Modeling bipolar disorder in mice by increasing acetylcholine or dopamine: chronic lithium treats most, but not all features.
Psychopharmacology (Berl). 2015 Jul 5;
Authors: van Enkhuizen J, Milienne-Petiot M, Geyer MA, Young JW
RATIONALE: Bipolar disorder (BD) is a disabling and life-threatening disease characterized by states of depression and mania. New and efficacious treatments have not been forthcoming partly due to a lack of well-validated models representing both facets of BD.
OBJECTIVES: We hypothesized that cholinergic- and dopaminergic-pharmacological manipulations would model depression and mania respectively, each attenuated by lithium treatment.
METHODS: C57BL/6 J mice received the acetylcholinesterase inhibitor physostigmine or saline before testing for "behavioral despair" (immobility) in the tail suspension test (TST) and forced swim test (FST). Physostigmine effects on exploration and sensorimotor gating were assessed using the cross-species behavioral pattern monitor (BPM) and prepulse inhibition (PPI) paradigms. Other C57BL/6 J mice received chronic lithium drinking water (300, 600, or 1200 mg/l) before assessing their effects alone in the BPM or with physostigmine on FST performance. Another group was tested with acute GBR12909 (dopamine transporter inhibitor) and chronic lithium (1000 mg/l) in the BPM.
RESULTS: Physostigmine (0.03 mg/kg) increased immobility in the TST and FST without affecting activity, exploration, or PPI. Lithium (600 mg/l) resulted in low therapeutic serum concentrations and normalized the physostigmine-increased immobility in the FST. GBR12909 induced mania-like behavior in the BPM of which hyper-exploration was attenuated, though not reversed, after chronic lithium (1000 mg/ml).
CONCLUSIONS: Increased cholinergic levels induced depression-like behavior and hyperdopaminergia induced mania-like behavior in mice, while chronic lithium treated some, but not all, facets of these effects. These data support a cholinergic-monoaminergic mechanism for modeling BD aspects and provide a way to assess novel therapeutics.
PMID: 26141192 [PubMed - as supplied by publisher]
Demonstrating the Role of Anticholinergic Activity in a Mood Disorder.
Neurodegener Dis. 2015;15(3):175-81
Authors: Hori K, Konishi K, Hanashi T, Tani M, Tomioka H, Kitajima Y, Akashi N, Inamoto A, Kurosawa K, Hasegawa S, Izuno T, Kikuchi N, Hosoi M, Hachisu M
We report a case of a 54-year-old woman presenting with amnesia, apathy, work-related difficulties and mental stress. At presentation, her Mini-Mental State Examination score was 27 and her serum anticholinergic activity (SAA) was positive without medication or recent physical illnesses. In addition, magnetic resonance imaging revealed mild atrophy of the frontal and temporal lobes, with a relatively intact hippocampus. Consequently, we diagnosed mild cognitive impairment due to Alzheimer's disease and prescribed a cholinesterase inhibitor (donepezil, 10 mg/day); her SAA fully disappeared and clinical symptoms partially resolved. Addition of duloxetine coupled with environmental adjustments caused her cognitive function to return to a normal level, so we diagnosed pseudodementia due to depression. In this case, we believe that the simultaneous cholinergic burden and mental stress led to positive SAA, which made it reasonable to prescribe a cholinesterase inhibitor to ameliorate the associated acetylcholine hypoactivity. We believe that it is essential to recognize the importance of prescribing a cholinesterase inhibitor for specific patients, even those with pseudodementia, to control their clinical symptoms. Moreover, SAA might be a useful biomarker for identifying this subgroup of patients. We propose that anticholinergic activity appears endogenously in mood disorders (depression and bipolar disorder) and set out our rationalization for this hypothesis. © 2015 S. Karger AG, Basel.
PMID: 26138496 [PubMed - in process]
Demographic and clinical factors associated with benzodiazepine prescription at discharge from psychiatric inpatient treatment.
Gen Hosp Psychiatry. 2015 Jun 10;
Authors: Peters SM, Knauf KQ, Derbidge CM, Kimmel R, Vannoy S
OBJECTIVE: We sought to characterize diagnostic and treatment factors associated with receiving a prescription for benzodiazepines at discharge from a psychiatric inpatient unit. We hypothesized that engaging in individual behavioral interventions while on the unit would decrease the likelihood of receiving a benzodiazepine prescription at discharge.
METHOD: This is an observational study utilizing medical chart review (n=1007) over 37 months (2008-2011). Descriptive statistics characterized patient demographics and diagnostic/prescription frequency. Multivariate regression was used to assess factors associated with receiving a benzodiazepine prescription at discharge.
RESULTS: The sample was 61% female with mean age=40.5 (S.D.=13.6). Most frequent diagnoses were depression (54.7%) and bipolar disorder (18.6%). Thirty-eight percent of participants engaged in an individual behavioral intervention. Benzodiazepines were prescribed in 36% of discharges. Contrary to our hypothesis, individual behavioral interventions did not influence discharge benzodiazepine prescriptions. However, several other factors did, including having a substance use disorder [odds ratio (OR)=0.40]. Male sex (OR=0.56), Black race (OR=0.40) and age (OR=1.03) were nonclinical factors with strong prescribing influence.
CONCLUSION: Benzodiazepines are frequently prescribed at discharge. Our results indicate strong racial and sex biases when prescribing benzodiazepines, even after controlling for diagnosis.
