[SHIFTING FUNCTION OF WORKING MEMORY IN PSYCHOTIC DISORDERS].
Ideggyogy Sz. 2015 Mar 30;68(3-4):121-6
Authors: Domján N, Greminger N, Drótos G, Janka Z, Szendi I
BACKGROUND AND AIMS: Mental disorders with psychotic features are overlapping in many ways and there are a growing number of comparative studies in the last decades regarding this. Cognitive deficit is well underpinned in schizophrenia, but fewer studies are conducted in this area including patients with bipolar affective disorder. Therefore the aim of the present study was to investigate the cognitive performance of these two patient groups and healthy controls. The Wisconsin Card Sorting Task is a very sensitive measure of the shifting function. Schizophrenic patients perform consistently poorer on this task than healthy controls, while there are not much data about individuals with bipolar affective disorder.
METHODS: The Wisconsin Card Sorting Task and clinical symptom rating scales were administered to 26 patients with schizophrenia, 24 with bipolar affective disorder and 21 healthy controls.
RESULTS: Significant differences were found among the performance of the three groups using four different dimensions of the Wisconsin Card Sorting Task. The schizophrenic group made more perseverative errors and achieved less conceptual level responses and completed fewer categories compared to healthy controls. Patients with schizophrenia were able to complete fewer categories and had fewer conceptual level responses than the bipolar group. No significant differences were observed between patients with bipolar disorder and healthy controls.
CONCLUSIONS: According to these results, patients with schizophrenia and bipolar affective disorder showed no similarities on the Wisconsin Card Sorting Task. Bipolar patients performed the task on the same level as healthy individuals did. The two mental disorders influence cognitive performance differently.
PMID: 26434200 [PubMed - in process]
Right hippocampus size is negatively correlated with leptin serum levels in bipolar disorder.
Psychiatry Res. 2015 Sep 28;
Authors: Vianna-Sulzbach M, Rocha NP, Teixeira AL, Rosa ED, Goldani AA, Kauer-Sant Anna M, Gama CS
Obesity is more frequent in bipolar disorder. Adipokines are associated with depression and obesity via the inflammatory process. Twenty-six DSM-IV patients with BD and 39 controls were enrolled to assess the relationship between serum leptin and adiponectin with hippocampal volumes. Among patients, there was a significant negative correlation between right hippocampal volume and serum leptin levels. This result sum for the hypothesis of a pro-inflammatory state associated with BD and the prevalent co-morbid obesity.
PMID: 26434408 [PubMed - as supplied by publisher]
Assessing personal financial management in patients with bipolar disorder and its relation to impulsivity and response inhibition.
Cogn Neuropsychiatry. 2015 Sep;20(5):424-437
Authors: Cheema MK, MacQueen GM, Hassel S
INTRODUCTION: Impulsivity and risk-taking behaviours are reported in bipolar disorder (BD). We examined whether financial management skills are related to impulsivity in patients with BD.
METHODS: We assessed financial management skills using the Executive Personal Finance Scale (EPFS), impulsivity using the Barratt Impulsiveness Scale (BIS) and response inhibition using an emotional go/no-go task in bipolar individuals (N?=?21) and healthy controls (HC; N?=?23).
RESULTS: Patients had fewer financial management skills and higher levels of impulsivity than HC. In patients and controls, increased impulsivity was associated with poorer personal financial management. Patients and HC performed equally on the emotional go/no-go task. Higher BIS scores were associated with faster reaction times in HC. In patients, however, higher BIS scores were associated with slower reaction times, possibly indicating compensatory cognitive strategies to counter increased impulsivity.
CONCLUSIONS: Patients with BD may have reduced abilities to manage personal finances, when compared against healthy participants. Difficulty with personal finance management may arise in part as a result of increased levels of impulsivity. Patients may learn to compensate for increased impulsivity by modulating response times in our experimental situations although whether such compensatory strategies generalize to real-world situations is unknown.
PMID: 26436337 [PubMed - as supplied by publisher]
Quetiapine and its metabolite norquetiapine: translation from in vitro pharmacology to in vivo efficacy in rodent models.
Br J Pharmacol. 2015 Oct 5;
Authors: Cross AJ, Widzowski D, Maciag C, Zacco A, Hudzik T, Liu J, Nyberg S, Wood MW
BACKGROUND AND PURPOSE: Quetiapine has a range of clinical activity distinct from other atypical antipsychotic drugs, demonstrating efficacy as monotherapy in bipolar depression, major depressive disorder and generalized anxiety disorder. The neuropharmacological mechanisms underlying this clinical profile are not completely understood; however, the major active metabolite, norquetiapine, has been shown to have a distinct in vitro pharmacological profile consistent with a broad therapeutic range and may contribute to the clinical profile of quetiapine.
EXPERIMENTAL APPROACH: We evaluated quetiapine and norquetiapine, using in vitro binding and functional assays of targets known to be associated with antidepressant and anxiolytic drug actions, and compared these activities to a representative range of established antipsychotics and antidepressants. To determine how the in vitro pharmacological properties translate into in vivo activity, we used preclinical animal models with translational relevance to established antidepressant-like and anxiolytic-like drug action.
KEY RESULTS: Norquetiapine had equivalent activity to established antidepressants at norepinephrine transporter (NET), while quetiapine was inactive. Norquetiapine was active in the mouse forced swimming and rat learned helplessness tests. In in vivo receptor occupancy studies, norquetiapine had significant occupancy at NET at behaviourally relevant doses. Both quetiapine and norquetiapine were agonists at 5-HT1A receptors, and the anxiolytic-like activity of norquetiapine in rat punished responding was blocked by the 5-HT1A antagonist, WAY100635.
