Abstract
The high heterogeneity of psychiatric disorders leads to a lack of diagnostic precision. Therefore, the search of biomarkers is a fundamental aspect in psychiatry to reach a more personalized medicine. The endocannabinoid system (ECS) has gained increasing interest due to its involvement in many different functional processes in the brain, including the regulation of emotions, motivation, and cognition. This article reviews the role of the main components of the ECS as biomarkers in certain psychiatric disorders. Studies carried out in rodents evaluating the effects of pharmacological and genetic manipulation of cannabinoid receptors or endocannabinoids (eCBs) degrading enzymes were included. Likewise, the ECS-related alterations occurring at the molecular level in animal models reproducing some behavioral and/or neuropathological aspects of psychiatric disorders were reviewed. Furthermore, clinical studies evaluating gene or protein alterations in post-mortem brain tissue or in vivo blood, plasma, and cerebrospinal fluid (CSF) samples were analyzed. Also, the results from neuroimaging studies using positron emission tomography (PET) or functional magnetic resonance (fMRI) were included. This review shows the close involvement of cannabinoid receptor 1 (CB1r) in stress regulation and the development of mood disorders [anxiety, depression, bipolar disorder (BD)], in post-traumatic stress disorder (PTSD), as well as in the etiopathogenesis of schizophrenia, attention deficit hyperactivity disorder (ADHD), or eating disorders (i.e. anorexia and bulimia nervosa). On the other hand, recent results reveal the potential therapeutic action of the endocannabinoid tone manipulation by inhibition of eCBs degrading enzymes, as well as by the modulation of cannabinoid receptor 2 (CB2r) activity on anxiolytic, antidepressive, or antipsychotic associated effects. Further clinical research studies are needed; however, current evidence suggests that the components of the ECS may become promising biomarkers in psychiatry to improve, at least in part, the diagnosis and pharmacological treatment of psychiatric disorders.
Highlights
Psychiatric disorders are one of the main causes of disability in the general population [1]
Animal Studies The involvement of CB1 receptor (CB1r) in posttraumatic stress disorder (PTSD) is supported by the presence of this receptor in brain areas regulating the response to stress and to changes observed in different animal models of PTSD
Considering the urgent need to identify new and better biomarkers in psychiatry, the evidence included in this review provides an overview of the opportunities that cannabinoid receptors (Table 1), endogenous cannabinoid ligands (Table 2), or their metabolizing enzymes (Table 3) offer as potential biomarkers in the clinical setting
Summary
Psychiatric disorders are one of the main causes of disability in the general population [1]. Electron microscopy revealed CB1r expression in the rat lateral habenula (LHb), mediating the actions of increased 2AG levels after acute stress exposure, while its blockade by SR141716 (rimonabant) significantly reduced anxiety-like behavior [108]. Stress exposure induces anxiety-like behavior and reduces AEA brain levels [143] by increasing FAAH activity in the Amy [144], a brain region closely involved in AEA-mediated emotional regulation [145].
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