Dataset Information

Depression Preceding Diagnosis of Bipolar Disorder.

ABSTRACT: This paper focuses on depression that precedes an onset of manifest bipolar disorder as early stage bipolar disorder. First, we review how to pragmatically identify the clinical characteristics of patients presenting with an episode of depression who subsequently go on to develop episodes of mania or hypomania. The existing literature shows a strong consensus: accurate identification of depression with early onset and recurrent course with multiple episodes, subthreshold hypomanic and/or mixed symptoms, and family history of bipolar disorder or completed suicide have been shown by multiple authors as signs pointing to bipolar diagnosis. This contrasts with relatively limited information available to guide management of such "pre-bipolar" (pre-declared bipolar) patients, especially those in the adult age range. Default assumption of unipolar depression at this stage carries significant risk. Antidepressants are still the most common pharmacological treatment used, but clinicians need to be aware of their potential harm. In some patients with unrecognized bipolar depression, antidepressants can not only produce switch to (hypo)mania, but also mixed symptoms, or worsening of depression with an increased risk of suicide. We review pragmatic management strategies in the literature beyond clinical guidelines that can be considered for this at-risk group encompassing the more recent child and adolescent literature. In the future, genetic research could make the early identification of bipolar depression easier by generating informative markers and polygenic risk scores.

SUBMITTER: O'Donovan C

PROVIDER: S-EPMC7300293 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Depression Preceding Diagnosis of Bipolar Disorder.

O'Donovan Claire C Alda Martin M

Frontiers in psychiatry 20200611

This paper focuses on depression that precedes an onset of manifest bipolar disorder as early stage bipolar disorder. First, we review how to pragmatically identify the clinical characteristics of patients presenting with an episode of depression who subsequently go on to develop episodes of mania or hypomania. The existing literature shows a strong consensus: accurate identification of depression with early onset and recurrent course with multiple episodes, subthreshold hypomanic and/or mixed s ...[more]

PMID: 32595530

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Project description:OBJECTIVE:Family and twin studies indicate substantial overlap of genetic influences on psychotic and mood disorders. Linkage and candidate gene studies have also suggested overlap across schizophrenia, bipolar disorder, and major depressive disorder. The purpose of this study was to apply genomewide association study (GWAS) analysis to address the specificity of genetic effects on these disorders. METHOD:The authors combined GWAS data from three large effectiveness studies of schizophrenia (CATIE, genotyped: N=741), bipolar disorder (STEP-BD, geno-typed: N=1,575), and major depressive disorder (STAR*D, genotyped: N=1,938) as well as from psychiatrically screened control subjects (NIMH-Genetics Repository: N=1,204). A two-stage analytic procedure involving an omnibus test of allele frequency differences among case and control groups was applied, followed by a model selection step to identify the best-fitting model of allelic effects across disorders. RESULTS:The strongest result was seen for a single nucleotide polymorphism near the adrenomedullin (ADM) gene (rs6484218), with the best-fitting model indicating that the effect was specific to bipolar II disorder. Findings also revealed evidence suggesting that several genes may have effects that transcend clinical diagnostic boundaries, including variants in NPAS3 that showed pleiotropic effects across schizophrenia, bipolar disorder, and major depressive disorder. CONCLUSIONS:This study provides the first genomewide significant evidence implicating variants near the ADM gene on chromosome 11p15 in psychopathology, with effects that appear to be specific to bipolar II disorder. Although genomewide significant evidence of cross-disorder effects was not detected, the results provide evidence that there are both pleiotropic and disorder-specific effects on major mental illness and illustrate an approach to dissecting the genetic basis of mood and psychotic disorders that can inform future large-scale cross-disorder GWAS analyses.

Dataset Information

Depression Preceding Diagnosis of Bipolar Disorder.

Publications

Depression Preceding Diagnosis of Bipolar Disorder.

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