CONCLUSIONS AND IMPLICATIONS: Quetiapine and norquetiapine have multiple in vitro pharmacological actions and results from preclinical studies suggest that activity at NET and 5-HT1A receptors contributes to the antidepressant and anxiolytic effects in patients treated with quetiapine. This article is protected by copyright. All rights reserved.
PMID: 26436896 [PubMed - as supplied by publisher]
Differentiating Bipolar Disorder from Attention-Deficit/Hyperactivity Disorder in Children.
South Med J. 2015 Oct;108(10):621
Authors: Shah VC, Patel L, Lippmann S
PMID: 26437195 [PubMed - as supplied by publisher]
Emotion-relevant impulsivity predicts sustained anger and aggression after remission in bipolar I disorder.
J Affect Disord. 2015 Sep 25;189:169-175
Authors: Johnson SL, Carver CS
Recent evidence suggests that anger and aggression are of concern even during remission for persons with bipolar I disorder, although there is substantial variability in the degree of anger and aggression across individuals. Little research is available to examine psychological models of anger and aggression for those with remitted bipolar disorder, and that was the goal of this study. Participants were 58 persons diagnosed with bipolar I disorder using the Structured Clinical Interview for DSM-IV, who were followed with monthly symptom severity interviews until they achieved remission, and then assessed using the Aggression-Short Form. We examined traditional predictors of clinical parameters and trauma exposure, and then considered three trait domains that have been shown to be elevated in bipolar disorder and have also been linked to aggression outside of bipolar disorder: emotion-relevant impulsivity, approach motivation, and dominance-related constructs. Emotion-relevant impulsivity was related to anger, hostility, verbal aggression, and physical aggression, even after controlling for clinical variables. Findings extend the importance of emotion-relevant impulsivity to another important clinical outcome and suggest the promise of using psychological models to understand the factors driving aggression and anger problems that persist into remission among persons with bipolar disorder.
PMID: 26437231 [PubMed - as supplied by publisher]
White matter microstructural characteristics in Bipolar I and Bipolar II Disorder: A diffusion tensor imaging study.
J Affect Disord. 2015 Sep 25;189:176-183
Authors: Ambrosi E, Chiapponi C, Sani G, Manfredi G, Piras F, Caltagirone C, Spalletta G
BACKGROUND: Diffusion tensor imaging (DTI) studies of bipolar disorder (BD) report contrasting results and are mainly focused on bipolar I (BD-I) samples. We aimed at investigating how and where DTI parameters differ between BD-I and bipolar II (BD-II) and between BD and healthy control subjects (HC).
METHODS: We conducted a tract-based spatial statistics analysis of DTI derived parameters, namely fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) in a matched sample of 50 BD (25 BD-I and 25 BD-II) during the chronic course of the illness and 50 HC.
RESULTS: Compared to BD-I and HC, BD-II showed lower FA but no significant AD or RD differences in the right inferior longitudinal fasciculus (ILF). Both patient groups showed lower AD and RD in the left internal capsule and lower AD across the left ILF, the cortico-spinal tract within the right hemisphere and bilaterally in the cerebellum with respect to HC.
LIMITATIONS: Patients were medicated at the time of scanning; the BD-II group had higher Hamilton Rating Scale for Depression scores than the BD-I group.
CONCLUSIONS: BD-II patients differ from BD-I in the ILF. Both BD subtypes showed widespread white matter (WM) changes in the internal capsule, cortico-spinal tract and cerebellum. The loss of WM integrity in BD-II might be due to demyelination whereas WM changes common to both subgroups could be attributable to axonal damage.
PMID: 26437232 [PubMed - as supplied by publisher]
Glutathione deficit affects the integrity and function of the fimbria/fornix and anterior commissure in mice: relevance for schizophrenia.
Int J Neuropsychopharmacol. 2015 Oct 3;
Authors: Corcoba A, Steullet P, Duarte JM, Van de Looij Y, Monin A, Cuenod M, Gruetter R, Do KQ
BACKGROUND: Structural anomalies of white matter (WM) are found in various brain regions of patients with schizophrenia, bipolar and other psychiatric disorders, but the causes at cellular and molecular levels remain unclear. Oxidative stress and redox dysregulation have been proposed to play a role in the pathophysiology of several psychiatric conditions, but their anatomical and functional consequences are poorly understood. The aim of this study was to investigate WM throughout the brain in a pre-clinical model of redox dysregulation.
METHODS: In a mouse model with impaired glutathione synthesis (Gclm KO), a state-of-the-art multimodal magnetic resonance protocol at high field (14.1 T) was used to assess longitudinally the WM structure, prefrontal neurochemical profile and ventricular volume. Electrophysiological recordings in the abnormal WM tracts identified by DTI were performed to characterize the functional consequences of fractional anisotropy (FA) alterations.
RESULTS: Structural alterations observed at peri-pubertal age and adulthood in Gclm KO mice were restricted to the anterior commissure (AC) and fornix-fimbria (FF). Reduced FA in the AC (-7.5%±1.9, p<0.01) and FF (-4.5%±1.3, p<0.05) were accompanied by reduced conduction velocity in fast-conducting fibers of the posterior limb of the AC (-14.3%±5.1, p<0.05) and slow-conducting fibers of the FF (-8.6%±2.6, p<0.05). Ventricular enlargement was found at peri-puberty (+25%±8 p<0.05) but not in adult Gclm KO mice.
CONCLUSIONS: Glutathione deficit in Gclm KO mice affects ventricular size and the integrity of the FF and AC. This suggests that redox dysregulation could contribute during neurodevelopment to the impaired WM and ventricle enlargement observed in schizophrenia and other psychiatric disorders.
PMID: 26433393 [PubMed - as supplied by publisher]
Studying epilepsy to understand bipolar disorder?
