Heading off depressive illness evolution and progression to treatment resistance.
Dialogues Clin Neurosci. 2015 Jun;17(2):105-9
Authors: Post RM
Viewing recurrent depression as a potentially progressive illness may help transform treatment toward earlier, more consistent intervention and prevention. Evidence indicates that recurrent stressors, episodes of depression, and bouts of substance abuse can each show sensitization (increased reactivity upon repetition) and cross-sensitization to the others, and drive illness progression and treatment resistance. These long-lasting increases in pathological responsivity appear to be mediated by epigenetic mechanisms involving alterations in chemical marks placed on DNA and histories. These types of sensitization effects are amenable to clinical attempts at amelioration and prevention, and provide treatment targets and strategies to minimize the likelihood of illness progression to treatment resistance.
PMID: 26246786 [PubMed - indexed for MEDLINE]
ADHD (ATTENTION DEFFICIT HYPERACTIVITY DISORDER)--A TROUBLING ENTITY, SOMETIMES PERPETUATING DURING ADULT LIFE.
Rev Med Chir Soc Med Nat Iasi. 2016 Jan-Mar;120(1):10-4
Authors: Amih?esei IC, Zamfir CL
Attention deficit hyperactivity disorder (ADHD) is considered a neurologic development disorder resulting in impairment of attention and inhibitory control, manifested as attention deficit, hyperactivity, impulsiveness; symptoms should develop between age six and twelve and have to persist for more than six months. Approximately 30-50% of the diagnosed cases are manifesting the disorder during adulthood and 2.5-5% of the adults are suffering of ADHD. Genetics are important factors in ADHD, being involved in 75% of the cases, as well in the persistence of ADHD during adult life. Three subtypes of ADHD are described--one in which is predominating the attention deficit, one with predominant hyperactivity and impulsiveness and a third combined subtype. Diagnosis criteria in ADHD are established by the American Psychiatric Association (DSM criteria) and by World Health Organization. Differential diagnosis is mainly considering bipolar disorder and borderline personality disorder. Management of ADHD is including behavioral therapies and medication, alone or combined. Stimulant medications such as amphetamine represent the therapy of choice, being effective in 80% of the cases. New data are underlying the need for following up of the cases during adulthood, since the risk for development of psychiatric conditions such as depression, anxiety, as well as the suicidal behavior is higher than in the general population.
PMID: 27125066 [PubMed - in process]
Behavior Rating Inventory of Executive Function Adult Version in Patients with Neurological and Neuropsychiatric Conditions: Symptom Levels and Relationship to Emotional Distress.
J Int Neuropsychol Soc. 2016 Apr 29;:1-13
Authors: Løvstad M, Sigurdardottir S, Andersson S, Grane VA, Moberget T, Stubberud J, Solbakk AK
OBJECTIVES: The present study explored the level of self-and informant reported executive functioning in daily living using the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) in a large sample comprising healthy adults and patient cohorts with neurological and neuropsychiatric disorders. The relationship to neuropsychological test performance and self-reported emotional distress was explored, as well as the applicability of U.S. normative data.
METHODS: Scores on the self- and informant reported BRIEF-A are presented, along with scores on standardized cognitive tests, and on rating scales of self-reported emotional distress in a Norwegian healthy comparison group (n=115), patients with severe traumatic brain injury (n=125), focal frontal lobe damage (n=29), focal cerebellar lesion (n=24), Parkinson's disease (n=42), attention deficit hyperactivity disorder (n=34), type II bipolar disorder (n=21), and borderline personality disorder (n=18).
RESULTS: Strong associations were observed between the BRIEF-A and emotional distress in both the healthy group and in neurological groups, while no or weak relationships with IQ and performance-based tests of executive function were seen. The relationship between BRIEF-A and emotional distress was weaker in the neuropsychiatric patient groups, despite high symptom load in both domains. Healthy participants tended to have BRIEF-A scores 1/2-3/4 SD below the U.S. normative mean of T score=50.
CONCLUSIONS: The study demonstrates the need to interpret BRIEF-A results within a broad differential diagnostic context, where measures of psychological distress are included in addition to neuropsychological tests. Uncertainty about the appropriateness of U.S. normative data in non-U.S. countries adds to the need for interpretive caution. (JINS, 2016, 22, 1-13).
PMID: 27126218 [PubMed - as supplied by publisher]
White blood cell count correlates with mood symptom severity and specific mood symptoms in bipolar disorder.
Aust N Z J Psychiatry. 2016 Apr 28;
Authors: Köhler O, Sylvia LG, Bowden CL, Calabrese JR, Thase M, Shelton RC, McInnis M, Tohen M, Kocsis JH, Ketter TA, Friedman ES, Deckersbach T, Ostacher MJ, Iosifescu DV, McElroy S, Nierenberg AA
OBJECTIVE: Immune alterations may play a role in bipolar disorder etiology; however, the relationship between overall immune system functioning and mood symptom severity is unknown.
METHODS: The two comparative effectiveness trials, the Clinical and Health Outcomes Initiatives in Comparative Effectiveness for Bipolar Disorder Study (Bipolar CHOICE) and the Lithium Treatment Moderate-Dose Use Study (LiTMUS), were similar trials among patients with bipolar disorder. At study entry, white blood cell count and bipolar mood symptom severity (via Montgomery-Aasberg Depression Rating Scale and Bipolar Inventory of Symptoms Scale) were assessed. We performed analysis of variance and linear regression analyses to investigate relationships between deviations from median white blood cell and multinomial regression analysis between higher and lower white blood cell levels. All analyses were adjusted for age, gender, body mass index, smoking, diabetes, hypertension and hyperlipidemia.
