Understanding the molecular mechanisms underlying mood stabilizer treatments in bipolar disorder: potential involvement of epigenetics.
Neurosci Lett. 2016 Jun 22;
Authors: Pisanu C, Papadima EM, Del Zompo M, Squassina A
Mood stabilizers constitute a category of medications used in the management of mood disorders. The mood stabilizing properties of lithium were first discovered in 1949, and since then it has been considered the first line treatment for bipolar disorder. Despite presenting more differences than similarities, mood stabilizers are all characterized by high variability in response in treated patients. This feature has inspired a vast research on potential predictive markers of clinical response, with promising but often inconclusive findings. Pharmacogenetics has provided valuable hints toward the involvement of specific genes and pathways in modulating response. However, with the exception of lithium, the number of studies is still too sparse to draw definite conclusions. Moreover, the mechanism of action of mood stabilizers has yet to be completely elucidated. A growing body of research has focused on the involvement of a group of specific molecular players involved in regulation of gene expression without interfering with the DNA sequence in response to mood stabilizers. These processes, defined as epigenetics, represent the mechanisms through which our biological systems interact with environmental factors, including drug treatments. In this review we focused on findings from preclinical and clinical studies suggesting that mood stabilizers may interfere with the epigenetic machinery, thus providing an intriguing perspective that may help us filling the gap between molecular functions and clinical efficacy of mood stabilizers.
PMID: 27343410 [PubMed - as supplied by publisher]
The Bipolar Prodrome: Meta-Analysis of Symptom Prevalence Prior to Initial or Recurrent Mood Episodes.
J Am Acad Child Adolesc Psychiatry. 2016 Jul;55(7):543-55
Authors: Van Meter AR, Burke C, Youngstrom EA, Faedda GL, Correll CU
OBJECTIVE: The aim of this study was to meta-analyze the prevalence of symptoms before an initial mood episode of bipolar disorder (BD) and the prevalence of subthreshold symptoms before a BD mood episode recurrence, to facilitate early identification and prevention.
METHOD: Systematic literature reviews were conducted in PsycINFO and PubMed for prospective or retrospective studies reporting on the prevalence and longest duration of symptoms before an initial or recurrent mood episode of BD. Random effects meta-regression explored whether geographic location, age, percentage of female individuals, and study quality moderated the overall prevalence.
RESULTS: In 11 studies (n = 1,078), the prodrome preceding an initial mood episode lasted 27.1 ± 23.1 months (range, 4.6-130 months). In 10 studies (n = 1,000), the subthreshold symptoms preceding a recurrent mood episode lasted 1.0 ± 0.9 months (range, 0.5-1.3 months). The most common symptoms were largely consistent with diagnostic criteria symptoms associated with the subsequent mood polarity for both the initial prodrome and the period prior to a recurrent mood episode. Few moderators of symptom prevalences emerged, and significant heterogeneity remained.
CONCLUSION: The initial prodromal period is sufficiently long and characterized by symptoms of the subsequent mood episode to make early identification and intervention programs feasible. Conversely, the period of subthreshold symptoms before a recurrent mood episode is short, mandating adequate psychoeducation of patients and families, monitoring of changes in sleep and activity, plus sufficiently frequent follow-up visits to identify patients before a mood episode recurrence. Future prospective investigations, designed to address the identified shortcomings in the extant literature, are needed to identify more clinically applicable information.
PMID: 27343882 [PubMed - in process]
The Status of Irritability in Psychiatry: A Conceptual and Quantitative Review.
J Am Acad Child Adolesc Psychiatry. 2016 Jul;55(7):556-70
Authors: Vidal-Ribas P, Brotman MA, Valdivieso I, Leibenluft E, Stringaris A
OBJECTIVE: Research and clinical interest in irritability have been on the rise in recent years. Yet several questions remain about the status of irritability in psychiatry, including whether irritability can be differentiated from other symptoms, whether it forms a distinct disorder, and whether it is a meaningful predictor of clinical outcomes. In this article, we try to answer these questions by reviewing the evidence on how reliably irritability can be measured and its validity.
METHOD: We combine a narrative and systematic review and meta-analysis of studies. For the systematic review and meta-analysis, we searched studies in PubMed and Web of Science based on preselected criteria. A total of 163 articles were reviewed, and 24 were included.
RESULTS: We found that irritability forms a distinct dimension with substantial stability across time, and that it is specifically associated with depression and anxiety in longitudinal studies. Evidence from genetic studies reveals that irritability is moderately heritable, and its overlap with depression is explained mainly by genetic factors. Behavioral and neuroimaging studies show that youth with persistent irritability exhibit altered activations in the amygdala, striatum, and frontal regions compared with age-matched healthy volunteers. Most knowledge about the treatment of irritability is based on effects of treatment on related conditions or post hoc analyses of trial data.
CONCLUSION: We identify a number of research priorities including innovative experimental designs and priorities for treatment studies, and conclude with recommendations for the assessment of irritability for researchers and clinicians.
PMID: 27343883 [PubMed - in process]
The effect of mood-stabilizing drugs on cytokine levels in bipolar disorder: A systematic review.
J Affect Disord. 2016 Jun 7;203:364-373
Authors: van den Ameele S, van Diermen L, Staels W, Coppens V, Dumont G, Sabbe B, Morrens M
OBJECTIVES: Cytokine level alterations suggest a role for the immune system in the pathophysiology of bipolar disorder (BD). Pharmacotherapy is an important confounding factor in clinical research on cytokine levels. In this systematic review we collate the evidence on blood cytokine levels in medication-free BD and the effects of single mood-stabilizing drugs on these levels.
METHODS: A systematic review was conducted according to the PRISMA statement. We searched the Pubmed and Embase databases for clinical studies reporting either on cytokine levels in medication-free BD or on the effects of single mood-stabilizing drugs on cytokine levels in BD.
