A panel of biomarkers may aid in diagnosis of mood disorders, allowing for early detection and precision medicine. These findings were published in Molecular Psychiatry.
Patients (n=44) with mood disorders were assessed by full genome sequencing to discover biomarkers of diametric changes in mood state. These biomarkers were validated among an independent cohort of patients with severe depression (n=30) or mania (n=17). These biomarkers were assessed in independent cohorts of patients (low mood: n=190, depression: n=226, future hospitalizations: n=170) for whether or not they could predict the state and trajectory of their mood disorder. The top candidates were assessed for potential drug targets of existing psychiatric drugs.
The initial selection of biomarkers comprised genes which changed in expression on the basis of self-reported low or high mood states across psychiatry visits. These candidate genes were cross referenced with literature. Genes with high support in literature and correlation with mood (n=4960 genes) were selected for further testing.
The top candidates were validated in the demographically matched cohort of patients with clinically severe depression or mania. A total of 283 of these candidates were nominally significant. The genes which were selected as significant comprised 23 genes represented in 26 total biomarkers. These genes exhibited patters of over expression (n=14) and under expression (n=9) in high mood.
In pathway analyses, these genes were involved in circadian, neurotrophic, and cell differentiation pathways and with serotonergic and glutamatergic signaling, indicating a probable role in mood.
With data from electronic medical records (11.27 years of follow-up), these top 23 genes were assessed for precision medicine. The top biomarker for low mood and depression was neuregulin 1 (NRG1) with an area under the receiver operating characteristic curve (AUC) of 62% (P =6.8×10–3) and 64% (P =3.5×10–2), respectively. NRG1 also predicted future hospitalizations for depression with an odds ratio (OR) of 1.17 (P =2.5zx10–2) and for mania with an OR of 2.7 (P =3.3×10–2).
Currently available psychiatric medications were observed to modulate many of these top targets (lithium: n=3, antidepressants n=4, and nutraceutical omega-3 fatty acids n=5). Bioinformatic analyses identified that these biomarkers may potentially be modulated by pindolol, ciprofibrate, pioglitazone, or adiphenine for the treatment of low mood or depression.
These biomarkers, although tested in multiple independent cohorts, should be evaluated for their efficacy in clinical practice.
These findings suggested a panel of blood biomarkers may aid in the diagnosis of mood disorders and in the optimization of therapeutics, making precision medicine a potential option for patients with mood disorders.
Disclosure: Multiple authors declared industry affiliations. Please refer to the original article for a full list of disclosures.
Le-Niculescu H, Roseberry K, Gill SS, et al. Precision medicine for mood disorders: objective assessment, risk prediction, pharmacogenomics, and repurposed drugs. Mol Psychiatry. Published online April 8, 2021. doi:10.1038/s41380-021-01061-w