RESULTS: Among 482 Bipolar CHOICE participants, for each 1.0?×?10(9)/L white blood cell deviation, the overall Bipolar Inventory of Symptoms Scale severity increased significantly among men (coefficient?=?2.13; 95% confidence interval?=?[0.46, -3.79]; p?=?0.013), but not among women (coefficient?=?0.87; 95% confidence interval?=?[-0.87, -2.61]; p?=?0.33). Interaction analyses showed a trend toward greater Bipolar Inventory of Symptoms Scale symptom severity among men (coefficient?=?1.51; 95% confidence interval?=?[-0.81, -3.82]; p?=?0.2). Among 283 LiTMUS participants, higher deviation from the median white blood cell showed a trend toward higher Montgomery-Aasberg Depression Rating Scale scores among men (coefficient?=?1.33; 95% confidence interval?=?[-0.22, -2.89]; p?=?0.09), but not among women (coefficient?=?0.34; 95% confidence interval?=?[-0.64, -1.32]; p?=?0.50). When combining LiTMUS and Bipolar CHOICE, Montgomery-Aasberg Depression Rating Scale scores increased significantly among men (coefficient?=?1.09; 95% confidence interval?=?[0.31, -1.87]; p?=?0.006) for each 1.0?×?10(9)/L white blood cell deviation, whereas we found a weak association among women (coefficient?=?0.55; 95% confidence interval?=?[-0.20, -1.29]; p?=?0.14). Lower and higher white blood cell levels correlated with greater symptom severity and specific symptoms, varying according to gender.
CONCLUSION: Deviations in an overall immune system marker, even within the normal white blood cell range, correlated with mood symptom severity in bipolar disorder, mostly among males. Studies are warranted investigating whether white blood cell count may predict response to mood-stabilizing treatment.
PMID: 27126391 [PubMed - as supplied by publisher]
DNA Damage in Major Psychiatric Diseases.
Neurotox Res. 2016 Apr 28;
Authors: Raza MU, Tufan T, Wang Y, Hill C, Zhu MY
Human cells are exposed to exogenous insults and continuous production of different metabolites. These insults and unwanted metabolic products might interfere with the stability of genomic DNA. Recently, many studies have demonstrated that different psychiatric disorders show substantially high levels of oxidative DNA damage in the brain accompanied with morphological and functional alterations. It reveals that damaged genomic DNA may contribute to the pathophysiology of these mental illnesses. In this article, we review the roles of oxidative damage and reduced antioxidant ability in some vastly studied psychiatric disorders and emphasize the inclusion of treatment options involving DNA repair. In addition, while most currently used antidepressants are based on the manipulation of the neurotransmitter regulation in managing different mental abnormalities, they are able to prevent or reverse neurotoxin-induced DNA damage. Therefore, it may be plausible to target on genomic DNA alterations for psychiatric therapies, which is of pivotal importance for future antipsychiatric drug development.
PMID: 27126805 [PubMed - as supplied by publisher]
Point Prevalence of Co-Occurring Behavioral Health Conditions and Associated Chronic Disease Burden Among Adolescents.
J Am Acad Child Adolesc Psychiatry. 2016 May;55(5):408-14
Authors: Kline-Simon AH, Weisner C, Sterling S
OBJECTIVE: To examine the point prevalence of behavioral health conditions (BHCs) and co-occurring chronic medical conditions among adolescents in an integrated health system.
METHOD: The sample consisted of adolescents in an integrated health care system diagnosed with at least 1 of the 5 most prevalent BHCs in 2014 (n = 30,643), and patients without a BHC matched on age, sex, and medical home facility (n = 30,643). Electronic health record data was used to identify all adolescents aged 11 to 18 years with at least 1 BHC diagnosis on their diagnosis list, which included current and pre-existing diagnoses from an outpatient (including psychiatry and chemical dependency specialty treatment), inpatient, or emergency department visit at a Kaiser Permanente Northern California (KPNC) facility between January 1, 2014, and December 31, 2014. The odds of having general medical conditions and specific chronic diseases were compared between adolescents with and without BHCs.
RESULTS: Among adolescents with at least 1 BHC in 2014, the 5 most common BHCs were: depressive disorders (42%), anxiety disorders (40%), attention-deficit/hyperactivity disorders (ADHDs; 37%), substance use disorders (SUDs; 10%), and bipolar spectrum disorders (8%). Overall, patients with a BHC did not have higher odds of any medical comorbidity compared with non-BHC patients. However, compared to individuals without BHCs, adolescents with depression (odds ratio [OR] = 1.16, 95% CI = 1.08-1.26), anxiety (OR = 1.30, 95% CI = 1.20-1.41), and substance use (OR = 1.25, 95% CI = 1.05-1.49) disorders had significantly higher odds of any medical comorbidities; individuals with ADHD and bipolar disorder did not differ from patients without BHCs.
CONCLUSION: BHCs were common and were associated with a disproportionately higher burden of chronic medical disease among adolescents in a large, private health care delivery system. As comorbidity can lead to elevated symptom burden, functional impairment, and treatment complexity, the study findings call for implementation of effective collaborative models of care for these patients.
PMID: 27126855 [PubMed - in process]
Psychoeducation in bipolar disorder with a SIMPLe smartphone application: Feasibility, acceptability and satisfaction.
