5 results on '"Comai, Stefano"'
Search Results
2. Tryptophan via serotonin/kynurenine pathways abnormalities in a large cohort of aggressive inmates: markers for aggression.
- Author
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Comai, Stefano, Bertazzo, Antonella, Vachon, Jeanne, Daigle, Marc, Toupin, Jean, Côté, Gilles, Turecki, Gustavo, and Gobbi, Gabriella
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AGGRESSION (Psychology) , *TRYPTOPHAN , *KYNURENINE , *BIOMARKERS , *PSYCHIATRY , *THERAPEUTICS - Abstract
Aggressive behavior is one of the most challenging symptoms in psychiatry, and biological markers for aggression lack of large sample validations. Serotonin (5-HT) and other neuroactive compounds deriving from Tryptophan (Trp), including kynurenine (Kyn), have not yet been investigated in large cohorts of aggressive individuals to validate their potential as biomarkers of aggression. In 361 male inmates we measured serum levels of Trp, 5-hydroxytryptophan, 5-HT, Kyn, the ratios 5-HT/Trp ∗ 1000 and Kyn/Trp ∗ 1000, and performed Structured Clinical Interview for DSM-IV Axis-I and -II Disorders (SCID-I and -II), global assessment of functioning (GAF), and scales for aggressive behavior, impulsivity, adult attention-deficit/hyperactivity disorder (ADHD), and intelligent quotient (IQ). Aggressive compared to non-aggressive inmates exhibited lower Trp and Kyn serum levels but higher levels of 5-HT and 5-HT/Trp ∗ 1000, higher levels of impulsivity and ADHD indices, lower IQ and GAF, higher prevalence of mood disorders, drug abuse/dependence, and borderline, conduct and antisocial behaviors. Interestingly, Kyn/Trp ∗ 1000 was positively correlated to the number of severe aggressive acts (r = 0.593, P < 0.001). After adjusting for confounding factors, logistic regression analysis indicated that 5-HT/Trp ∗ 1000, antisocial behavior, and GAF were predictors of aggressive behavior. The model combining these three predictors had an area under the ROC curve of 0.851 (95% CI 0.806–0.895). This study indicates that while circulating Trp is reduced in aggressive individuals, the combination of biological (5-HT/Trp ratio) and psychopathological (antisocial behavior and GAF) markers discriminates between aggressive and non-aggressive behavior suggesting the potential of a multi-marker approach in psychiatry given the heterogenic nature of mental diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
3. Therapeutic modulation of the kynurenine pathway in severe mental illness and comorbidities: A potential role for serotonergic psychedelics.
- Author
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Campanale, Antonella, Inserra, Antonio, and Comai, Stefano
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MENTAL illness , *KYNURENINE , *GUT microbiome , *HALLUCINOGENIC drugs , *COMORBIDITY , *SEROTONIN , *ENZYME regulation , *PSILOCYBIN - Abstract
Mounting evidence points towards a crucial role of the kynurenine pathway (KP) in the altered gut-brain axis (GBA) balance in severe mental illness (SMI, namely depression, bipolar disorder, and schizophrenia) and cardiometabolic comorbidities. Preliminary evidence shows that serotonergic psychedelics and their analogues may hold therapeutic potential in addressing the altered KP in the dysregulated GBA in SMI and comorbidities. In fact, aside from their effects on mood, psychedelics elicit therapeutic improvement in preclinical models of obesity, metabolic syndrome, and vascular inflammation, which are highly comorbid with SMI. Here, we review the literature on the therapeutic modulation of the KP in the dysregulated GBA in SMI and comorbidities, and the potential application of psychedelics to address the altered KP in the brain and systemic dysfunction underlying SMI and comorbidities. Psychedelics might therapeutically modulate the KP in the altered GBA in SMI and comorbidities either directly, via altering the metabolic pathway by influencing the rate-limiting enzymes of the KP and affecting the levels of available tryptophan, or indirectly, by affecting the gut microbiome, gut metabolome, metabolism, and the immune system. Despite promising preliminary evidence, the mechanisms and outcomes of the KP modulation with psychedelics in SMI and systemic comorbidities remain largely unknown and require further investigation. Several concerns are discussed surrounding the potential side effects of this approach in specific cohorts of individuals with SMI and systemic comorbidities. • KP imbalance could be a common denominator in SMI and cardiometabolic comorbidities. • Serotonergic psychedelics may potentially address SMI-associated dysregulations, including KP alterations. • Psychedelics may modulate KP directly through metabolic enzyme regulation. • Psychedelics may modulate KP indirectly via gut microbiome and immune system interactions. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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4. Anxiolytic effects of the melatonin MT2 receptor partial agonist UCM765: Comparison with melatonin and diazepam
- Author
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Ochoa-Sanchez, Rafael, Rainer, Quentin, Comai, Stefano, Spadoni, Gilberto, Bedini, Annalida, Rivara, Silvia, Fraschini, Franco, Mor, Marco, Tarzia, Giorgio, and Gobbi, Gabriella
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TRANQUILIZING drugs , *MELATONIN , *DIAZEPAM , *NEUROHORMONES , *ANXIETY , *G protein coupled receptors , *PHARMACODYNAMICS - Abstract
Abstract: Melatonin (MLT) is a neurohormone known to be involved in the regulation of anxiety. Most of the physiological actions of MLT in the brain are mediated by two high-affinity G-protein-coupled receptors, denoted MT1 and MT2. However, the particular role of these receptors in anxiety remains to be defined. Here we used a novel MT2-selective partial agonist, UCM765 to evaluate the involvement of MT2 receptors in anxiety. Adult male rats were acutely injected with UCM765 (5–10–20mg/kg), MLT (20mg/kg) or diazepam (DZ, 1mg/kg). Anxiety-related behaviors were assessed in the elevated plus maze test (EPMT), novelty suppressed feeding test (NSFT) and open field test (OFT). UCM765 at the dose of 10mg/kg showed anxiolytic-like properties by increasing the time spent in the open arm of the EPMT, and by reducing the latency to eat in a novel environment in the NSFT. In the EPMT, animals treated with UCM765 (10mg/kg) or MLT (20mg/kg) spent more time in the open arms compared to vehicle-treated animals, but to a lesser extent compared to DZ (1mg/kg). In the NSFT, all treatments similarly decreased the latency to eat in a novel environment compared to vehicle. UCM765 and MLT did not affect the total time and the number of entries into the central area of the OFT, but unlike DZ, did not impair locomotion. The anxiolytic effects of UCM765 and MLT in the EPMT and the NSFT were blocked using a pre-treatment with the MT1/MT2 antagonist luzindole (10mg/kg) or the MT2 antagonist 4P-PDOT (10mg/kg). These results demonstrated, for the first time, the anxiolytic properties of UCM765 and suggest that MT2-receptors may be considered a novel target for the development of anxiolytic drugs. [Copyright &y& Elsevier]
- Published
- 2012
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5. Dysfunction of the serotonergic system in the brain of synapsin triple knockout mice is associated with behavioral abnormalities resembling synapsin-related human pathologies.
- Author
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Tassan Mazzocco, Margherita, Guarnieri, Fabrizia Claudia, Monzani, Elena, Benfenati, Fabio, Valtorta, Flavia, and Comai, Stefano
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KNOCKOUT mice , *RAPHE nuclei , *HIGH performance liquid chromatography , *SYNAPTIC vesicles , *SOCIAL anxiety , *HIPPOCAMPUS (Brain) - Abstract
Synapsins (Syns) are a family of phosphoproteins associated with synaptic vesicles (SVs). Their main function is to regulate neurotransmitter release by maintaining a reserve pool of SVs at the presynaptic terminal. Previous studies reported that the deletion of one or more Syn genes in mice results in an epileptic phenotype and autism-related behavioral abnormalities. Here we aimed at characterizing the behavioral phenotype and neurobiological correlates of the deletion of Syns in a Syn triple knockout (TKO) mouse model. Wild type (WT) and TKO mice were tested in the open field, novelty suppressed feeding, light-dark box, forced swim, tail suspension and three-chamber sociability tests. Using in vivo electrophysiology, we recorded the spontaneous activity of dorsal raphe nucleus (DRN) serotonin (5-HT) and ventral tegmental area (VTA) dopamine (DA) neurons. Levels of 5-HT and DA in the frontal cortex and hippocampus of WT and TKO mice were also assessed using a High-Performance Liquid Chromatography. TKO mice displayed hyperactivity and impaired social and anxiety-like behavior. Behavioral dysfunctions were accompanied by reduced firing activity of DRN 5-HT, but not VTA DA, neurons. TKO mice also showed increased responsiveness of DRN 5-HT-1A autoreceptors, measured as a reduced dose of the 5-HT-1A agonist 8-OH-DPAT necessary to inhibit DRN 5-HT firing activity by 50%. Finally, hippocampal 5-HT levels were lower in TKO than in WT mice. Overall, Syns deletion in mice leads to a reduction in DRN 5-HT firing activity and hippocampal 5-HT levels along with behavioral alterations reminiscent of human neuropsychiatric conditions associated with Syn dysfunction. • Syn triple knockout (TKO) mice display hyperactivity and impaired social behavior. • TKO mice show reduced dorsal raphe serotonergic neuronal activity. • TKO mice have lower hippocampal serotonin levels. • TKO mice are a model of humans diseases associated with Syn dysfunctions. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
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