[An analysis of clinical features and therapies of patients with psychogenic dizziness].
Zhonghua Nei Ke Za Zhi. 2014 Oct;53(10):768-71
Authors: Dong Q, Qi X
OBJECTIVE: To accumulate clinical experience and to direct clinical work.
METHODS: A total of 208 patients with psychogenic dizziness from department of neurology of Navy General Hospital of PLA were included in the study. Self-rating anxiety scale (SAS), self-rating depression scale (SDS) and Bech-Rafaelsen mania rating scale (BRMS) were used for the evaluation.
RESULTS: Among all the patients aged from 17 to 77 (the average age: 52), 152 were female and 56 were male. There were 3 types according to different clinical features and therapy prognosis: anxiety and depression type (176 cases, 84.6%) , hysteria type (18 cases, 8.7%) and mania type (14 cases, 6.7%) . The drugs increasing the concentration of excitatory had a good therapeutic efficacy on anxiety and depression type. Alluding cure had notable effect on hysteria type and mood stabilizer had notable effect on mania type.
CONCLUSIONS: Women tended to have psychogenic dizziness. It can be divided into three types: anxiety and depression type, hysteria type and mania type. Clinical symptoms and laboratory examination of each type have their own characteristics, and treatment strategies are also different.
PMID: 25567146 [PubMed - indexed for MEDLINE]
Patient-Important Outcomes in the Long-Term Treatment of Bipolar Disorder: A Mixed-Methods Approach Investigating Relative Preferences and a Proposed Taxonomy.
Patient. 2015 May 20;
Authors: Eiring Ø, Nylenna M, Nytrøen K
BACKGROUND: In patient-centered healthcare, the assessment and selection of treatment should be based on outcomes important to patients and the relative importance patients place on these outcomes. The evidence base on long-term treatment outcomes important to patients with bipolar disorder is inconclusive.
OBJECTIVE: The aim of this study was to investigate the relative importance of patient-important outcomes in bipolar disorder, and to construct a holistic and logically sound shortlist of treatment outcomes relevant in the evaluation and selection of pharmacological treatment in bipolar disorder.
METHOD: Overall, 22 outpatients from southern and eastern Norway participated in four focus groups, and suggested outcomes important in treatment decisions. Quantitative, relative importance weights for treatment outcomes identified in literature reviews were elicited from each participant, employing a self-explicated approach (SEA). The method combined a ranking- and rating-stated preference exercise and resulted in a 0-100 SEA-score for each outcome.
RESULTS: Outcomes from the literature accommodated the outcomes suggested in the focus groups. Mean age in the sample was 42 years and 64 % were women. All patients completed the exercises with consistent results. The most important outcomes were severe depression (median SEA 95 [interquartile range 26]), severe mania (76 ), quality of life (65 ), work/school functioning (58 ), and social functioning (54 ). Avoiding severe mania was significantly more important to patients with bipolar disorder type I compared with patients with type II. Outcome scores correlated strongly (p < 0.01) across the ranking and rating exercises. Based on the results, a simplified and consistent set of outcomes was constructed.
CONCLUSIONS: Patients' preferences for outcomes in the long-term treatment of bipolar disorder vary considerably. To advance patient-centered healthcare, we propose that researchers, clinical guideline producers, and patient-clinician dyads integrate a taxonomy of patient-important outcomes, such as constructed in this study, when assessing treatment options.
PMID: 25990222 [PubMed - as supplied by publisher]
Bipolar patients referred to specialized services of care: Not resistant but impaired by sub-syndromal symptoms. Results from the FACE-BD cohort.
Aust N Z J Psychiatry. 2015 May 19;
Authors: Henry C, Etain B, Godin O, Dargel AA, Azorin JM, Gard S, Bellivier F, Bougerol T, Kahn JP, Passerieux C, Aubin V, Courtet P, Leboyer M, FACE-BD group
OBJECTIVE: A national network of expert centers for bipolar disorders was set up in France to provide support, mainly for psychiatrists, who need help for managing bipolar disorder patients. The aims of this article are to present the main characteristics of the patients referred to an expert center in order to highlight the major disturbances affecting these patients and to understand the most significant difficulties encountered by practitioners dealing with bipolar disorder patients.
METHODS: Patients were evaluated by trained psychiatrists and psychologists, with standardized and systematic assessment using interviews and self-report questionnaires.
RESULTS: All patients (n = 839) met Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria for bipolar disorder I (48.4%), bipolar disorder II (38.1%) or bipolar disorder-not otherwise specified (13.5%). Mean illness duration was 17 years (±11.3), with 41.9% of patients having a history of suicide attempts. Lifetime comorbidities were 43.8% for anxiety disorders and 32.8% for substance abuse. At the point of inclusion, most patients (76.2%) were not in an acute phase, being considered to have a syndromal remission, but which still required referral to a tertiary system of care. Among these patients, 37.5% had mild to moderate residual depressive symptoms (Montgomery and Asberg Depression Rating Scale ranging from 7 to 19) despite 39% receiving an antidepressant. However, 47.8% were considered to be poorly adherent to medication; 55% showed evidence of sleep disturbances, with half being overweight; 68.1% of patients showed poor functioning (Functioning Assessment Short Test ? 12) with this being linked to residual depressive symptoms, sleep disturbances and increased body mass index.
CONCLUSIONS: It appears that bipolar disorder patients referred to an expert center in most cases do not suffer from a severe or resistant illness but they rather have residual symptoms, including subtle but chronic perturbations that have a major impact on levels of functioning. The longitudinal follow-up of these patients will enable a better understanding of the evolution of such residual symptoms.
PMID: 25991763 [PubMed - as supplied by publisher]
Delays before Diagnosis and Initiation of Treatment in Patients Presenting to Mental Health Services with Bipolar Disorder.
PLoS One. 2015;10(5):e0126530
Authors: Patel R, Shetty H, Jackson R, Broadbent M, Stewart R, Boydell J, McGuire P, Taylor M
BACKGROUND: Bipolar disorder is a significant cause of morbidity and mortality. Although existing treatments are effective, there is often a substantial delay before diagnosis and treatment initiation. We sought to investigate factors associated with the delay before diagnosis of bipolar disorder and the onset of treatment in secondary mental healthcare.