J Affect Disord. 2016 Apr 20;200:58-66
Authors: Hidalgo-Mazzei D, Mateu A, Reinares M, Murru A, Del Mar Bonnín C, Varo C, Valentí M, Undurraga J, Strejilevich S, Sánchez-Moreno J, Vieta E, Colom F
BACKGROUND: During the last fifteen years, the possibility of delivering psychoeducation programs through Internet-based platforms have been explored. Studies evaluating those programs have shown good to acceptable retention rates. In this context, we developed a smartphone application (SIMPLe) collecting information about mood symptoms and offering personalized psychoeducation messages. The main aims of this study were to evaluate the feasibility, acceptability and satisfaction of the smartphone application.
METHODS: The study was conducted from March to August 2015. Participation in the study was proposed to a consecutive sample of adult patients attending an outpatient mental health clinic. Sociodemographic data, clinical and functional assessments alongside smartphone ownership and uses were collected at baseline and at 3 months' follow-up. A 5 item Likert-scale satisfaction questionnaire was also employed.
RESULTS: 51 participants were initially enrolled in the study, 36 (74%) remained actively using the application after 3 months. The whole sample interacted with the application a mean of 77 days (SD=26.2). During these days they completed 88% of the daily tests. Over 86% of the participants agreed that the experience using the application was satisfactory.
LIMITATIONS: The diversity of smartphones operating systems led to a moderate, although representative, sample number. Additionally, the subjective data reporting, narrow time frame of use and stability of the patients could have affected the results.
CONCLUSIONS: The results confirm that this particular intervention is feasible and represent a satisfactory and acceptable instrument for the self-management of bipolar disorder as an add-on to the usual treatment but future clinical trials must still probe its efficacy.
PMID: 27128358 [PubMed - as supplied by publisher]
Differential endorsement of suicidal ideation and attempt in bipolar versus unipolar depression: a testlet response theory analysis.
J Affect Disord. 2016 Apr 20;200:67-73
Authors: Weinstock LM, Strong D, Uebelacker LA, Miller IW
BACKGROUND: Published data concerning differences in suicide risk across the mood disorders spectrum remain mixed. The current study used testlet response theory methods to evaluate differences in the endorsement of suicidal ideation and attempt in an epidemiological sample of individuals with bipolar and unipolar depression.
METHOD: Participants with lifetime history of bipolar I (n=1154), bipolar II (n=494), and unipolar (n=5695) depression were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions, which included 4 structured queries concerning suicidal ideation/attempt. We estimated differential item functioning between groups with a 2-pl parametric item response model.
RESULTS: Endorsement of suicide items increased as a function of underlying depression severity. Equating for severity, endorsement of suicidal ideation and attempt was generally more frequent in bipolar versus unipolar depression, and in bipolar I versus bipolar II depression. Yet findings were not consistent across all suicide items, and differences were small in magnitude.
LIMITATIONS: The NESARC relied upon lifetime endorsement of suicide items, and suicide risk was only evaluated within the context of a major depressive episode. Thus, this study could not evaluate endorsement of suicide items within the context of (hypo)manic or mixed states.
CONCLUSION: Although there were some group differences, patterns of item endorsement were more similar than different. These data support a transdiagnostic model of suicide that emphasizes underlying depression severity over mood disorder class.
PMID: 27128359 [PubMed - as supplied by publisher]
Inhibitors of Glycogen Synthase Kinase 3 with Exquisite Kinome-wide Selectivity and their Functional Effects.
ACS Chem Biol. 2016 Apr 29;
Authors: Wagner FF, Bishop JA, Gale JP, Shi X, Walk M, Ketterman J, Patnaik D, Barker D, Walpita D, Campbell AJ, Nguyen S, Lewis M, Ross L, Weiwer M, An WF, Germain AR, Nag PP, Metkar S, Kaya T, Dandapani S, Olson DE, Barbe AL, Lazzaro F, Sacher JR, Cheah JH, Fei D, Perez JR, Munoz B, Palmer M, Stegmaier K, Schreiber SL, Scolnick E, Zhang YL, Haggarty SJ, Holson EB, Pan JQ
The mood stabilizer, lithium, is the first line treatment for bipolar disorder and is hypothesized to exert its effects through direct inhibition of glycogen synthase kinase 3 (GSK3) and indirectly by increasing GSK3's inhibitory serine phosphorylation. GSK3 comprises two highly similar paralogs, GSK3? and GSK3?, which are key regulatory kinases in the canonical Wnt pathway. GSK3 stands as a nodal target within this pathway and is an attractive therapeutic target for multiple indications. Despite being an active field of research for the past 20 years, many GSK3 inhibitors demonstrate either poor to moderate selectivity versus the broader human kinome or physicochemical properties unsuitable for use in in vitro systems or in vivo models. A non-conventional analysis of data from a GSK3? inhibitor high-throughput screening campaign, that excluded known GSK3 inhibitor chemotypes, led to the discovery of a novel pyrazolo-tetrahydroquinolinone scaffold with unparalleled kinome-wide selectivity for the GSK3 kinases. Taking advantage of an uncommon tridentate interaction with the hinge region of GSK3, we developed highly selective and potent GSK3 inhibitors, BRD1652 and BRD0209, which demonstrated in vivo efficacy in a dopaminergic signaling paradigm modeling mood related disorders. These new chemical probes open the way for exclusive analyses of the GSK3 kinases function in multiple signaling pathways involved in many prevalent disorders.