Epilepsy Behav. 2015 Sep 30;
Authors: Mula M
PMID: 26433442 [PubMed - as supplied by publisher]
A genome-wide association study of bipolar disorder with comorbid eating disorder replicates the SOX2-OT region.
J Affect Disord. 2015 Sep 25;189:141-149
Authors: Liu X, Bipolar Genome Study (BiGS), Kelsoe JR, Greenwood TA
BACKGROUND: Bipolar disorder is a heterogeneous mood disorder associated with several important clinical comorbidities, such as eating disorders. This clinical heterogeneity complicates the identification of genetic variants contributing to bipolar susceptibility. Here we investigate comorbidity of eating disorders as a subphenotype of bipolar disorder to identify genetic variation that is common and unique to both disorders.
METHODS: We performed a genome-wide association analysis contrasting 184 bipolar subjects with eating disorder comorbidity against both 1370 controls and 2006 subjects with bipolar disorder only from the Bipolar Genome Study (BiGS).
RESULTS: The most significant genome-wide finding was observed bipolar with comorbid eating disorder vs. controls within SOX2-OT (p=8.9×10(-8) for rs4854912) with a secondary peak in the adjacent FXR1 gene (p=1.2×10(-6) for rs1805576) on chromosome 3q26.33. This region was also the most prominent finding in the case-only analysis (p=3.5×10(-7) and 4.3×10(-6), respectively). Several regions of interest containing genes involved in neurodevelopment and neuroprotection processes were also identified.
LIMITATIONS: While our primary finding did not quite reach genome-wide significance, likely due to the relatively limited sample size, these results can be viewed as a replication of a recent study of eating disorders in a large cohort.
CONCLUSIONS: These findings replicate the prior association of SOX2-OT with eating disorders and broadly support the involvement of neurodevelopmental/neuroprotective mechanisms in the pathophysiology of both disorders. They further suggest that different clinical manifestations of bipolar disorder may reflect differential genetic contributions and argue for the utility of clinical subphenotypes in identifying additional molecular pathways leading to illness.
PMID: 26433762 [PubMed - as supplied by publisher]
Interaction between BDNF rs6265 Met allele and low family cohesion is associated with smaller left hippocampal volume in pediatric bipolar disorder.
J Affect Disord. 2015 Sep 25;189:94-97
Authors: Zeni CP, Mwangi B, Cao B, Hasan KM, Walss-Bass C, Zunta-Soares G, Soares JC
BACKGROUND: Genetic and environmental factors are implicated in the onset and evolution of pediatric bipolar disorder, and may be associated to structural brain abnormalities. The aim of our study was to assess the impact of the interaction between the Brain-Derived Neurotrophic Factor (BDNF) rs6265 polymorphism and family functioning on hippocampal volumes of children and adolescents with bipolar disorder, and typically-developing controls.
METHODS: We evaluated the family functioning cohesion subscale using the Family Environment Scale-Revised, genotyped the BDNF rs6265 polymorphism, and performed structural brain imaging in 29 children and adolescents with bipolar disorder, and 22 healthy controls.
RESULTS: We did not find significant differences between patients with BD or controls in left or right hippocampus volume (p=0.44, and p=0.71, respectively). However, we detected a significant interaction between low scores on the cohesion subscale and the presence of the Met allele at BNDF on left hippocampal volume of patients with bipolar disorder (F=3.4, p=0.043). None of the factors independently (BDNF Val66Met, cohesion scores) was significantly associated with hippocampal volume differences.
LIMITATIONS: small sample size, cross-sectional study.
CONCLUSIONS: These results may lead to a better understanding of the impact of the interaction between genes and environment factors on brain structures associated to bipolar disorder and its manifestations.
PMID: 26432032 [PubMed - as supplied by publisher]
Differentiating the bipolar disorders from borderline personality disorder.
Acta Psychiatr Scand. 2015 Oct 3;
Authors: Bayes AJ, McClure G, Fletcher K, Ruiz Y, Hadzi-Pavlovic D, Stevenson JL, Manicavasagar VL, Parker GB
OBJECTIVE: To identify features differentiating bipolar disorder (BP) from borderline personality disorder (BPD) and with each condition variably defined.
METHOD: Participants were assigned a BP or BPD diagnosis on the basis of DSM criteria and, separately, by clinical judgment, and undertook a diagnostic interview and completed self-report measures.
RESULTS: Predictors of BPD status varied according to diagnostic decisions, but with the most consistent items being childhood sexual abuse, childhood depersonalization, personality variables relating to relationship difficulties and sensitivity to criticism, and the absence of any BP family history. Across diagnostic groups, personality measure items alone predicted diagnostic allocation with an accuracy of 81-84%, the refined study variables other than hypo/manic features improved the classification rates to 88%, and when the presence or absence of hypo/manic features was added, classification rates increased to 92-95%.
CONCLUSION: Study findings indicate that BPD can be differentiated from BP with a high degree of accuracy.
PMID: 26432099 [PubMed - as supplied by publisher]
Computational modeling of psychiatric illnesses via well-defined neurophysiological and neurocognitive biomarkers.
Neurosci Biobehav Rev. 2015 Sep 29;
Authors: Siekmeier PJ
A good deal of recent research has centered on the identification of biomarkers and endophenotypic measures of psychiatric illnesses using in vivo and in vitro studies. This is understandable, as these measures-as opposed to complex clinical phenotypes-may be more closely related to neurobiological and genetic vulnerabilities. However, instantiation of such biomarkers using computational models-in silico studies-has received less attention. This approach could become increasingly important, given the wealth of detailed information produced by recent basic neuroscience research, and increasing availability of high capacity computing platforms. The purpose of this review is to survey the current state of the art of research in this area. We discuss computational approaches to schizophrenia, bipolar disorder, Alzheimer's disease, fragile X syndrome, and autism, and argue that this represents a promising, and underappreciated, research modality. In conclusion, we outline specific avenues for future research; also, potential uses of in silico models to conduct "virtual experiments" and to generate novel hypotheses, and as an aid in neuropsychiatric drug development are discussed.