RESULTS: Of the 564 articles screened, 17 were included. Fourteen articles report on medication-free patients with BD and indicate state-related cytokine alterations. Six articles discuss the effect of lithium. Whereas no data on short-term effects of lithium were found, ?2 months lithium use in euthymic populations is associated with normal cytokine levels. Two studies report no effect of valproate and no studies were found on carbamazepine, lamotrigine or antipsychotics.
LIMITATIONS: The available studies are characterized by a broad methodological heterogeneity and limited replication between studies.
CONCLUSIONS: This systematic review suggests the presence of state-related cytokine level alterations in medication-free BD with most evidence pointing to a proinflammatory cytokine response in mania. Euthymia and long-term lithium use are associated with normal cytokine levels. To improve our understanding of the impact of mood-stabilizing drugs on cytokine levels, longitudinal studies with medication-free baseline, randomized controlled single-drug treatment protocols and close mood state monitoring are needed.
PMID: 27344047 [PubMed - as supplied by publisher]
Seeing more clearly through psychosis: Depth inversion illusions are normal in bipolar disorder but reduced in schizophrenia.
Schizophr Res. 2016 Jun 22;
Authors: Keane BP, Silverstein SM, Wang Y, Roché MW, Papathomas TV
Schizophrenia patients with more positive symptoms are less susceptible to depth inversion illusions (DIIs) in which concave objects appear as convex. It remains unclear, however, the extent to which this perceptual advantage uniquely characterizes the schizophrenia phenotype. To address the foregoing, we compared 30 bipolar disorder patients to a previously published sample of healthy controls (N=25) and schizophrenia patients (N=30). The task in all cases was to judge the apparent convexity of physically concave faces and scenes. Half of the concave objects were painted with realistic texture to enhance the convexity illusion and the remaining objects were untextured to reduce the illusion. Subjects viewed objects stereoscopically or via monocular motion parallax depth cues. For each group, DIIs were stronger with texture than without, and weaker with stereoscopic information than without, indicating a uniformly normal response to stimulus alterations across groups. Bipolar patients experienced DIIs more frequently than schizophrenia patients but as commonly as controls, irrespective of the face/scene category, texture, or viewing condition (motion/stereo). More severe positive and disorganized symptoms predicted reduced DIIs for schizophrenia patients and across all patients. These results suggest that people with schizophrenia, but not bipolar disorder, more accurately perceive object depth structure. Psychotic symptoms-or their accompanying neural dysfunction-may primarily drive the effect presumably through eroding the visual system's generalized tendency to construe unusual or ambiguous surfaces as convex. Because such symptoms are by definition more common in schizophrenia, DIIs are at once state-sensitive and diagnostically specific, offering a potential biomarker for the presence of acute psychosis.
PMID: 27344363 [PubMed - as supplied by publisher]
Emotional dysregulation in those with bipolar disorder, borderline personality disorder and their comorbid expression.
J Affect Disord. 2016 Jun 15;204:103-111
Authors: Bayes A, Parker G, McClure G
BACKGROUND: Differentiation of the bipolar disorders (BP) from a borderline personality disorder (BPD) can be challenging owing to shared features, with emotional dysregulation being the likely principal one.
AIM: To assess differences in emotion regulation strategies in those with BP alone, BPD alone and those comorbid for both.
METHODS: We interviewed participants previously receiving a BP or BPD diagnosis, studying those who met DSM criteria for one or both conditions.
RESULTS: The sample comprised 83 with bipolar disorder, 53 with BPD and 54 comorbid for both. Analyses established linear trends, with the greatest impairment in emotion regulation strategies in the comorbid group followed by the BPD group, and with the lowest in the BP group. Specific deficits in the comorbid group included impulsivity, difficulties with goal directed behaviour, and accessing strategies. A similar linear profile was quantified for maladaptive cognitive emotion regulation strategies, weighted to catastrophizing and rumination. Adaptive emotion regulation strategies were superior in the bipolar group, without significant differences observed between the comorbid and BPD groups.
LIMITATIONS: Reliance on self-report measures; combined BP I and II participants limits generalisability of results to each bipolar sub-type; use of DSM diagnoses risking artefactual comorbidity; while there was an over-representation of females in all groups.
CONCLUSIONS: Differences in emotion regulation strategies advance differentiation of those with either BP or BPD, while we identify the specificity of differing strategies to each condition and their synergic effect in those comorbid for both conditions. Study findings should assist the development and application of targeted strategies for those with either or both conditions.
PMID: 27344618 [PubMed - as supplied by publisher]
Validity of a common quality of life measurement in homeless individuals with bipolar disorder and schizophrenia.
J Affect Disord. 2016 Jun 15;204:131-137
Authors: Girard V, Tinland A, Boucekine M, Loubière S, Lancon C, Boyer L, Auquier P, French Housing First Study Group
OBJECTIVE: To provide new evidence regarding the validity, reliability, sensitivity to change and acceptability of a schizophrenia (SCZ) quality of life measurement (S-QoL 18) in homeless people with bipolar disorder (BPD).
METHODS: This multi-centre prospective study was conducted in the following 4 French cities: Lille, Marseille, Paris and Toulouse. In addition to the S-QoL 18, data on sociodemographic information, disease severity using the Modified Colorado Symptom Index (MCSI), recovery using the Recovery Assessment Scale (RAS) and QoL using the Short-Form Health Survey (SF-36) were collected. The S-QoL 18 was tested for construct validity, reliability, external validity, sensitivity to change and acceptability.
RESULTS: In total, 216 homeless patients with BPD participated in this study. The eight-factor structure of the S-QoL 18 was confirmed by confirmatory factor analysis (RMSEA=0.058, CFI=0.98, TLI=0.966). The scalability was satisfactory, with INFIT statistics within an acceptable range (from 0.77 to 1.20). The internal consistency (from 0.43 to 0.76) and reliability coefficients (Cronbach's alpha from 0.65 to 0.86) were satisfactory for all dimensions. The external validity testing revealed that the S-QoL 18 dimension scores were significantly correlated with the MCSI, the RAS and the SF-36 scores. The percentage of missing data for the dimensions (<15%) and sensitivity to change were satisfactory.