PMID: 27128528 [PubMed - as supplied by publisher]
Ultrabrief Electroconvulsive Therapy for Manic Episodes of Bipolar Disorder.
J ECT. 2016 Apr 28;
Authors: Anand S
Right unilateral ultrabrief-pulse electroconvulsive therapy (RUL-UB ECT) is gaining popularity and is being used for the treatment of severe major depression. Though brief pulse-width ECT has shown to have robust antimanic effects, the efficacy of UB ECT for mania has not been studied, and there are very few reports on its use in mania. A brief case series of 3 patients with manic episode of bipolar disorder who were treated with RUL-UB ECT is presented here. The successful treatment of 2 patients in this report suggests that some manic episodes can be rapidly and effectively treated with RUL-UB ECT.
PMID: 27128723 [PubMed - as supplied by publisher]
[Clinical polymorphism of depression and cognitive deficit].
Zh Nevrol Psikhiatr Im S S Korsakova. 2014;114(8):19-24
Authors: Bobrov AE, Kursakov AA
OBJECTIVE: To study the relation between psychometric assessment of depression and parameters of cognitive functioning.
MATERIAL AND METHODS: Authors examined 90 patients (75 women and 15 men), aged from 20 to 75 years, with depression. Twenty-five patients were diagnosed with depressive episode, 40 with recurrent depression, 6 with bipolar depression, 8 with dysthymia and 11 with sub-depression. The diagnosis was made according to ICD-10 criteria. Its were used the following scales: HAMD, BDI, MMPI, ACE-R.
RESULTS: The nosographic differentiation of depression only partially reflected the presence of cognitive deficit. An analysis of depressive syndromes identified psychometrically revealed that cognitive deficit on ACE-R was correlated with behavioral stereotypes on MMPI but not with scores on HAM-D and BDI.
CONCLUSION: Observational criteria (registration of abnormal behavioral stereotypes) should be used in assessment of cognitive deficit in patients with depression. This fact should be also taken into consideration in the studies of antidepressant effects on cognitive function.
PMID: 25345626 [PubMed - indexed for MEDLINE]
The importance of melatonin and mitochondria interaction in mood disorders and schizophrenia: A current assessment.
Curr Med Chem. 2016 Apr 27;
Authors: U?uz AC, Demirci K, Palma JE
Mitochondria play have a critical role in regulating cellular functions, such as redox signaling, calcium homeostasis, and apoptosis. Also, mitochondria are crucial for neurogenesis and neuronal functions. Melatonin is an indole analog hormone, which is generally produced by the pineal gland. It plays a vital role in circadian rhythm and act as a powerful antioxidant by scavenging free radicals, immunomodulators, and anticancer agents. Schizophrenia and mood disorders are the two major psychiatric disorders. Disturbances of sleep and circadian rhythms are well-known symptoms of schizophrenia and mood disorders (bipolar disorder, major depression). Since melatonin has a regulator effect on circadian rhythm and sleep quality, it has a close interaction with between schizophrenia and mood disorders. Herein, we aimed to summarize the effects of melatonin on mitochondrial activity in schizophrenia and mood disorders.
PMID: 27121187 [PubMed - as supplied by publisher]
Inhaled loxapine for the urgent treatment of acute agitation associated with schizophrenia or bipolar disorder.
Curr Med Res Opin. 2016 Apr 28;:1-29
Authors: Pollack CV
BACKGROUND: Acute agitation is a serious complication of schizophrenia and bipolar disorder, which may escalate quickly to aggressive behavior. Rapid treatment is therefore important to calm and stabilize the patient, reducing the potential for harm to the patient and others, and allowing further assessment. Current guidelines suggest that where pharmacologic intervention is indicated, medication should preferably be non-invasive, should have a rapid onset and should control aggressive behavior in the short term without compromising the physician-patient relationship in the long term.
OBJECTIVES: This article presents an overview of a new inhaled formulation of the established antipsychotic loxapine, which aims to provide a more rapidly acting agent for the treatment of acute agitation without the disadvantages of intramuscular or intravenous injection.
DISCUSSION: Inhaled loxapine is rapidly absorbed with intravenous-like pharmacokinetics, with a time to maximum plasma concentration of 2?minutes and a plasma half life of approximately 6?hours. In Phase III studies, loxapine reduced agitation within 10?minutes of inhalation; agitation was decreased at all subsequent assessments during a 24-hour evaluation period. Inhaled loxapine was generally well tolerated with no undue sedation. The most common adverse events were dysgeusia, mild sedation, and dizziness. Inhaled loxapine is contraindicated in patients with asthma, COPD or other pulmonary disease associated with bronchospasm.
CONCLUSIONS: Inhaled loxapine rapidly reduces acute agitation in patients with schizophrenia or bipolar disorder and is generally well tolerated. The non-invasive route of delivery respects the patient's autonomy, reducing the perception of coercion or forced medication. Inhaled loxapine is therefore an effective and appropriate option for use in the emergency setting in patients with acute agitation.
PMID: 27121764 [PubMed - as supplied by publisher]
Comparison of social functioning in community-living older individuals with schizophrenia and bipolar disorder: a catchment area-based study.
Int J Geriatr Psychiatry. 2016 Apr 27;
Authors: van Liempt S, Dols A, Schouws S, Stek ML, Meesters PD
OBJECTIVE: Preserved social functioning is of utmost importance for older individuals living in the community to maintain independency. However, in patients with schizophrenia or bipolar disorder, it remains unclear which factors influence social functioning in later life.