PMID: 26139289 [PubMed - as supplied by publisher]
What happens to episode duration and cycle length over the course of bipolar disorder?
Australas Psychiatry. 2015 Jul 2;
Authors: Subramanian K, Kattimani S, Rajkumar RP, Bharadwaj B, Sarkar S
OBJECTIVES: Published scientific literature on cycle acceleration over the course of bipolar disorder has been equivocal. The present analysis aimed to find whether episode duration and cycle lengths become shorter over the course of bipolar disorder with predominantly manic polarity.
METHODS: The present study comprised 150 patients diagnosed with bipolar I disorder using SCID-I for DSM-IV TR. The course of illness was charted according to the NIMH Life Chart Methodology - Clinician Retrospective Chart (NIMH - LCM CRC). Spearman correlation was used to assess the relationship of episode duration and cycle length with the number of episodes.
RESULTS: The mean age of the sample was 37.8 years and the average duration of illness was 13.4 years. Unipolar mania comprised 52.7% of the sample. The episode duration and the cycle length decreased with increasing number of episodes (r=-0.245, p<0.001 & r=-0.299, p<0.001 respectively).
CONCLUSION: The present study suggests that over the course of bipolar I disorder, cycle length and episode duration become shorter.
PMID: 26139697 [PubMed - as supplied by publisher]
Cognitive remediation: potential novel brain-based treatment for bipolar disorder in children and adolescents.
CNS Spectr. 2015 Jul 2;:1-9
Authors: Dickstein DP, Cushman GK, Kim KL, Weissman AB, Wegbreit E
Bipolar disorder (BD) is among the most impairing psychiatric disorders affecting children and adolescents, despite our best psychopharmacological and psychotherapeutic treatments. Cognitive remediation, defined as a behavioral intervention designed to improve cognitive functions so as to reduce psychiatric illness, is an emerging brain-based treatment approach that has thus far not been studied in pediatric BD. The present article reviews the basic principles of cognitive remediation, describes what is known about cognitive remediation in psychiatric disorders, and delineates potential brain/behavior alterations implicated in pediatric BD that might be targets for cognitive remediation. Emerging data show that cognitive remediation may be useful in children and adults with schizophrenia, ADHD, and anxiety disorders, and in adults with BD. Potential targets for cognitive remediation in pediatric BD include face processing, response inhibition, frustration, and cognitive flexibility. Further study is warranted to determine if cognitive remediation for these targets, or others, may serve as a novel, brain-based treatment for pediatric BD.
PMID: 26135596 [PubMed - as supplied by publisher]
Executive function and suicidality: A systematic qualitative review.
Clin Psychol Rev. 2015 Jun 20;40:170-183
Authors: Bredemeier K, Miller IW
Deficits in executive function (EF) have been proposed as a possible explanation for the "cognitive rigidity" often observed in suicidal individuals. This article provides a systematic review of the existing literature testing the relations between EF and suicidality, across various diagnostic and demographic populations, using the influential multidimensional model of EF proposed by Miyake and colleagues (2000) as an organizing framework. Forty-three journal articles on this topic published before January of 2014 were reviewed. Collectively, results from these studies provide tentative support for an association between EF deficits and suicidality. However, there is some evidence that this association is moderated by other factors (e.g., suicide attempt lethality). Importantly, this relationship may vary across diagnostic groups. Specifically, more studies that used depressive disorder samples reported some positive findings (75%), followed by mixed diagnostic samples (54%). In contrast, fewer positive findings have emerged from studies with bipolar or psychotic disorder samples (29% and 33% respectively), and some even found that suicidality is associated with better EF in individuals with psychotic disorders. Firm conclusions about relationships between specific dimensions of EF and/or aspects of suicidality are difficult to draw this time. Limitations of the existing literature and corresponding directions for future research are discussed.
PMID: 26135816 [PubMed - as supplied by publisher]
Diversity and plasticity of microglial cells in psychiatric and neurological disorders.
Pharmacol Ther. 2015 Jun 27;
Authors: Nakagawa Y, Chiba K
Recent advanced immunological analyses have revealed that the diversity and plasticity of macrophages lead to the identification of functional polarization states (classically activated M1 type and alternatively activated M2 type) which are dependent on the extracellular environment. ?M1 and M2 polarization states of macrophages play an important role in controlling the balance between pro-inflammatory and anti-inflammatory conditions. Microglial cells are resident mononuclear phagocytes in the central nervous system (CNS), express several macrophage-associated markers, and appear to display functional polarization states similar to macrophages. Like M1 macrophages, M1 polarized microglia can produce pro-inflammatory cytokines and mediators such as interleukin (IL) 1?, IL-6, tumor necrosis factor-?, CC-chemokine ligand 2, nitric oxide, and reactive oxygen species, suggesting that these molecules contribute to dysfunction of neural network in the CNS. On the other hand, M2 polarized microglia can produce anti-inflammatory cytokine, IL-10 and express several receptors that are implicated in inhibiting inflammation and restoring homeostasis. In this review, we summarize the diversity, plasticity, and immunoregulatory functions of M1 and M2 microglia in psychiatric and neurological disorders. Based on these aspects, we propose a contribution of imbalance between M1 and M2 polarization of microglia in bipolar disorder, obesity, amyotrophic lateral sclerosis, and Rett syndrome. Consequently, molecules that normalize the imbalance between M1 and M2 microglial polarization states may provide a beneficial therapeutic target for the treatment of these disorders.