CONCLUSIONS: These results demonstrate adequate acceptability and psychometric properties of the S-QoL 18 among homeless patients with BPD. The S-QoL 18 can be a common instrument for measuring QoL in homeless people with SCZ and BD.
PMID: 27344622 [PubMed - as supplied by publisher]
Affective disorders as potential complication of anti-acne treatment with isotretinoin: A case series.
J Affect Disord. 2016 Jun 16;204:154-158
Authors: Hanna KJ, Agnieszka KP, Michal D, Dariusz J, Izabela D, Agata M, Halina DS
OBJECTIVE: To analyse cases of 9 patients (18-27 yo) who were consequently admitted to our department and treated with affective disorders (AD) while undergoing isotretinoin (INN) therapy.
METHODS: A semi-structured questionnaire designed by the authors was used to analyse many variables related to demographic characteristics, dermatologic and psychiatrics symptoms, AD course and treatment, family history of mental disorders, building on medical histories of patients and their families, and available medical records.
RESULTS: Patients were diagnosed (DSM-IV-TR) with: a major depressive episode (4 patients), a recurrent major depressive episode (3), a bipolar mixed episode (1), and rapid cycling bipolar I disorder (1). The mean time from the first use of INN to: I. the onset of mental disorders was approximately 2 months (1-6 months), II. a visit with a psychiatrist was about 12 months (1-38 months). The predictors of occurrence of AD included a family history of AD and a prior episode of mental disorders. The onset of AD was in most cases preceded by prodromal symptoms such as headaches, sleep disorders, fatigue, drowsiness, or general weakness. Five patients reported suicidal ideation, four patients showed suicidal tendencies, and two persons attempted to commit suicide during the treatment.
CONCLUSIONS: Psychiatrists should pay special attention to isotretinoin as a drug that may trigger episodes of AD, particularly in patients with a family history of AD or prior episodes of mental disorders. Isotretinoin therapy of patients with acne and a family history of AD or prior episodes of mental disorders requires special care and, if symptoms of depression develop or worsen during the INN treatment, collaboration between a dermatologist and a psychiatrist is needed.
PMID: 27344625 [PubMed - as supplied by publisher]
Epigenetic basis of sensitization to stress, affective episodes, and stimulants: implications for illness progression and prevention.
Bipolar Disord. 2016 Jun;18(4):315-24
Authors: Post RM
OBJECTIVES: The process of sensitization (increased responsivity) to the recurrence of stressors, affective episodes, and bouts of substance abuse that can drive illness progression in the recurrent affective disorders requires a memory of and increased reactivity to the prior exposures. A wealth of studies now supports the postulate that epigenetic mechanisms underlie both normal and pathological memory processes.
METHODS: We selectively reviewed the literature pertinent to the role of epigenetics in behavioral sensitization phenomena and discuss its clinical implications.
RESULTS: Epigenetics means above genetics and refers to environmental effects on the chemistry of DNA, histones (around which DNA is wound), and microRNA that change how easily genes are turned on and off. The evidence supports that sensitization to repeated stressor, affective episodes, and substance is likely based on epigenetic mechanisms and that these environmentally based processes can then become targets for prevention, early intervention, and ongoing treatment. Sensitization processes are remediable or preventable risk factors for a poor illness outcome and deserve increased clinical, public health, and research attention in the hopes of making the recurrent unipolar and bipolar affective disorders less impairing, disabling, and lethal by suicide and increased medical mortality.
CONCLUSIONS: The findings that epigenetic chemical marks, which change in the most fundamental way how genes are regulated, mediate the long-term increased responsivity to recurrent stressors, mood episodes, and bouts of substance abuse should help change how the affective disorders are conceptualized and move treatment toward earlier, more comprehensive, and sustained pharmacoprophylaxis.
PMID: 27346321 [PubMed - in process]
Crack cocaine addiction, early life stress and accelerated cellular aging among women.
Prog Neuropsychopharmacol Biol Psychiatry. 2016 Jun 21;
Authors: Levandowski ML, Tractenberg SG, de Azeredo LA, De Nardi T, Rovaris DL, Bau CH, Rizzo LB, Maurya PK, Brietzke E, Tyrka AR, Grassi-Oliveira R
BACKGROUND: Early life stress (ELS) and addiction are related to age-related diseases and telomere shortening. However, the role of telomere length (TL) in crack cocaine addiction remains unknown. The purpose of this study was to investigate the TL in a sample of crack cocaine dependent-women who reported an ELS history and in a community-based sample of elderly women as a reference group for senescence.
METHODS: This study included treatment seeking crack cocaine dependents women (n=127) and elderly women without a psychiatric diagnosis (ELD, n=49). The crack cocaine sample was divided in two groups according to their Childhood Trauma Questionnaire (CTQ) scores: presence of history of childhood abuse and neglect (CRACK-ELS) and absence of ELS history (CRACK). TL was assessed by T/S ratio obtained from peripheral blood DNA using quantitative PCR assay.
RESULTS: CRACK and CRACK-ELS subjects exhibited shortened TL in comparison to the ELD group, despite their younger age. Among crack cocaine sample, CRACK-ELS group had significantly shorter telomeres than the CRACK group. Correlation analysis within crack cocaine group indicated that TL was negatively correlated with emotional abuse scores.
CONCLUSIONS: These results support previous findings associating telomere shortening with both ELS and drug addiction. This study suggests new evidence of a distinct biological phenotype for drug-dependent women with ELS. The results support the biological senescence hypothesis underpinning ELS experience.
PMID: 27346744 [PubMed - as supplied by publisher]
Mice that lack the C-terminal region of Reelin exhibit behavioral abnormalities related to neuropsychiatric disorders.