PMID: 26432502 [PubMed - as supplied by publisher]
The Danish High Risk and Resilience Study - VIA 7 - a cohort study of 520 7-year-old children born of parents diagnosed with either schizophrenia, bipolar disorder or neither of these two mental disorders.
BMC Psychiatry. 2015;15(1):233
Authors: Thorup AA, Jepsen JR, Ellersgaard DV, Burton BK, Christiani CJ, Hemager N, Skjærbæk M, Ranning A, Spang KS, Gantriis DL, Greve AN, Zahle KK, Mors O, Plessen KJ, Nordentoft M
BACKGROUND: Severe mental illnesses like schizophrenia and bipolar disorder are known to be diseases that to someextent, but not entirely can be understood genetically. The dominating hypothesis is that these disorders should be understood in a neurodevelopmental perspective where genes and environment as well as gene-environment-interactions contribute to the risk of developing the disease. We aim to analyse the influences of genetic risk and environmental factors in a population of 520 7-year-old children with either 0, 1 or 2 parents diagnosed with schizophrenia spectrum psychosis or bipolar disorder on mental health and level of functioning. We hypothesize that a larger proportion of children growing up with an ill parent will display abnormal or delayed development, behavioural problems or psychiatric symptoms compared to the healthy controls.
METHODS/DESIGN: We are establishing a cohort of 5207 year old children and both their parents for a comprehensiveinvestigation with main outcome measures being neurocognition, behaviour, psychopathology and neuromotor development of the child. Parents and children are examined with a comprehensive battery of instruments and are asked for genetic material (saliva or blood) for genetic analyses. The participants arerecruited via Danish registers to ensure representativity. Data from registers concerning social status, birth complications, somatic illnesses and hospitalization are included in the database. Psychological and relational factors like emotional climate in the family, degree of stimulation and support in the home and attachment style are also investigated.
DISCUSSION: Data collection started January 1, 2013, and is successfully ongoing. By Aug 2015 424 families areincluded. About 20 % of the invited families decline to participate, equal for all groups.
PMID: 26432691 [PubMed - as supplied by publisher]
Improving the understanding of the link between cognition and functional capacity in schizophrenia and bipolar disorder.
Schizophr Res. 2015 Sep 28;
Authors: Moore RC, Harmell AL, Harvey PD, Bowie CR, Depp CA, Pulver AE, McGrath JA, Patterson TL, Cardenas V, Wolyniec P, Thornquist MH, Luke JR, Palmer BW, Jeste DV, Mausbach BT
OBJECTIVE: Deficits in cognitive functioning are related to functional disability in people with serious mental illness. Measures of functional capacity are commonly used as a proxy for functional disabilities for cognitive remediation programs, and robust linear relationships between functional capacity and cognitive deficits are frequently observed. This study aimed to determine whether a curvilinear relationship better approximates the association between cognitive functioning and functional capacity.
METHOD: Two independent samples were studied. Study 1: participants with schizophrenia (n=435) and bipolar disorder (n=390) aged 18-83 completed a neuropsychological battery and a performance-based measure of functional capacity. Study 2: 205 participants with schizophrenia (age range=39-72) completed a brief neuropsychological screening battery and a performance-based measure of functional capacity. For both studies, linear and quadratic curve estimations were conducted with cognitive performance predicting functional capacity scores.
RESULTS: Significant linear and quadratic trends were observed for both studies. Study 1: in both the schizophrenia and bipolar participants, when cognitive composite z-scores were >0 (indicating normal to above normal performance), cognition was not related to functional capacity. Study 2: when neuropsychological screening battery z-scores were >-1 (indicating low average to average performance), cognition was not related to functional capacity.
CONCLUSIONS: These results illustrate that in cognitively normal adults with serious mental illness, the relationship between cognitive function and functional capacity is relatively weak. These findings may aid clinicians and researchers determine who may optimally benefit from cognitive remediation programs, with greater benefits possibly being achieved for individuals with cognitive deficits relative to individuals with normal cognition.
PMID: 26427917 [PubMed - as supplied by publisher]
A Longitudinal (6-week) 3T (1)H-MRS Study on the Effects of Lithium Treatment on Anterior Cingulate Cortex Metabolites in Bipolar Depression.
Eur Neuropsychopharmacol. 2015 Sep 25;
Authors: Machado-Vieira R, Gattaz WF, Zanetti MV, De Sousa RT, Carvalho AF, Soeiro-de-Souza MG, Leite CC, Otaduy MC
The anterior cingulate cortex (ACC) is a key area in mood regulation. To date, no longitudinal study has specifically evaluated lithium?s effects on ACC metabolites using (1)H-MRS, as well as its association with clinical improvement in bipolar depression. This (1)H-MRS (TE=35ms) study evaluated 24 drug-free BD patients during depressive episodes and after lithium treatment at therapeutic levels. Brain metabolite levels (N-acetyl aspartate (NAA), creatine (tCr), choline, myo-inositol, and glutamate levels) were measured in the ACC at baseline (week 0) and after lithium monotherapy (week 6). The present investigation showed that ACC glutamate (Glu/tCr) and glutamate+glutamine (Glx/tCr) significantly increased after six weeks of lithium therapy. Regarding the association with clinical improvement, remitters showed an increase in myoinositol levels (mI/tCr) after lithium treatment compared to non-remitters. The present findings reinforce a role for ACC glutamate-glutamine cycling and myoinositol pathway as key targets for lithium?s therapeutic effects in BD.