PMID: 26129625 [PubMed - as supplied by publisher]
A Comparison of Bipolar Electrocautery and Chemical Cautery for Control of Pediatric Recurrent Anterior Epistaxis.
Otolaryngol Head Neck Surg. 2015 Jun 30;
Authors: Johnson N, Faria J, Behar P
OBJECTIVE: To compare the outcome of children with anterior epistaxis treated intraoperatively with either bipolar electrocautery or silver nitrate chemical cautery.
STUDY DESIGN: Case series with chart review.
SETTING: Tertiary-care pediatric otolaryngology practice.
SUBJECTS: Children aged 2 to 18 years treated with either intraoperative bipolar electrocautery or silver nitrate chemical cautery of the anterior nasal septum for recurrent anterior epistaxis.
METHODS: Any reported bleeding event after surgery was recorded. The mean time from surgery to recurrent epistaxis was compared between groups.
RESULTS: Fifty patients underwent bipolar electrocautery, while 60 patients underwent silver nitrate chemical cautery. Within 2 years, 1 (2%) patient in the bipolar electrocautery group and 13 (22%) patients in the silver nitrate chemical cautery group had recurrent epistaxis (P = .003). Two years after treatment, there was no difference between treatment groups. Overall, 4 patients (8%) had recurrent epistaxis postoperatively in the bipolar electrocautery group at a mean of 4.34 years after treatment, while 17 (28.3%) patients recurred after a mean of 1.53 years of treatment in the silver nitrate chemical cautery group (P = .01).
CONCLUSION: Compared to those treated with chemical cautery, those treated with bipolar electrocautery had a longer nosebleed-free period and a lower incidence of recurrent epistaxis within 2 years of treatment. Beyond 2 years, the treatment methods are equivocal. Bipolar electrocautery may be a superior treatment in children who will not tolerate in-office chemical cautery, in those with a risk of severe bleeding, or when it can be combined with other operative procedures.
PMID: 26129737 [PubMed - as supplied by publisher]
THE AMERICAN SOCIETY OF CLINICAL PSYCHOPHARMACOLOGY SURVEY OF PSYCHOPHARMACOLOGISTS' PRACTICE PATTERNS FOR THE TREATMENT OF MOOD DISORDERS.
Depress Anxiety. 2015 Jun 30;
Authors: Goldberg JF, Freeman MP, Balon R, Citrome L, Thase ME, Kane JM, Fava M
BACKGROUND: Optimal successive treatment decisions are not well established after an initial medication nonresponse in major depressive disorder or bipolar disorder. While practice guidelines offer consensus-based expert treatment recommendations, little is known about "real world" pharmacology decision making by practicing psychopharmacologists.
MATERIALS AND METHODS: We surveyed via Internet the national membership of the American Society of Clinical Psychopharmacology (ASCP) to study preferred pharmacotherapy strategies and factors that influence medication choices for patients with mood disorders.
RESULTS: Surveys were returned by 154/752 ASCP members (21%). After nonresponse to a serotonin reuptake inhibitor in major depressive disorder, participants equally favored switching within or across antidepressant classes. After a partial response, adjunctive bupropion was the preferred intervention, followed by changing antidepressant classes. Atypical antipsychotic augmentation was only a fourth-line consideration, even though moderate or marked efficacy was perceived in most instances with olanzapine, aripiprazole, and quetiapine. Respondents favored avoiding antidepressants in bipolar I patients with mixed/cycling features or prior antidepressant-associated mania/hypomania. In rapid cyclers, they advocated antidepressant cessation and preferred the use of atypical antipsychotics and lamotrigine.
CONCLUSIONS: Participating psychopharmacologists treating adults with mood disorders report prescribing medications that largely mirror the evidence base with only a few notable exceptions, in consideration of the characteristics of definable clinical subpopulations.
PMID: 26129956 [PubMed - as supplied by publisher]
The Long and Winding Road to Bipolar Disorder.
Am J Psychiatry. 2015 Jul 1;172(7):599-600
Authors: Miklowitz DJ
PMID: 26130197 [PubMed - in process]
Gluten-Free Diet Regimens and Psychiatric Symptoms.
Am J Psychiatry. 2015 Jul 1;172(7):685-6
Authors: Dell'Osso B, Elli L
PMID: 26130204 [PubMed - in process]
CNVs in neuropsychiatric disorders.
Hum Mol Genet. 2015 Jun 30;
Authors: Kirov G
Over the last few years at least 11 copy number variations (CNVs) have been shown convincingly to increase risk to developing schizophrenia: deletions at 1q21.1, NRXN1, 3q29, 15q11.2, 15q13.3 and 22q11.2, and duplications at 1q21.1, 7q11.23, 15q11.2-q13.1, 16p13.1 and proximal 16p11.2. They are very rare, found cumulatively in 2.4% of patients with schizophrenia and in only 0.5% of controls. They all increase risk for other neurodevelopmental disorders, such as developmental delay and autism spectrum disorders, where they are found at higher rates (3.3%). Their involvement in bipolar affective disorder is much less prominent. All of them affect multiple genes (apart from NRXN1) and cause substantial increases in risk to develop schizophrenia (odds ratios of 2 to over 50). Their penetrance for any neurodevelopmental disorder is high, from ?10% to nearly 100%. Carriers of these CNVs display cognitive deficits, even when free of neuropsychiatric disorders.
