scholarly journals Ketogenic diet reduces alcohol withdrawal symptoms in humans and alcohol intake in rodents

2021 ◽  
Vol 7 (15) ◽  
pp. eabf6780
Author(s):  
Corinde E. Wiers ◽  
Leandro F. Vendruscolo ◽  
Jan-Willem van der Veen ◽  
Peter Manza ◽  
Ehsan Shokri-Kojori ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Alcohol Withdrawal ◽  
Alcohol Use Disorder ◽  
Alcohol Intake ◽  
Anterior Cingulate ◽  
Dorsal Anterior Cingulate Cortex ◽  
Beneficial Effects ◽  
Alcohol Cues ◽  
History Of ◽  
To Receive

Individuals with alcohol use disorder (AUD) show elevated brain metabolism of acetate at the expense of glucose. We hypothesized that a shift in energy substrates during withdrawal may contribute to withdrawal severity and neurotoxicity in AUD and that a ketogenic diet (KD) may mitigate these effects. We found that inpatients with AUD randomized to receive KD (n = 19) required fewer benzodiazepines during the first week of detoxification, in comparison to those receiving a standard American (SA) diet (n = 14). Over a 3-week treatment, KD compared to SA showed lower “wanting” and increased dorsal anterior cingulate cortex (dACC) reactivity to alcohol cues and altered dACC bioenergetics (i.e., elevated ketones and glutamate and lower neuroinflammatory markers). In a rat model of alcohol dependence, a history of KD reduced alcohol consumption. We provide clinical and preclinical evidence for beneficial effects of KD on managing alcohol withdrawal and on reducing alcohol drinking.

scholarly journals Ibudilast, a neuroimmune modulator, reduces heavy drinking and alcohol cue-elicited neural activation: a randomized trial

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Erica N. Grodin ◽  
Spencer Bujarski ◽  
Brandon Towns ◽  
Elizabeth Burnette ◽  
Steven Nieto ◽  
...  
Keyword(s):  
Macrophage Migration Inhibitory Factor ◽  
Alcohol Use Disorder ◽  
Cue Reactivity ◽  
Negative Mood ◽  
Heavy Drinking ◽  
Neural Activation ◽  
Daily Diary Study ◽  
Alcohol Cues ◽  
To Receive ◽  
The Brain

AbstractIbudilast, a neuroimmune modulator which selectively inhibits phosphodiesterases (PDE)-3, -4, -10, and -11, and macrophage migration inhibitory factor (MIF), shows promise as a novel pharmacotherapy for alcohol use disorder (AUD). However, the mechanisms of action underlying ibudilast’s effects on the human brain remain largely unknown. Thus, the current study examined the efficacy of ibudilast to improve negative mood, reduce heavy drinking, and attenuate neural reward signals in individuals with AUD. Fifty-two nontreatment-seeking individuals with AUD were randomized to receive ibudilast (n = 24) or placebo (n = 28). Participants completed a 2-week daily diary study during which they filled out daily reports of their past day drinking, mood, and craving. Participants completed an functional magnetic resonance imaging (fMRI) alcohol cue-reactivity paradigm half-way through the study. Ibudilast did not have a significant effect on negative mood (β = −0.34, p = 0.62). However, ibudilast, relative to placebo, reduced the odds of heavy drinking across time by 45% (OR = 0.55, (95% CI: 0.30, 0.98)). Ibudilast also attenuated alcohol cue-elicited activation in the ventral striatum (VS) compared to placebo (F(1,44) = 7.36, p = 0.01). Alcohol cue-elicited activation in the VS predicted subsequent drinking in the ibudilast group (F(1,44) = 6.39, p = 0.02), such that individuals who had attenuated ventral striatal activation and took ibudilast had the fewest number of drinks per drinking day in the week following the scan. These findings extend preclinical and human laboratory studies of the utility of ibudilast to treat AUD and suggest a biobehavioral mechanism through which ibudilast acts, namely, by reducing the rewarding response to alcohol cues in the brain leading to a reduction in heavy drinking.

scholarly journals Increased anticipatory but decreased consummatory brain responses to food in sisters of anorexia nervosa patients

