evaluate the literature, and to explore possible approaches for future research. PubMed/MEDLINE and PsycINFO databases were searched using several terms related to severe mental illness in successive combinations with terms describing victimization. The searches identified 34 studies. Nine epidemiological studies indicate that patients with severe mental illness are more likely to be violently victimized than other community members. Young age, comorbid substance use, and homelessness are risk factors for victimization. Victimized patients are more likely to engage in violent behavior than other members of the community. Violent victimization of persons with severe mental illness has long-term adverse consequences for the course of their illness, and further impairs the quality of lives of patients and their families. Victimization of persons with severe mental illness is a serious medical and social problem. Prevention and management of victimization should become a part of routine clinical care for patients with severe mental illness.
PMID: 25336958 [PubMed]
The association between prostate cancer and mood disorders: a nationwide population-based study in Taiwan.
Int Psychogeriatr. 2014 Oct 22;:1-10
Authors: Chen PM, Chen SC, Liu CJ, Hung MH, Tsai CF, Hu YW, Chen MH, Shen CC, Su TP, Yeh CM, Lu T, Chen TJ, Hu LY
ABSTRACT Background: This study identified possible risk factors for newly diagnosed mood disorders, including depressive and bipolar disorders, in prostate cancer patients. Methods: From 2000 to 2006, two cohorts were evaluated on the occurrence of mood disorder diagnosis and treatment. For the first cohort, data of patients diagnosed with prostate cancer was obtained from the Taiwan National Health Insurance (NHI) Research Database. As the second cohort, a cancer-free comparison group was matched for age, comorbidities, geographic region, and socioeconomic status. Results: Final analyses involved 12,872 men with prostate cancer and 12,872 matched patients. Increased incidence of both depressive (IRR 1.52, 95% CI 1.30-1.79, P <0.001) and bipolar disorder (IRR 1.84, 95% CI 1.25-2.74, P = 0.001) was observed among patients diagnosed with prostate cancer. Multivariate matched regression models show that cerebrovascular disease (CVD) and radiotherapy treatment could be independent risk factors for developing subsequent depressive and bipolar disorders. Conclusion: We observed that the risk of developing newly diagnosed depressive and bipolar disorders is higher among Taiwanese prostate cancer patients. Clinicians should be aware of the possibility of increased depressive and bipolar disorders among prostate cancer patients in Taiwan. A prospective study is necessary to confirm these findings.
PMID: 25335499 [PubMed - as supplied by publisher]
The rare DAT coding variant Val559 perturbs DA neuron function, changes behavior, and alters in vivo responses to psychostimulants.
Proc Natl Acad Sci U S A. 2014 Oct 20;
Authors: Mergy MA, Gowrishankar R, Gresch PJ, Gantz SC, Williams J, Davis GL, Wheeler CA, Stanwood GD, Hahn MK, Blakely RD
Despite the critical role of the presynaptic dopamine (DA) transporter (DAT, SLC6A3) in DA clearance and psychostimulant responses, evidence that DAT dysfunction supports risk for mental illness is indirect. Recently, we identified a rare, nonsynonymous Slc6a3 variant that produces the DAT substitution Ala559Val in two male siblings who share a diagnosis of attention-deficit hyperactivity disorder (ADHD), with other studies identifying the variant in subjects with bipolar disorder (BPD) and autism spectrum disorder (ASD). Previously, using transfected cell studies, we observed that although DAT Val559 displays normal total and surface DAT protein levels, and normal DA recognition and uptake, the variant transporter exhibits anomalous DA efflux (ADE) and lacks capacity for amphetamine (AMPH)-stimulated DA release. To pursue the significance of these findings in vivo, we engineered DAT Val559 knock-in mice, and here we demonstrate in this model the presence of elevated extracellular DA levels, altered somatodendritic and presynaptic D2 DA receptor (D2R) function, a blunted ability of DA terminals to support depolarization and AMPH-evoked DA release, and disruptions in basal and psychostimulant-evoked locomotor behavior. Together, our studies demonstrate an in vivo functional impact of the DAT Val559 variant, providing support for the ability of DAT dysfunction to impact risk for mental illness.