PMID: 26130694 [PubMed - as supplied by publisher]
Maintaining the initial clinical response after ketamine in bipolar and unipolar depression: an important next-step challenge.
J Clin Psychiatry. 2015 Jun;76(6):738-740
Authors: Iosifescu DV
In the treatment of bipolar disorder, the manic phase has received the most attention from the pharmaceutical industry. However, it is actually the bipolar depressed phase that has the largest impact on public health due to the proportion of time spent depressed and the associated disability. The bipolar depressive episodes are also the most lethal phase of the disorder, associated with the majority of lifetime suicide attempts, which occur in 25%-56% of patients, and deaths by suicide, which occur in 10%-19%.
PMID: 26132676 [PubMed - as supplied by publisher]
Setting the stage for success or failure: making an accurate diagnosis of bipolar depression.
J Clin Psychiatry. 2015 Jun;76(6):e17
Authors: Nasrallah HA
A diagnosis of bipolar disorder is difficult to make when a depressed patient can provide no evidence of having experienced mania or hypomania, either because the elevated mood states are not recognized as periods of illness or because depression is the initial episode and the patient has yet to experience the other polarity of the disorder. In these instances, clinicians can investigate other signs and symptoms that may indicate bipolar disorder, including family history, onset, irritability, hypersomnia, weight gain, and comorbid anxiety or substance abuse, among others. A patient with depression who exhibits any of these characteristics cannot be definitively diagnosed with bipolar depression, but these signs should indicate to the clinician that bipolarity is a possibility and further investigation is warranted.
PMID: 26132679 [PubMed - as supplied by publisher]
Prosodic and semantic affect perception in remitted patients with bipolar I disorder.
J Clin Psychiatry. 2015 Jun;76(6):e779-e786
Authors: Hoertnagl CM, Biedermann F, Yalcin-Siedentopf N, Muehlbacher M, Rauch AS, Baumgartner S, Kaufmann A, Kemmler G, Deisenhammer EA, Hausmann A, Hofer A
OBJECTIVE: Bipolar disorder is associated with impairments in emotion processing that are present during both mood episodes and periods of remission. In this context, most previous studies have investigated facial emotion recognition abilities. In contrast, the current study focused on the perception of prosodic and semantic affect.
METHOD: The present study directly contrasted the perception of prosodic and semantic affect in 58 remitted patients meeting DSM-IV criteria for bipolar I disorder and 45 healthy volunteers by using 2 subtests of the Comprehensive Affective Testing System (CATS) and investigated the relationship of prosodic and semantic affect perception with patients' outcomes. Participants were investigated from June 2011 until May 2013.
RESULTS: Patients and controls did not differ regarding the recognition of the vocal emotion while ignoring the affective meaning of test trials (CATS 1), but patients significantly more often misinterpreted sad as happy prosody (P = .039). In addition, patients were impaired in recognizing the affective meaning of test trials while ignoring the vocal emotion (CATS 2; P = .052). Again, they significantly more often misinterpreted a sad affective meaning as a happy one (P = .025). However, the findings on misinterpretations did not withstand Bonferroni correction for multiple testing. CATS 1 test performance was negatively correlated with depression scores, whereas a positive association was found between performance on both tests and patients' functioning. Patients indicated a significantly lower quality of life (P < .001); however, multiple mediation analysis revealed that this finding was not mediated by differences in prosodic and/or semantic affect perception between the 2 groups.
CONCLUSIONS: Even during periods of remission, patients with bipolar disorder may be impaired in semantic but not prosodic affect perception. Notably, they may frequently misinterpret sadly expressed emotions as happy ones. Our findings underscore the relevance of these deficits in the psychosocial context.
PMID: 26132686 [PubMed - as supplied by publisher]
Clinical risk factors for weight gain during psychopharmacologic treatment of depression: results from 2 large German observational studies.
J Clin Psychiatry. 2015 Jun;76(6):e802-e808
Authors: Kloiber S, Domschke K, Ising M, Arolt V, Baune BT, Holsboer F, Lucae S
OBJECTIVE: Weight gain during psychopharmacologic treatment has considerable impact on the clinical management of depression, treatment continuation, and risk for metabolic disorders. As no profound clinical risk factors have been identified so far, the aim of our analyses was to determine clinical risk factors associated with short-term weight development in 2 large observational psychopharmacologic treatment studies for major depression.
METHOD: Clinical variables at baseline (age, gender, depression psychopathology, anthropometry, disease history, and disease entity) were analyzed for association with percent change in body mass index (BMI; normal range, 18.5 to 25 kg/m(2)) during 5 weeks of naturalistic psychopharmacologic treatment in patients who had a depressive episode as single depressive episode, in the course of recurrent unipolar depression or bipolar disorder according to DSM-IV criteria. 703 patients participated in the Munich Antidepressant Response Signature (MARS) project, an ongoing study since 2002, and 214 patients participated in a study conducted at the University of Muenster from 2004 to 2006 in Germany.
