RESUMO
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.
RESUMO
INTRODUCTION: Emergency workers dedicate their lives to promoting public health and safety, yet suffer higher rates of post-traumatic stress disorder (PTSD) and major depression (MD) compared with the general population. They also suffer an associated increased risk for physical health problems, which may be linked to specific immunological and endocrine markers or changes in relevant markers. Poor physical and mental health is costly to organisations, the National Health Service and society. Existing interventions aimed at reducing risk of mental ill health in this population are not very successful. More effective preventative interventions are urgently needed. We first conducted a large-scale prospective study of newly recruited student paramedics, identifying two cognitive factors (rumination and resilience appraisals) that predicted episodes of PTSD and MD over a 2-year period. We then developed internet-delivered cognitive training for resilience (iCT-R), a supported online intervention, to modify cognitive predictors. This protocol is for a randomised controlled trial to evaluate the efficacy of the resilience intervention. METHODS AND ANALYSIS: 570 student paramedics will be recruited from participating universities. They will be randomly allocated to iCT-R or to supported online training of an alternative, widely available intervention or to training-as-usual. Follow-up will occur after the intervention/standard practice period and at 6, 12 and 24 months. Primary outcomes include rates of PTSD and MD and subsydnromal PTSD and MD, measured by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, fifth edition, the Patient-Health Questionnaire-9 and the Post-traumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Secondary outcomes include measures of resilience, rumination, anxiety, psychological distress, well-being, salivary cortisol, plasma levels of C-reactive protein, smoking and alcohol use, weight gain, sleep problems, health-related quality of life, health resource utilisation and productivity. ETHICS AND DISSEMINATION: The Medical Sciences Inter-Divisional Research Ethics Committee at the University of Oxford granted approval, reference: R44116/RE001. The results will be published in a peer-reviewed journal. Access to raw data and participant information will be available only to members of the research team. TRIAL REGISTRATION NUMBER: ISRCTN16493616; Pre-results.