Sci Rep. 2016;6:28636
Authors: Sakai K, Shoji H, Kohno T, Miyakawa T, Hattori M
The secreted glycoprotein Reelin is believed to play critical roles in the pathogenesis of several neuropsychiatric disorders. The highly basic C-terminal region (CTR) of Reelin is necessary for efficient activation of its downstream signaling, and the brain structure of knock-in mice that lack the CTR (?C-KI mice) is impaired. Here, we performed a comprehensive behavioral test battery on ?C-KI mice, in order to evaluate the effects of partial loss-of-function of Reelin on brain functions. The ?C-KI mice were hyperactive and exhibited reduced anxiety-like and social behaviors. The working memory in ?C-KI mice was impaired in a T-maze test. There was little difference in spatial reference memory, depression-like behavior, prepulse inhibition, or fear memory between ?C-KI and wild-type mice. These results suggest that CTR-dependent Reelin functions are required for some specific normal brain functions and that ?C-KI mice recapitulate some aspects of neuropsychiatric disorders, such as schizophrenia, bipolar disorder, and autism spectrum disorder.
PMID: 27346785 [PubMed - in process]
Endoxifen, a New Treatment Option for Mania: A Double-Blind, Active-Controlled Trial Demonstrates the Antimanic Efficacy of Endoxifen.
Clin Transl Sci. 2016 Jun 27;
Authors: Ahmad A, Sheikh S, Shah T, Reddy MS, Prasad B, Verma KK, Chandrakant BB, Paithankar M, Kale P, Solanki RV, Patel R, Barkate H, Ahmad I
The protein kinase C (PKC) signaling system plays a role in mood disorders and PKC inhibitors such as endoxifen may be an innovative medicine for bipolar disorder (BP) patients. In this study we show for the first time the antimanic properties of endoxifen in patients with bipolar I disorder (BPD I) with current manic or mixed episode. In a double-blind, active-controlled study, 84 subjects with BPD I were randomly assigned to receive endoxifen (4 mg/day or 8 mg/day) or divalproex in a 2:1 ratio. Patients orally administered 4 mg/day or 8 mg/day endoxifen showed significant improvement in mania assessed by the Young Mania Rating Scale as early as 4 days. The effect remained significant throughout the 21-day period. At study end point, response rates were 44.44% and 64.29% at 4 mg/day and 8 mg/day of endoxifen treatment, respectively. Thus, endoxifen has been shown as a promising novel antimanic or mood stabilizing agent.
PMID: 27346789 [PubMed - as supplied by publisher]
Quality of Life in Carotid Atherosclerosis: The Role of Co-morbid Mood Disorders.
Clin Pract Epidemiol Ment Health. 2016;12:1-8
Authors: Lecca M, Saba L, Sanfilippo R, Pintus E, Cadoni M, Sancassiani F, Francesca Moro M, Craboledda D, Lo Giudice C, Montisci R
INTRODUCTION/OBJECTIVE: To study in severe carotid atherosclerosis (CA): the frequency of mood disorders (MD); the impairment of quality of life (QoL); the role of co-morbid MD in such impairment.
METHODS: Case-control study.
CASES: consecutive in-patients with CA (stenosis ? 50%).
CONTROLS: subjects with no diagnosis of CA randomized from a database of a community survey. Psychiatric diagnosis according to DSM-IV made by clinicians and semi-structured interview, QoL measured by the Short Form Health Survey (SF-12).
RESULTS: This is the first study on comorbidity on CA disease and MD in which psychiatric diagnoses are conducted by clinicians according to DSM-IV diagnostic criteria. Major Depressive Disorder (MDD) (17.4% vs 2.72%, P <0.0001) but not Bipolar Disorders (BD) (4.3% vs 0.5%, P = 0.99) was higher in cases (N=46) than in controls (N= 184). SF-12 scores in cases were lower than in controls (30.56±8.12 vs 36.81±6:40; p <0.001) with QoL comparable to serious chronic diseases of the central nervous system. The burden of a concomitant MDD or BD amplifies QoL impairment.
CONCLUSION: Comorbid MD aggravates the impairment of QoL in CA. Unlike autoimmune diseases or degenerative diseases of the Central Nervous System, CA shows a strong risk of MDD than BD.
PMID: 27346995 [PubMed]
Swedish Version of Mood Spectrum Self-Report Questionnaire: Psychometric Properties of Lifetime and Last-week Version.
Clin Pract Epidemiol Ment Health. 2016;12:14-23
Authors: Ioannou M, Dellepiane M, Benvenuti A, Feloukatzis K, Skondra N, Dell'Osso L, Steingrímsson S
BACKGROUND: Mood Spectrum Self Report (MOODS-SR) is an instrument that assesses mood spectrum symptomatology including subthreshold manifestations and temperamental features. There are different versions of the MOODS-SR for different time frames of symptom assessment: lifetime (MOODS-LT), last-month and last-week (MOODS-LW) versions.
OBJECTIVE: To evaluate the psychometric properties of the MOODS-LT the MOODS-LW.
METHODS: The reliability of the MOODS-LT and MOODS-LW was evaluated in terms of internal consistency and partial correlations among domains and subdomains. The known-group validity was tested by comparing out-patients with bipolar disorder (n=27), unipolar depression (n=8) healthy controls (n=68). The convergent and divergent validity of MOODS-LW were evaluated using the Montgomery Åsberg Depression Rating Scale (MADRS), the Young-Ziegler Mania Rating Scale (YMRS) in outpatients as well the General Health Questionnaire (GHQ-12) in healthy controls.
RESULTS: Both MOODS-LT and MOOODS-LW showed high internal consistency with the Kuder-Richardson coefficient ranging from 0.823 to 0.985 as well as consistent correlations for all domains and subdomains. The last-week version correlated significantly with MADRS (r= 0.79) and YMRS (r=0.46) in outpatients and with GHQ-12 (r= 0.50 for depression domain, r= 0.29 for rhythmicity) in healthy controls.
CONCLUSION: The Swedish version of the MOODS-LT showed similar psychometric properties to other translated versions. Regarding MOODS-LW, this first published psychometric evaluation of the scale showed promising psychometric properties including good correlation to established symptom assessment scales. In healthy controls, the depression and rhythmicity domain scores of the last-week version correlated significantly with the occurrence of mild psychological distress.