RESULTS: Lower BMI, weight-increasing side effects of medication, severity of depression, and psychotic symptoms could be identified as clinical risk factors associated with elevated weight gain during the initial treatment phase of 5 weeks in both studies. Based on these results, a composite risk score for weight gain consisting of BMI ? 25 kg/m(2), Hamilton Depression Rating Scale (17-item) score > 20, presence of psychotic symptoms, and administration of psychopharmacologic medication with potential weight-gaining side effects was highly discriminative for mean weight gain (F4,909 = 26.77, P = 5.14E-21) during short-term psychopharmacologic treatment.
CONCLUSIONS: On the basis of our results, depressed patients with low to normal BMI, severe depression, or psychotic symptoms should be considered at higher risk for weight gain during acute antidepressant treatment. We introduce a new risk score that might be considered in psychopharmacologic decisions for the prevention of weight gain and resulting metabolic disorders.
PMID: 26132689 [PubMed - as supplied by publisher]
Functional versus syndromal recovery in patients with major depressive disorder and bipolar disorder.
J Clin Psychiatry. 2015 Jun;76(6):e809-e814
Authors: van der Voort TY, Seldenrijk A, van Meijel B, Goossens PJ, Beekman AT, Penninx BW, Kupka RW
OBJECTIVE: Many patients with major depressive disorder (MDD) or bipolar disorder (BD) experience impairments in daily life. We investigated whether patients with single-episode MDD (MDD-s), recurrent MDD (MDD-r), and BD differ in functional impairments, whether time since last episode (syndromal state, in 4 categories) contributes to impairment, whether this association is moderated by diagnosis, and the role of depressive symptoms.
METHOD: Data were derived from 1,664 participants in the Netherlands Study of Depression and Anxiety (MDD-s, n = 483; MDD-r, n = 1,063; BD, n = 118), from 2006 into 2009. In additional analyses, 530 healthy controls were included. DSM-IV-TR diagnosis and information about syndromal state were based on the Composite International Diagnostic Interview. Psychosocial impairment was assessed with the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). Adjusted associations between diagnosis, syndromal state, impairment, and depression severity were investigated.
RESULTS: Syndromal state not being taken into account, patients with BD experienced more functional impairment than patients with MDD-s or with MDD-r, and in all diagnostic groups, impairments decreased with increasing time since last episode. However, impact of syndromal state on functioning showed a different course between diagnostic groups (mean [SD] WHODAS score: current: MDD-s 30.8 [2.8], MDD-r 32.7 [0.9], BD 37.7 [2.1], P = .07; recently remitted: MDD-s 21.7 [3.5], MDD-r 24.0 [1.2], BD 22.1[3.2], P = .7; remitted: MDD-s 10.6 [3.7], MDD-r 21.6 [1.4], BD 19.2 [4.4], P = .02; remitted > 1 year: MDD-s 13.3 [0.6], MDD-r 14.7 [0.5], BD 17.1 [2.2], P = .8). Depression severity accounted for these differences. Moreover, functioning in all remitted patients remained impaired when compared to that in healthy controls.
CONCLUSION: Functional recovery may take up to 1 year after syndromal remission in recurrent depressive and bipolar disorder, mainly due to residual depressive symptoms, emphasizing the need for prolonged continuation treatment.
PMID: 26132690 [PubMed - as supplied by publisher]
Distinguishing functional from syndromal recovery: implications for clinical care and research.
J Clin Psychiatry. 2015 Jun;76(6):e832-e834
Authors: Rush AJ
The report by van der Voort and colleagues provides persuasive evidence that both major depressive and bipolar disorders are associated with substantial functional impairment not only during but also following the end of syndromal episodes. Some reports have suggested that most depressed patients have full functional recovery once they achieve symptomatic remission; others are less certain. The present report is based on a sample of patients larger and far more representative than samples of subjects selected for clinical trials.
PMID: 26132699 [PubMed - as supplied by publisher]
Dose-Dependent effect of lithium on cognition in mild cognitive impairment.
J Clin Psychiatry. 2015 Jun;76(6):e835
Authors: Lozano R, Marín R, Santacruz MJ
To the Editor: Miskowiak et al showed that recombinant human erythropoietin (rhEPO) has the potential to treat cognitive dysfunction in bipolar disorder patients. Specifically, they found that rhEPO enhanced both sustained attention and speed of complex information processing across learning, attention, and executive function in bipolar disorder patients with moderate to severe cognitive problems. However, an important potential confound was not considered: patients were allowed to continue taking antidepressant or mood-stabilizing drugs.
PMID: 26132700 [PubMed - as supplied by publisher]
Dr Miskowiak and colleagues reply.
J Clin Psychiatry. 2015 Jun;76(6):e835-e836
Authors: Miskowiak KW, Ehrenreich H, Kessing LV, Vinberg M
To the Editor: We thank Dr Lozano and colleagues for their comments on our study "Recombinant Human Erythropoietin to Target Cognitive Dysfunction in Bipolar Disorder: A Double-Blind, Randomized, Placebo-Controlled Phase 2 Trial," which give us the opportunity to address some conceptually important points regarding the effects of erythropoietin (EPO) on cognition. Lozano et al note that it is a potential confound that patients remained on their mood-stabilizing treatment including lithium for the duration of the study for 2 reasons: first, lithium has dose-dependent procognitive effects in patients with amnestic mild cognitive impairment in doses from 150 mg to 600 mg but harmful effects on cognition at doses ? 1 g; second, lithium and EPO may activate similar signaling pathways and thus exert synergistic actions on neuroplasticity. Lozano et al point out that the EPO-associated improvement of cognition could have therefore been influenced by patients' lithium treatment during or prior to the study and request (1) explicit data regarding lithium exposure for each study group and (2) analysis of whether EPO and lithium have independent cognitive effects, or whether the beneficial effects attributed to EPO could be partially due to lithium or an interaction between EPO and lithium.