PMID: 26428274 [PubMed - as supplied by publisher]
Transcranial Magnetic Stimulation for Bipolar Disorder with Catatonic Stupor: A Case Report.
Brain Stimul. 2015 Sep 7;
Authors: Takamiya A, Kishimoto T, Watanabe K, Mimura M, Kito S
PMID: 26428351 [PubMed - as supplied by publisher]
Frequency and Correlates of Distant Visual Impairment in Patients with Schizophrenia, Bipolar Disorder, and Major Depressive Disorder.
East Asian Arch Psychiatry. 2015 Sep;25(3):115-21
Authors: Zheng W, Tang LR, Correll CU, Ungvari GS, Chiu HF, Xiang YQ, Xiang YT
OBJECTIVE: Distant visual impairment in the severely mentally ill is under-researched. This study aimed to assess the frequency and correlates of distant visual impairment in a cohort of Chinese psychiatric patients, including its effect on their quality of life.
METHODS: Adult psychiatric inpatients with schizophrenia, bipolar disorder, and major depressive disorder consecutively admitted to a psychiatric hospital in Beijing, China underwent assessments of psychopathology (Brief Psychiatric Rating Scale, 16-item Quick Inventory of Depressive Symptomatology [Self-Report]), quality of life (12-item Short-Form Medical Outcomes Study [SF-12], 25-item National Eye Institute Visual Function Questionnaire [NEI-VFQ25]), adverse effects (Udvalg for Kliniske Undersøgelser Side Effect Rating Scale), and presenting (as opposed to uncorrected) distant visual acuity (Logarithm of the Minimum Angle of Resolution [LogMAR] chart with patients wearing spectacles, if they owned them). Distant visual impairment was defined as binocular distant visual acuity of a LogMAR score of ? 0.5 (< 6/18 Snellen acuity).
RESULTS: Among 356 patients who met the study criteria, the frequency of distant visual impairment was 12.6% (15.2% with schizophrenia, 11.9% with bipolar disorder, 8.8% with major depressive disorder). In multiple logistic regression analysis, distant visual impairment was significantly associated with ocular disease only (p = 0.002, odds ratio = 3.2, 95% confidence interval = 1.5-6.7). Controlling for the confounding effect of ocular disease, patients with distant visual impairment had a lower quality of life in the general vision domain of the NEI-VFQ25 (F[2, 353] = 9.5, p = 0.002) compared with those without. No differences in the physical and mental domains of the SF-12 and in other domains of the NEI-VFQ25 were noted in these 2 groups.
CONCLUSION: One-eighth of middle-aged severely mentally ill patients had distant visual impairment. Considering the impact of distant visual impairment on daily functioning, severely mentally ill patients need to be screened for impaired eyesight as part of their comprehensive health assessment.
PMID: 26429838 [PubMed - in process]
Severity of Psychiatric Disorders and Dental Health Among Psychiatric Outpatients in Jerusalem, Israel.
Isr J Psychiatry Relat Sci. 2015;52(2):119-120
Authors: Cooper-Kazaz R, Levy DH, Zini A, Sgan-Cohen HD
The association between severity of psychiatric disorder and dental disease has not been adequately studied. The aim of the present study was to examine the level of dental caries morbidity and the association with Severe Mental Illness (SMI) and mild/moderate psychiatric disorders. The population sample included patients aged 30 to 50, treated at the Hadassah psychiatric outpatient clinic, after giving written informed consent. Exclusion criteria included eating disorders which are recognized as being associated with several dental pathologies. The term SMI, frequently used in the literature (1), refers to psychiatric patients suffering from a significant mental disorder and implies a greater burden of illness and dysfunction. The SMI group in this study included patients suffering from schizophrenia, bipolar disorder, resistant depression and chronic post-traumatic stress disorder (PTSD). The mild/ moderate illness group consisted of all other psychiatric disorders on Axis I or II according to DSM IV-TR (2).
PMID: 26431416 [PubMed - as supplied by publisher]
Determinants of hospital length of stay for people with serious mental illness in England and implications for payment systems: a regression analysis.
BMC Health Serv Res. 2015;15(1):439
Authors: Jacobs R, Gutacker N, Mason A, Goddard M, Gravelle H, Kendrick T, Gilbody S
BACKGROUND: Serious mental illness (SMI), which encompasses a set of chronic conditions such as schizophrenia, bipolar disorder and other psychoses, accounts for 3.4 m (7 %) total bed days in the English NHS. The introduction of prospective payment to reimburse hospitals makes an understanding of the key drivers of length of stay (LOS) imperative. Existing evidence, based on mainly small scale and cross-sectional studies, is mixed. Our study is the first to use large-scale national routine data to track English hospitals' LOS for patients with a main diagnosis of SMI over time to examine the patient and local area factors influencing LOS and quantify the provider level effects to draw out the implications for payment systems.
METHODS: We analysed variation in LOS for all SMI admissions to English hospitals from 2006 to 2010 using Hospital Episodes Statistics (HES). We considered patients with a LOS of up to 180 days and estimated Poisson regression models with hospital fixed effects, separately for admissions with one of three main diagnoses: schizophrenia; psychotic and schizoaffective disorder; and bipolar affective disorder. We analysed the independent contribution of potential determinants of LOS including clinical and socioeconomic characteristics of the patient, access to and quality of primary care, and local area characteristics. We examined the degree of unexplained variation in provider LOS.
RESULTS: Most risk factors did not have a differential effect on LOS for different diagnostic sub-groups, however we did find some heterogeneity in the effects. Shorter LOS in the pooled model was associated with co-morbid substance or alcohol misuse (4 days), and personality disorder (8 days). Longer LOS was associated with older age (up to 19 days), black ethnicity (4 days), and formal detention (16 days). Gender was not a significant predictor. Patients who self-discharged had shorter LOS (20 days). No association was found between higher primary care quality and LOS. We found large differences between providers in unexplained variation in LOS.
