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Inflammation: opportunities for treatment stratification among individuals diagnosed with mood disorders.

ABSTRACT: Mood disorders continue to be a significant burden to those affected, resulting in significant illness-associated disability and premature mortality. In addition to mood disturbance, individuals also suffer from other transdiagnostic impairments (eg, anhedonia and cognitive impairment). Although there have been significant advancements in psychiatric treatment over the last few decades, treatment efficacy (eg, symptom remission, lack of functional recovery, and disease modification) continues to be an important limitation. Consequently, there is an urgent need to identify novel approaches capable of addressing the foregoing needs, providing the basis for the exploration of conceptual models and treatment opportunities that consider inflammation to be a key factor in mood disorder development. In part driven by metabolic comorbidities, a large proportion of individuals with mood disorders also have an imbalance in the inflammatory milieu. The aim of this review is to highlight evidence implicating inflammation in various effector systems in mood disorders, with a particular focus on the intercommunication with glutamatergic signaling, immune system signaling, as well as metabolic parameters (eg, L-methyl folate bioavailability). This article also briefly reviews novel and repurposed agents that are capable of targeting the innate immune inflammatory system and possibly correcting an abnormal immune/inflammatory milieu (eg, infliximab).

SUBMITTER: Subramaniapillai M

PROVIDER: S-EPMC5442361 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Inflammation: opportunities for treatment stratification among individuals diagnosed with mood disorders.

Subramaniapillai Mehala M Carmona Nicole E NE Rong Carola C McIntyre Roger S RS

Dialogues in clinical neuroscience 20170301 1

Mood disorders continue to be a significant burden to those affected, resulting in significant illness-associated disability and premature mortality. In addition to mood disturbance, individuals also suffer from other transdiagnostic impairments (eg, anhedonia and cognitive impairment). Although there have been significant advancements in psychiatric treatment over the last few decades, treatment efficacy (eg, symptom remission, lack of functional recovery, and disease modification) continues to ...[more]

PMID: 28566945

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Project description:Personalized medicine (personalized psychiatry in a specific setting) is a new model towards individualized care, in which knowledge from genomics and other omic pillars (microbiome, epigenomes, proteome, and metabolome) will be combined with clinical data to guide efforts to new drug development and targeted prescription of the existing treatment options. In this review, we summarize pharmacogenomic studies in mood disorders that may lay the foundation towards personalized psychiatry. In addition, we have discussed the possible strategies to integrate data from omic pillars as a future path to personalized psychiatry. So far, the progress of uncovering single nucleotide polymorphisms (SNPs) underpinning treatment efficacy in mood disorders (e.g., SNPs associated with selective serotonin re-uptake inhibitors or lithium treatment response in patients with bipolar disorder and major depressive disorder) are encouraging, but not adequate. Genetic studies have pointed to a number of SNPs located at candidate genes that possibly influence response to; (a) antidepressants COMT, HTR2A, HTR1A, CNR1, SLC6A4, NPY, MAOA, IL1B, GRIK4, BDNF, GNB3, FKBP5, CYP2D6, CYP2C19, and ABCB1 and (b) mood stabilizers (lithium) 5-HTT, TPH, DRD1, FYN, INPP1, CREB1, BDNF, GSK3?, ARNTL, TIM, DPB, NR3C1, BCR, XBP1, and CACNG2. We suggest three alternative and complementary strategies to implement knowledge gained from pharmacogenomic studies. The first strategy can be to implement diagnostic, therapeutic, or prognostic genetic testing based on candidate genes or gene products. The second alternative is an integrative analysis (systems genomics approach) to combine omics data obtained from the different pillars of omics investigation, including genomics, epigenomes, proteomics, metabolomics and microbiomes. The main goal of system genomics is an identification and understanding of biological pathways, networks, and modules underlying drug-response. The third strategy aims to the development of multivariable diagnostic or prognostic algorithms (tools) combining individual's genomic information (polygenic score) with other predictors (e.g., omics pillars, neuroimaging, and clinical characteristics) to finally predict therapeutic outcomes. An integration of molecular science with that of traditional clinical practice is the way forward to drug discoveries and novel therapeutic approaches and to characterize psychiatric disorders leading to a better predictive, preventive, and personalized medicine (PPPM) in psychiatry. With future advances in the omics technology and methodological developments for data integration, the goal of PPPM in psychiatry is promising.

Project description:BackgroundParental history of mood or anxiety disorders is one of the strongest and most consistent risk factors for the development of these disorders in offspring. Gaps remain however in our knowledge of whether maternal or paternal disorders are more strongly associated with offspring disorders, and whether the association exists in non-clinical samples. This study uses a large population-based sample to test if maternal or paternal history of mood and/or anxiety disorders increases the risk of mood and/or anxiety disorders, or symptoms of specific anxiety disorders, in offspring.MethodsData were drawn from the Nicotine Dependence in Teens Study, a prospective cohort investigation of 1293 grade 7 students. Data on mental health outcomes were collected in mailed self-report questionnaires when participants were aged 20.4 (0.7) years on average. Parental data were collected in mailed self-report questionnaires. This current analysis pertains to 564 participants with maternal and/or paternal data. The association between maternal and paternal history and each of diagnosed anxiety disorder, diagnosed mood disorder, and symptoms of specific anxiety disorders in offspring was studied in multivariate logistic regression.ResultsA higher proportion of mothers than fathers had a diagnosed mood/anxiety disorder (23% versus 12%). Similarly, 14% of female offspring had a diagnosed mood/anxiety disorder, compared to 6% of male offspring. The adjusted odds ratio (95% confidence interval) for maternal history was 2.2 (1.1, 4.5) for diagnosed mood disorders, 4.0 (2.1, 7.8) for diagnosed anxiety disorders, and 2.2 (1.2, 4.0) for social phobia symptoms. Paternal history was not associated with any of the mental health outcomes in offspring.ConclusionMaternal, but not paternal mood/anxiety disorders were associated with diagnosed psychiatric disorders, as well as symptoms of specific anxiety disorders, in offspring. Efforts to detect mood and anxiety disorders in offspring with a maternal history should be encouraged.

Dataset Information

Inflammation: opportunities for treatment stratification among individuals diagnosed with mood disorders.

Publications

Inflammation: opportunities for treatment stratification among individuals diagnosed with mood disorders.

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