PMID: 26132701 [PubMed - as supplied by publisher]
Bipolar spectrum disorders in a clinical sample of patients with Internet addiction: Hidden comorbidity or differential diagnosis?
J Behav Addict. 2015 Jun;4(2):101-105
Authors: Wölfling K, Beutel ME, Dreier M, Müller KW
Background and aims Behavioral addictions and bipolar disorders have a certain probability of co-occurrence. While the presence of a manic episode has been defined as an exclusion criterion for gambling disorder, no such exclusion has been formulated for Internet addiction. Methods A clinical sample of 368 treatment seekers presenting with excessive to addictive Internet use was screened for bipolar spectrum disorders using the Mood Disorder Questionnaire. Psychopathology was assessed by the Symptom Checklist 90R and a clinical interview was administered to screen for comorbid disorders. Results Comorbid bipolar disorders were more frequent in patients meeting criteria for Internet addiction (30.9%) than among the excessive users (5.6%). This subgroup showed heightened psychopathological symptoms, including substance use disorders, affective disorders and personality disorders. Further differences were found regarding frequency of Internet use regarding social networking sites and online-pornography. Discussion Patients with Internet addiction have a heightened probability for meeting criteria of bipolar disorders. It is not possible to draw conclusions regarding the direction of this association but it is recommended to implement screening for bipolar disorders in patients presenting with Internet addiction. Conclusion Similar to gambling disorder, it might prove necessary to subsume bipolar disorders as an exclusion criterion for the future criteria of Internet addiction.
PMID: 26132914 [PubMed - as supplied by publisher]
Mind over matter? The role of individual perceptions in understanding the social ecology of housing environments for individuals with psychiatric disabilities.
Am J Community Psychol. 2014 Dec;54(3-4):205-18
Authors: Townley G, Kloos B
There is a disagreement in place-based research regarding whether objective indicators or individual perceptions of environments are better predictors of well-being. This study assessed environmental influences on well-being for 373 individuals with psychiatric disabilities living independently in 66 neighborhoods in the southeastern United States. Three questions were examined utilizing random effects models: (1) How much variance in personal and neighborhood well-being can be explained by neighborhood membership? (2) What is the relationship between participant perceptions of neighborhood quality and researcher ratings of neighborhood quality? and (3) What is the relative influence of individual perceptions, perceptions aggregated by neighborhood, and researcher ratings of neighborhood quality in predicting personal and neighborhood well-being? Results indicate that individual perceptions of neighborhood quality were more closely related to well-being than either aggregated perceptions or researcher ratings. Thus, participants' perceptions of their neighborhoods were more important indicators of their well-being than objective ratings made by researchers. Findings have implications for measurement approaches and intervention design in placed-based research.
PMID: 24917220 [PubMed - indexed for MEDLINE]
Lithium-induced differential expression of SAT1 in suicide completers and controls is not correlated with polymorphisms in the promoter region of the gene.
Psychiatry Res. 2014 Dec 30;220(3):1167-8
Authors: Niola P, Gross JA, Lopez JP, Chillotti C, Deiana V, Manchia M, Georgitsi M, Patrinos GP, Alda M, Turecki G, Del Zompo M, Squassina A
PMID: 25288042 [PubMed - indexed for MEDLINE]
Polygenic dissection of major depression clinical heterogeneity.
Mol Psychiatry. 2015 Jun 30;
Authors: Milaneschi Y, Lamers F, Peyrot WJ, Abdellaoui A, Willemsen G, Hottenga JJ, Jansen R, Mbarek H, Dehghan A, Lu C, CHARGE inflammation working group, Boomsma DI, Penninx BW
The molecular mechanisms underlying major depressive disorder (MDD) are largely unknown. Limited success of previous genetics studies may be attributable to heterogeneity of MDD, aggregating biologically different subtypes. We examined the polygenic features of MDD and two common clinical subtypes (typical and atypical) defined by symptom profiles in a large sample of adults with established diagnoses. Data were from 1530 patients of the Netherlands Study of Depression and Anxiety (NESDA) and 1700 controls mainly from the Netherlands Twin Register (NTR). Diagnoses of MDD and its subtypes were based on DSM-IV symptoms. Genetic overlap of MDD and subtypes with psychiatric (MDD, bipolar disorder, schizophrenia) and metabolic (body mass index (BMI), C-reactive protein, triglycerides) traits was evaluated via genomic profile risk scores (GPRS) generated from meta-analysis results of large international consortia. Single nucleotide polymorphism (SNP)-heritability of MDD and subtypes was also estimated. MDD was associated with psychiatric GPRS, while no association was found for GPRS of metabolic traits. MDD subtypes had differential polygenic signatures: typical was strongly associated with schizophrenia GPRS (odds ratio (OR)=1.54, P=7.8e-9), while atypical was additionally associated with BMI (OR=1.29, P=2.7e-4) and triglycerides (OR=1.21, P=0.006) GPRS. Similar results were found when only the highly discriminatory symptoms of appetite/weight were used to define subtypes. SNP-heritability was 32% for MDD, 38% and 43% for subtypes with, respectively, decreased (typical) and increased (atypical) appetite/weight. In conclusion, MDD subtypes are characterized by partially distinct polygenic liabilities and may represent more homogeneous phenotypes. Disentangling MDD heterogeneity may help the psychiatric field moving forward in the search for molecular roots of depression.Molecular Psychiatry advance online publication, 30 June 2015; doi:10.1038/mp.2015.86.