CONCLUSIONS: By identifying key determinants of LOS our results contribute to a better understanding of the implications of case-mix to ensure prospective payment systems reflect accurately the resource use within sub-groups of patients with SMI.
PMID: 26424408 [PubMed - in process]
Low unesterified:esterified eicosapentaenoic acid (EPA) plasma concentration ratio is associated with bipolar disorder episodes, and omega-3 plasma concentrations are altered by treatment.
Bipolar Disord. 2015 Oct 1;
Authors: Saunders EF, Reider A, Singh G, Gelenberg AJ, Rapoport SI
OBJECTIVES: Omega (n)-3 and n-6 polyunsaturated fatty acids (PUFAs) are molecular modulators of neurotransmission and inflammation. We hypothesized that plasma concentrations of n-3 PUFAs would be lower and those of n-6 PUFAs higher in subjects with bipolar disorder (BD) compared to healthy controls (HCs), and would correlate with symptom severity in subjects with BD, and that effective treatment would correlate with increased n-3 but lower n-6 PUFA levels. Additionally, we explored clinical correlations and group differences in plasma levels of saturated and monounsaturated fatty acids.
METHODS: This observational, parallel group study compared biomarkers between HCs (n = 31) and symptomatic subjects with BD (n = 27) when ill and after symptomatic recovery (follow-up). Plasma concentrations of five PUFAs [linoleic acid (LA), arachidonic acid (AA), alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA)], two saturated fatty acids (palmitic acid and stearic acid) and two monounsaturated fatty acids (palmitoleic acid and oleic acid) were measured in esterified (E) and unesterified (UE) forms. Calculated ratios included UE:E for the five PUFAs, ratios of n-3 PUFAs (DHA:ALA, EPA:ALA and EPA:DHA), and the ratio of n-6:n-3 AA:EPA. Comparisons of plasma fatty acid levels and ratios between BD and HC groups were made with Student t-tests, and between the BD group at baseline and follow-up using paired t-tests. Comparison of categorical variables was performed using chi-square tests. Pearson's r was used for bivariate correlations with clinical variables, including depressive and manic symptoms, current panic attacks, and psychosis.
RESULTS: UE EPA was lower in subjects with BD than in HCs, with a large effect size (Cohen's d = 0.86, p < 0.002); however, it was not statistically significant after correction for multiple comparisons. No statistically significant difference was seen in any plasma PUFA concentration between the BD and HC groups after Bonferroni correction for 40 comparisons, at p < 0.001. Neither depressive severity nor mania severity was correlated significantly with any PUFA concentration. Exploratory comparison showed lower UE:E EPA in the BD than the HC group (p < 0.0001). At follow-up in the BD group, UE, E DHA:ALA, and UE EPA:ALA were decreased (p < 0.002). Exploratory correlations of clinical variables revealed that mania severity and suicidality were positively correlated with UE:E EPA ratio, and that several plasma levels and ratios correlated with panic disorder and psychosis. Depressive severity was not correlated with any ratio. No plasma fatty acid level or ratio correlated with self-reported n-3 PUFA intake or use of medication by class.
CONCLUSIONS: A large effect size of reduced UE EPA, and a lower plasma UE:E concentration ratio of EPA in the symptomatic BD state may be important factors in vulnerability to a mood state. Altered n-3 PUFA ratios could indicate changes in PUFA metabolism concurrent with symptom improvement. Our findings are consistent with preclinical and postmortem data and suggest testing interventions that increase n-3 and decrease n-6 dietary PUFA intake.
PMID: 26424416 [PubMed - as supplied by publisher]
Dysregulation of the NF-?B pathway as a potential inducer of bipolar disorder.
J Psychiatr Res. 2015 Aug 11;70:18-27
Authors: Elhaik E, Zandi P
A century of investigations enhanced our understanding of bipolar disorder although it remains a complex multifactorial disorder with a mostly unknown pathophysiology and etiology. The role of the immune system in this disorder is one of the most controversial topics in genetic psychiatry. Though inflammation has been consistently reported in bipolar patients, it remains unclear how the immunologic process influences the disorder. One of the core components of the immune system is the NF-?B pathway, which plays an essential role in the development of innate and adaptive immunity. Remarkably, the NF-?B pathway received only little attention in bipolar studies, as opposed to studies of related psychiatric disorders where immune dysregulation has been proposed to explain the neurodegeneration in patient conditions. If immune dysregulation can also explains the neurodegeneration in bipolar disorder, it will underscore the role of the immune system in the chronicity and pathophysiology of the disorder and may promote personalized therapeutic strategies. This is the first review to summarize the current knowledge of the pathophysiological functions of NF-?B in bipolar disorder.
PMID: 26424419 [PubMed - as supplied by publisher]
Positron emission tomography quantification of serotonin transporter binding in medication-free bipolar disorder.
Synapse. 2015 Oct 1;
Authors: Miller JM, Everett BA, Oquendo MA, Ogden RT, Mann JJ, Parsey RV
OBJECTIVES: Bipolar disorder (BD) is associated with abnormalities in the serotonin transporter (5-HTT), but specific in vivo findings have been discrepant. Using positron emission tomography (PET) and [(11) C]DASB, we compared 5-HTT binding between unmedicated depressed BD subjects and healthy volunteers (HVs).
EXPERIMENTAL DESIGN: 5-HTT binding in six brain regions was compared between 17 depressed, unmedicated BD subjects and 31 HVs, using the outcome measure of VT /fP (proportional to the total number of available transporters). Alternative outcome measures were examined as well. 50% of BD were BP I; 67% reported a prior suicide attempt.
