Bipolar Disorder: Malhi GS

Malhi GS, Adams D, Lampe L, Paton M, O'Connor N, Newton LA, Walter G, Taylor A, Porter R, Mulder RT, Berk M, Anonymous00020, Anonymous00021, Anonymous00022. · CADE Clinic, Department of Psychiatry, Royal North Shore Hospital, St Leonards, NSW, Australia. · Acta Psychiatr Scand Suppl. · Pubmed #19356155 No free full text.

Abstract: OBJECTIVE: To provide clinically relevant evidence-based recommendations for the management of bipolar disorder in adults that are informative, easy to assimilate and facilitate clinical decision-making. METHOD: A comprehensive literature review of over 500 articles was undertaken using electronic database search engines (e.g. MEDLINE, PsychINFO and Cochrane reviews). In addition articles, book chapters and other literature known to the authors were reviewed. The findings were then formulated into a set of recommendations that were developed by a multidisciplinary team of clinicians who routinely deal with mood disorders. These preliminary recommendations underwent extensive consultative review by a broader advisory panel that included experts in the field, clinical staff and patient representatives. RESULTS: The clinical practice recommendations for bipolar disorder (bipolar CPR) summarise evidence-based treatments and provide a synopsis of recommendations relating to each phase of the illness. They are designed for clinical use and have therefore been presented succinctly in an innovative and engaging manner that is clear and informative. CONCLUSION: These up-to-date recommendations provide an evidence-based framework that incorporates clinical wisdom and consideration of individual factors in the management of bipolar disorder. Further, the novel style and practical approach should promote their uptake and implementation.

Ghaemi SN, Bauer M, Cassidy F, Malhi GS, Mitchell P, Phelps J, Vieta E, Youngstrom E, Anonymous00020. · Bipolar Disorder Research Program, Department of Psychiatry, Emory University, Atlanta, GA 30322, USA. · Bipolar Disord. · Pubmed #18199230 No free full text.

Abstract: The Diagnostic Guidelines Task Force of the International Society for Bipolar Disorders (ISBD) presents in this document and this special issue a summary of the current nosological status of bipolar illness, a discussion of possible revisions to current DSM-IV and ICD-10 definitions, an examination of the relevant literature, explication of areas of consensus and dissensus, and proposed definitions that might guide clinicians in the most valid approach to diagnosis of these conditions given the current state of our knowledge.

Malhi GS. · No affiliation provided · Bipolar Disord. · Pubmed #19594500 No free full text.

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Malhi GS. · No affiliation provided · Bipolar Disord. · Pubmed #19538680 No free full text.

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Malhi GS, Goodwin GM. · No affiliation provided · Aust N Z J Psychiatry. · Pubmed #17828650 No free full text.

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Malhi GS, Yatham LN. · Guest Editors. · Acta Psychiatr Scand Suppl. · Pubmed #17688457 No free full text.

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Dodd S, Dean O, Copolov DL, Malhi GS, Berk M. · University of Melbourne, Department of Clinical and Biomedical Sciences, Barwon Health, PO Box 281, Geelong 3220, Victoria, Australia. · Expert Opin Biol Ther. · Pubmed #18990082 No free full text.

Abstract: BACKGROUND: Glutathione is an endogenous antioxidant and has a ubiquitous role in many of the body's defences. Treatment with N-acetylcysteine (NAC) has been shown to increase levels of glutathione. NAC has been proposed as a treatment for several illnesses. OBJECTIVES: The efficacy and tolerability of NAC was examined across a range of conditions to evaluate the evidence supporting the use of NAC for each indication. METHODS: A literature search was conducted using PubMed. Information was also collected from other online sources including the websites of the Therapeutic Goods Administration of Australia and the FDA. RESULTS: Reports ranged from case studies to clinical trials. There is strong evidence to support the use of NAC for the treatment of paracetamol overdose and emerging evidence suggesting it has utility in psychiatric disorders, particularly schizophrenia and bipolar disorder. NAC is safe and well tolerated when administered orally but has documented risks with intravenous administration.

Berk M, Malhi GS, Hallam K, Gama CS, Dodd S, Andreazza AC, Frey BN, Kapczinski F. · Department of Clinical and Biomedical Sciences, University of Melbourne, PO Box 281, Geelong, Australia. · J Affect Disord. · Pubmed #18819715 No free full text.