PMID: 26122587 [PubMed - as supplied by publisher]
Expanding care for perinatal women with depression (EXPONATE): study protocol for a randomized controlled trial of an intervention package for perinatal depression in primary care.
BMC Psychiatry. 2015;15:136
Authors: Gureje O, Oladeji BD, Araya R, Montgomery AA, Kola L, Kirmayer L, Zelkowitz P, Groleau D
BACKGROUND: Depression is common among women during perinatal period and is associated with long-term adverse consequences for the mother and infant. In Nigeria, as in many other low- and-middle-income countries (LMIC), perinatal depression usually goes unrecognized and untreated. The aim of EXPONATE is to test the effectiveness and cost-effectiveness of an intervention package for perinatal depression delivered by community midwives in primary maternal care in which physician support and enhanced patient compliance are implemented using mobile phones.
METHODS/STUDY DESIGN: A pragmatic two-arm parallel cluster randomized controlled trial was designed. The units of allocation are the primary maternal care clinics. Thirty eligible and consenting clinics were randomized but, due to problems with logistics, 29 eventually participated. Consenting pregnant women with a gestational age between 16 and 28 weeks who screened positive on the Edinburgh Postnatal Depression Scale (EPDS score ?12), absent psychosis or bipolar disorder, and not actively suicidal were recruited into the trial (N?=?686). Midwives in the intervention arm were trained to deliver psychoeducation, problem solving treatment, and parenting skills. Eight weekly sessions were delivered following entry into the study. Further sessions during pregnancy and 6 weeks following childbirth were determined by level of depressive symptoms. Clinical support and supervision, delivered mainly by mobile phone, were provided by general physicians and psychiatrists. Automated text and voice messages, also delivered by mobile phones, were used to facilitate patient compliance with clinic appointments and 'homework' tasks. Patients in the control arm received care as usual enhanced by further training of the providers in that arm in the recognition and standard treatment of depression. Assessments are undertaken at baseline, 2 months following recruitment into the study and 3, 6, 9 and 12 months after childbirth. The primary outcome is recovery from depression (EPDS?<?6) at 6 months. Secondary outcomes include measures of disability, parenting skills, maternal attitudes, health care utilization as well as infant physical and cognitive development comprehensively assessed using the Bayley's Scales.
DISCUSSION: To the best of our knowledge, this is the largest randomized controlled trial of an intervention package delivered by community midwives in sub-Saharan Africa.
TRIAL REGISTRATION: Trial is registered with the ISRTCN registry at isrtcn.com; Trial number ISRCTN60041127 . Date of registration is 15/05/2013.
PMID: 26122982 [PubMed - in process]
A voxel-based morphometry study of gray matter correlates of facial emotion recognition in bipolar disorder.
Psychiatry Res. 2015 May 27;
Authors: Neves MC, Albuquerque MR, Malloy-Diniz L, Nicolato R, Silva Neves F, de Souza-Duran FL, Busatto G, Corrêa H
Facial emotion recognition (FER) is one of the many cognitive deficits reported in bipolar disorder (BD) patients. The aim of this study was to investigate neuroanatomical correlates of FER impairments in BD type I (BD-I). Participants comprised 21 euthymic BD-I patients without Axis I DSM IV-TR comorbidities and 21 healthy controls who were assessed using magnetic resonance imaging and the Penn Emotion Recognition Test (ER40). Preprocessing of images used DARTEL (diffeomorphic anatomical registration through exponentiated Lie algebra) for optimized voxel-based morphometry in SPM8. Compared with healthy subjects, BD-I patients performed poorly in on the ER40 and had reduced gray matter volume (GMV) in the left orbitofrontal cortex, superior portion of the temporal pole and insula. In the BD-I group, the statistical maps indicated a direct correlation between FER on the ER40 and right middle cingulate gyrus GMV. Our findings are consistent with the previous studies regarding the overlap of multiple brain networks of social cognition and BD neurobiology, particularly components of the anterior-limbic neural network.
PMID: 26123449 [PubMed - as supplied by publisher]
Alterations in hippocampal connectivity across the psychosis dimension.