PMID: 27346997 [PubMed]
Lithium-Induced Downbeat Nystagmus and Horizontal Gaze Palsy.
Open Ophthalmol J. 2016;10:126-8
Authors: Jørgensen JS, Landschoff Lassen L, Wegener M
We report a case of lithium-induced downbeat nystagmus and horizontal gaze palsy in a 62-year-old woman who was treated for a bipolar affective disorder with lithium carbonate for one month. At presentation serum lithium was within therapeutic range. No alternative causes of the ocular motility disturbances were found, and the patient improved significantly as lithium carbonate was discontinued.
PMID: 27347248 [PubMed]
Advanced Practice Registered Nurses: Gateway to Screening for Bipolar Disorder in Primary Care.
Open Nurs J. 2016;10:59-72
Authors: Kriebel-Gasparro AM
OBJECTIVE: The goal of this mixed methods descriptive study was to explore Advanced Practice Registered Nurses' (APRNs') knowledge of bipolar disorder (BPD) and their perceptions of facilitators and barriers to screening patients with known depression for BPD.
METHODS: A mixed method study design using surveys on BPD knowledge and screening practices as well as focus group data collection method for facilitators and barriers to screening.
RESULTS: 89 APRNs completed the survey and 12 APRNs participated in the focus groups. APRNs in any practice setting had low knowledge scores of BPD. No significant differences in screening for BPD for primary and non primary care APRNs. Qualitative findings revealed screening relates to tool availability; time, unsure of when to screen, fear of sigma, symptoms knowledge of BPD, accessible referral system, personal experiences with BPD, and therapeutic relationships with patients.
CONCLUSION: Misdiagnosis of BPD as unipolar depression is common in primary care settings, leading to a long lag time to optimal diagnosis and treatment. The wait time to diagnosis and treatment could be reduced if APRNs in primary care settings screen patients with a diagnosis of depression by using validated screening tools. These results can inform APRN practice and further research on the effectiveness of screening for reducing the morbidity and mortality of BPDs in primary care settings; underscores the need for integration of mental health care into primary care as well as the need for more APRN education on the diagnosis and management of bipolar disorders.
PMID: 27347256 [PubMed]
GBR 12909 administration as an animal model of bipolar mania: time course of behavioral, brain oxidative alterations and effect of mood stabilizing drugs.
Metab Brain Dis. 2015 Oct;30(5):1207-15
Authors: Queiroz AI, de Araújo MM, da Silva Araújo T, de Souza GC, Cavalcante LM, de Jesus Souza Machado M, de Lucena DF, Quevedo J, Macêdo D
Polymorphisms in the human dopamine transporter (DAT) are associated with bipolar endophenotype. Based on this, the acute inhibition of DAT using GBR12909 causes behavioral alterations that are prevented by valproate (VAL), being related to a mania-like model. Herein our first aim was to analyze behavioral and brain oxidative alterations during a 24 h period post-GBR12909 to better characterize this model. Our second aim was to determine the preventive effects of lithium (Li) or VAL 2 h post-GBR12909. For this, adult male mice received GBR12909 or saline being evaluated at 2, 4, 8, 12 or 24 h post-administration. Hyperlocomotion, levels of reduced glutathione (GSH) and lipid peroxidation in brain areas were assessed at all these time-points. GBR12909 caused hyperlocomotion at 2 and 24 h. Rearing behavior increased only at 2 h. GSH levels decreased in the hippocampus and striatum at the time points of 2, 4, 8 and 12 h. Increased lipid peroxidation was detected at the time-points of 2 and 12 h in all brain areas studied. At the time-point of 2 h post-GBR12909 Li prevented the hyperlocomotion and rearing alterations, while VAL prevented only rearing alterations. Both drugs prevented pro-oxidative changes. In conclusion, we observed that the main behavioral and oxidative alterations took place at the time-period of 2 h post-GBR12909, what points to this time-period as the best for the assessment of alterations in this model. Furthermore, the present study expands the predictive validity of the model by the determination of the preventive effects of Li.
PMID: 26073232 [PubMed - indexed for MEDLINE]
Social Rhythm Therapies for Mood Disorders: an Update.
Curr Psychiatry Rep. 2016 Aug;18(8):75
Authors: Haynes PL, Gengler D, Kelly M
Social rhythms are patterns of habitual daily behaviors that may impact the timing of the circadian system directly or indirectly through light exposure. According to the social rhythm hypothesis of depression, depressed individuals possess a vulnerability in the circadian timing system that inhibits natural recovery after disrupting life events. Social rhythm therapies (SRTs) support the implementation of regular, daily patterns of activity in order to facilitate recovery of circadian biological processes and also to improve mood. The majority of SRT research has examined interpersonal and social rhythm therapy (IPSRT) for bipolar disorder. Recent studies have examined IPSRT in inpatient settings, using alternative modes of delivery (group, combined individual and group, internet-based applications) and with brief timeframes. New forms of SRTs are developing that target mood in individuals who have experienced specific types of stressful life events. This manuscript reviews the theoretical and biological bases of SRTs and current literature on SRT outcomes.
PMID: 27338753 [PubMed - in process]
Anti-CGRP monoclonal antibodies in migraine: current perspectives.