Abstract: In the absence of clear targets for primary prevention of many psychiatric illnesses, secondary prevention becomes the most feasible therapeutic target, and is best encompassed by the concept of early intervention. This construct encompasses the goals of minimising diagnostic delay and the prompt initiation of clinically appropriate therapy. This paper develops the rationale for early intervention in bipolar disorder. Three interrelated themes are discussed; the clinical data supporting the value of prompt diagnosis and treatment in bipolar disorder, the putative biochemical mechanisms underlying the pathophysiological processes, and the parallel concept of neuroprotection, and the developing neuroimaging data that supports early intervention. Early initiation of appropriate therapy may potentially facilitate improved clinical outcomes, and further might allow the secondary prevention of the sequelae of untreated illness, which include the deleterious impact on family relationships, psychosexual and vocational development, identity and self-concept and self-stigma.

Jairam R, Hanstock TL, Cahill CM, Hazell PL, Walter GJ, Malhi GS. · Gna Ka Lun Adolescent Mental Health Unit, Sydney South West Area Health Service, University of New South Wales, Sydney, Australia. · Minerva Pediatr. · Pubmed #18277366 No free full text.

Abstract: Over the past decade, there has been greater acceptance of the existence of bipolar disorder (BD) in adolescents. The onset of BD during this period severely affects the acquisition of key developmental skills. Debate around diagnosis, comorbidity and treatment is strong and little is known about the long-term impact BD has on an adolescents as they approach adulthood, from both illness and functional perspectives. A review of psychological and medical databases using the search terms ''adolescent onset'', ''pediatric onset'', ''juvenile onset'', ''bipolar disorder'', ''course'' and ''outcome'' was conducted. Emphasis was placed on the information available from studies, which have described the outcome of adolescent onset BD either prospectively, retrospectively, or both. Twelve studies were identified that focused on the long-term course of adolescent onset BD. Findings on the course and outcomes are conflicting. These studies are from few centres or research groups and have small sample sizes, varied methodologies and relatively brief follow-up durations. There are few studies available on the course and outcome of adolescent onset BD. Although there seems to be less controversy in this age group compared to the prepubertal age group, there remains a need for prospective studies of large systematically ascertained samples.

Malhi GS, Green M, Fagiolini A, Peselow ED, Kumari V. · Northern Clinical School, University of Sydney, Sydney, Australia. · Bipolar Disord. · Pubmed #18199238 No free full text.

Abstract: OBJECTIVE: Difficulties surrounding the classification of mixed psychotic and affective syndromes continue to plague psychiatric nosology. This paper addresses the controversy regarding the diagnostic validity of schizoaffective disorder (SAD), a diagnosis that is used in both DSM-IV and ICD-10 and one that encroaches on both schizophrenia (SCZ) and bipolar disorder (BD). METHODS: A systematic synthesis of clinical and empirical literature, including evidence from cognitive, neurobiological, genetic, and epidemiological research, was undertaken with the aim of evaluating the utility of the SAD classification. RESULTS: Distinctions between the diagnostic categories of SCZ, SAD and BD are not clearly demarcated by findings from neuropsychological, neuroimaging, molecular neurobiology, or genetic epidemiology studies. On the contrary, convergent evidence purports overlap across current diagnostic boundaries in the heritability and pathophysiology of psychotic and affective disorders. However, there are some disorder-specific findings. CONCLUSIONS: Schizoaffective disorder is a prototypic boundary condition that epitomizes the pitfalls of the current categorical classification system. Future revisions to the DSM should consider the implementation of one of two alternative models to account for individuals presenting with mixed psychotic and affective symptoms. These include the views that (i) SAD is a comorbid set of symptoms that occur as a by-product of two separate disorders (SCZ and BD) or, that (ii) SAD exists as the mid-point on a continuum between SCZ and BD, such that the incorporation of these two disorders onto one dimension may be a suitable alternative. Hence the category SAD should be omitted in future revisions of DSM, allowing the development of meaningful nomenclature that rests upon further rigorous investigation of differences and similarities between disorders.

Cahill CM, Green MJ, Jairam R, Malhi GS. · Academic Discipline of Psychological Medicine, Royal North Shore Hospital, Northern Clinical School, University of Sydney, Australia. · J Nerv Ment Dis. · Pubmed #18000450 No free full text.

