International Journal of Molecular Sciences
September 23, 2018
Domenico de Berardis, Michele Fornaro, Alessandro Valchera et al.
171 citations
Suicide remains difficult to predict despite advances in neuroscience. The World Health Organization reports one million suicide deaths annually, with one every 40 seconds. Recent genomic studies suggest genetics influence suicide risk. Combining genomic and clinical assessments has identified biomarkers for suicidal ideation involved in neural connectivity, mood, and immune response, including the mammalian target of rapamycin (mTOR) signaling pathway. This provides a neurobiological basis for drugs like ketamine, an NMDA antagonist, which has shown rapid antidepressant and anti-suicidal effects. This review examines preclinical and clinical evidence for ketamine's efficacy in treating suicidal ideation in mood disorders, addressing the neurobiological processes of suicide and potential therapeutics.
Current Topics in Medicinal Chemistry
January 31, 2020
Domenico de Berardis, Carmine Tomasetti, Maurizio Pompili et al.
38 citations
Abnormalities in glutamatergic neurotransmission are hypothesized to play a role in mood disorders, prompting investigation of NMDA receptor modulators for Major Depressive Disorder (MDD). Intranasal esketamine, an NMDA receptor antagonist, has been developed for treatment-resistant depression (TRD) and for rapidly reducing depressive symptoms, including suicidal ideation, in MDD patients at imminent suicide risk. A systematic review of literature up to October 2019 found that intravenous esketamine elicits rapid and sustained antidepressant effects in refractory patients. Phase II studies showed intranasal esketamine had rapid onset and persistent efficacy in TRD and MDD patients at suicide risk, though phase III data had discrepancies.
Human psychopharmacology
May 1, 2020
Laura Orsolini, Stefania Chiappini, Duccio Papanti et al.
27 citations
Ayahuasca, a hallucinogenic plant preparation used in sacred ceremonies by indigenous Amazonian groups, may offer therapeutic benefits for mental health. Evidence from preclinical, observational, and experimental studies suggests it acts as a fast-acting and enduring antidepressant, emotional regulator, anxiolytic, and antiaddictive drug. It appears safe and well tolerated, with nausea and vomiting as the most common transient side effects. However, findings indicate it should not be used in bipolar or psychotic patients due to increased risk of manic switch or psychotic onset. Further research with randomized, double-blind, placebo-controlled trials and neuroimaging is needed to better evaluate its therapeutic potential in mental disorders.
Progress in neuro-psychopharmacology & biological psychiatry
October 1, 2015
Andrea De Bartolomeis, Francesco Errico, Giuseppe Aceto et al.
Elevated D-aspartate levels in mice altered expression of key postsynaptic density genes involved in glutamate signaling. In mice lacking D-aspartate oxidase (Ddo-/-), which have persistently high brain D-aspartate, Homer1a expression decreased in the prefrontal cortex, Homer1b/c increased in the striatum, and PSD-95 decreased in both striatum and cortex. Acute treatment with phencyclidine (PCP) restored and even potentiated Homer1a expression in the prefrontal cortex of these mutant mice but had limited effects on other genes. These findings suggest that sustained D-aspartate elevation may trigger adaptive changes in Homer1a that could explain protective effects against PCP-induced behavioral alterations.