Intern Emerg Med. 2016 Jun 23;
Authors: Giamberardino MA, Affaitati G, Curto M, Negro A, Costantini R, Martelletti P
Migraine is a highly disabling neurological pain disorder in which management is frequently problematic. Most abortive and preventative treatments employed are classically non-specific, and their efficacy and safety and tolerability are often unsatisfactory. Mechanism-based therapies are, therefore, needed. Calcitonin gene-related peptide (CGRP) is recognized as crucial in the pathophysiology of migraine, and new compounds that target the peptide have been increasingly explored in recent years. First tested were CGRP receptor antagonists; they proved effective in acute migraine treatment in several trials, but were discontinued due to liver toxicity in long-term administration. Monoclonal antibodies against CGRP (LY2951742, ALD-403, and LBR-101/TEV-48125) or its receptor (AMG334) were subsequently developed. As reviewed in this study, numerous phase 1 and 2 trials and preliminary results of phase 3 trials have shown a good safety/tolerability profile and efficacy in migraine prevention, especially in high frequent episodic and chronic forms. Being macromolecules, these mAbs are not suitable for oral administration; however, their intravenous or subcutaneous delivery can be performed at relatively low frequency-every month or even quarterly-which enhances patients' compliance. Although not all migraineurs respond to this treatment, and longer administration periods will be needed to assess long-term effects, the results so far obtained are extraordinarily promising. The future introduction of mAbs on the market will probably represent a turning point for prevention similar to that represented by triptans for abortive treatment in migraine.
PMID: 27339365 [PubMed - as supplied by publisher]
Bilateral cataracts in a young patient with bipolar disorder on treatment with risperidone.
Aust N Z J Psychiatry. 2016 Jun 23;
Authors: Patel E, Gallego JA
PMID: 27340108 [PubMed - as supplied by publisher]
Aripiprazole for Patients with Bipolar Disorder: A Review of the Clinical Effectiveness, Cost-effectiveness and Guidelines
Book. 2016 05 25
This Rapid Response report aims to review the clinical and cost-effectiveness of aripiprazole for patients with bipolar disorder. Guidelines associated with the use of aripiprazole for patients with bipolar disorder will also be examined.
Integrating multiple data sources (MUDS) for meta-analysis to improve patient-centered outcomes research: a protocol for a systematic review.
Syst Rev. 2015;4:143
Authors: Mayo-Wilson E, Hutfless S, Li T, Gresham G, Fusco N, Ehmsen J, Heyward J, Vedula S, Lock D, Haythornthwaite J, Payne JL, Cowley T, Tolbert E, Rosman L, Twose C, Stuart EA, Hong H, Doshi P, Suarez-Cuervo C, Singh S, Dickersin K
BACKGROUND: Systematic reviews should provide trustworthy guidance to decision-makers, but their credibility is challenged by the selective reporting of trial results and outcomes. Some trials are not published, and even among clinical trials that are published partially (e.g., as conference abstracts), many are never published in full. Although there are many potential sources of published and unpublished data for systematic reviews, there are no established methods for choosing among multiple reports or data sources about the same trial.
METHODS: We will conduct systematic reviews of the effectiveness and safety of two interventions following the Institute of Medicine (IOM) guidelines: (1) gabapentin for neuropathic pain and (2) quetiapine for bipolar depression. For the review of gabapentin, we will include adult participants with neuropathic pain who do not require ventilator support. For the review of quetiapine, we will include adult participants with acute bipolar depression (excluding mixed or rapid cycling episodes). We will compare these drugs (used alone or in combination with other interventions) with placebo or with the same intervention alone; direct comparisons with other medications will be excluded. For each review, we will conduct highly sensitive electronic searches, and the results of the searches will be assessed by two independent reviewers. Outcomes, study characteristics, and risk of bias ratings will be extracted from multiple reports by two individuals working independently, stored in a publicly available database (Systematic Review Data Repository) and analyzed using commonly available statistical software. In each review, we will conduct a series of meta-analyses using data from different sources to determine how the results are affected by the inclusion of data from multiple published sources (e.g., journal articles and conference abstracts) as well as unpublished aggregate data (e.g., "clinical study reports") and individual participant data (IPD). We will identify patient-centered outcomes in each report and identify differences in the reporting of these outcomes across sources.
SYSTEMATIC REVIEW REGISTRATION: CRD42015014037 , CRD42015014038.
PMID: 26525044 [PubMed - indexed for MEDLINE]
Athanasios Koukopoulos' psychiatry: The primacy of mania and the uselessness of antidepressants.
Curr Neuropharmacol. 2016 Jun 21;
Authors: Ghaemi SN, Vohringer PA
BACKGROUND: Athanasios Koukopoulos provided a radical model for understanding depressive and manic conditions.
OBJECTIVE: To review, explain, and analyze Koukopoulos' concept of the primacy of mania, with special attention to the role of antidepressants.
METHOD: A conceptual review of Koukopoulos' writings and lectures on this topic is given.
RESULTS: Koukopoulos held that depressive states are caused by manic states; the former do not occur without the latter. The most common scenario of the inseparability of depressive and manic symptoms occurs in mixed states, which we estimate to represent about one-half of all depressive episodes in all patients (not just bipolar illness). In a review of the empirical evidence for this topic, we conclude that empirical evidence exists to support this view in almost 80% of depressed patients. Since antidepressants worsen mania, they would be expected to worsen depression as well in this model. We provide evidence that supports this view in most persons with depressive states.
CONCLUSION: Koukopoulos' model of affective illness is one where manic states are the primary pathology, and depressive conditions are a secondary consequence. Hence treatment of depression with antidepressants would be less effective than treatment with mood stabilizers, since treating an effect is less successful than treating its cause. This approach would reverse current assumptions in psychiatry.
PMID: 27334019 [PubMed - as supplied by publisher]
Severe Mental Illness and Acute Stress: A Study of Service Utilization in a Conflict Zone.
Psychiatr Q. 2016 Jun 22;
Authors: Halperin D, Levy T, Avissar S, Schreiber G
Patients suffering from severe mental illness (SMI) are considered especially vulnerable to stress. In this study, their use of acute stress services in a military context affecting civilian populations was assessed, using naturally occurring data. The proportion of patients with a previously known SMI, defined as any chronic psychotic disorder or bipolar disorder, among all civilians examined at a center for treatment of stress during a military conflict versus at the ER in usual times, was compared, using the Chi square statistical test. Among 354 subjects examined at the center for treatment of stress, 12 had a SMI diagnosis. Among 404 subjects examined at the ER in usual times, 16 had a SMI diagnosis. Patients with SMI were under-represented, but not in a statistically significant manner, at the center for treatment of stress (?(2) = 0.31, p = ns). Although these results may imply that patients with SMI are not more vulnerable to external stress than the general population, we believe that they may have difficulties in seeking immediate help in such traumatogenic contexts. In order to reduce the occurrence of PTSD and gain efficacy in the treatment of the primary disorder, psychiatric services should perhaps make a reaching out effort to identify and examine these patients in the community. .