Abstract: This article reviews neuropsychological research in adults with bipolar disorder and compares the findings with emergent data on neuropsychological function in juvenile bipolar disorder. Despite a recent surge of interest in childhood onset bipolar disorder, there remains a scarcity of neuropsychological literature investigating this population. From the study of adult bipolar disorder a substantial body of literature points to the existence of trait deficits in verbal and executive function that are detectable even during euthymia. In the nascent literature on neuropsychology in early onset bipolar, there is growing evidence to suggest that some of the deficits apparent in adults are also discernible in adolescents. Precise knowledge about when, how, and why these deficits appear requires future research of prodromal changes in neurocognition in childhood and adolescent bipolar disorder.

Berk M, Conus P, Lucas N, Hallam K, Malhi GS, Dodd S, Yatham LN, Yung A, McGorry P. · Barwon Health and The Geelong Clinic, Geelong, Victoria, Australia. · Bipolar Disord. · Pubmed #17988356 No free full text.

Abstract: Bipolar disorder is common, and both difficult to detect and diagnose. Treatment is contingent on clinical needs, which differ according to phase and stage of the illness. A staging model could allow examination of the longitudinal course of the illness and the temporal impact of interventions and events. It could allow for a structured examination of the illness, which could set the stage for algorithms that are tailored to the individuals needs. A staging model could further provide as structure for assessment, gauging treatment and outcomes. The model incorporates prodromal stages and emphasizes early detection and algorithm appropriate intervention where possible. At the other end of the spectrum, the model attempts to operationalize treatment resistance. The utility of the model will need to be validated by empirical research.

Berk M, Dodd S, Kauer-Sant'anna M, Malhi GS, Bourin M, Kapczinski F, Norman T. · Department of Clinical and Biomedical Sciences, Barwon Health and The Geelong Clinic, University of Melbourne, Geelong, Victoria, Australia. · Acta Psychiatr Scand Suppl. · Pubmed #17688462 No free full text.

Abstract: OBJECTIVE: Rational therapeutic development in bipolar is hampered by a lack of pathophysiological model. However, there is a wealth of converging data on the role of dopamine in bipolar disorder. This paper therefore examines the possibility of a dopamine hypothesis for bipolar disorder. METHOD: A literature search was conducted using standard search engines Embase, PyschLIT, PubMed and MEDLINE. In addition, papers and book chapters known to the authors were retrieved and examined for further relevant articles. RESULTS: Collectively, in excess of 100 articles were reviewed from which approximately 75% were relevant to the focus of this paper. CONCLUSION: Pharmacological models suggest a role of increased dopaminergic drive in mania and the converse in depression. In Parkinson's disease, administration of high-dose dopamine precursors can produce a 'maniform' picture, which switches into a depressive analogue on withdrawal. It is possible that in bipolar disorder there is a cyclical process, where increased dopaminergic transmission in mania leads to a secondary down regulation of dopaminergic receptor sensitivity over time. This may lead to a period of decreased dopaminergic transmission, corresponding with the depressive phase, and the repetition of the cycle. This model, if verified, may have implications for rational drug development.

Wijeratne C, Malhi GS. · School of Psychiatry, University of NSW, The Prince of Wales Hospital, Sydney, New South Wales, Australia. · Acta Psychiatr Scand Suppl. · Pubmed #17688461 No free full text.

Abstract: OBJECTIVE: To review the evidence for an association between vascular disease and mania, and in this context, to assess the suitability of previously proposed diagnostic criteria. METHOD: Relevant articles were retrieved and reviewed with the aid of search engines [MEDLINE, PsychInfo and EMBASE from 1996 to 2006] using pertinent search terms. Because of the paucity of data, systematic criteria for levels of evidence could not be applied. RESULTS: The literature is limited by the preponderance of case reports or case series, the use of overlapping terms, such as secondary mania, disinhibition syndrome and poststroke mania, and variable definitions of mania per se. There is general support for a tentative association between mania and vascular risk factors, and also between mania and cerebrovascular disease. Such associations seem best described by the term vascular mania for the sake of clinical utility, although it erroneously conveys causality. Proposed diagnostic criteria have defined a late-age at onset (50 years +) sub-type of mania, with associated neuroimaging and neuropsychological changes which are not specific to this age group. CONCLUSION: Further studies are needed to determine whether mania associated with vascular disease is a specific and separate sub-type with a late-age at onset. An alternative framework for considering vascular mania is proposed.

