Screening for bipolar spectrum disorders:a comprehensive meta-analysis of accuracy studies

Background: Bipolar spectrum disorders are frequently under-recognized and/or misdiagnosed in various settings. Several in fl uential publications recommend the routine screening of bipolar disorder. A systematic review and meta-analysis of accuracy studies for the bipolar spectrum diagnostic scale (BSDS), the hypomania checklist (HCL-32) and the mood disorder questionnaire (MDQ) were performed. Methods: The Pubmed, EMBASE, Cochrane, PsycINFO and SCOPUS databases were searched. Studies were included if the accuracy properties of the screening measures were determined against a DSM or ICD-10 structured diagnostic interview. The QUADAS-2 tool was used to rate bias. Results: Fifty three original studies met inclusion criteria ( N ¼ 21,542). At recommended cutoffs, summary sensitivities were 81%, 66% and 69%, while speci fi cities were 67%, 79% and 86% for the HCL-32, MDQ, and BSDS in psychiatric services, respectively. The HCL-32 was more accurate than the MDQ for the detection of type II bipolar disorder in mental health care centers ( P ¼ 0.018). At a cutoff of 7, the MDQ had a summary sensitivity of 43% and a summary speci fi city of 95% for detection of bipolar disorder in primary care or general population settings. Limitations: Most studies were performed in mental health care settings. Several included studies had a high risk of bias. Conclusions: Although accuracy properties of the three screening instruments did not consistently differ in mentalhealthcareservices,theHCL-32wasmoreaccuratethantheMDQforthedetectionoftypeIIBD. More studies in other settings (for example, in primary care) are necessary

Exploring the Role of Inflammatory Cytokines in the Pathophysiology, Cognitive Dysfunction and Treatment of Bipolar Disorder: Integrative Evidence Provided by a Proof-of-Concept Study with Adjunctive Minocycline

Background: Bipolar disorder (BD) is associated with increased levels of inflammatory cytokines, which may contribute to cognitive dysfunction. Anti-inflammatory intervention with minocycline is hypothesized to exert antidepressant and pro-cognitive effects in BD. The aims of the investigations were: 1) to identify inflammatory cytokine abnormalities in BD; 2) to identify inflammatory cytokines associated with cognitive dysfunction in BD; 3) to evaluate the efficacy of adjunctive minocycline for symptoms of bipolar depression and cognitive dysfunction. Method: The first two study aims were evaluated with cross-sectional exploratory methods, comparing 29 depressed (HAMD-17 ≥ 20) and 46 euthymic (4 week verification) adults with DSM-IV-TR-defined BD as well as of 31 healthy controls (HCs). Plasma cytokine levels were measured with a 30 V-PLEX immunoassay. Evaluated cognitive domains were verbal memory, executive function and psychomotor speed. The efficacy of adjunctive minocycline (100 mg b.i.d.) was evaluated in an overlapping sample of depressed individuals (intent-to-treat: n=27) using an 8-week, open-label study. The primary efficacy measure was the MADRS, while, cognitive composites and plasma cytokines were secondary outcome measures. Results: Results from multinomial logistic regression analyses indicate that IL-6 levels were increased in depressed and euthymic individuals with BD when compared to HCs, while, levels of CCL3, IL-15, and IL-17A were reduced below levels of HCs in euthymic individuals (Pseudo R2=.648, pPh.D

Novel therapeutic targets in depression: Minocycline as a candidate treatment

Mood disorders are marked by high rates of non-recovery, recurrence, and chronicity, which are insufficiently addressed by current therapies. Several patho-etiological models have been proposed that are not mutually exclusive and include but are not limited to the monoamine, inflammatory, neurotrophic, gliotrophic, excitatory, and oxidative stress systems. A derivative of these observations is that treatment(s) which target one or more of these mechanistic steps may be capable of mitigating, or preventing, disparate psychopathological features. Minocycline is an agent with pleiotropic properties that targets multiple proteins and cellular processes implicated in the patho-etiology of mood disorders. Moreover, preclinical and preliminary clinical evidence suggests that minocycline possesses antidepressant properties. Herein, we provide the rationale for conducting a randomized, controlled trial to test the antidepressant properties of minocycline. (C) 2012 Elsevier B.V. All rights reserved.Eli LillyJanssen-OrthoAstra ZenecaBristol-Meyers SquibbClera, Inc.Glaxo Smith KlineLundbeckPfizerServierSt. Jude MedicalConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Toronto Rehabilitation InstituteHeart and Stroke Foundation Centre for Stroke RecoveryStanley Medical Research InstituteNational Alliance for Research on Schizophrenia and Depression (NARSAD)National Institutes of Mental HealthShireAstra-ZenecaForestSepracorUniv Toronto, Mood Disorders Psychopharmacol Unit, Univ Hlth Network, Dept Psychiat, Toronto, ON M5T 2S8, CanadaUniv Toronto, Inst Med Sci, Toronto, ON M5T 2S8, CanadaUniversidade Federal de São Paulo, Dept Psychiat, Program Recognit & Intervent Individuals Risk Men, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, Interdisciplinary Lab Clin Neurosci LINC, São Paulo, BrazilUniv Toronto, Dept Pharmacol, Toronto, ON M5T 2S8, CanadaUniv Toronto, Dept Toxicol, Toronto, ON M5T 2S8, CanadaSunnybrook Hlth Sci Ctr, Neuropsychopharrnacol Res Grp, Toronto, ON M4N 3M5, CanadaUniversidade Federal de São Paulo, Dept Psychiat, Program Recognit & Intervent Individuals Risk Men, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, Interdisciplinary Lab Clin Neurosci LINC, São Paulo, BrazilWeb of Scienc