PMID: 27334286 [PubMed - as supplied by publisher]
Brain functional changes in first-degree relatives of patients with bipolar disorder: evidence for default mode network dysfunction.
Psychol Med. 2016 Jun 23;:1-9
Authors: Alonso-Lana S, Valentí M, Romaguera A, Sarri C, Sarró S, Rodríguez-Martínez A, Goikolea JM, Amann BL, Maristany T, Salvador R, Vieta E, McKenna PJ, Pomarol-Clotet E
BACKGROUND: Relatively few studies have investigated whether relatives of patients with bipolar disorder show brain functional changes, and these have focused on activation changes. Failure of de-activation during cognitive task performance is also seen in the disorder and may have trait-like characteristics since it has been found in euthymia.
METHOD: A total of 20 euthymic patients with bipolar disorder, 20 of their unaffected siblings and 40 healthy controls underwent functional magnetic resonance imaging during performance of the n-back working memory task. An analysis of variance (ANOVA) was fitted to individual whole-brain maps from each set of patient-relative-matched pair of controls. Clusters of significant difference among the groups were used as regions of interest to compare mean activations/de-activations between them.
RESULTS: A single cluster of significant difference among the three groups was found in the whole-brain ANOVA. This was located in the medial prefrontal cortex, a region of task-related de-activation in the healthy controls. Both the patients and their siblings showed significantly reduced de-activation compared with the healthy controls in this region, but the failure was less marked in the relatives.
CONCLUSIONS: Failure to de-activate the medial prefrontal cortex in both euthymic bipolar patients and their unaffected siblings adds to evidence for default mode network dysfunction in the disorder, and suggests that it may act as a trait marker.
PMID: 27334766 [PubMed - as supplied by publisher]
Risk Prediction Models in Psychiatry: Toward a New Frontier for the Prevention of Mental Illnesses.
J Clin Psychiatry. 2016 Jun 21;
Authors: Bernardini F, Attademo L, Cleary SD, Luther C, Shim RS, Quartesan R, Compton MT
OBJECTIVE: We conducted a systematic, qualitative review of risk prediction models designed and tested for depression, bipolar disorder, generalized anxiety disorder, posttraumatic stress disorder, and psychotic disorders. Our aim was to understand the current state of research on risk prediction models for these 5 disorders and thus future directions as our field moves toward embracing prediction and prevention.
DATA SOURCES: Systematic searches of the entire MEDLINE electronic database were conducted independently by 2 of the authors (from 1960 through 2013) in July 2014 using defined search criteria. Search terms included risk prediction, predictive model, or prediction model combined with depression, bipolar, manic depressive, generalized anxiety, posttraumatic, PTSD, schizophrenia, or psychosis.
STUDY SELECTION: We identified 268 articles based on the search terms and 3 criteria: published in English, provided empirical data (as opposed to review articles), and presented results pertaining to developing or validating a risk prediction model in which the outcome was the diagnosis of 1 of the 5 aforementioned mental illnesses. We selected 43 original research reports as a final set of articles to be qualitatively reviewed.
DATA EXTRACTION: The 2 independent reviewers abstracted 3 types of data (sample characteristics, variables included in the model, and reported model statistics) and reached consensus regarding any discrepant abstracted information.
RESULTS: Twelve reports described models developed for prediction of major depressive disorder, 1 for bipolar disorder, 2 for generalized anxiety disorder, 4 for posttraumatic stress disorder, and 24 for psychotic disorders. Most studies reported on sensitivity, specificity, positive predictive value, negative predictive value, and area under the (receiver operating characteristic) curve.
CONCLUSIONS: Recent studies demonstrate the feasibility of developing risk prediction models for psychiatric disorders (especially psychotic disorders). The field must now advance by (1) conducting more large-scale, longitudinal studies pertaining to depression, bipolar disorder, anxiety disorders, and other psychiatric illnesses; (2) replicating and carrying out external validations of proposed models; (3) further testing potential selective and indicated preventive interventions; and (4) evaluating effectiveness of such interventions in the context of risk stratification using risk prediction models.
PMID: 27337225 [PubMed - as supplied by publisher]
Nonmedical Prescription Opioid Use and DSM-5 Nonmedical Prescription Opioid Use Disorder in the United States.
J Clin Psychiatry. 2016 Jun;77(6):772-780
Authors: Saha TD, Kerridge BT, Goldstein RB, Chou SP, Zhang H, Jung J, Pickering RP, Ruan WJ, Smith SM, Huang B, Hasin DS, Grant BF
OBJECTIVE: The authors present 12-month and lifetime prevalence, correlates, psychiatric comorbidity, and treatment of nonmedical prescription opioid use (NMPOU) and DSM-5 NMPOU disorder (NMPOUD).
METHODS: Data were derived from the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III) (N = 36,309).
RESULTS: Prevalences of 12-month and lifetime NMPOU were 4.1% and 11.3%, exceeding rates in the 2001-2002 NESARC (1.8%, 4.7%). Twelve-month and lifetime rates of DSM-5 NMPOUD were 0.9% and 2.1%. NESARC-III DSM-IV NMPOUD rates (0.8%, 2.9%) were greater than those observed in the 2001-2002 NESARC (0.4% and 1.4%). Rates of NMPOU were greater among men, but no sex differential was observed for NMPOUD. Prevalences of NMPOU and NMPOUD were generally greater among 18- to 64-year-old individuals, whites, and Native Americans, and individuals with lower socioeconomic status. Associations were observed between 12-month and lifetime NMPOU and NMPOUD and other drug use disorders, posttraumatic stress disorder, and borderline, schizotypal, and antisocial personality disorders; persistent depression and major depressive disorder (for NMPOU); and bipolar I disorder (for NMPOUD). Only 5.5% and 17.7% of individuals with 12-month NMPOU and NMPOUD were ever treated.