METHODS: In a catchment area-based study in Amsterdam, The Netherlands, 120 older (>60?years) community-living patients with schizophrenia (n?=?73) and with bipolar disorder (n?=?47) were included. Clinical interviews on social functioning and psychometric measurements were applied.
RESULTS: Patients with schizophrenia scored lower on all social measures (social functioning, social participation, network size, availability of confidants) compared with their peers with bipolar disorder. In patients with schizophrenia, lower social functioning was associated with having more negative symptoms and depressive symptoms. Age of onset was also associated with social functioning in schizophrenia, with higher scores in very late-onset schizophrenia-like psychosis. Unfavourable social functioning in patients with bipolar disorder was associated with lower cognitive functioning. Furthermore, in both groups, social functioning was not related to age, having offspring or the presence of a partner.
CONCLUSIONS: In community-living older patients, schizophrenia has a more disruptive effect on social functioning than bipolar disorder, except in those with a very late-onset schizophrenia-like psychosis. Minimizing residual depressive symptoms and optimizing cognitive functioning may be targets for improving social functioning and independent-living in older patients with severe mental illness.
PMID: 27121916 [PubMed - as supplied by publisher]
What we need to know about the effect of lithium on the kidney.
Am J Physiol Renal Physiol. 2016 Apr 27;:ajprenal.00145.2016
Authors: Gong R, Wang P, Dworkin LD
Lithium has been a valuable treatment for bipolar affective disorders for decades. Clinical use of lithium, however, has been problematic due to its narrow therapeutic index and concerns for its toxicity in various organ systems. Renal side effects associated with lithium include polyuria, nephrogenic diabetes insipidus, proteinuria, distal renal tubular acidosis and reduction in glomerular filtration rate. Histologically, chronic lithium nephrotoxicity is characterized by interstitial nephritis with microcyst formation and occasional focal segmental glomerulosclerosis. Nevertheless, this type of toxicity is uncommon with the strongest risk factors being high serum levels of lithium and longer time on lithium therapy. In contrast, in experimental models of acute kidney injury and glomerular disease, lithium has antiproteinuric, kidney protective and reparative effects. This paradox may be partially explained by lower lithium doses and short duration of therapy. While long term exposure to higher psychiatric doses of lithium may be nephrotoxic, short term low dose of lithium may be beneficial and ameliorate kidney and podocyte injury. Mechanistically, lithium targets GSK3?, a ubiquitously expressed serine/threonine protein kinase implicated in the processes of tissue injury, repair, and regeneration in multiple organ systems, including the kidney. Future studies are warranted to discover the exact "kidney protective dose" of lithium and test the effects of low dose lithium on acute and chronic kidney disease in humans.
PMID: 27122541 [PubMed - as supplied by publisher]
[Influence factors of dislocation after bipolar prosthetic replacement].
Zhonghua Yi Xue Za Zhi. 2016 Apr 19;96(15):1212-4
Authors: Li YL, Weng XS, Li T, Dong YL, Xiao K
OBJECTIVE: To discuss the influence factors of dislocation after bipolar prosthetic replacement.
METHODS: A total of 374 patients who received bipolar prosthetic replacement in our hospital from October 2001 to October 2015 were retrospectively studied. The clinic data of patients with dislocation after operation was summarized to analyze the causes.
RESULTS: Dislocation happened in 12 patients among all the 374 patients.10 cases received manual relocation, 2 cases open relocation. Most of the 12 patients were accompanied with neurological and psychiatric disorders, such as Alzheimer's disease, Parkinson's disease, sequelae of cerebral infarction, etc. Some factors like improper body position caused by these complications were the main influence factors of dislocation.
CONCLUSION: Accompanied with neurological and psychiatric disorders is the important influence factor of dislocation after bipolar prosthetic replacement.
PMID: 27117371 [PubMed - in process]
Social cognition in schizophrenia in comparison to bipolar disorder: A meta-analysis.
Schizophr Res. 2016 Apr 22;
Authors: Bora E, Pantelis C
OBJECTIVE: Cognitive dysfunction is a common characteristic of both schizophrenia and bipolar disorder (BP). While these deficits are more severe in schizophrenia, there is a significant overlap between conditions. However, it was hypothesized that social cognitive deficits might be more specific to schizophrenia.
METHODS: We conducted a meta-analysis of studies comparing facial emotion recognition and theory of mind (ToM) abilities in schizophrenia and BP. 26 studies comparing 1301 patients with schizophrenia and 1075 with BP were included.
RESULTS: Schizophrenia patients significantly underperformed compared with BP patients in both facial emotion recognition (d=0.39) and ToM (d=0.57). Neurocognitive deficits significantly contributed to schizophrenia-BP group differences for ToM. However, between-group differences for social cognition were not statistically more severe than neurocognition.
CONCLUSION: Social cognitive impairment is more severe in schizophrenia in comparison to BP. However, between-group differences are modest and are comparable to other neurocognitive differences between schizophrenia and BP. There is significant overlap in social cognitive performance deficits observed in both schizophrenia and BP.
PMID: 27117677 [PubMed - as supplied by publisher]
Classification Of Schizophrenia And Bipolar Patients Using Static And Dynamic Resting-State Fmri Brain Connectivity.