PMID: 25331903 [PubMed - as supplied by publisher]
Identification of Rare, Single-Nucleotide Mutations in NDE1 and Their Contributions to Schizophrenia Susceptibility.
Schizophr Bull. 2014 Oct 20;
Authors: Kimura H, Tsuboi D, Wang C, Kushima I, Koide T, Ikeda M, Iwayama Y, Toyota T, Yamamoto N, Kunimoto S, Nakamura Y, Yoshimi A, Banno M, Xing J, Takasaki Y, Yoshida M, Aleksic B, Uno Y, Okada T, Iidaka T, Inada T, Suzuki M, Ujike H, Kunugi H, Kato T, Yoshikawa T, Iwata N, Kaibuchi K, Ozaki N
Background: Nuclear distribution E homolog 1 (NDE1), located within chromosome 16p13.11, plays an essential role in microtubule organization, mitosis, and neuronal migration and has been suggested by several studies of rare copy number variants to be a promising schizophrenia (SCZ) candidate gene. Recently, increasing attention has been paid to rare single-nucleotide variants (SNVs) discovered by deep sequencing of candidate genes, because such SNVs may have large effect sizes and their functional analysis may clarify etiopathology. Methods and Results: We conducted mutation screening of NDE1 coding exons using 433 SCZ and 145 pervasive developmental disorders samples in order to identify rare single nucleotide variants with a minor allele frequency ?5%. We then performed genetic association analysis using a large number of unrelated individuals (3554 SCZ, 1041 bipolar disorder [BD], and 4746 controls). Among the discovered novel rare variants, we detected significant associations between SCZ and S214F (P = .039), and between BD and R234C (P = .032). Furthermore, functional assays showed that S214F affected axonal outgrowth and the interaction between NDE1 and YWHAE (14-3-3 epsilon; a neurodevelopmental regulator). Conclusions: This study strengthens the evidence for association between rare variants within NDE1 and SCZ, and may shed light into the molecular mechanisms underlying this severe psychiatric disorder.
PMID: 25332407 [PubMed - as supplied by publisher]
Naturally Occurring Peer Support through Social Media: The Experiences of Individuals with Severe Mental Illness Using YouTube.
PLoS One. 2014;9(10):e110171
Authors: Naslund JA, Grande SW, Aschbrenner KA, Elwyn G
Increasingly, people with diverse health conditions turn to social media to share their illness experiences or seek advice from others with similar health concerns. This unstructured medium may represent a platform on which individuals with severe mental illness naturally provide and receive peer support. Peer support includes a system of mutual giving and receiving where individuals with severe mental illness can offer hope, companionship, and encouragement to others facing similar challenges. In this study we explore the phenomenon of individuals with severe mental illness uploading videos to YouTube, and posting and responding to comments as a form of naturally occurring peer support. We also consider the potential risks and benefits of self-disclosure and interacting with others on YouTube. To address these questions, we used qualitative inquiry informed by emerging techniques in online ethnography. We analyzed n?=?3,044 comments posted to 19 videos uploaded by individuals who self-identified as having schizophrenia, schizoaffective disorder, or bipolar disorder. We found peer support across four themes: minimizing a sense of isolation and providing hope; finding support through peer exchange and reciprocity; sharing strategies for coping with day-to-day challenges of severe mental illness; and learning from shared experiences of medication use and seeking mental health care. These broad themes are consistent with accepted notions of peer support in severe mental illness as a voluntary process aimed at inclusion and mutual advancement through shared experience and developing a sense of community. Our data suggest that the lack of anonymity and associated risks of being identified as an individual with severe mental illness on YouTube seem to be overlooked by those who posted comments or uploaded videos. Whether or not this platform can provide benefits for a wider community of individuals with severe mental illness remains uncertain.