Green MJ, Cahill CM, Malhi GS. · School of Psychiatry, University of New South Wales, Sydney NSW 2031, Australia. · J Affect Disord. · Pubmed #17328959 No free full text.

Abstract: BACKGROUND: Bipolar disorder is characterized by fluctuating affect and mood, and is associated with specific neurocognitive deficits consistent with neuropathology in cerebello-striatal-prefrontal neural networks. This network is critical for emotion regulation. METHODS: Relevant literature was located via PsychINFO and Medline to provide a comprehensive review of cognitive and neural mechanisms of social information processing and affect generation in bipolar disorder (BD) in the context of recent research examining the neural mechanisms of emotion regulation via conscious cognitive strategies. RESULTS: Emotion regulation relies on synergy within brainstem, limbic and cortical processes that promote the adaptive generation and regulation of affect, with prefrontal and cingulate regions inhibiting sub-cortical and cortical emotion processing systems in the cognitive control of emotional experience. Current evidence of structural and functional brain abnormalities in BD alongside aberrant social cognition, affect generation, and neuropsychological function are consistent with a model of emotion dysregulation to account for the symptoms of BD. LIMITATIONS: A precise understanding of emotion dysregulation in BD is currently limited by a paucity of longitudinal research directly examining these issues. CONCLUSION: Aberrant emotion perception alongside increased limbic activity during emotion perception and affect generation in BD, alongside impaired executive control associated with aberrant neurophysiological abnormalities in sub-regions of the prefrontal cortex, is consistent with impaired emotion regulation. We propose a cognitive and neurophysiological framework within which the variations of mood that are characteristic of BD can be understood as specific impairments of the cognitive control of emotion.

Malhi GS, Berk M. · Psychological Medicine, Northern Clinical School, University of Sydney, NSW, Australia. · Acta Psychiatr Scand Suppl. · Pubmed #17280577 No free full text.

Abstract: OBJECTIVE: To examine the evidence that dopamine (DA) dysfunction contributes to melancholic depression. METHOD: Database (EMBASE, PsychLit and MEDLINE) searches using relevant key words were conducted and citations were scrutinized. RESULTS: In this paper, we assume that the definition of melancholia is contingent upon the presence of psychomotor disturbance (PMD). In melancholic depression PMD comprises both a cognitive and motor component and DA is found to be important in both. DA neurotransmission modulates cognition in particular in attention, adaptation and motivational processes and has a pivotal role in motor function. CONCLUSION: DA is a credible aetiological candidate for the PMD in melancholic depression. However, melancholia needs first to be characterized both clinically and in terms of its pathophysiology. In this regard, illnesses such as bipolar depression and Parkinson's disease warrant consideration as they provide suitable models of both the cognitive and motor aspects of PMD, and hold the necessary markers to better define melancholia.

Mitchell PB, Malhi GS. · School of Psychiatry, University of New South Wales, Black Dog Institute, Prince of Wales Hospital, Randwick, Sydney, NSW 2031, Australia. · Expert Opin Emerg Drugs. · Pubmed #17064222 No free full text.

Abstract: Bipolar disorder is a relatively common condition characterised by recurrent episodes of mania and depression, and associated with high levels of morbidity and mortality. Although there have been substantial advances in the pharmacotherapeutics of this condition over the last 10-15 years, the benefits have been predominantly in terms of tolerability and safety, with no new treatments being demonstrated to be more effective than lithium--the prototype mood stabiliser. This article reviews current and emerging medications for bipolar disorder. Most of the emerging treatments in pharmaceutical industry developmental programmes are new or modified anticonvulsants or atypical antipsychotics. A number of possible future directions and challenges for the field are discussed. The treatment of bipolar disorder is unlikely to advance substantially until the causative pathogenetic molecular processes are elucidated.

