Toward stratified treatments for bipolar disorders

Hasler, Gregor; Wolf, Andreas

doi:10.1016/j.euroneuro.2014.12.006

Cited by 20 publications

(10 citation statements)

References 133 publications

(120 reference statements)

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“…Clinical syndrome subtyping has failed to inform personalization of treatments in psychiatry ( 10 , 19 , 79 ). This is partly because even more narrowly defined clinical presentations, such as those included in the BD-I category still represent heterogeneous endpoints of different underlying causal pathways.…”

Section: Discussionmentioning

confidence: 99%

Can an Integrated Science Approach to Precision Medicine Research Improve Lithium Treatment in Bipolar Disorders?

2018

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Clinical practice guidelines identify lithium as a first line treatment for mood stabilization and reduction of suicidality in bipolar disorders (BD); however, most individuals show sub-optimal response. Identifying biomarkers for lithium response could enable personalization of treatment and refine criteria for stratification of BD cases into treatment-relevant subgroups. Existing systematic reviews identify potential biomarkers of lithium response, but none directly address the conceptual issues that need to be addressed to enhance translation of research into precision prescribing of lithium. For example, although clinical syndrome subtyping of BD has not led to customized individual treatments, we emphasize the importance of assessing clinical response phenotypes in biomarker research. Also, we highlight the need to give greater consideration to the quality of prospective longitudinal monitoring of illness activity and the differentiation of non-response from partial or non-adherence with medication. It is unlikely that there is a single biomarker for lithium response or tolerability, so this review argues that more research should be directed toward the exploration of biosignatures. Importantly, we emphasize that an integrative science approach may improve the likelihood of discovering the optimal combination of clinical factors and multimodal biomarkers (e.g., blood omics, neuroimaging, and actigraphy derived-markers). This strategy could uncover a valid lithium response phenotype and facilitate development of a composite prediction algorithm. Lastly, this narrative review discusses how these strategies could improve eligibility criteria for lithium treatment in BD, and highlights barriers to translation to clinical practice including the often-overlooked issue of the cost-effectiveness of introducing biomarker tests in psychiatry.

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Section: Discussionmentioning

confidence: 99%

Can an Integrated Science Approach to Precision Medicine Research Improve Lithium Treatment in Bipolar Disorders?

2018

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“…As with other diseases, genetic information has the potential to inform and improve bipolar disorder treatments, both by highlighting targets and pathways and by enabling personalized medicine . However, the magnitude and immediacy of such effects are limited because of the complexities of the genetic architecture and the many steps that lie between identification of a genetic locus and validation of a drug target …”

Section: Therapeutic Potential Of Bipolar Disorder Geneticsmentioning

confidence: 99%

Innovative approaches to bipolar disorder and its treatment

Harrison

Cipriani

Harmer

et al. 2016

Annals of the New York Academy of Sciences

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All psychiatric disorders have suffered from a dearth of truly novel pharmacological interventions. In bipolar disorder, lithium remains a mainstay of treatment, six decades since its effects were serendipitously discovered. The lack of progress reflects several factors, including ignorance of the disorder's pathophysiology and the complexities of the clinical phenotype. After reviewing the current status, we discuss some ways forward. First, we highlight the need for a richer characterization of the clinical profile, facilitated by novel devices and new forms of data capture and analysis; such data are already promoting a reevaluation of the phenotype, with an emphasis on mood instability rather than on discrete clinical episodes. Second, experimental medicine can provide early indications of target engagement and therapeutic response, reducing the time, cost, and risk involved in evaluating potential mood stabilizers. Third, genomic data can inform target identification and validation, such as the increasing evidence for involvement of calcium channel genes in bipolar disorder. Finally, new methods and models relevant to bipolar disorder, including stem cells and genetically modified mice, are being used to study key pathways and drug effects. A combination of these approaches has real potential to break the impasse and deliver genuinely new treatments.

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“…One issue that has complicated the study of theory of mind in bipolar disorder is that this diagnostic label actually comprises a group of disorders with heterogeneous clinical presentation, course, and outcome ( 43 , 44 ). Not only does the clinical course change as a patient cycles through recurrent depressive, manic, and sometimes mixed mood states ( 45 ), there are subtypes of bipolar disorder based on the severity of mania experienced, variable occurrence of psychosis within these subtypes ( 46 ), and related sub-syndromal bipolar subtypes to contend with ( 47 ).…”

Section: Impairments Of Theory Of Mind In Bipolar Disordermentioning

confidence: 99%

Theory of Mind in Bipolar Disorder, with Comparison to the Impairments Observed in Schizophrenia

Mitchell

Young

2016

Front. Psychiatry

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Our ability to make sense of information on the potential intentions and dispositions of others is of paramount importance for understanding their communicative intent, and for judging what an appropriate reaction might be. Thus, anything that impinges on this ability has the potential to cause significant social impairment, and compromise an individual’s level of functioning. Both bipolar disorder and schizophrenia are known to feature theory of mind impairment. We conducted a theoretical review to determine the extent and types of theory of mind impairment in bipolar disorder, and evaluate their relationship to medication and symptoms. We also considered possible mediatory mechanisms, and set out to discover what else could be learnt about the impairment in bipolar disorder by comparison to the profile of impairment in schizophrenia. The literature established that in bipolar disorder (i) some form of theory of mind impairment has been observed in all mood states, including euthymia, (ii) the form of theory of mind assessed and task used to make the assessment influence the impairment observed, and (iii) there might be some relationship to cognitive impairment, although a relationship to standard clinical variables was harder to establish. What also became clear in the literature on bipolar disorder itself was the possible relationship of theory of mind impairment to history of psychotic symptoms. Direct comparative studies, including patients with schizophrenia, were thus examined, and provided several important directions for future research on the bases of impairment in bipolar disorder. Particularly prominent was the issue of whether theory of mind impairment could be considered a candidate endophenotype for the psychoses, although current evidence suggests that this may be premature. The differences in impairment across schizophrenia and bipolar disorder may, however, have genuine differential effects on social functioning and the likely success of remediation.

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Toward stratified treatments for bipolar disorders

Cited by 20 publications

References 133 publications

Can an Integrated Science Approach to Precision Medicine Research Improve Lithium Treatment in Bipolar Disorders?

Can an Integrated Science Approach to Precision Medicine Research Improve Lithium Treatment in Bipolar Disorders?

Innovative approaches to bipolar disorder and its treatment

Theory of Mind in Bipolar Disorder, with Comparison to the Impairments Observed in Schizophrenia

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