BJPsych Open ◽  
2016 ◽  
Vol 2 (4) ◽  
pp. 255-261 ◽  
Author(s):  
Stefanie Horndasch ◽  
Sophie O'Keefe ◽  
Anneka Lamond ◽  
Katie Brown ◽  
Ciara McCabe
Keyword(s):  
Anorexia Nervosa ◽  
Family History ◽  
Neural Response ◽  
Anterior Cingulate ◽  
Neural Responses ◽  
Food Cues ◽  
Dorsal Anterior Cingulate Cortex ◽  
Brain Responses ◽  
History Of ◽  
Increased Activity

BackgroundWe have previously shown increased anticipatory and consummatory neural responses to rewarding and aversive food stimuli in women recovered from anorexia nervosa (AN).AimsTo determine whether these differences are trait markers for AN, we examined the neural response in those with a familial history but no personal history of AN.MethodThirty-six volunteers were recruited: 15 who had a sister with anorexia nervosa (family history) and 21 control participants. Using fMRI we examined the neural response during an anticipatory phase (food cues, rewarding and aversive), an effort phase and a consummatory phase (rewarding and aversive tastes).ResultsFamily history (FH) volunteers showed increased activity in the caudate during the anticipation of both reward and aversive food and in the thalamus and amygdala during anticipation of aversive only. FH had decreased activity in the dorsal anterior cingulate cortex, the pallidum and the superior frontal gyrus during taste consumption.ConclusionsIncreased neural anticipatory but decreased consummatory responses to food might be a biomarker for AN. Interventions that could normalise these differences may help to prevent disorder onset.

scholarly journals Brief Training in Mindfulness Meditation Reduces Symptoms in Patients with a Chronic or Recurrent Lifetime History of Depression: A Randomized Controlled Study

2017 ◽  
Author(s):  
Emilia Winnebeck ◽  
Maria Fissler ◽  
Matti Gärtner ◽  
Paul Chadwick ◽  
Thorsten Barnhofer
Keyword(s):  
Mindfulness Meditation ◽  
Controlled Study ◽  
Stress Buffering ◽  
Beneficial Effects ◽  
Lifetime History ◽  
Brief Training ◽  
Treatment Of Depression ◽  
Before And After ◽  
History Of ◽  
To Receive

Background: Training in mindfulness has been introduced to the treatment of depression as a means of relapse prevention. However, from a stress-buffering perspective, mindfulness techniques would be expected to unfold their beneficial effects particularly in those who are currently suffering from symptoms. This study investigated whether a brief and targeted mindfulness-based intervention can reduce symptoms in acutely depressed patients.Methods: Seventy-four patients with a chronic or recurrent lifetime history were randomly allocated to receive either a brief mindfulness-based intervention (MBI) encompassing three individual sessions and regular home practice or a control condition that combined psycho-educational components and regular rest periods using the same format as the MBI. Self-reported severity of symptoms, mindfulness in every day life, ruminative tendencies and cognitive reactivity were assessed before and after intervention.Results: Patients in the MBI condition showed pronounced and significantly stronger reductions in symptoms than those in the control condition. In the MBI group only, patients showed significant increases in mindfulness, and significant reductions in ruminative tendencies and cognitive reactivity.Conclusions: Findings are in line with a stress-buffering account of mindfulness and suggest that brief targeted mindfulness interventions can help to reduce symptoms in acutely depressed patients with chronic or recurrent lifetime history.

scholarly journals Mood and neural responses to social rejection do not seem to be altered in resilient adolescents with a history of adversity

2019 ◽  
Vol 32 (2) ◽  
pp. 411-423
Author(s):  
Jessica Fritz ◽  
Jason Stretton ◽  
Adrian Dahl Askelund ◽  
Susanne Schweizer ◽  
Nicholas D. Walsh ◽  
...  
Keyword(s):  
Mental Health ◽  
Mental Health Problems ◽  
Childhood Adversity ◽  
Health Problems ◽  
Social Rejection ◽  
Anterior Cingulate ◽  
Neural Responses ◽  
Social Feedback ◽  
Dorsal Anterior Cingulate Cortex ◽  
History Of