Neuroimage. 2016 Apr 23;
Authors: Rashid B, Arbabshirani MR, Damaraju E, Cetin MS, Miller R, Pearlson GD, Calhoun VD
Recently, functional network connectivity (FNC, defined as the temporal correlation among spatially distant brain networks) has been used to examine the functional organization of brain networks in various psychiatric illnesses. Dynamic FNC is a recent extension of the conventional FNC analysis that takes into account FNC changes over short periods of time. While such dynamic FNC measures may be more informative about various aspects of connectivity, there has been no detailed head-to-head comparison of the ability of static and dynamic FNC to perform classification in complex mental illnesses. This paper proposes a framework for automatic classification of schizophrenia, bipolar and healthy subjects based on their static and dynamic FNC features. Also, we compare cross-validated classification performance between static and dynamic FNC. Results show that the dynamic FNC significantly outperforms the static FNC in terms of predictive accuracy, indicating that features from dynamic FNC have distinct advantages over static FNC for classification purposes. Moreover, combining static and dynamic FNC features does not significantly improve the classification performance over the dynamic FNC features alone, suggesting that static FNC does not add any significant information when combined with dynamic FNC for classification purposes. A three-way classification methodology based on static and dynamic FNC features discriminates individual subjects into appropriate diagnostic groups with high accuracy. Our proposed classification framework is potentially applicable to additional mental disorders.
PMID: 27118088 [PubMed - as supplied by publisher]
Promising 2-Pronged Approach to Genetic Basis of Bipolar Disorder.
JAMA Psychiatry. 2016 Apr 27;
Authors: Kember RL, Bucan M
PMID: 27119721 [PubMed - as supplied by publisher]
Exome Sequencing of Familial Bipolar Disorder.
JAMA Psychiatry. 2016 Apr 27;
Authors: Goes FS, Pirooznia M, Parla JS, Kramer M, Ghiban E, Mavruk S, Chen YC, Monson ET, Willour VL, Karchin R, Flickinger M, Locke AE, Levy SE, Scott LJ, Boehnke M, Stahl E, Moran JL, Hultman CM, Landén M, Purcell SM, Sklar P, Zandi PP, McCombie WR, Potash JB
Importance: Complex disorders, such as bipolar disorder (BD), likely result from the influence of both common and rare susceptibility alleles. While common variation has been widely studied, rare variant discovery has only recently become feasible with next-generation sequencing.
Objective: To utilize a combined family-based and case-control approach to exome sequencing in BD using multiplex families as an initial discovery strategy, followed by association testing in a large case-control meta-analysis.
Design, Setting, and Participants: We performed exome sequencing of 36 affected members with BD from 8 multiplex families and tested rare, segregating variants in 3 independent case-control samples consisting of 3541 BD cases and 4774 controls.
Main Outcomes and Measures: We used penalized logistic regression and 1-sided gene-burden analyses to test for association of rare, segregating damaging variants with BD. Permutation-based analyses were performed to test for overall enrichment with previously identified gene sets.
Results: We found 84 rare (frequency <1%), segregating variants that were bioinformatically predicted to be damaging. These variants were found in 82 genes that were enriched for gene sets previously identified in de novo studies of autism (19 observed vs. 10.9 expected, P?=?.0066) and schizophrenia (11 observed vs. 5.1 expected, P?=?.0062) and for targets of the fragile X mental retardation protein (FMRP) pathway (10 observed vs. 4.4 expected, P?=?.0076). The case-control meta-analyses yielded 19 genes that were nominally associated with BD based either on individual variants or a gene-burden approach. Although no gene was individually significant after correction for multiple testing, this group of genes continued to show evidence for significant enrichment of de novo autism genes (6 observed vs. 2.6 expected, P?=?.028).
Conclusions and Relevance: Our results are consistent with the presence of prominent locus and allelic heterogeneity in BD and suggest that very large samples will be required to definitively identify individual rare variants or genes conferring risk for this disorder. However, we also identify significant associations with gene sets composed of previously discovered de novo variants in autism and schizophrenia, as well as targets of the FRMP pathway, providing preliminary support for the overlap of potential autism and schizophrenia risk genes with rare, segregating variants in families with BD.
PMID: 27120077 [PubMed - as supplied by publisher]
[A case of colchicine overdose progressing to death rapidly].
Chudoku Kenkyu. 2015 Dec;28(4):371-3
Authors: Matsuyoshi T
PMID: 26975079 [PubMed - indexed for MEDLINE]
Cognitive variability in bipolar II disorder: who is cognitively impaired and who is preserved.
Bipolar Disord. 2016 Apr 26;
Authors: Solé B, Jiménez E, Torrent C, Bonnin CD, Torres I, Reinares M, Priego Á, Salamero M, Colom F, Varo C, Vieta E, Martínez-Arán A
OBJECTIVES: Although it is well established that euthymic patients with bipolar disorder can have cognitive impairment, substantial heterogeneity exists and little is known about the extent and severity of impairment within the bipolar II disorder subtype. Therefore, the main aim of this study was to analyze cognitive variability in a sample of patients with bipolar II disorder.
METHODS: The neuropsychological performance of 116 subjects, including 64 euthymic patients with bipolar II disorder and 52 healthy control subjects, was examined and compared by means of a comprehensive neurocognitive battery. Neurocognitive data were analyzed using a cluster analysis to examine whether there were specific groups based on neurocognitive patterns. Subsequently, subjects from each cluster were compared on demographic, clinical, and functional variables.
RESULTS: A three-cluster solution was identified with an intact neurocognitive group (n = 29, 48.3%), an intermediate or selectively impaired group (n = 24, 40.0%), and a globally impaired group (n = 7, 11.6%). Among the three clusters, statistically significant differences were observed in premorbid intelligence quotient (p = 0.002), global functional outcome (p = 0.021), and leisure activities (p = 0.001), with patients in the globally impaired cluster showing the lowest attainments. No differences in other clinical characteristics were found among the groups.