Mitchell PB, Ball JR, Best JA, Gould BM, Malhi GS, Riley GJ, Wilson IG. · School of Psychiatry, Prince of Wales Hospital, University of New South Wales, Sydney, NSW. · Med J Aust. · Pubmed #16768664 links to  free full text

Abstract: General practitioners have a key role in managing patients with bipolar disorder, a condition which affects at least one in 200 Australians each year and is the sixth leading cause of disability in the population. Although diagnosis and treatment of the illness is complex, effective treatment can lead to good outcomes for many patients. GPs can contribute significantly to early recognition of bipolar disorder, avoiding the long delays in accurate diagnosis that have been reported. As in other complex recurrent or persistent illnesses, GPs are well placed to coordinate multidisciplinary "shared care" with specialists and other health care professionals. GPs also provide continuing general medical care for patients with bipolar disorder, and are in a unique position to understand patients' life circumstances and to monitor their progress over time. The last decade has seen many advances in medication for bipolar disorder, including the introduction of new therapies and the refinement of treatment protocols using older medications. There has also been increasing recognition of the contribution of psychological therapies to symptom relief, relapse prevention, optimal function, and quality of life.

Cahill CM, Malhi GS, Ivanovski B, Lagopoulos J, Cohen M. · University of New South Wales, School of Psychiatry, Sydney, Australia. · Expert Rev Neurother. · Pubmed #16623657 No free full text.

Abstract: This article briefly reviews the neuropsychological deficits associated with bipolar disorder and examines how substance abuse, in particular chronic cannabis use, may contribute to these. The focus of the article is cannabis, owing to its popularity in patients with bipolar disorder, although many studies focus on its use in conjunction with other substances. The findings are contextualized within bipolar disorder, examining functional outcome.

Malhi GS, Berk M, Bourin M, Ivanovski B, Dodd S, Lagopoulos J, Mitchell PB. · Mood Disorder Unit, Black Dog Institute, Prince of Wales Hospital, Sydney, Australia. · Acta Psychiatr Scand Suppl. · Pubmed #16104066 No free full text.

Abstract: OBJECTIVE: To assess the potential role of atypical antipsychotics as mood stabilizers.METHOD: A MedLine, PsychLIT, PubMed, and EMBASE literature search of papers published up to December 2004 was conducted using the names of atypical antipsychotics and a number of key terms relevant to bipolar disorder. Additional articles were retrieved by scrutinizing the bibliographies of review papers and literature known to the authors. Data pertinent to the objective was reviewed according to the various phases of bipolar disorder.RESULTS: The data is most substantive for the use of atypical antipsychotics in mania, to the extent that an argument for a class effect of significant efficacy can be made. This does not extend to bipolar depression, however, good data is now emerging for some agents and will need to be considered for each individual agent as it accumulates. As regards mixed states and rapid cycling the evidence is thus far sparse and too few maintenance studies have been conducted to make any firm assertions. However, with respect to long-term therapy the atypical antipsychotics do have clinically significant side-effects of which clinicians need to be aware.CONCLUSION: Based on the evidence thus far it is perhaps premature to describe the atypical antipsychotics as mood stabilizers. Individual agents may eventually be able to claim this label, however, much further research is needed especially with respect to maintenance and relapse prevention.

Olley A, Malhi GS, Mitchell PB, Batchelor J, Lagopoulos J, Austin MP. · School of Psychiatry, University of New South Wales and Mood Disorders Unit, Black Dog Institute, Prince of Wales Hospital, Sydney, Australia. · J Nerv Ment Dis. · Pubmed #15870616 No free full text.

Abstract: Bipolar disorder (BD) is a debilitating psychiatric illness that is uniquely characterized by switching between psychopathologically contrasting phases of mania and depression, often with intervening periods of euthymia. However, these periods of apparent clinical recovery (euthymia) are marked by subtle social, occupational, and cognitive impairments, profiled by recent neuropsychological investigations. Determining the cognitive changes across these three phases may help differentiate the disruptions that are mood state-dependent from those associated with underlying pathology. This article therefore critically reviews the reported neuropsychological impairments in BD and the methodological limitations facing such research. Integration of the available evidence, principally from the field of neuropsychology, when synthesized, implicates the prefrontal cortex in the etiopathogenesis of BD and posits cortical-subcortical-limbic disruption in recovered euthymic patients that manifests as cognitive dysfunction.

Mitchell PB, Malhi GS. · University of New South Wales, School of Psychiatry, Prince of Wales Hospital, Randwick, New South Wales 2031, Australia. · Expert Rev Neurother. · Pubmed #15853476 No free full text.