AbstractChildhood adversity (CA) increases the risk of subsequent mental health problems. Adolescent social support (from family and/or friends) reduces the risk of mental health problems after CA. However, the mechanisms of this effect remain unclear, and we speculate that they are manifested on neurodevelopmental levels. Therefore, we investigated whether family and/or friendship support at ages 14 and 17 function as intermediate variables for the relationship between CA before age 11 and affective or neural responses to social rejection feedback at age 18. We studied 55 adolescents with normative mental health at age 18 (26 with CA and therefore considered “resilient”), from a longitudinal cohort. Participants underwent a Social Feedback Task in the magnetic resonance imaging scanner. Social rejection feedback activated the dorsal anterior cingulate cortex and the left anterior insula. CA did not predict affective or neural responses to social rejection at age 18. Yet, CA predicted better friendships at age 14 and age 18, when adolescents with and without CA had comparable mood levels. Thus, adolescents with CA and normative mood levels have more adolescent friendship support and seem to have normal mood and neural responses to social rejection.

scholarly journals Structural and functional imaging of the hippocampus in young people at familial risk of depression

2014 ◽  
Vol 44 (14) ◽  
pp. 2939-2948 ◽  
Author(s):  
Z. N. Mannie ◽  
N. Filippini ◽  
C. Williams ◽  
J. Near ◽  
C. E. Mackay ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Young People ◽  
Familial Risk ◽  
Memory Task ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Resonance Spectroscopy ◽  
Dorsal Anterior Cingulate Cortex ◽  
Parental History ◽  
History Of

BackgroundMajor depression is associated with abnormalities in the function and structure of the hippocampus. However, it is unclear whether these abnormalities might also be present in people ‘at risk’ of illness.MethodWe studied 62 young people (mean age 18.8 years) at familial risk of depression (FH+) but who had never been depressed themselves. Participants underwent magnetic resonance imaging to assess hippocampal structure and neural responses to a task designed to activate hippocampal memory networks. Magnetic resonance spectroscopy was used to measure levels of a combination of glutamine and glutamate (Glx) in the right hippocampus. A total of 59 matched controls with no history of mood disorder in a first-degree relative underwent the same investigations.ResultsHippocampal volume did not differ between FH+ participants and controls; however, relative to controls, during the memory task, FH+ participants showed increased activation in brain regions encompassing the insular cortices, putamen and pallidum as well as the dorsal anterior cingulate cortex (ACC). FH+ participants also had increased hippocampal levels of Glx.ConclusionsEuthymic individuals with a parental history of depression demonstrate increased activation of hippocampal-related neural networks during a memory task, particularly in brain regions involved in processing the salience of stimuli. Changes in the activity of the ACC replicate previous findings in FH+ participants using different psychological tasks; this suggests that task-related abnormalities in the ACC may be a marker of vulnerability to depression. Increased levels of Glx in the hippocampus might also represent a risk biomarker but follow-up studies will be required to test these various possibilities.

scholarly journals Mood and neural responses to social rejection are not altered in resilient adolescents with a history of adversity

2018 ◽  
Author(s):  
Jessica Fritz ◽  
Jason Stretton ◽  
Adrian Dahl Askelund ◽  
Susanne Schweizer ◽  
Nicholas Walsh ◽  
...  
Keyword(s):  
Mental Health ◽  
Mental Health Problems ◽  
Health Problems ◽  
Social Rejection ◽  
Anterior Cingulate ◽  
Neural Responses ◽  
Social Feedback ◽  
Dorsal Anterior Cingulate Cortex ◽  
History Of ◽  
Intermediate Variables

THIS IS A PRE-PRINT OF AN ARTICLE PUBLISHED IN “DEVELOPMENT AND PSYCHOPATHOLOGY (1–13)”. THE FINAL AUTHENTICATED VERSION IS AVAILABLE ONLINE AT: https://doi.org/10.1017/S0954579419000178Childhood adversity (CA) increases the risk of subsequent mental health problems. Adolescent social support (from family and/or friends) reduces the risk of mental health problems after CA. However, the mechanisms of this effect remain unclear and we speculate that they are manifested on neurodevelopmental levels. Therefore, we investigated whether family and/or friendship support at age 14 and 17 function as intermediate variables for the relationship between CA before age 11 and affective or neural responses to social rejection feedback at age 18. We studied 55 adolescents (26 with CA) with normative mental health at age 18 (‘resilient’), from a longitudinal cohort. Participants underwent a Social Feedback Task in the MRI scanner. Social rejection feedback activated the dorsal Anterior Cingulate Cortex (dACC) and the left anterior Insula (AI). CA did not predict affective or neural responses to social rejection at age 18. Yet, CA predicted better friendships at age 14 and age 18, when adolescents with and without CA had comparable mood levels. Thus, adolescents with CA and normative mood levels have more adolescent friendship support and seem to have normal mood and neural responses to social rejection.

