Agents In Neuropsychiatric Disorders Research Articles

Back to the Future: The Role of Infections in Psychopathology. Focus on OCD.

ObjectiveRecently, there has been a resurgence of interest in the relationship between infections and psychopathology, given the increasing data on the neurotropism and neurological/psychiatric morbidity of the SARS-COV2 virus, responsible for the current worldwide pandemic. Although the majority of observations were those obtained in mood and schizophrenic disorders, a few data are also available on the presence of bacterial or viral infections in patients suffering from obsessive-compulsive disorder (OCD). Therefore, given the limited information, the present paper aimed at reviewing the most updated evidence of infections in neuropsychiatric disorders and their possible mechanisms of actions, with a narrow focus on microbes in OCD.MethodThis paper is a narrative review. The databases of PubMed, Scopus, Embase, PsycINFO and Google Scholar were accessed to research and collect English language papers published between 1 January 1980 and 31 December 2021. The data on PANDAS/PANS and those observed during severe brain infections were excluded.ResultsSeveral pathogens have been associated with an increased risk to develop a broad spectrum of neuropsychiatric conditions, such as schizophrenia, mood disorders, autism, attention-deficit/hyperactivity disorder, anorexia nervosa, and post-traumatic stress disorder. Some evidence supported a possible role of infections also in the pathophysiology of OCD. Infections from Herpes simplex virus 1, Borna disease virus, Group A-Beta Hemolytic Streptococcus, Borrelia spp., and Toxoplasma gondii were actually found in patients with OCD. Although different mechanisms have been hypothesized, all would converge to trigger functional/structural alterations of specific circuits or immune processes, with cascade dysfunctions of several other systems.ConclusionsBased on the current evidence, a possible contribution of different types of microbes has been proposed for different neuropsychiatric disorders including OCD. However, the currently available literature is meager and heterogeneous in terms of sample characteristics and methods used. Therefore, further studies are needed to better understand the impact of infectious agents in neuropsychiatric disorders. Our opinion is that deeper insights in this field might contribute to a better definition of biological underpinnings of specific clinical pictures, as well as to promote psychiatric precision medicine, with treatments based on altered pathological pathways of single patients. This might be particularly relevant in OCD, a disorder with a high proportion of patients who are resistant or do not respond to conventional therapeutic strategies.

Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders.

Salvinorin A is a potent hallucinogen, isolated from the ethnomedical plant Salvia divinorum. Salvinorin A is a selective high efficacy kappa-opioid receptor (KOPr) agonist, and thus implicates the KOPr system and its endogenous agonist ligands (the dynorphins) in higher functions, including cognition and perceptual effects. Salvinorin A is the only selective KOPr ligand to be widely available outside research or medical settings, and salvinorin A-containing products have undergone frequent non-medical use. KOPr/dynorphin systems in the brain are known to be powerful counter-modulatory mechanisms to dopaminergic function, which is important in mood and reward engendered by natural and chemical reinforcers (including drugs of abuse). KOPr activation (including by salvinorin A) can thus cause aversion and anhedonia in preclinical models. Salvinorin A is also a completely new scaffold for medicinal chemistry approaches, since it is a non-nitrogenous neoclerodane, unlike other known opioid ligands. Ongoing efforts have the goal of discovering novel semi-synthetic salvinorin analogs with potential KOPr-mediated pharmacotherapeutic effects (including partial agonist or biased agonist effects), with a reduced burden of undesirable effects associated with salvinorin A.

Putative neuroprotective agents in neuropsychiatric disorders

In many individuals with major neuropsychiatric disorders including depression, bipolar disorder and schizophrenia, their disease characteristics are consistent with a neuroprogressive illness. This includes progressive structural brain changes, cognitive and functional decline, poorer treatment response and an increasing vulnerability to relapse with chronicity. The underlying molecular mechanisms of neuroprogression are thought to include neurotrophins and regulation of neurogenesis and apoptosis, neurotransmitters, inflammatory, oxidative and nitrosative stress, mitochondrial dysfunction, cortisol and the hypothalamic-pituitary-adrenal axis, and epigenetic influences. Knowledge of the involvement of each of these pathways implies that specific agents that act on some or multiple of these pathways may thus block this cascade and have neuroprotective properties. This paper reviews the potential of the most promising of these agents, including lithium and other known psychotropics, aspirin, minocycline, statins, N-acetylcysteine, leptin and melatonin. These agents are putative neuroprotective agents for schizophrenia and mood disorders.

Managing psychiatric disorders with antidiabetic agents: translational research and treatment opportunities

The objective of this paper is to synthesise extant studies describing the neurotherapeutic effects of antidiabetic agents in neuropsychiatric disorders. The authors conducted a MedLine search of all English-language articles published between 1966 and March 2006. The search terms were the nonproprietary names of established and putative antidiabetic agents (e.g., insulin, insulin secretagogues and sensitisers) cross-referenced with the individual names of Diagnostic and Statistical Manual of Mental Disorders (DSM)-III-R/IV/-TR-defined mood, psychotic, anxiety and dementing disorders. The search was augmented with a manual review of article reference lists. Contemporary models of disease pathophysiology in major depressive disorder, bipolar disorder and several dementing disorders (e.g., Alzheimer’s disease) emphasise alterations in cellular plasticity and cytoarchitecture, with associated regional abnormalities in neuronal and glial density and morphology. Antidiabetic treatments (e.g., thiazolidinediones) may be capable of attenuating this pathological process via disparate mechanisms (e.g., neuroprotective, neurotrophic, anti-inflammatory). Enhanced insulin signalling with antidiabetic treatments may preserve and/or augment cognitive function in several neuropsychiatric disorders. Antidiabetic treatments, which maintain euglycaemia, hold promise as potent and clinically significant therapeutic interventions for several neuropsychiatric disorders.