Abstract: Recent studies have highlighted significant limitations in our capacity to effectively treat bipolar depression. This article reviews the present status of treatments for this condition, highlighting emerging new pharmacotherapies such as lamotrigine, olanzapine and quetiapine, while also addressing modern psychologic interventions such as cognitive behavioral therapy and psychoeducation. The role of older treatments such as lithium and the antidepressants is also discussed, particularly as a recent meta-analysis has thrown into question current heightened concern over antidepressant-induced mania. The advent of new pharmacologic and psychologic treatments provides optimism for improved outcomes for this highly disabling condition.

Monkul ES, Malhi GS, Soares JC. · Department of Psychiatry, Dokuz Eylul University School of Medicine, Izmir, Turkey. · Aust N Z J Psychiatry. · Pubmed #15777357 No free full text.

Abstract: AIM: Morphometric brain imaging studies have revealed regional brain abnormalities in patients with bipolar disorder, which may play a role in illness pathophysiology. It is not known whether such changes are of neurodevelopmental, neurodegenerative, or combined origin. We reviewed the anatomical brain imaging literature in bipolar disorder, in an attempt to determine whether there is evidence to suggest that such abnormalities are progressive. METHOD: Literature searches were conducted using MEDLINE for the period from 1966 to June 2004, using specific key words; bipolar disorder and the names of the individual brain structures. Papers were selected according to their salience in relation to whether reported changes are progressive. RESULTS: Available findings suggest reduced grey matter in prefrontal brain regions such as anterior cingulate and subgenual prefrontal cortex, and abnormalities in amygdala size in adult and paediatric bipolar patients. White matter hyperintensities, which are non-specific abnormalities, are also common in bipolar patients. Bipolar patients may lose more brain grey matter by ageing. There is also evidence for impaired myelination of the corpus callosum in bipolar disorder. Lithium may reverse or prevent grey matter prefrontal cortex abnormalities in bipolar patients by its neuroprotective effects. CONCLUSIONS: Both early developmental and later neurodegenerative processes may play a role in the pathophysiology of bipolar disorder. Findings from anatomical brain imaging studies implicate key regions involved in mood regulation. The evidence for the progressive nature of this illness is tentative, as no follow-up study with bipolar patients has been reported to this date.

Berk M, Dodd S, Malhi GS. · Barwon Health and The Geewong Clinic, Swanston Centre, PO Box 281, Geelong, Victoria 3220, Australia. · Aust N Z J Psychiatry. · Pubmed #15777356 No free full text.

Abstract: OBJECTIVE: To explore diagnostic and treatment issues concerning bipolar mixed states. METHOD: Bipolar mixed states are described and concerns about diagnostic and treatment difficulties are summarized and discussed. RESULT: Mixed states can present with equal admixtures of depressive or manic symptoms, or more commonly one component predominates. There is fair consensus, although little data, regarding the management of manic mixed states. However depressive mixed states are far more complex both in terms of recognition and management. People suffering from mixed states characteristically present with complaints of depression. CONCLUSIONS: The boundaries between depressive mixed states and agitated depression are vague, yet carry substantial therapeutic implications. Bipolar mixed states are often difficult to treat, and tend to take much longer to settle than either pure mania or depression. Furthermore there is data that treatment with antidepressants can worsen the course of mixed states. Hence missed diagnoses can potentially have negative clinical implications. Therefore in this paper the clinical presentation, diagnosis and therapy of mixed states is reviewed with a view to improving management.

Malhi GS, Ivanovski B, Szekeres V, Olley A. · Black Dog Institute, Prince of Wales Hospital, Sydney, Australia. · Can J Psychiatry. · Pubmed #15679204 No free full text.

Abstract: OBJECTIVE: To compare and contrast the neuropsychological profile of the 3 phases of bipolar disorder (BD) to achieve a better definition of BD and to identify potential state and trait deficits. METHODS: We conducted a search for English-language papers published in journals from 1965 onward, using the following terms in Medline and Embase: neuropsychology or neuropsychological and BD, depression, mania, and euthymia. We scrutinized suitable subheadings and retrieved familiar papers and literature. RESULTS: We initially identified more than 100 articles and then excluded reviews and papers that did not directly administer neuropsychological tests. This left 27 papers, which we further examined and the findings of which we tabulated and discussed. Cognitive and executive functioning deficits were found, including set-shifting, verbal fluency, planning, attention, and memory. CONCLUSIONS: The neuropsychological deficits found in bipolar depression, mania or hypomania, and euthymia provide important insights into the pathophysiology of BD and may, in future studies, form the basis of clinically meaningful subtypes.