CONCLUSIONS: NMPOU and NMPOUD have considerably increased over the past decade, are associated with a broad array of risk factors and comorbidities, and largely go untreated in the United States. More information on the determinants, characteristics, and outcomes of NMPOU and NMPOUD is needed to support evidence-based interventions and prevention.
PMID: 27337416 [PubMed - as supplied by publisher]
Nocturnal Wakefulness Is Associated With Next-Day Suicidal Ideation in Major Depressive Disorder and Bipolar Disorder.
J Clin Psychiatry. 2016 Jun;77(6):825-831
Authors: Ballard ED, Vande Voort JL, Bernert RA, Luckenbaugh DA, Richards EM, Niciu MJ, Furey ML, Duncan WC, Zarate CA
OBJECTIVE: Self-reported sleep disturbances may confer elevated risk for suicidal ideation, suicide attempts, and death. However, limited research has evaluated polysomnographically determined sleep disturbance as an acute physiologic risk factor for suicidal thoughts. This study sought to investigate the relationship between nocturnal wakefulness in association with next-day suicidal ideation using overnight polysomnography assessment from data collected between 2006 and 2013.
METHODS: Sixty-five participants with DSM-IV-diagnosed major depressive disorder or bipolar depression underwent overnight polysomnography monitoring in a sleep laboratory. The Hamilton Depression Rating Scale (HDRS) was administered the morning after polysomnography recording to assess next-day suicidal ideation, severity of depressive symptoms, and subjective sleep disturbances.
RESULTS: Using a generalized linear mixed model, a significant time-by-ideation interaction was found indicating greater nocturnal wakefulness at 4:00 am among participants with suicidal ideation (F4,136 = 3.65, P = .007). Increased time awake during the 4:00 am hour (4:00 to 4:59) was significantly associated with elevated suicidal thoughts the next day (standardized ? = 0.31, P = .008). This relationship persisted after controlling for age, gender, diagnosis, and severity of depressive symptoms.
CONCLUSIONS: Greater nocturnal wakefulness, particularly in the early morning hours, was significantly associated with next-day suicidal thoughts. Polysomnographically documented sleep disruption at specific times of night may represent an acute risk factor of suicidal ideation that warrants additional research.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00024635.
PMID: 27337418 [PubMed - as supplied by publisher]
Irritability in boys with autism spectrum disorders: an investigation of physiological reactivity.
J Child Psychol Psychiatry. 2015 Oct;56(10):1118-26
Authors: Mikita N, Hollocks MJ, Papadopoulos AS, Aslani A, Harrison S, Leibenluft E, Simonoff E, Stringaris A
BACKGROUND: Irritability in people with autism spectrum disorders (ASD) is common and impairing, yet its mechanisms remain understudied. We investigated symptom reporting and mechanisms of irritability in ASD, focusing on the relation between irritability and physiological stress responses.
METHODS: Forty-seven unmedicated boys with high-functioning ASD (hfASD) and 23 typically developing boys aged 10-16 years completed a psychosocial stress test. Changes in cortisol, heart rate and heart rate variability throughout the test were recorded. Self- and parent-reported measures of irritability were obtained. Irritability symptom reporting in the hfASD group was compared to two groups of boys without ASD: highly irritable boys (severe mood dysregulation, SMD; n = 40) and healthy-control boys (HC; n = 30).
RESULTS: Boys with hfASD scored significantly higher on irritability than HC boys, and they reported a pattern of irritability symptoms closely resembling that of boys with SMD. The internal consistency of irritability in hfASD was high by parent- and self-report. Although boys with hfASD showed significant stress-induced changes in cortisol and heart rate, those who rated themselves as highly irritable had lower cortisol levels throughout the test compared to those low on irritability. Participants rated as highly irritable by their parents showed blunted cortisol and heart rate responses to stress. The effects of irritability on heart rate, but not cortisol, were accounted for by trait anxiety.
CONCLUSIONS: Irritability can be measured reliably in hfASD and is associated with distinct biological responses to stress.
PMID: 25626926 [PubMed - indexed for MEDLINE]
Pathways from maternal depressive symptoms to adolescent depressive symptoms: the unique contribution of irritability symptoms.
J Child Psychol Psychiatry. 2015 Oct;56(10):1092-100
Authors: Whelan YM, Leibenluft E, Stringaris A, Barker ED
BACKGROUND: The authors tested three possible pathways linking prenatal maternal depressive symptoms to adolescent depressive symptoms. These pathways went through childhood Irritability Symptoms, Anxiety/Depressive Symptoms or Conduct Problems.
METHOD: Data were collected from 3,963 mother-child pairs participating in the Avon Longitudinal Study of Parents and Children. Measures include maternal depressive symptoms (pre- and postnatal); toddler temperament (2 years); childhood (7-13 years) irritability symptoms, anxiety/depressive symptoms, conduct problems, and adolescent depressive symptoms (16 years).
RESULTS: Irritability Symptoms: This pathway linked sequentially - prenatal maternal depressive symptoms, toddler temperament (high perceived intensity and low perceived adaptability), childhood irritability symptoms, and adolescent depressive symptoms. Anxiety/Depressive symptoms: This pathway linked sequentially - prenatal maternal depressive symptoms, toddler temperament (negative perceived mood), childhood anxiety/depressive symptoms, and adolescent depressive symptoms. Childhood conduct problems were not associated with adolescent depressive symptoms, above and beyond irritability symptoms and anxiety/depressive symptoms.
CONCLUSIONS: Results suggest evidence for two distinct developmental pathways to adolescent depressive symptoms that involve specific early and midchildhood features.
PMID: 25665134 [PubMed - indexed for MEDLINE]