CONCLUSIONS: These results confirm that neurocognitive variability is also present among patients with bipolar II disorder. Approximately one-half of the patients with bipolar II disorder were cognitively impaired, and among them 12% were severely and globally impaired. The identification of different cognitive profiles may help to develop cognitive remediation programs specifically tailored for each cognitive profile.
PMID: 27112120 [PubMed - as supplied by publisher]
Mania secondary to focal brain lesions: implications for understanding the functional neuroanatomy of bipolar disorder.
Bipolar Disord. 2016 Apr 26;
Authors: Satzer D, Bond DJ
OBJECTIVES: Approximately 3.5 million Americans will experience a manic episode during their lifetimes. The most common causes are psychiatric illnesses such as bipolar I disorder and schizoaffective disorder, but mania can also occur secondary to neurological illnesses, brain injury, or neurosurgical procedures.
METHODS: For this narrative review, we searched Medline for articles on the association of mania with stroke, brain tumors, traumatic brain injury, multiple sclerosis, neurodegenerative disorders, epilepsy, and neurosurgical interventions. We discuss the epidemiology, features, and treatment of these cases. We also review the anatomy of the lesions, in light of what is known about the neurobiology of bipolar disorder.
RESULTS: The prevalence of mania in patients with brain lesions varies widely by condition, from <2% in stroke to 31% in basal ganglia calcification. Mania occurs most commonly with lesions affecting frontal, temporal, and subcortical limbic brain areas. Right-sided lesions causing hypo-functionality or disconnection (e.g., stroke; neoplasms) and left-sided excitatory lesions (e.g., epileptogenic foci) are frequently observed.
CONCLUSIONS: Secondary mania should be suspected in patients with neurological deficits, histories atypical for classic bipolar disorder, and first manic episodes after the age of 40 years. Treatment with antimanic medications, along with specific treatment for the underlying neurologic condition, is typically required. Typical lesion locations fit with current models of bipolar disorder, which implicate hyperactivity of left-hemisphere reward-processing brain areas and hypoactivity of bilateral prefrontal emotion-modulating regions. Lesion studies complement these models by suggesting that right-hemisphere limbic-brain hypoactivity, or a left/right imbalance, may be relevant to the pathophysiology of mania.
PMID: 27112231 [PubMed - as supplied by publisher]
A fast and powerful W-test for pairwise epistasis testing.
Nucleic Acids Res. 2016 Apr 25;
Authors: Wang MH, Sun R, Guo J, Weng H, Lee J, Hu I, Sham PC, Zee BC
Epistasis plays an essential role in the development of complex diseases. Interaction methods face common challenge of seeking a balance between persistent power, model complexity, computation efficiency, and validity of identified bio-markers. We introduce a novel W-test to identify pairwise epistasis effect, which measures the distributional difference between cases and controls through a combined log odds ratio. The test is model-free, fast, and inherits a Chi-squared distribution with data adaptive degrees of freedom. No permutation is needed to obtain the P-values. Simulation studies demonstrated that the W-test is more powerful in low frequency variants environment than alternative methods, which are the Chi-squared test, logistic regression and multifactor-dimensionality reduction (MDR). In two independent real bipolar disorder genome-wide associations (GWAS) datasets, the W-test identified significant interactions pairs that can be replicated, including SLIT3-CENPN, SLIT3-TMEM132D, CNTNAP2-NDST4 and CNTCAP2-RTN4R The genes in the pairs play central roles in neurotransmission and synapse formation. A majority of the identified loci are undiscoverable by main effect and are low frequency variants. The proposed method offers a powerful alternative tool for mapping the genetic puzzle underlying complex disorders.
PMID: 27112568 [PubMed - as supplied by publisher]
Microtubule and microtubule associated protein anomalies in psychiatric disease.
Cytoskeleton (Hoboken). 2016 Apr 26;
Authors: Marchisella F, Coffey ET, Hollos P
Anomalies in neuronal cell architecture, in particular dendritic complexity and synaptic density changes, are widely observed in the brains of subjects with schizophrenia or mood disorders. The concept that a disturbed microtubule cytoskeleton underlies these abnormalities and disrupts synaptic connectivity is supported by evidence from clinical studies and animal models. Prominent changes in tubulin expression levels are commonly found in disease specific regions such as the hippocampus and prefrontal cortex of psychiatric patients. Genetic linkage studies associate tubulin-binding proteins such as the dihydropyrimidinase family with an increased risk to develop schizophrenia and bipolar disorder. For many years, altered immunoreactivity of microtubule associated protein-2 (MAP2) has been a hallmark found in the brains of individuals with schizophrenia. In this review, we present a growing body of evidence that connects a dysfunctional microtubule cytoskeleton with neuropsychiatric illnesses. Findings from animal models are discussed together with clinical data with a particular focus on tubulin post-translational modifications and on microtubule-binding proteins. This article is protected by copyright. All rights reserved.
PMID: 27112918 [PubMed - as supplied by publisher]
Proteomics strategies for bipolar disorder evaluation: From sample preparation to validation.
J Proteomics. 2016 Apr 22;
Authors: de Jesus JR, de Souza Pessôa G, Sussulini A, Martínez JL, Arruda MA
PMID: 27113133 [PubMed - as supplied by publisher]
Glutathione S-Transferase Deletion Polymorphisms in Early-Onset Psychotic and Bipolar Disorders: A Case-Control Study.