METHOD: Retrospective cohort study using anonymised electronic mental health record data from the South London and Maudsley NHS Foundation Trust (SLaM) Biomedical Research Centre (BRC) Case Register on 1364 adults diagnosed with bipolar disorder between 2007 and 2012. The following predictor variables were analysed in a multivariable Cox regression analysis: age, gender, ethnicity, compulsory admission to hospital under the UK Mental Health Act, marital status and other diagnoses prior to bipolar disorder. The outcomes were time to recorded diagnosis from first presentation to specialist mental health services (the diagnostic delay), and time to the start of appropriate therapy (treatment delay).
RESULTS: The median diagnostic delay was 62 days (interquartile range: 17-243) and median treatment delay was 31 days (4-122). Compulsory hospital admission was associated with a significant reduction in both diagnostic delay (hazard ratio 2.58, 95% CI 2.18-3.06) and treatment delay (4.40, 3.63-5.62). Prior diagnoses of other psychiatric disorders were associated with increased diagnostic delay, particularly alcohol (0.48, 0.33-0.41) and substance misuse disorders (0.44, 0.31-0.61). Prior diagnosis of schizophrenia and psychotic depression were associated with reduced treatment delay.
CONCLUSIONS: Some individuals experience a significant delay in diagnosis and treatment of bipolar disorder after initiation of specialist mental healthcare, particularly those who have prior diagnoses of alcohol and substance misuse disorders. These findings highlight a need for further study on strategies to better identify underlying symptoms and offer appropriate treatment sooner in order to facilitate improved clinical outcomes, such as developing specialist early intervention services to identify and treat people with bipolar disorder.
PMID: 25992560 [PubMed - as supplied by publisher]
Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder.
JAMA Psychiatry. 2015 May 20;
Authors: Genetics of Personality Consortium, de Moor MH, van den Berg SM, Verweij KJ, Krueger RF, Luciano M, Arias Vasquez A, Matteson LK, Derringer J, Esko T, Amin N, Gordon SD, Hansell NK, Hart AB, Seppälä I, Huffman JE, Konte B, Lahti J, Lee M, Miller M, Nutile T, Tanaka T, Teumer A, Viktorin A, Wedenoja J, Abecasis GR, Adkins DE, Agrawal A, Allik J, Appel K, Bigdeli TB, Busonero F, Campbell H, Costa PT, Davey Smith G, Davies G, de Wit H, Ding J, Engelhardt BE, Eriksson JG, Fedko IO, Ferrucci L, Franke B, Giegling I, Grucza R, Hartmann AM, Heath AC, Heinonen K, Henders AK, Homuth G, Hottenga JJ, Iacono WG, Janzing J, Jokela M, Karlsson R, Kemp JP, Kirkpatrick MG, Latvala A, Lehtimäki T, Liewald DC, Madden PA, Magri C, Magnusson PK, Marten J, Maschio A, Medland SE, Mihailov E, Milaneschi Y, Montgomery GW, Nauck M, Ouwens KG, Palotie A, Pettersson E, Polasek O, Qian Y, Pulkki-Råback L, Raitakari OT, Realo A, Rose RJ, Ruggiero D, Schmidt CO, Slutske WS, Sorice R, Starr JM, St Pourcain B, Sutin AR, Timpson NJ, Trochet H, Vermeulen S, Vuoksimaa E, Widen E, Wouda J, Wright MJ, Zgaga L, Porteous D, Minelli A, Palmer AA, Rujescu D, Ciullo M, Hayward C, Rudan I, Metspalu A, Kaprio J, Deary IJ, Räikkönen K, Wilson JF, Keltikangas-Järvinen L, Bierut LJ, Hettema JM, Grabe HJ, van Duijn CM, Evans DM, Schlessinger D, Pedersen NL, Terracciano A, McGue M, Penninx BW, Martin NG, Boomsma DI
Importance: Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63?000 participants (including MDD cases).
Objectives: To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD.
Design, Setting, and Participants: Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63?661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014.
Main Outcomes and Measures: Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts.
Results: A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P?=?9.26?×?10-9 in the discovery meta-analysis). This association was not replicated (P?=?.32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P?=?2.38?×?10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09?×?10-12?<?P?<?.05) and MDD (4.02?×?10-9?<?P?<?.05) in the 2 other cohorts.
Conclusions and Relevance: This study identifies a novel locus for neuroticism. The variant is located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies. In addition, the study shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagged by common variants. These genetic variants also influence MDD. Future studies should confirm the role of the MAGI1 locus for neuroticism and further investigate the association of MAGI1 and the polygenic association to a range of other psychiatric disorders that are phenotypically correlated with neuroticism.
PMID: 25993607 [PubMed - as supplied by publisher]
The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders.
Neuroscience. 2015 May 14;
Authors: Réus GZ, Fries GR, Stertz L, Badawy M, Passos IC, Barichello T, Kapczinski F, Quevedo J
Psychiatric disorders, including major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia, affect a significant percentage of the world population. These disorders are associated with educational difficulties, decreased productivity and reduced quality of life, but their underlying pathophysiological mechanisms are not fully elucidated. Recently, studies have suggested that psychiatric disorders could be considered as inflammatory disorders, even though the exact mechanisms underlying this association are not known. An increase in inflammatory response and oxidative stress may lead to inflammation, which in turn can stimulate microglia in the brain. Microglial activation is roused by M1 phenotype, which is associated with an increase in interleukin-1? (IL-1?) and tumor necrosis factor-? (TNF-?). On the contrary, M2 phenotype is associated with a release of anti-inflammatory cytokines. Thus, it is possible that the inflammatory response from microglial activation can contribute to brain pathology, as well as influence treatment responses. This review will highlight the role of inflammation in the pathophysiology of psychiatric disorders, such as MDD, BD, schizophrenia, and autism. More specifically, the role of microglial activation and associated molecular cascades will also be discussed as a means by which these neuroinflammatory mechanisms take place, when appropriate.