PRINCIPAL OBSERVATIONS: 5-HTT binding (VT /fP ) did not differ between BD and HV groups considering six brain regions of interest simultaneously (p=0.24). In contrast, alternative outcome measures (BPF *, BPP *, and BPND *) indicated lower binding in BD compared with HV across these six regions of interest (BPF *: p=0.047; BPP *: p=0.032; BPND *: p=0.031). 5-HTT binding was unrelated to suicide attempt history, depression severity, bipolar subtype, or history of past substance use disorder.
CONCLUSIONS: Choice of outcome measure strongly affects comparisons of serotonin transporter binding using PET with [(11) C]DASB. We do not find evidence of abnormal 5-HTT binding in bipolar depression using our primary outcome measure, VT /fP . However, we did observe lower 5-HTT binding in BD with alternative outcome measures that are frequently used with [(11) C]DASB. Relative merits and assumptions of different outcome measures are discussed. Evaluation in larger samples and during different mood states, including remission, is warranted. This article is protected by copyright. All rights reserved.
PMID: 26426356 [PubMed - as supplied by publisher]
The Relationship Between Educational Years and Phonemic Verbal Fluency (PVF) and Semantic Verbal Fluency (SVF) Tasks in Spanish Patients Diagnosed With Schizophrenia, Bipolar Disorder, and Psychotic Bipolar Disorder.
Medicine (Baltimore). 2015 Sep;94(39):e1596
Authors: García-Laredo E, Maestú F, Castellanos MÁ, Molina JD, Peréz-Moreno E
Semantic and verbal fluency tasks are widely used as a measure of frontal capacities. It has been well described in literature that patients affected by schizophrenic and bipolar disorders present a worse execution in these tasks. Some authors have also noted the importance of educational years. Our objective is to analyze whether the effect of cognitive malfunction caused by apathology is superior to the expected effect of years of education in phonemic verbal fluency (PVF) and semantic verbal fluency (SVF) task execution.A total of 62 individuals took part in this study, out of which 23 were patients with schizophrenic paranoid disorder, 11 suffered from bipolar disorder with psychotic symptomatology, 13 suffered from bipolar disorder without psychotic symptomatology, and 15 participants were nonpathological individuals. All participants were evaluated with the PVF and SVF tests (animals and tools). The performance/execution results were analyzed with a mixed-model ANCOVA, with educational years as a covariable.The effect of education seems to be more determined by PVF FAS tests than by SVF. With PVF FAS tasks, the expected effect of pathology disappears when the covariable EDUCATION is introduced. With SVF tasks, the effect continues to be significant, even though the EDUACTION covariable dims such effect.These results suggest that SVF tests (animals category) are better evaluation tools as they are less dependent on the patients' education than PVF FAS tests.
PMID: 26426640 [PubMed - as supplied by publisher]
Effect of cariprazine across the symptoms of mania in bipolar I disorder: Analyses of pooled data from phase II/III trials.
Eur Neuropsychopharmacol. 2015 Sep 5;
Authors: Vieta E, Durgam S, Lu K, Ruth A, Debelle M, Zukin S
Bipolar I disorder is a chronic disorder characterized by episodic recurrences of mania, depression, and mixed affective states interspersed with periods of full or partial remission; subsyndromal residual symptoms between episodes are common and disabling. Cariprazine, an atypical antipsychotic, is a potent dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors. Post-hoc analyses of pooled data from 3 positive trials were conducted to evaluate the effect of cariprazine 3-12mg/d on the symptoms of mania in inpatients (18-65 years) with bipolar I disorder and a current manic episode. Analyses were based on the pooled intent-to-treat (ITT) population (placebo=429; cariprazine=608). Mean change from baseline to the end of treatment on individual Young Mania Rating Scale (YMRS) items was analysed using a mixed-effects model for repeated measures (MMRM); categorical symptom severity shifts were analysed using logistic regression. Statistically significant improvement in mean change was seen for cariprazine versus placebo on all 11 YMRS items (p<0.0001); significantly more cariprazine- versus placebo-treated patients had mild/no symptoms at the end of treatment on 11 YMRS items (p<0.0001) and concurrently on the 4 YMRS core symptoms (irritability, speech, content, and disruptive-aggressive behaviour) (p<0.0001). Significantly more cariprazine- versus placebo-treated patients shifted from a Moderate/Worse or Marked/Worse Symptoms categories to Mild/No Symptoms on all 11 (p<0.0001) and 9 of 11 YMRS items (p<0.05), respectively. Results suggest that cariprazine treatment improved mania across YMRS symptoms; a significant percentage of cariprazine- versus placebo-treated patients had mild/no symptoms at the end of treatment.
PMID: 26419293 [PubMed - as supplied by publisher]
Abnormal behaviours during pramipexole treatment for Cotard's syndrome: a case report.
Psychogeriatrics. 2015 Sep 29;
Authors: Maruo J, Haraguchi Y, Tateishi H, Noguchi T, Mizoguchi Y, Kato TA, Kawashima T, Monji A
Cotard's syndrome is a relatively rare condition that involves a delusion of negation in which an individual believes he or she has lost his or her soul, is dead, or is without functional body systems. This syndrome is observed in various neuropsychiatric disorders but most commonly in mood disorders. Pramipexole has often been used in the adjunctive treatment of both bipolar and unipolar depression, and it is known to cause rare but serious adverse effects such as compulsive behaviours in the treatment of Parkinson's disease. Here we report a case of Cotard's syndrome in treatment-resistant major depression associated with abnormal behaviours that might be caused by pramipexole. In the present case, the patient's abnormal behaviours gradually disappeared about 2 months after the discontinuation of pramipexole. The hypoperfusion in the bilateral parieto-occipital lobe found on single-photon emission computed tomography suggests the presence of Lewy body disease pathology. Nonetheless, the patient's abnormal behaviours disappeared after the discontinuation of pramipexole, indicating that they are mainly attributable to pramipexole treatment. However, the possible existence of Lewy body pathology could facilitate the emergence of abnormal behaviours after treatment with pramipexole. The patient's abnormal behaviours, such as eating other patients' food and taking her medicine before the scheduled time, might differ from typical compulsive behaviours induced by pramipexole (such as pathological gambling and hypersexuality), but they could be regarded as disinhibition. Therefore, we should follow up on the clinical course of this case carefully through neuroimaging investigation and neurocognitive assessment.