PMID: 25333470 [PubMed - as supplied by publisher]
Severe Rhabdomyolysis Induced Electrolyte Abnormalities Mimicking ST Elevation Myocardial Infarction.
Chest. 2014 Oct 1;146(4_MeetingAbstracts):115A
Authors: Patel R, Auraha N, Dyal H, Fernandez J, Nazneen W
SESSION TITLE: Cardiovascular Student/Resident Case Report Posters ISESSION TYPE: Medical Student/Resident Case ReportPRESENTED ON: Tuesday, October 28, 2014 at 01:30 PM - 02:30 PMINTRODUCTION: Rhabdomyolysis is characterized by expulsion of intracellular contents of striated muscle following direct insult to sarcoplasmic reticulum or exhaustion of myocyte ATP. This in turn causes electrolyte abnormalities including hypocalcemia and hyperkalemia which can produce EKG changes that rarely mimic an ST elevation myocardial infarction.CASE PRESENTATION: A 39 year old African-American male presented to the ED by EMS after being found down in his home for an unknown period of time. Prior to presentation, he had ingested 50 tablets of acetaminophen-hydrocodone in a suicide attempt. The gentleman had a history of bipolar disorder, schizoaffective disorder and previous suicide attempts by self-mutilation. On presentation, the patient was afebrile and hemodynamically stable, and orientated only to person and place. He did not complain of chest pain at any time during his hospitalization. Laboratory findings were significant for potassium of 7.0meq/L, calcium of 7.6mg/dL, aspartate aminotransferase of 13,347u/L, alanine aminotransferase of 5,309u/L, troponin of 1.4 ng/mL, CPK of 33,427u/L, INR of 1.94 and acetaminophen level of 37.9ug/mL. Troponin peaked at 15.93 and CPK peaked at 101,731 IU/L. Initial EKG showed left axis deviation, widened QRS interval, prolonged QTc of 540ms, flattened p waves, RBBB and ST segment elevation along V1-V3 and aVR (Figure 1). Stat transthoracic echocardiogram was performed which was negative for wall motion abnormalities or signs of ventricular dysfunction. Following immediate administration of N-acetyl cysteine, normal saline and calcium replacement, his hyperkalemia and hypocalcemia resolved. Subsequent EKGs taken following correction of electrolyte abnormalities showed resolution of EKG changes without q wave development (Figure 2).DISCUSSION: EKG changes due to electrolyte abnormalities are thought to be related to their effects on the cardiac myocyte action potential. Calcium primarily effects phase two of the action potential in cardiac contractile cells and phase one of pacemaker cells(1). Potassium will most commonly affect the repolarization phase of the SA node and cardiac contractile cell(1). Hypocalcemia may decrease the gradient to enter the cell resulting in prolongation of the plateau phase, leading to the potential for coronary vasospasm and elevated troponin(2). Hyperkalemia can result in prolonged periods of repolarization, manifested as a widened QRS interval as was seen in this patient's initial EKG(1).CONCLUSIONS: Anterior STEMI pattern by EKG and troponin elevation in this patient is most likely related to sequela of severe rhabdomyolysis.Reference #1: Grant, AO. Cardiac Ion Channels. Circ Arrhythm Electrophysiol.2009;2:185-194Reference #2: Lehmann, G, Deisenhofer, I, Ndrepepa, G, et al. ECG changes in a 25-year old woman with hypocalcemia due to hypoparathyroidism: hypocalcemia mimicking acute myocardial infarction. Chest. 2000;118:260-262DISCLOSURE: The following authors have nothing to disclose: Ruchir Patel, Nena Auraha, Herman Dyal, Juan Fernandez, Waheeda NazneenNo Product/Research Disclosure Information.
PMID: 25334111 [PubMed - as supplied by publisher]