Nalmefene effectiveness in reducing alcohol consumption and prevention of craving: A case report

2017 ◽  
Vol 41 (S1) ◽  
pp. S873-S873
Author(s):  
G. Pardo de Santayana ◽  
R. Landera ◽  
M. Juncal ◽  
O. Porta ◽  
L. Sánchez ◽  
...  
Keyword(s):  
Side Effects ◽  
Alcohol Consumption ◽  
Alcohol Use ◽  
Opioid Receptors ◽  
Alcohol Withdrawal ◽  
Alcohol Use Disorder ◽  
Alcohol Intake ◽  
Therapeutic Option ◽  
Observation Time ◽  
Psychiatric Consultation

IntroductionAlcohol use disorder is a pressing problem in our society. However, only a small percentage of patients with alcohol use disorder are ever treated. Nalmefene acts as an antagonist of mu opioid receptors preventing the pleasurable sensation that often accompanies alcohol consumption, while its modulation of kappa opioid receptors can decrease the dysphoria associated with alcohol withdrawal.AimStudying the effect of nalmefene on patients with alcohol use disorder who are trying to reduce their daily alcohol consumption.MethodsThis is a descriptive study that pretends to assess the effect of nalmefene 18 mg/day on alcohol intake in a sample of five patients (3 men and 2 women) that came to our psychiatric consultation from March to September 2016. They all had tried in the past to stop or reduce their alcohol consumption but were unable to do so. We initiate follow-up with the patients in psychiatric consultation for the next three months with a monthly frequency.ResultsOut of the 5 patients, 4 reported to have reduced their alcohol consumption over the observation time, going from 32 drinks per week to 18 drinks per week on average. The fifth patient abandoned prematurely the treatment due to the appearance of side effects (nausea). No other relevant side effects were detected.ConclusionsNalmefene appears to be effective and safe reducing abusive alcohol intake and avoiding alcohol withdrawal syndrome. Therefore, nalmefene can be considered a good therapeutic option helping reduce alcohol consumption in patients with alcohol use disorder.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Anterior cingulate metabolite levels, memory, and inhibitory control in abstinent men and women with Alcohol Use Disorder

2022 ◽  
Author(s):  
Emily N. Oot ◽  
Kayle S. Sawyer ◽  
Marlene Oscar-Berman ◽  
Riya B. Luhar ◽  
John Eric Jensen ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Inhibitory Control ◽  
Alcohol Use Disorder ◽  
Anterior Cingulate ◽  
Resonance Spectroscopy ◽  
Functional Domain ◽  
Dorsal Anterior Cingulate Cortex ◽  
Significant Group ◽  
Men And Women ◽  
Brain Metabolite

Aims: Alcohol use disorder (AUD), has been shown to have harmful cognitive and physiological effects, including altered brain chemistry. Further, although men and women may differ in vulnerability to the neurobiological effects of AUD, results of existing studies have been conflicting. Brain metabolite levels and cognitive functions were examined in a cross section of men with AUD (AUDm) and women with AUD (AUDw) to determine degree of abnormalities after extended periods of abstinence (mean, six years), and to evaluate gender differences in cognitive and metabolite measures. Methods: Participants were 40 abstinent individuals with AUD (22 AUDw, 18 AUDm) and 50 age-equivalent non-AUD comparison participants (26 NCw, 24 NCm). Proton magnetic resonance spectroscopy (MRS) was employed at 3 Tesla to acquire metabolite spectra from the dorsal anterior cingulate cortex (dACC). Brain metabolites N-acetylaspartate (NAA), choline (Cho), myo-Inositol (mI), and glutamate & glutamine (Glx) were examined relative to measures of memory and inhibitory control. Results: Metabolite levels in the AUD group showed no significant differences from the NC group. Memory and inhibitory-control impairments were observed in the AUD group. There also were significant group-specific associations between metabolite ratios and measures of inhibitory control. There were no Group-by-Gender interactions for the four metabolite ratios. Conclusions: These findings demonstrate that brain metabolite levels in men and women with AUD, following long-term abstinence, do not differ from individuals without AUD. The data also provide evidence of associations between metabolite levels and measures of inhibitory control, a functional domain important for curtailing harmful drinking.

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