PMID: 26419319 [PubMed - as supplied by publisher]
Mandatory implementation of NICE Guidelines for the care of bipolar disorder and other conditions in England and Wales.
BMC Med. 2015;13(1):246
Authors: Morriss R
BACKGROUND: Bipolar disorder is a common long-term mental health condition characterised by episodes of mania or hypomania and depression resulting in disability, early death, and high health and society costs. Public money funds the National Institute of Healthcare and Clinical Excellence (NICE) to produce clinical guidelines by systematically identifying the most up to date research evidence and costing its main recommendations for healthcare organisations and professionals to follow in England and Wales. Most governments, including those of England and Wales, need to improve healthcare but at reduced cost. There is evidence, particularly in bipolar disorder, that systematically following clinical guidelines achieves these outcomes.
DISCUSSION: NICE clinical guidelines, including those regarding bipolar disorder, remain variably implemented. They give clinicians and patients a non-prescriptive basis for deciding their care. Despite the passing of the Health and Social Care Act in 2012 in England requiring all healthcare organisations to consider NICE clinical guidelines in commissioning, delivering, and inspecting healthcare services, healthcare organisations in the National Health Service may ignore them with little accountability and few consequences. There is no mechanism to ensure that healthcare professionals know or consider them. Barriers to their implementation include the lack of political and professional leadership, the complexity of the organisation of care and policy, mistrust of some processes and recommendations of clinical guidelines, and a lack of a clear implementation model, strategy, responsibility, or accountability. Mitigation to these barriers is presented herein. The variability, safety, and quality of healthcare might be improved and its cost reduced if the implementation of NICE clinical guidelines, such as those for bipolar disorder, were made the minimum starting point for clinical decision-making and mandatory responsibilities of all healthcare organisations and professionals.
PMID: 26420497 [PubMed - in process]
Relationship between personality traits and perceived internalized stigma in bipolar patients and their treatment partners.
Psychiatry Res. 2015 Sep 25;
Authors: Bassirnia A, Briggs J, Kopeykina I, Mednick A, Yaseen Z, Galynker I
Internalized stigma of mental disorders has significant negative outcomes for patients with bipolar disorder and their families. The aim of this study is to evaluate the association between personality traits and internalized stigma of mental disorders in bipolar patients and their treatment partners. Five different questionnaires were utilized in this study: (1) Demographic data questionnaire, (2) Millon Clinical Multiaxial Inventory-III (MCMI-III) for personality traits, (3) Internalized Stigma of Mental Illness (ISMI) for stigma, (4) Self Report Manic Inventory (SRMI) for mania and (5) Center for Epidemiological Studies-Depression Scale (CES-D) for depression. The scores of personality traits were combined to create externalizing and internalizing personality trait scores. Results showed that patients with bipolar disorder and their treatment partners both experienced internalized stigma of mental health disorders. There was a significant positive correlation between internalized stigma and internalizing personality traits, but not externalizing traits. In a multi-variate regression analysis, internalizing personality trait score was found to be a significant predictor of internalized stigma. In conclusion, patients with bipolar disorder and their treatment partners perceive higher level of internalized stigma of mental disorders if they have internalizing personality traits.
PMID: 26421901 [PubMed - as supplied by publisher]
Association of interleukin-10 levels with age of onset and duration of illness in patients with major depressive disorder.
Rev Bras Psiquiatr. 2015 Sep 29;
Authors: Gazal M, Jansen K, Souza LD, Oses JP, Magalhães PV, Pinheiro R, Ghisleni G, Quevedo L, Kaster MP, Kapczinski F, Silva RA
OBJECTIVE: To investigate peripheral levels of interleukin-10 (IL-10) in patients with major depressive disorder (MDD) and bipolar disorder (BD) and evaluate the relationship between IL-10, age of disease onset, and duration of illness.
METHODS: Case-control study nested in a population-based cohort of 231 individuals (age 18-24 years) living in Pelotas, state of Rio Grande do Sul, Brazil. Participants were screened for psychopathology using the Mini-International Neuropsychiatric Interview (MINI) and the Structured Clinical Interview for DSM-IV (SCID-I). Serum IL-10 was measured using commercially available immunoassay kits.
RESULTS: Peripheral levels of IL-10 were not significantly different in individuals with MDD or BD as compared to controls. However, higher IL-10 levels were found in MDD patients with a later disease onset as compared with controls or early-onset patients. In addition, IL-10 levels correlated negatively with illness duration in the MDD group. In the BD group, age of onset and duration of illness did not correlate with IL-10 levels.
CONCLUSION: Higher levels of IL-10 are correlated with late onset of MDD symptoms. Moreover, levels of this cytokine might decrease with disease progression, suggesting that an anti-inflammatory balance may be involved in the onset of depressive symptoms and disease progression in susceptible individuals.
PMID: 26421934 [PubMed - as supplied by publisher]
Pharmacotherapy for bipolar depression: comparative efficacy and acceptability is in the eye of the beholder.
Evid Based Ment Health. 2015 Aug;18(3):88
Authors: Citrome L, Ketter TA
PMID: 25989992 [PubMed - indexed for MEDLINE]