PMID: 25981208 [PubMed - as supplied by publisher]
Free thyroxine levels are associated with cognitive abilities in subjects with early psychosis.
Schizophr Res. 2015 May 14;
Authors: Barbero JD, Gutiérrez-Zotes A, Montalvo I, Creus M, Cabezas Á, Solé M, Algora MJ, Garcia-Parés G, Vilella E, Labad J
INTRODUCTION: Subjects with a psychotic disorder show mild to moderate cognitive impairment, which is an important determinant of functional outcome. The underlying biological process of cognitive impairment in psychosis is unclear. We aimed to explore whether hypothalamic-pituitary-thyroid axis hormones or thyroid autoimmunity modulate cognitive functioning in subjects with early psychosis.
METHODS: We studied 70 patients with a psychotic disorder (<3years of illness) and a control group of 37 healthy subjects (HS). Plasma levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroid-peroxidase (TPO-Abs) and thyroglobulin antibodies (TG-Abs) were determined. Cognitive assessment was performed with the MATRICS Cognitive Consensus Cognitive Battery. We also explored the relationship between thyroid variables and cognition in three subgroups of psychotic patients: psychosis not otherwise specified, affective psychosis (bipolar disorder or schizoaffective disorder) and non-affective psychosis (schizophrenia or schizophreniphorm disorder).
RESULTS: In patients with early psychosis, higher FT4 levels (but not TSH or thyroid antibodies) were associated with better cognitive performance in attention/vigilance and overall cognition. The relationship between FT4 levels and the attention/vigilance domain remained significant in a multivariate analysis after adjusting for education level, age, gender, substance use, and benzodiazepine and antipsychotic treatments. We did not find a significant association between FT4 and cognitive performance in HS. In the exploratory analysis by psychotic subtypes, subjects with affective psychosis had increased FT4 levels and better cognitive profile than those with non-affective psychosis.
CONCLUSIONS: Our study suggests that FT4 levels are associated with cognitive abilities (attention/vigilance and overall cognition) in individuals with early psychosis.
PMID: 25982813 [PubMed - as supplied by publisher]
Verbal learning impairment in euthymic bipolar disorder: BDI v BDII.
J Affect Disord. 2015 Apr 20;182:95-100
Authors: Bourne C, Bilderbeck A, Drennan R, Atkinson L, Price J, Geddes JR, Goodwin GM
OBJECTIVES: Cognitive impairment is known to occur in bipolar disorder (BD), even in euthymic patients, with largest effect sizes often seen in Verbal Learning and Memory Tasks (VLT). However, comparisons between BD Type-I and Type-II have produced inconsistent results partly due to low sample sizes.
METHODS: This study compared the performance of 183 BDI with 96 BDII out-patients on an adapted version of the Rey Verbal Learning Task. Gender, age, years of education, mood scores and age at onset were all used as covariates. Current medication and a variety of illness variables were also investigated for potential effects on VLT performance.
RESULTS: BDI patients were significantly impaired relative to BDII patients on all five VLT outcome measures after controlling for the other variables [Effect Sizes=.13-.17]. The impairments seem to be unrelated to drug treatment and largely unrelated to illness variables, although age of onset affected performance on three outcome measures and number of episodes of mood elevation affected performance on one.
LIMITATIONS: This study used historical healthy controls. Analysis of potential drug effects was limited by insufficient participants not being drug free. Cross-sectional nature of the study limited the analysis of the potential effect of illness variables.
CONCLUSIONS: This study replicates earlier findings of increased verbal learning impairment in BDI patients relative to BDII in a substantially larger sample. Such performance cannot be wholly explained by medication effects or illness variables. Thus, the cognitive impairment is likely to reflect a phenotypic difference between bipolar sub-types.
PMID: 25983304 [PubMed - as supplied by publisher]
Guidelines concordance of maintenance treatment in euthymic patients with bipolar disorder: Data from the national bipolar mania pathway survey (BIPAS) in mainland China.
J Affect Disord. 2015 Apr 23;182:101-105
Authors: Wang Z, Chen J, Zhang C, Gao K, Hong W, Xing M, Wu Z, Yuan C, Huang J, Peng D, Wang Y, Lu W, Yi Z, Yu X, Zhao J, Fang Y
BACKGROUND: Although the treatment guidelines of bipolar disorders (BPD) have spread more than a decade, the concordance with evidence-based guidelines was typically low in routine clinical practice. This study is to present the data on the maintenance treatment of BPD in mainland China.
METHODS: One thousand and twenty-three patients who had experienced a euthymia were eligible for entry into this survey on the maintenance treatment of BPD. Guidelines disconcordance was determined by comparing the medication(s) that patients were prescribed with the recommendations in the guidelines of the Canadian Network for Mood and Anxiety Treatments.
RESULTS: Three hundred and sixty-four patients (35.6%) had not been prescribed with the maintenance treatment as guidelines recommendations, and 208 patients (20.3%) were prescribed with the antidepressants. A longer duration of BPD, a depressive episode at first onset, and a recent depressive or mixed episode significantly increased the risk for guidelines disconcordance and prescribing antidepressant. In contrast, a hospitalization history due to manic episode was associated with a significant decrease in the risk for guidelines disconcordance and prescribing antidepressant.
LIMITATION: This study was a cross-sectional and retrospective investigation based on medical records.
CONCLUSIONS: Considering the potentially hazardous effects of inappropriate treatment, individualized psychoeducational strategies for subjects with BPD are necessary to enhance treatment adherence and close the gap between guidelines and clinical practice in mainland China.
PMID: 25983305 [PubMed - as supplied by publisher]
Cost-effectiveness of lurasidone versus quetiapine extended-release (XR) in patients with bipolar depression.