Lab Med. 2016 Apr 25;
Authors: Pejovic-Milovancevic MM, Mandic-Maravic VD, Coric VM, Mitkovic-Voncina MM, Kostic MV, Savic-Radojevic AR, Ercegovac MD, Matic MG, Peljto AN, Lecic-Tosevski DR, Simic TP, Pljesa-Ercegovac MS
OBJECTIVE: To examine glutathione S-transferase (GST) deletion polymorphisms in development of early-onset severe mental disorders, with the hypothesis that patients with GSTM1-null and GSTT1-null genotypes will develop psychotic disorders at a younger age.
METHODS: We identified GSTM1 and GSTT1 deletion polymorphisms by multiplex polymerase chain reaction (PCR) in 93 patients with early onset severe mental disorders and 278 control individuals. The diagnoses were confirmed by Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version and Schedule for Affective Disorders and Schizophrenia-Life-Time Version (K-SADS-PL) interviews.
RESULTS: Individuals with the GSTM1-null genotype were at 3.36-fold higher risk of developing early-onset severe mental disorders than carriers of a corresponding active genotype. The risk of those disorders was increased by 6.59-fold in patients with GSTM1-null/GSTT1-active genotype. Patients with the GSTM1-null genotype were at approximately 2-fold increased risk for developing early-onset schizophrenia-spectrum disorder (EOS), early-onset bipolar disorder (EOBD) with psychotic symptoms, or early-onset first-episode psychosis (EOFEP), compared with patients with the GSTM1-active genotype.
CONCLUSION: The GSTM1-null genotype might be associated with higher risk for early onset severe mental disorders.
PMID: 27114251 [PubMed - as supplied by publisher]
Age associations with neural processing of reward anticipation in adolescents with bipolar disorders.
Neuroimage Clin. 2016;11:476-85
Authors: Uro?evi? S, Luciana M, Jensen JB, Youngstrom EA, Thomas KM
Reward/behavioral approach system hypersensitivity is implicated in bipolar disorders (BD) and in normative development during adolescence. Pediatric onset of BD is associated with a more severe illness course. However, little is known about neural processing of rewards in adolescents with BD or developmental (i.e., age) associations with activation of these neural systems. The present study aims to address this knowledge gap. The present sample included 21 adolescents with BD and 26 healthy adolescents, ages 13 to 19. Participants completed a functional magnetic resonance imaging (fMRI) protocol using the Monetary Incentive Delay (MID) task. Behavioral performance was similar between groups. Group differences in BOLD activation during target anticipation and feedback anticipation periods of the task were examined using whole-brain analyses, as were group differences in age effects. During both target anticipation and feedback anticipation, adolescents with BD, compared to adolescents without psychopathology, exhibited decreased engagement of frontal regions involved in cognitive control (i.e., dorsolateral prefrontal cortex). Healthy adolescents exhibited age-related decreases, while adolescents with BD exhibited age-related increases, in activity of other cognitive control frontal areas (i.e., right inferior frontal gyrus), suggesting altered development in the BD group. Longitudinal research is needed to examine potentially abnormal development of cognitive control during reward pursuit in adolescent BD and whether early therapeutic interventions can prevent these potential deviations from normative development.
PMID: 27114896 [PubMed - in process]
Pleiotropy between neuroticism and physical and mental health: findings from 108?038 men and women in UK Biobank.
Transl Psychiatry. 2016;6:e791
Authors: Gale CR, Hagenaars SP, Davies G, Hill WD, Liewald DC, Cullen B, Penninx BW, International Consortium for Blood Pressure GWAS, CHARGE Consortium Aging and Longevity Group, Boomsma DI, Pell J, McIntosh AM, Smith DJ, Deary IJ, Harris SE
People with higher levels of neuroticism have an increased risk of several types of mental disorder. Higher neuroticism has also been associated, less consistently, with increased risk of various physical health outcomes. We hypothesised that these associations may, in part, be due to shared genetic influences. We tested for pleiotropy between neuroticism and 17 mental and physical diseases or health traits using linkage disequilibrium regression and polygenic profile scoring. Genetic correlations were derived between neuroticism scores in 108?038 people in the UK Biobank and health-related measures from 14 large genome-wide association studies (GWASs). Summary information for the 17 GWASs was used to create polygenic risk scores for the health-related measures in the UK Biobank participants. Associations between the health-related polygenic scores and neuroticism were examined using regression, adjusting for age, sex, genotyping batch, genotyping array, assessment centre and population stratification. Genetic correlations were identified between neuroticism and anorexia nervosa (rg=0.17), major depressive disorder (rg=0.66) and schizophrenia (rg=0.21). Polygenic risk for several health-related measures were associated with neuroticism, in a positive direction in the case of bipolar disorder, borderline personality, major depressive disorder, negative affect, neuroticism (Genetics of Personality Consortium), schizophrenia, coronary artery disease, and smoking (? between 0.009-0.043), and in a negative direction in the case of body mass index (?=-0.0095). A high level of pleiotropy exists between neuroticism and some measures of mental and physical health, particularly major depressive disorder and schizophrenia.
PMID: 27115122 [PubMed - as supplied by publisher]
Bipolar disorders: key clinical considerations.
Lancet. 2016 Apr 9;387(10027):1492-1494
Authors: Malhi GS
PMID: 27115960 [PubMed - as supplied by publisher]