The Medical clinics of North America
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Med. Clin. North Am. · Jan 2023
ReviewThe Role of Inflammation in the Pathophysiology of Depression and Suicidal Behavior: Implications for Treatment.
Depression and suicidal behavior are 2 complex psychiatric conditions of significant public health concerns due to their debilitating nature. The need to enhance contemporary treatments and preventative approaches for these illnesses not only calls for distillation of current views on their pathogenesis but also provides an impetus for further elucidation of their novel etiological determinants. ⋯ This review highlights key evidence that supports the presence of dysregulated neurometabolic and immunologic signaling and abnormal interaction with microbial species as putative etiological hallmarks of inflammation in depression as well as their contribution to the development of suicidal behavior. Furthermore, therapeutic insights addressing candidate mechanisms of pathological inflammation in these disorders are proposed.
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Initial studies suggested that the fluctuations in the quantity, variety, and composition of the gut microbiota can significantly affect disease processes. This change in the gut microbiota causing negative health benefits was coined dysbiosis. ⋯ However, the gut microbiome was found to affect more than just gastrointestinal diseases. Numerous studies have proven that the gut microbiome can influence neuropsychiatric diseases such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis.
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Depression commonly onsets in adolescence, affecting approximately 1 in 4 female adolescents and 1 in 10 males in the United States. Adolescent depression is a significant risk factor for suicide, the cause of over a third of all American adolescent deaths. ⋯ Protective factors and contemporary special topics of the COVID-19 pandemic and social media use are reviewed. Therapeutic options and clinical barriers are highlighted before a summary of findings and conclusion.
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Schizophrenia is a disabling condition impacting approximately 1% of the worldwide population. Symptoms include positive symptoms (eg, hallucinations, delusions), negative symptoms (eg, avolition, anhedonia), and cognitive impairment. ⋯ Nondopaminergic medications targeting alternative receptors are under investigation. Supportive psychosocial treatments can work in tandem with antipsychotic medications and optimize patient care.
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Med. Clin. North Am. · Jan 2023
ReviewFrom Mouse to Man: N-Methyl-d-Aspartic Acid Receptor Activation as a Promising Pharmacotherapeutic Strategy for Autism Spectrum Disorders.
The BALB/c mouse displays hypersensitivity to behavioral effects of MK-801 (dizocilpine), a noncompetitive N-methyl-d-aspartic acid (NMDA) receptor "open-channel" blocker, and shows both no preference for an enclosed stimulus mouse over an inanimate object and reduced social interaction with a freely behaving stimulus mouse. NMDA receptor agonist interventions improved measures of social preference and social interaction of the BALB/c mouse model of autism spectrum disorder (ASD). A "proof of principle/proof of concept" translational 10-week clinical trial with 8-week of active medication administration was conducted comparing 20 DSM-IV-TR-diagnosed older adolescent/young adult patients with ASD randomized to once-weekly pulsed administration (50 mg/d) versus daily administration of d-cycloserine (50 mg/d). ⋯ NMDA receptor activation contributes to the regulation of mTOR signaling, a pathologic point of convergence in several monogenic syndromic forms of ASD. Furthermore, both NMDA receptor hypofunction and imbalance between NMDA receptor activation mediated by GluN2B and GluN2A-containing NMDA receptors occur as "downstream" consequences of several genetically unrelated abnormalities associated with ASD. NMDA receptor-subtype selective "positive allosteric modulators (PAMs)" are particularly appealing medication candidates for future translational trials.