J Med Econ. 2015 May 18;:1-22
Authors: Rajagopalan K, Meyer K, O'Day K, Denno M, Loebel A
OBJECTIVE: Bipolar disorder imposes a high economic burden on patients and society. Lurasidone and quetiapine extended-release (XR) are atypical antipsychotic agents indicated for monotherapy treatment of bipolar depression. Lurasidone is also indicated as adjunctive therapy with lithium or valproate for depressive episodes associated with bipolar disorder. The objective of this analysis was to estimate the cost-effectiveness of lurasidone and quetiapine XR in patients with bipolar depression.
METHODS: A cost-effectiveness model was developed to compare lurasidone to quetiapine XR. The model was based on a United States third-party payer perspective over a 3-month time horizon. The effectiveness measure in the model was the percentage of patients achieving remission (Montgomery-Åsberg Depression Rating Scale [MADRS] total score ?12 by week 6 to 8). The comparison of remission rates was made through an adjusted indirect treatment comparison of lurasidone and quetiapine XR pivotal trials using placebo as the common comparator. Resource utilization for remission versus no remission was estimated from published expert panel data, and resource costs were obtained from a retrospective database study of bipolar I depression patients. Drug costs were estimated using the mean dose from clinical trials and wholesale acquisition costs.
RESULTS: Over the 3-month model time period, lurasidone and quetiapine XR patients, respectively, had similar mean numbers of emergency department visits (0.48 vs 0.50), inpatient days (2.1 vs 2.2), and office visits (9.3 vs 9.6). More lurasidone than quetiapine XR patients achieved remission (52.0% vs 43.2%) with slightly higher total costs ($4,982 vs $4,676), resulting in an incremental cost-effectiveness ratio of $3,474 per remission. The probabilistic sensitivity analysis showed lurasidone had an 86% probability of being cost-effective compared to quetiapine XR at a willingness-to-pay of $10,000 per remission.
CONCLUSIONS: Lurasidone may be a cost-effective option when compared to quetiapine XR for the treatment of adults with bipolar depression.
PMID: 25985265 [PubMed - as supplied by publisher]
Predictors of functional outcome after a manic episode.
J Affect Disord. 2015 May 2;182:121-125
Authors: Bonnín CM, Reinares M, Hidalgo-Mazzei D, Undurraga J, Mur M, Sáez C, Nieto E, Vázquez GH, Balanzá-Martínez V, Tabarés-Seisdedos R, Vieta E
BACKGROUND: The identification of functional outcome predictors after acute episodes of bipolar disorders (BD) may allow designing appropriate treatment aiming at restoring psychosocial functioning. Our objective was to identify the best functional outcome predictors at a 6-month follow-up after an index manic episode.
METHODS: We conducted a naturalistic trial (MANACOR) focusing on the global burden of BD, with special emphasis on manic episode-associated costs. We observed patients with BD seen in services of four hospitals in Catalonia (Spain).The total sample included 169 patients with chronic DSM-IV-TR BD I suffering from an acute manic episode who were followed-up for 6 months. In this subanalysis we report the results of a stepwise multiple regression conducted by entering in the model those clinical and sociodemographic variables that were identified through preliminary bivariate Pearson correlations and using total scores on the Functioning Assessment Short Test (FAST) at the 6-month follow-up as the dependent variable.
RESULTS: Number of previous depressive episodes (Beta=3.25; t=3.23; p=0.002), presence of psychotic symptoms during the manic index episode (Beta=7.007; t=2.2; p=0.031) and the Body Mass Index (BMI) at baseline (Beta=0.62; t=2.09; p=0.041) were best predictors of functional outcome after a manic episode.
LIMITATIONS: The main limitations of this study include the retrospective assessment of the episodes, which can be a source of bias, and the 6-month follow-up might have been too short for assessing the course of a chronic illness.
CONCLUSIONS: Psychotic symptoms at index episode, number of past depressive episodes, and BMI predict worse outcome after 6 months follow-up after a manic episode, and may constitute the target of specific treatment strategies.
PMID: 25985381 [PubMed - as supplied by publisher]
Acute kidney injury, hyperbilirubinemia, and ischemic skin necrosis due to massive sulindac overdose.
Curr Drug Saf. 2015;10(2):190-2
Authors: Vaughn JL, Shah KV, Ghossein MM, Meyer WL, Kirkpatrick RB
Sulindac is a long-acting nonsteroidal anti-inflammatory drug (NSAID) widely used for the management of osteoarthritis, rheumatoid arthritis, ankylosing sponydlitis, and acute gouty arthritis. Reports of sulindac toxicity in the literature are rare. We report the case of a 22-year old male with a history of bipolar disorder who was brought to the emergency department after ingesting approximately 15 g of sulindac in a suicide attempt. He was found to have acute kidney injury and hyperbilirubinemia. Despite aggressive fluid resuscitation, his renal function progressively worsened requiring the initiation of hemodialysis. Ten days following ingestion of sulindac, he began to develop ischemic skin changes with a gangrenous appearance in his hands and feet. He continued to receive supportive treatment, and his acute kidney injury, hyperbillirubinemia, and ischemic skin necrosis eventually resolved. Clinicians should be aware of this long-acting NSAID and its ability to cause prolonged multisystem organ dysfunction.
PMID: 25986039 [PubMed - in process]
Expression profiles of human CCN genes in patients with osteoarthritis or rheumatoid arthritis.
J Orthop Sci. 2015 May 19;
Authors: Komatsu M, Nakamura Y, Maruyama M, Abe K, Watanapokasin R, Kato H
OBJECTIVE: Osteoarthritis (OA) and rheumatoid arthritis (RA) are widespread disabling joint disorders that are considered to be polygenic in nature. This study investigated the spatial expression patterns of all six known human CCN genes using end-stage OA and RA joint samples.
DESIGN: We performed in situ hybridization and histological analysis to investigate the spatial expression patterns of human CCN genes using joint tissues obtained during total knee and hip joint replacement procedures on patients with advanced OA or RA. Normal joint tissues taken while performing bipolar hip replacement surgeries were used as controls.
RESULTS: All CCN genes were expressed at higher levels in OA and RA synovial samples as compared with normal controls. Whereas CCN3 and CCN6 were undetectable in control, OA, and RA cartilage, CCN1, CCN2, CCN4, and CCN5 were expressed to a greater extent in OA and RA knee cartilage.
