Molecular psychiatry
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Molecular psychiatry · Jan 2021
ReviewThe changing opioid crisis: development, challenges and opportunities.
The current opioid epidemic is one of the most severe public health crisis in US history. Responding to it has been difficult due to its rapidly changing nature and the severity of its associated outcomes. ⋯ Successfully addressing the epidemic will require advances in basic science, development of more acceptable and effective treatments, and implementation of public health approaches, including prevention. The advances achieved in addressing the current crisis should also serve to advance the science and treatment of other substance use disorders.
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Molecular psychiatry · Aug 2020
Epigenetic mechanisms in schizophrenia and other psychotic disorders: a systematic review of empirical human findings.
Schizophrenia and other psychotic disorders are highly debilitating psychiatric conditions that lack a clear etiology and exhibit polygenic inheritance underlain by pleiotropic genes. The prevailing explanation points to the interplay between predisposing genes and environmental exposure. Accumulated evidence suggests that epigenetic regulation of the genome may mediate dynamic gene-environment interactions at the molecular level by modulating the expression of psychiatric phenotypes through transcription factors. ⋯ However, heterogeneous results and cross-tissue extrapolations call for future work. Integrating epigenetics into systems biology may critically enhance research on psychosis and thus our understanding of the disorder. This may have implications for psychiatry in risk stratification, early recognition, diagnostics, precision medicine, and other interventional approaches targeting epigenetic fingerprints.
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Machine and deep learning methods, today's core of artificial intelligence, have been applied with increasing success and impact in many commercial and research settings. They are powerful tools for large scale data analysis, prediction and classification, especially in very data-rich environments ("big data"), and have started to find their way into medical applications. ⋯ We will also comment on an emerging area that so far has been much less well explored: by embedding semantically interpretable computational models of brain dynamics or behavior into a statistical machine learning context, insights into dysfunction beyond mere prediction and classification may be gained. Especially this marriage of computational models with statistical inference may offer insights into neural and behavioral mechanisms that could open completely novel avenues for psychiatric treatment.
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Molecular psychiatry · May 2018
ReviewDeep brain stimulation for treatment-resistant depression: an integrative review of preclinical and clinical findings and translational implications.
Although deep brain stimulation (DBS) is an established treatment choice for Parkinson's disease (PD), essential tremor and movement disorders, its effectiveness for the management of treatment-resistant depression (TRD) remains unclear. Herein, we conducted an integrative review on major neuroanatomical targets of DBS pursued for the treatment of intractable TRD. The aim of this review article is to provide a critical discussion of possible underlying mechanisms for DBS-generated antidepressant effects identified in preclinical studies and clinical trials, and to determine which brain target(s) elicited the most promising outcomes considering acute and maintenance treatment of TRD. ⋯ Preclinical studies suggest that stimulation parameters and neuroanatomical locations could influence DBS-related antidepressant effects, and also pointed that modulatory effects on monoamine neurotransmitters in target regions or interconnected brain networks following DBS could have a role in the antidepressant effects of DBS. Among several neuromodulatory targets that have been investigated, DBS in the neuroanatomical framework of the SCG, ALIC and MFB yielded more consistent antidepressant response rates in samples with TRD. Nevertheless, more well-designed randomized double-blind, controlled trials are warranted to further assess the efficacy, safety and tolerability of these more promising DBS targets for the management of TRD as therapeutic effects have been inconsistent across some controlled studies.
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Clinical studies have demonstrated that a single sub-anesthetic dose of the dissociative anesthetic ketamine induces rapid and sustained antidepressant actions. Although this finding has been met with enthusiasm, ketamine's widespread use is limited by its abuse potential and dissociative properties. Recent preclinical research has focused on unraveling the molecular mechanisms underlying the antidepressant actions of ketamine in an effort to develop novel pharmacotherapies, which will mimic ketamine's antidepressant actions but lack its undesirable effects. ⋯ Mechanisms that do not involve direct inhibition of the NMDAR, including a role for ketamine's (R)-ketamine enantiomer and hydroxynorketamine (HNK) metabolites, specifically (2R,6R)-HNK, are also discussed. Proposed mechanisms of ketamine's action are not mutually exclusive and may act in a complementary manner to exert acute changes in synaptic plasticity, leading to sustained strengthening of excitatory synapses, which are necessary for antidepressant behavioral actions. Understanding the molecular mechanisms underpinning ketamine's antidepressant actions will be invaluable for the identification of targets, which will drive the development of novel, effective, next-generation pharmacotherapies for the treatment of depression.