Psychiatry Res. 2015 Jun 16;
Authors: Samudra N, Ivleva EI, Hubbard NA, Rypma B, Sweeney JA, Clementz BA, Keshavan MS, Pearlson GD, Tamminga CA
Recent evidence demonstrates that hippocampal hyperactivity helps mediate psychosis. Using resting state functional magnetic resonance imaging (rsfMRI), we examined hippocampal connectivity alterations in individuals with psychosis (PS) versus healthy controls (HC). Because of its putative greater involvement in psychiatric disorders, we hypothesized that the anterior hippocampus network would show greater dysconnectivity in psychosis. We tested rsfMRI connectivity in 88 PS (including 21 with schizophrenia; 40 with schizoaffective disorder; 27 with psychotic bipolar I disorder) and 65 HC. Seed-based voxel-wise connectivity analyses were carried out using whole, anterior, and posterior hippocampal seeds. No significant differences in functional hippocampal connectivity were found across the three conventional diagnoses. PS were then contrasted with HC, showing strong reductions in anterior hippocampal connectivity to anterior neocortical regions, including medial frontal and anterior cingulate cortices, as well as superior temporal gyrus, precuneus, thalamus and cerebellum. Posterior hippocampal seeds also demonstrated decreased connectivity in PS, with fewer dysconnected regions and a posterior/cerebellar distribution. Whole hippocampal outcomes were consistent with anterior/posterior hippocampal connectivity changes. Connectivity alterations did not correlate with cognition, clinical symptoms, or medication effect variables. Our results suggest a psychosis network of decreased hippocampal connectivity with limbic and frontal contributions, independent of diagnostic categories.
PMID: 26123450 [PubMed - as supplied by publisher]
Pseudologia fantastica: forensic and clinical treatment implications.
Compr Psychiatry. 2015 Jan;56:17-20
Authors: Korenis P, Gonzalez L, Kadriu B, Tyagi A, Udolisa A
Pseudologia fantastica, also known as mythomania, or pathological lying, is a psychiatric phenomenon that is a mixture of fact and fiction involving fantasized events and self aggrandizing personal roles. It has been recognized in the field for over a century. In this case report we discuss three different cases, two of them presented in the acute inpatient setting and one outpatient setting. All three presented with the common theme of extensive and 'pathological lying' in a manner that was notably very destructive to them and posing significant challenges to the treatment team. In an attempt to shed light into some of the clinical and legal/forensic challenges it creates when faced in the clinical settings, we also raise the need for a better definition and classification of this symptom in the DSM.
PMID: 25280799 [PubMed - indexed for MEDLINE]
CENP-W plays a role in maintaining bipolar spindle structure.
PLoS One. 2014;9(10):e106464
Authors: Kaczmarczyk A, Sullivan KF
The CENP-W/T complex was previously reported to be required for mitosis. HeLa cells depleted of CENP-W displayed profound mitotic defects, with mitotic timing delay, disorganized prometaphases and multipolar spindles as major phenotypic consequences. In this study, we examined the process of multipolar spindle formation induced by CENP-W depletion. Depletion of CENP-W in HeLa cells labeled with histone H2B and tubulin fluorescent proteins induced rapid fragmentation of originally bipolar spindles in a high proportion of cells. CENP-W depletion was associated with depletion of Hec1 at kinetochores. The possibility of promiscuous centrosomal duplication was ruled out by immunofluorescent examination of centrioles. However, centrioles were frequently observed to be abnormally split. In addition, a large proportion of the supernumerary poles lacked centrioles, but were positively stained with different centrosomal markers. These observations suggested that perturbation in spindle force distribution caused by defective kinetochores could contribute to a mechanical mechanism for spindle pole disruption. 'Spindle free' nocodazole arrested cells did not exhibit pole fragmentation after CENP-W depletion, showing that pole fragmentation is microtubule dependent. Inhibition of centrosome separation by monastrol reduced the incidence of spindle pole fragmentation, indicating that Eg5 plays a role in spindle pole disruption. Surprisingly, CENP-W depletion rescued the monopolar spindle phenotype of monastrol treatment, with an increased frequency of bipolar spindles observed after CENP-W RNAi. We overexpressed the microtubule cross-linking protein TPX2 to create spindle poles stabilized by the microtubule cross-linking activity of TPX2. Spindle pole fragmentation was suppressed in a TPX2-dependent fashion. We propose that CENP-W, by influencing proper kinetochore assembly, particularly microtubule docking sites, can confer spindle pole resistance to traction forces exerted by motor proteins during chromosome congression. Taken together, our findings are consistent with a model in which centrosome integrity is controlled by the pathways regulating kinetochore-microtubule attachment stability.
PMID: 25329824 [PubMed - indexed for MEDLINE]
A preliminary investigation into theory of mind and attributional style in adults with grandiose delusions.
Cogn Neuropsychiatry. 2015;20(2):109-21
Authors: Boyden P, Knowles R, Corcoran R, Hamilton S, Rowse G
INTRODUCTION: A preliminary cognitive model of grandiose delusions has been put forward suggesting that persecutory and grandiose delusions shared distinct, yet overlapping psychological processes. This study aims to test this model and hypothesises that participants experiencing grandiose delusions may demonstrate a theory of mind (ToM) impairment and differences in attributional style compared to a control group.
METHODS: A cross-sectional design compared the performance of 18 individuals with grandiose delusions to a control group of 14 participants with depression. ToM was measured using a non-verbal joke appreciation task and a verbal stories task. Attributional style was measured using the internal, personal and situational attributions questionnaire.
RESULTS: Participants experiencing grandiose delusions performed significantly worse on both ToM tasks compared to controls. Furthermore, these participants provided significantly more atypical answers when explaining the joke behind the ToM cartoons. No differences for subjective funniness ratings or attributional style were found.
CONCLUSIONS: This preliminary study indicated participants experiencing grandiose delusions have ToM impairments which may contribute to the maintenance of this symptom.
PMID: 25384453 [PubMed - indexed for MEDLINE]