CONCLUSIONS: Our results indicate an involvement of several CCN genes in the pathophysiology of OA and RA.
PMID: 25986313 [PubMed - as supplied by publisher]
Does lithium reduce acute suicidal ideation and behavior? A protocol for a randomized, placebo-controlled multicenter trial of lithium plus Treatment As Usual (TAU) in patients with suicidal major depressive episode.
BMC Psychiatry. 2015 May 19;15(1):117
Authors: Lewitzka U, Jabs B, Fülle M, Holthoff V, Juckel G, Uhl I, Kittel-Schneider S, Reif A, Reif-Leonhard C, Gruber O, Djawid B, Goodday S, Haussmann R, Pfennig A, Ritter P, Conell J, Severus E, Bauer M
BACKGROUND: Lithium has proven suicide preventing effects in the long-term treatment of patients with affective disorders. Clinical evidence from case reports indicate that this effect may occur early on at the beginning of lithium treatment. The impact of lithium treatment on acute suicidal thoughts and/or behavior has not been systematically studied in a controlled trial. The primary objective of this confirmatory study is to determine the association between lithium therapy and acute suicidal ideation and/or suicidal behavior in inpatients with a major depressive episode (MDE, unipolar and bipolar disorder according to DSM IV criteria). The specific aim is to test the hypothesis that lithium plus treatment as usual (TAU), compared to placebo plus TAU, results in a significantly greater decrease in suicidal ideation and/or behavior over 5 weeks in inpatients with MDE.
METHODS/DESIGN: We initiated a randomized, placebo-controlled multicenter trial. Patients with the diagnosis of a moderate to severe depressive episode and suicidal thoughts and/or suicidal behavior measured with the Sheehan-Suicidality-Tracking Scale (S-STS) will be randomly allocated to add lithium or placebo to their treatment as usual. Change in the clinician administered S-STS from the initial to the final visit will be the primary outcome.
DISCUSSION: There is an urgent need to identify treatments that will acutely decrease suicidal ideation and/or suicidal behavior. The results of this study will demonstrate whether lithium reduces suicidal ideation and behavior within the first 5 weeks of treatment.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02039479.
PMID: 25986590 [PubMed - as supplied by publisher]
Genetic and genomic analyses as a basis for new diagnostic nosologies.
Dialogues Clin Neurosci. 2015 Mar;17(1):69-78
Authors: Gershon ES, Grennan KS
For schizophrenia, bipolar disorder, and autism, clinical descriptions are precise and reliable, but there is great overlap among diagnoses in associated genetic polymorphisms and rare variants, treatment response, and other phenomenological findings such as brain imaging. It is widely hoped that new diagnostic categories can be developed which are more precise and predictive of important features of illness, particularly response to pharmacological agents. It is the intent of this paper to describe the diagnostic implications of some current genetic findings, and to describe how the genetic associations with diagnosis may be teased apart into new associations with biologically coherent diagnostic entities and scales, based on the various functional aspects of the associated genes and functional genomic data.
PMID: 25987865 [PubMed - in process]
Genetic association study of circadian genes with seasonal pattern in bipolar disorders.
Sci Rep. 2015;5:10232
Authors: Geoffroy PA, Lajnef M, Bellivier F, Jamain S, Gard S, Kahn JP, Henry C, Leboyer M, Etain B
About one fourth of patients with bipolar disorders (BD) have depressive episodes with a seasonal pattern (SP) coupled to a more severe disease. However, the underlying genetic influence on a SP in BD remains to be identified. We studied 269 BD Caucasian patients, with and without SP, recruited from university-affiliated psychiatric departments in France and performed a genetic single-marker analysis followed by a gene-based analysis on 349 single nucleotide polymorphisms (SNPs) spanning 21 circadian genes and 3 melatonin pathway genes. A SP in BD was nominally associated with 14 SNPs identified in 6 circadian genes: NPAS2, CRY2, ARNTL, ARNTL2, RORA and RORB. After correcting for multiple testing, using a false discovery rate approach, the associations remained significant for 5 SNPs in NPAS2 (chromosome 2:100793045-100989719): rs6738097 (pc?=?0.006), rs12622050 (pc?=?0.006), rs2305159 (pc?=?0.01), rs1542179 (pc?=?0.01), and rs1562313 (pc?=?0.02). The gene-based analysis of the 349 SNPs showed that rs6738097 (NPAS2) and rs1554338 (CRY2) were significantly associated with the SP phenotype (respective Empirical p-values of 0.0003 and 0.005). The associations remained significant for rs6738097 (NPAS2) after Bonferroni correction. The epistasis analysis between rs6738097 (NPAS2) and rs1554338 (CRY2) suggested an additive effect. Genetic variations in NPAS2 might be a biomarker for a seasonal pattern in BD.
PMID: 25989161 [PubMed - as supplied by publisher]
Reduced prefrontal activation during performance of the Iowa Gambling Task in patients with bipolar disorder.
Psychiatry Res. 2015 Apr 30;
Authors: Ono Y, Kikuchi M, Hirosawa T, Hino S, Nagasawa T, Hashimoto T, Munesue T, Minabe Y
The Iowa Gambling Task (IGT) is a complex decision-making task in which monetary wins and losses guide the development of strategies. The objective of this study was to evaluate hemodynamic responses of patients with bipolar disorder (BD) during performance of the IGT using near-infrared spectroscopy (NIRS). Participants comprised 13 patients and 15 healthy control subjects who were matched for age, sex, handedness, and intelligence quotient. Relative changes in oxygenated and deoxygenated hemoglobin (oxy-Hb and deoxy-Hb) levels in the frontal region were measured using a 46-channel NIRS system. All subjects were evaluated using NIRS during a verbal fluency task (VFT) and the IGT. During performance of the IGT, BD patients showed significantly decreased oxy-Hb levels in the bilateral orbitofrontal cortex (OFC) and left prefrontal cortex (PFC) compared with normal control subjects. However, during the VFT, patients with BD showed no significant changes in oxy-Hb levels compared with control subjects. Changes in oxy-Hb levels in the bilateral OFC and the PFC during the IGT were negatively correlated with total scores on the Hamilton Rating Scale for Depression (HAM-D). Although the IGT was useful for differentiating patients with BP from control subjects, no significant differences in autonomic activity were observed.
