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Article ; Online: Active Cigarette Smoking Is Associated With Increased Age-Related Decline on Measures of Visuospatial Learning and Memory and Executive Function in Alcohol Use Disorder.

Padula, Claudia B / Durazzo, Timothy C

Alcohol and alcoholism (Oxford, Oxfordshire)

2022 Volume 57, Issue 6, Page(s) 656–663

Abstract: Aims: The goal of this study was to determine if active cigarette smoking in Veterans with alcohol use disorder (AUD) was associated with greater age-related neurocognitive decline.: Methods: Veterans with AUD, in residential treatment (n = 125; 47 ± ...

Abstract	Aims: The goal of this study was to determine if active cigarette smoking in Veterans with alcohol use disorder (AUD) was associated with greater age-related neurocognitive decline. Methods: Veterans with AUD, in residential treatment (n = 125; 47 ± 14 years of age, min = 24, max = 76, 29 ± 26 days of abstinence), completed measures of executive functions, learning and memory, processing speed and working memory. Actively smoking AUD (AsAUD, n = 47) were active daily cigarette smokers; former smoking AUD (FsAUD, n = 45) were predominately daily smokers prior to study but did not smoke at the time of study; non-smoking AUD (NsAUD, n = 33) never used cigarettes or smoked 'only a few times' during lifetime. Results: AsAUD demonstrated greater age-related decline on measures of visuospatial learning and memory, and response inhibition/cognitive flexibility, primarily relative to NsAUD; there were no age-related differences between FsAUD and NsAUD on any measure. There were few significant mean differences between groups across the 15 neurocognitive measures. In AsAUD, higher scores on indices of smoking severity were associated with poorer performance on measures of auditory-verbal learning and memory, response inhibition, set-shifting and working memory. In FsAUD, longer smoking cessation duration was related to lower PTSD, anxiety and depressive symptomatology. Conclusions: Active smoking was associated with accelerated age-related decline on cognitive functions implicated in response to common evidence-based AUD interventions. Results suggest that smoking history contributes to the considerable heterogeneity observed in neurocognitive function in early AUD recovery, and reinforce the clinical movement to offer smoking cessation resources concurrent with treatment for AUD.
MeSH term(s)	Humans ; Infant, Newborn ; Alcoholism/psychology ; Executive Function ; Temperance/psychology ; Cigarette Smoking ; Neuropsychological Tests
Language	English
Publishing date	2022-05-11
Publishing country	England
Document type	Journal Article
ZDB-ID	604956-4
ISSN	1464-3502 ; 0309-1635 ; 0735-0414
ISSN (online)	1464-3502
ISSN	0309-1635 ; 0735-0414
DOI	10.1093/alcalc/agac022
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Article ; Online: Leadership Styles Experienced During Military Service Predict Later Anhedonic Depressive Symptoms and Self-Efficacy in Veterans With Alcohol Use Disorder.

Durazzo, Timothy C / Humphreys, Keith / LaRocca, Michael A

Military medicine

2023

Abstract: Introduction: Lifetime and past-year alcohol use disorder (AUD) prevalence is significantly higher in US Armed Services Veterans than in non-veterans across adulthood. This study examined the associations of perceived transformational leadership styles ( ...

Abstract	Introduction: Lifetime and past-year alcohol use disorder (AUD) prevalence is significantly higher in US Armed Services Veterans than in non-veterans across adulthood. This study examined the associations of perceived transformational leadership styles (TLS) experienced during military service and anhedonic depression and self-efficacy related to confidence to abstain or reduce alcohol consumption in Veterans seeking treatment for AUD. The ramifications of perceived leadership styles on multiple aspects of follower psychiatric functioning, including depressive and PTSD symptomatology, during and after military service, may be substantial and enduring. Higher anhedonic depression and lower abstinence self-efficacy are related to increased risk of relapse after treatment. We predicted Veterans, in treatment for AUD, who reported higher perceived levels of transformational leadership during military service, demonstrate lower anhedonic depressive symptoms and higher alcohol abstinence self-efficacy. Materials and methods: Veterans with AUD (n = 60; 50 ± 14 years of age) were recruited from residential treatment at the VA Palo Alto Health Care System. All procedures were approved by the VA Palo Alto Health Care System and Stanford University institutional review boards. A series of mediation analyses were completed with The Multifactor Leadership Questionnaire measures of TLS (average across leadership measures [transformational leadership average; TLS average]) as predictor and the Alcohol Abstinence Self-Efficacy Scale, Mood and Anxiety Symptom Questionnaire, anhedonic depression subscale, as dependent measures. PTSD Checklist for DSM-5 score was tested as a mediator variable. Results: Higher reported perceived TLS average during military service was significantly related to lower anhedonic depressive symptoms. