Interaction of Heavy Drinking Patterns and Depression Severity Predicts Efficacy of Quetiapine Fumarate XR in Lowering Alcohol Intake in Alcohol Use Disorder Patients

Vatsalya, Vatsalya; Kong, Maiying; Marsano, Luis M; Kurlawala, Zimple; Chandras, Kan V.; Schwandt, Melanie L.; Ramchandani, Vijay A.; McClain, Craig J.

doi:10.1177/1178221820955185

Cited by 3 publications

(1 citation statement)

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“…The generation of gut microbiota derived neurotransmitters that invoke potent biological effects was demonstrated by several groups 54,69–72 . We also showed these effects on serotonin pathways previously 73,74 . Others have examined GABA 75,76 , dopamine synthesis 14 and the release of short chain fatty acids 77–80 (derived from the gut microbiome).…”

Section: Discussionsupporting

confidence: 60%

Illustration of a Novel Gut-Brain Axis of Alcohol Withdrawal, Withdrawal-Associated Depression, Craving and Alcohol-Severity Index in Alcohol Use Disorder Patients

Vatsalya

Ranganathan

Verster

et al. 2022

Preprint

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Pathways underlying the gut-brain axis and pro-inflammatory cytokine production influence brain functions and behavior. Alcohol use disorder (AUD) patients exhibit domains such as alcohol withdrawal, depression, and craving; and the gut-immune response may play a significant role in these domains of AUD. This study examined the role of intestinal permeability, pro-inflammatory cytokines, and hormones levels on the domains of AUD.Forty-eight AUD patients [male (n=34) and female (n=14)] aged 23-63 yrs. were grouped categorically using the Clinical Institute Withdrawal Assessment of alcohol scale (CIWA) as either clinically significant CIWA group (CS-CIWA [score>10] Gr.1 [n=22]), and clinically not-significant group (NCS-CIWA [score≤10] Gr.2 [n=26]). A sub-set of 13 AUD patient were also tested for reward response for drug-seeking using Penn-Alcohol Craving Score (PACS). Clinical data and blood samples were collected upon enrollment. Blood samples were analyzed for pro-inflammatory cytokines, and hormones, and markers of intestinal permeability. CIWA, 90-day timeline followback (TLFB90), and lifetime drinking history (LTDH) were also collected for comparison.As expected, recent and chronic heavy drinking were significantly higher in Gr.1: HDD90 (heavy drinking days), NDD90 (number of drinking days), as was LTDH, especially in Gr.1 females. Further, in Gr.1, adiponectin (associated with withdrawal) was significantly higher; and numerically higher levels of lipopolysaccharide (LPS) and LPS-binding protein (LBP) were also reported. Gr.1 patients exhibited higher effects of association on the withdrawal-associated depression domain for the parameters of LPS, sCD14, IL-6 and IL-8. Leptin also showed a significantly high effect of association with HDD90 in those AUD patients with craving. The craving domain (assessed by PACS, Penn-Alcohol Craving Scale) could be described as a gut-immune-brain model by the gut-dysregulation (LBP and Leptin) markers, and specific pro-inflammatory activity (IL-1β and TNF-α). Such pathway model describes the heavy drinking phenotype, HDD90 with even higher effects (R2=0.955, p=0.006) in the AUD patients who had higher ratings for craving (PACS>5).Interaction of gut-dysfunction, cytokines involved in both inflammation and in mediating-chemotactic activity constitute a novel pathophysiological gut-brain axis for withdrawal, and alcohol-associated depression and craving domains of AUD. AUD patient with higher craving show higher reinforcing effects of the gut-brain axis response for heavy drinking.

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Section: Discussionsupporting

confidence: 60%

Illustration of a Novel Gut-Brain Axis of Alcohol Withdrawal, Withdrawal-Associated Depression, Craving and Alcohol-Severity Index in Alcohol Use Disorder Patients

Vatsalya

Ranganathan

Verster

et al. 2022

Preprint

Self Cite

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The Anti-Inebriation of Probiotic Fermented Pollen on Acute Alcoholism Rats and Protection on Alcoholic Liver Injury

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2022

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Are Histamine H3 Antagonists the Definitive Treatment for Acute Methamphetamine Intoxication?

Kitanaka

Hall

Tomita

et al. 2022

CDRR

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Background: Methamphetamine (METH) is classified as a Schedule II stimulant drug under the United Nations Convention on Psychotropic Substances of 1971. METH and other amphetamine analogues (AMPHs) are powerful addictive drugs. Treatments are needed to treat the symptoms of METH addiction, chronic METH use, and acute METH overdose. No effective treatment for METH abuse has been established because alterations of brain functions under excessive intake of abused drug intake are largely irreversible due in part to brain damage that occurs in the course of chronic METH use. Objective: Modulation of brain histamine neurotransmission is involved in several neuropsychiatric disorders, including substance use disorders. This review discusses the possible mechanisms underlying the therapeutic effects of histamine H3 receptor antagonists on symptoms of methamphetamine abuse. Conclusion: : Treatment of mice with centrally acting histamine H3 receptor antagonists increases hypothalamic histamine contents and reduces high-dose METH effects, while potentiating low-dose effects, via histamine H1 receptors that bind released histamine. On the basis of experimental evidence, it is hypothesized that histamine H3 receptors may be an effective target for the treatment METH use disorder or other adverse effects of chronic METH use.

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Interaction of Heavy Drinking Patterns and Depression Severity Predicts Efficacy of Quetiapine Fumarate XR in Lowering Alcohol Intake in Alcohol Use Disorder Patients

Cited by 3 publications

References 46 publications

Illustration of a Novel Gut-Brain Axis of Alcohol Withdrawal, Withdrawal-Associated Depression, Craving and Alcohol-Severity Index in Alcohol Use Disorder Patients

Illustration of a Novel Gut-Brain Axis of Alcohol Withdrawal, Withdrawal-Associated Depression, Craving and Alcohol-Severity Index in Alcohol Use Disorder Patients

The Anti-Inebriation of Probiotic Fermented Pollen on Acute Alcoholism Rats and Protection on Alcoholic Liver Injury

Are Histamine H3 Antagonists the Definitive Treatment for Acute Methamphetamine Intoxication?

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