PMID: 25978934 [PubMed - as supplied by publisher]
Every family has a north star: family healing and recovery.
Psychiatr Rehabil J. 2014 Sep;37(3):261-2
Authors: Kaplan E
TOPIC: This contribution describes a personal recovery journey and the creation of an organization focused on rebuilding relationships between members of families living with a parent(s) with psychiatric disabilities.
PURPOSE: Adults living with serious mental illnesses have the same hopes and dreams of being successful and resourceful parents to their children and contributing family members as other parents. Specific suggestions highlight ways in which mental health and psychiatric rehabilitation practitioners can support and promote recovery for families.
SOURCES USED: Personal data and resource information available on the Child and Family Connections website located at http://www.childfamilyconnections.org.
CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Practical guidelines are offered to engage and work with parents living with mental illnesses. Improving our understanding and capacity to better meet the needs of parents with psychiatric disabilities will more likely enhance their roles as parents.
PMID: 25180527 [PubMed - indexed for MEDLINE]
Population pharmacokinetic modeling of quetiapine after administration of SEROQUEL and SEROQUEL XR formulations to western and Chinese patients with schizophrenia, schizoaffective disorder or bipolar disorder.
J Clin Pharmacol. 2015 May 14;
Authors: Zhou D, Bui KH, Li J, Al-Huniti N
A population model describing the quetiapine pharmacokinetics (PK) in Western and Chinese patients following oral administration of immediate release (IR) and extended release (XR) formulations was developed using plasma concentrations in 127 patients from 5 studies with quetiapine IR and/or XR in Western patients and one study with quetiapine XR in Chinese patients. A one-compartmental model with first-order absorption and first-order elimination adequately described the quetiapine PK. The typical apparent volume of distribution and elimination rate constant of quetiapine were 574 L and 0.12 h(-1) , respectively. The estimated population absorption rate constants were 1.46 and 0.10 h(-1) for quetiapine IR and XR, respectively. Covariate analysis revealed that race was not a significant covariate influencing the PK of quetiapine. Simulation conducted with final quetiapine population PK model predicted that administration of 200?mg twice daily dose of quetiapine IR in Chinese patients would achieve a steady-state AUC (AUCss ) (±?standard deviation) of 3087?±?1480?ng/mL*h, which is in close agreement with the reported value (3538?±?1728?ng/mL*h). The model also predicted that once-daily administration of 300?mg quetiapine IR or XR would achieve similar exposure in terms of AUCss in Chinese patients. This article is protected by copyright. All rights reserved.
PMID: 25975812 [PubMed - as supplied by publisher]
Evaluation of the Safety Profile of Zolafren(®), a Generic Olanzapine Formulation, in Patients with Bipolar Disorder: A Post-Authorization Safety Study.
Adv Ther. 2015 May 15;
Authors: Chudek J, Olszanecka-Glinianowicz M, Almgren-Rachtan A, Gabryelewicz T
INTRODUCTION: Prior to registration, no clinical trial evaluating safety and tolerability of Zolafren(®) (Adamed Sp. z o.o., Czosnów, Poland), a generic olanzapine formulation, had been performed. Therefore, the aim of this post-authorization safety study (PASS) was to evaluate the safety and tolerability of Zolafren in patients with bipolar disorder (BD).
METHODS: Adverse events (AEs) associated with the use of Zolafren were recorded in a PASS, in an open-label, non-randomized, multicenter observational study involving 20,698 outpatients with BD.
RESULTS: Zolafren was used in both monotherapy (82.8%) and polytherapy (17.2%) at a mean dose of 12.1 ± 4.2 mg. The most commonly used formulation was coated tablets (70.9%). Orally dissolving tablets (19.7%) and hard capsules (9.4%) were less commonly used. During a period of 171 ± 47 days of exposure to Zolafren, 5883 AEs were reported in 2138 patients (10.3% of the study population). None of the reported AEs were severe. Zolafren-associated AEs were the reason for discontinuation in 43 patients and the reason for dose reduction in a further 762 patients. The most common AE was weight gain (by 1.6 ± 3.3 kg) which was considered unrelated to the dose of Zolafren. During follow-up, the percentage of patients with very good tolerance with Zolafren increased from 44.4% to 59.8%. The percentage of patients who had confidence in Zolafren also increased.
CONCLUSION: The results of this PASS support the safety of Zolafren use and indicate a high tolerance in patients treated for BD.
FUNDING: Adamed Sp. z o.o., Czosnów, Poland.
PMID: 25975817 [PubMed - as supplied by publisher]
The first antenatal appointment: An exploratory study of the experiences of women with a diagnosis of mental illness.
Midwifery. 2015 Apr 16;
Authors: Phillips L, Thomas D
OBJECTIVE: to explore and gain insight into the expectations and experiences of women with a pre-existing diagnosis of mental illness, of their first booking appointment; to make recommendations for practice development and collaborative partnership working between healthcare professionals.
DESIGN: a qualitative design using semi structured interviews and thematic analysis of the data. QSR NVivo 10 software is used to organise the data into themes.
SETTING: the interviews took place either at the women?s homes, or within the antenatal service with the consent of the woman and relevant practitioners.
PARTICIPANTS: twelve participants were selected from one antenatal clinic and one perinatal mental health service.
FINDINGS: the themes identified within the data included the lack of information prior to the initial midwife booking appointment; the perception of too much information at the initial booking appointment and women not being clear about their mental health needs at this time; a general positivity about disclosing mental illness diagnoses; overall positive thoughts about midwives although some midwives appeared less knowledgeable about bipolar disorder, and perceptions about a lack of joined up working between antenatal and perinatal mental health services.
KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: it is recommended that GPs receive adequate training in order to equip them with the skills needed to discuss sensitive issues around perinatal mental illness and the impact on pregnancy and childbirth. Women require more information about their booking appointment, and it would be beneficial for their emotional and physical health needs to be assessed at each follow-up antenatal appointment. Midwives need to be facilitated to receive up-to-date knowledge of antenatal and postnatal mental illness and treatments, and the referral process to perinatal mental health services.
PMID: 25975830 [PubMed - as supplied by publisher]
Short- and Long-Term Outcomes of Mental Health Court Participants by Psychiatric Diagnosis.
Psychiatr Serv. 2015 May 15;:appips201400230
Authors: Comartin E, Kubiak SP, Ray B, Tillander E, Hanna J
OBJECTIVE: The goal of mental health courts (MHCs) is to decrease incarceration and recidivism while increasing continuity of mental health treatment. Although previous research has found positive outcomes, questions remain unanswered regarding the population for which MHCs work best. No studies have assessed potential differences in MHC outcomes by psychiatric diagnosis. This study filled the gap by addressing the following research question: Are there differences in short-term program outcomes and in long-term recidivism and mental health engagement outcomes by psychiatric diagnosis?
METHODS: The study was a cross-site evaluation of eight MHCs in a single state. To assess long-term outcomes, this study analyzed data from participants who had been discharged from an MHC for at least one year (N=234). Four diagnostic categories were used: bipolar disorder, depressive disorder, schizophrenia, and "other" disorder. Demographic, programmatic, recidivism, and mental health treatment data for each individual were collected from state administrative agencies.
RESULTS: The findings suggest no differences by diagnosis in short-term outcomes or recidivism; however, significant reductions in use of high-intensity mental health services were noted for individuals with schizophrenia.
CONCLUSIONS: Findings support inclusive eligibility for MHC participation across diagnostic categories and should inform policy and practice in regard to MHC development and operation. Future research should examine other key characteristics to determine ways in which resources can be best utilized.
PMID: 25975887 [PubMed - as supplied by publisher]
Influence of Criminal Justice Involvement and Psychiatric Diagnoses on Treatment Costs Among Adults With Serious Mental Illness.
Psychiatr Serv. 2015 May 15;:appips201500134
Authors: Robertson AG, Swanson JW, Lin H, Easter MM, Frisman LK, Swartz MS
The impact of criminal justice involvement and clinical characteristics on the cost of public treatment services for adults with serious mental illnesses is unknown. The authors examined differential effects of justice involvement on behavioral health treatment costs by primary psychiatric diagnosis (schizophrenia or bipolar disorder) and also by substance use diagnosis among 25,133 adult clients of Connecticut's public behavioral health system in fiscal years 2006 and 2007. Justice-involved adults with schizophrenia had the highest costs, strongly driven by forensic hospitalizations. Addressing the cross-system burdens of forensic hospitalizations may be a sensible starting point in the effort to reduce costs in both the public behavioral health and justice systems.
PMID: 25975893 [PubMed - as supplied by publisher]
[Magnetic resonance spectroscopy in lenticular nucleus of Bipolar II disorder and its relation with cognitive function].
Zhonghua Yi Xue Za Zhi. 2015 Mar;95(9):672-5
Authors: Zhang H, Wen S, Wang J, Cheng M, Wang H
OBJECTIVE: To explore the magnetic resonance spectroscopy characteristics of lenticular nucleus in Bipolar II disorder and its relation with cognitive function.
METHODS: Thirty Bipolar II disorder patients in hospital from 2012 September to 2013 April and twenty healthy controls were evaluated with Multi-Voxel 1H-MRS scans on lenticular nucleus to assess the NAA, Cho, Cr and MI. All subjects were assessed for attention using the Stroop Test and executive function by Wisconsin card sorting test.
RESULTS: NAA, Cho, Cr in right lenticular nucleus and Cr in left lenticular nucleus were lower than healthy controls (P < 0.05). The patients showed significant cognitive impairment in all aspects of Stroop Test and Wisconsin card sorting test (P < 0.05). NAA in right lenticular nucleus was positively correlated with correct number of Stroop-CW.
CONCLUSIONS: Neural dysfunction in right lenticular nucleus of Bipolar II disorder may influence attention function. Cellular energy metabolism rate was reduced in bilateral lenticular nucleus.
PMID: 25976048 [PubMed - in process]
CACNA1C rs1006737 Genotype and Bipolar Disorder: Focus on Intermediate Phenotypes and Cardiovascular Comorbidity.
Neurosci Biobehav Rev. 2015 May 11;
Authors: Ou X, Crane DE, MacIntosh BJ, Young LT, Arnold P, Ameis S, Goldstein BI
Recently, multiple genome-wide association studies have identified a genetic polymorphism (CACNA1C rs1006737) that appears to confer susceptibility for BD. This article aims to summarize the existing literature regarding the impact of rs1006737 on functional and structural neuroimaging intermediate phenotypes. Twenty-eight articles, representing 2486 healthy participants, 369 patients with BD and 104 healthy first-degree relatives of patients with BD, are incorporated. Multiple studies have demonstrated structural differences, functional differences associated with emotion-related and frontal-executive tasks, and/or differences in behavioral task performance in risk allele carriers (AA or AG). Results comparing participants with BD to healthy controls are generally less pronounced than within-group genetic comparisons. The review concludes with an integration of how cardiovascular comorbidity may be a relevant mediator of the observed findings, and proposes future directions toward optimized therapeutic use of calcium channel blockers in BD.
PMID: 25976633 [PubMed - as supplied by publisher]
Intervening early in children with bipolar disorder: is there a pot at the end of the Rainbow?
Evid Based Ment Health. 2015 May 14;
Authors: Miklowitz DJ
PMID: 25977406 [PubMed - as supplied by publisher]
Misdiagnosis, duration of untreated illness (DUI) and outcome in bipolar patients with psychotic symptoms: A naturalistic study.
J Affect Disord. 2015 Apr 22;182:70-75
Authors: Altamura AC, Buoli M, Caldiroli A, Caron L, Cumerlato Melter C, Dobrea C, Cigliobianco M, Zanelli Quarantini F
BACKGROUND: A number of data show the negative role of duration of untreated illness (DUI) on outcome in mood disorders, but no investigation has been carried out about the impact of this variable in bipolar disorder (BD) with psychotic symptoms. Clinical experience shows that many bipolar patients with psychotic symptoms receive other diagnoses and often are chronically treated with first generation antipsychotics, with the effect to reduce duration of untreated psychosis/untreated episode with psychotic symptoms (DUP), but not DUI. Purpose of the study was to define the rate of misdiagnosis and the impact of DUP/DUI on outcome of bipolar patients with psychotic symptoms.
METHOD: Clinical information (DUP, DUI, first received diagnosis) about bipolar outpatients with psychotic symptoms (N=240) were extrapolated through a retrospective review of the clinical charts, Lombardy database and, if necessary, through clinical interviews with patients and their relatives. Outcome measures included psychiatric and substance abuse comorbidity, occupational status, Global Assessment of Functioning (GAF), number of hospitalizations and of suicidal attempts, number of depressive/manic recurrences. Patients were divided in two groups according to the DUP (1 year) and DUI (8 years) median, and the groups were compared through analyses of variance (ANOVAs) for continuous variables or ?(2) tests for dichotomous ones. Multivariate analysis of variance (MANOVA) with duration of illness as covariate was then performed to eliminate the effect of this variable. Finally, binary logistic regressions were performed considering age at onset, DUI, DUP as independent variables and outcome variables as dependent ones (presence of hospitalizations/suicidal attempts, GAF scores<50, occupational status).
RESULTS: Most of patients (61.5%) received a first diagnosis different from BD with the most frequent DSM-diagnosis being delusional disorder (17.9%). Patients with longer DUP were not different in outcome measures with respect to patients with shorter DUP. Patients with a DUI >8 years presented higher number of hospitalizations (F=6.04, p=0.015), higher number of manic recurrences (F=5.25, p=0.023), higher number of depressive recurrences (F=7.13, p=0.008) and lower GAF scores (F=17.74, p<0.001). Statistical significance persisted for number of hospitalizations (p<0.001) and GAF scores (p=0.003) after MANOVA. Finally binary logistic regression showed that a longer DUI was predictive of GAF scores<50 (F=17.74, p<0.001).
DISCUSSION: More than half of bipolar patients with psychotic symptoms receive a different diagnosis at first contact with psychiatric services. DUI (but not DUP) is a predictor of outcome in bipolar patients with psychotic symptoms. This indicates that an early diagnosis and proper treatment with a mood stabilizer (or an atypical antipsychotic with mood stabilizing effects) may improve long-term outcome of these patients. In the light of the naturalistic design of the present paper, these results have to be considered as preliminary and have to be confirmed by prospective controlled studies.
PMID: 25978716 [PubMed - as supplied by publisher]
Placebo-Controlled Trial of Valproic Acid Versus Risperidone in Children 3-7 Years of Age with Bipolar I Disorder.
J Child Adolesc Psychopharmacol. 2015 May;25(4):306-313
Authors: Kowatch RA, Scheffer RE, Monroe E, Delgado S, Altaye M, Lagory D
OBJECTIVE: The objective of this study was to determine the efficacy and safety of valproic acid versus risperidone in children, 3-7 years of age, with bipolar I disorder (BPD), during a mixed or manic episode.
METHODS: Forty-six children with Diagnostic and Statistical Manual of Mental Disorders. 4th ed., Text Revision (DSM-IV-TR) diagnosis of bipolar disorder, manic, hypomanic, or mixed episode, were recruited over a 6 year period from two academic outpatient programs for a double-blinded, placebo-controlled trial in which subjects were randomized in a 2:2:1 ratio to risperidone solution, valproic acid, or placebo.
RESULTS: After 6 weeks of treatment, the least-mean Young Mania Rating Scale (YMRS) total scores change, adjusted for baseline YMRS scores, from baseline by treatment group was: Valproic acid 10.0±2.46 (p=0.50); risperidone 18.82±1.55 (p=0.008); and placebo 4.29±3.56 (F=3.93, p=0.02). The mixed models for repeated measure (MMRM) analysis found a significant difference for risperidone-treated subjects versus placebo treated subjects (p=0.008) but not for valproic acid-treated subjects versus placebo-treated subjects (p=0.50). Treatment with risperidone over 6 weeks led to increased prolactin levels, liver functions, metabolic measures, and weight/body mass index (BMI). Treatment with valproic acid led to increases in weight/BMI and decreases in total red blood cells (RBC), hemoglobin, and hematocrit.
CONCLUSIONS: In this small sample of preschool children with BPD, risperidone demonstrated clear efficacy versus placebo, whereas valproic acid did not. The laboratory and weight findings suggest that younger children with BPD are more sensitive to the effects of both of these psychotropics, and that, therefore, frequent laboratory and weight monitoring are warranted.
PMID: 25978742 [PubMed - as supplied by publisher]
Ziprasidone monotherapy is ineffective for bipolar-associated anxiety.
Evid Based Ment Health. 2014 Nov;17(4):109
Authors: Dunlop BW
PMID: 25239243 [PubMed - indexed for MEDLINE]
CACNB2: An Emerging Pharmacological Target for Hypertension, Heart Failure, Arrhythmia and Mental Disorders.
Curr Mol Pharmacol. 2015 May 6;
Authors: Soldatov NM
The voltage-gated Cav1.2 calcium channels respond to membrane depolarization by increasing the membrane permeability to Ca2+, a major signal for cardiac muscle contraction, regulation of vascular tone and CREB-dependent transcriptional activation. CACNB2 is one of the four homologous genes coding for the auxiliary Cav? subunits, which are important modulators of the Ca2+ channel activity. Five serious mental disorders - autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia, - and three major cardiovascular diseases - hypertension, heart failure and sudden cardiac death, -have recently been linked to the CACNB2 gene coding for the Cav?2 subunits. Here I will focus on the Cav?2-specific molecular determinant as an emerging pharmacological target.
PMID: 25966706 [PubMed - as supplied by publisher]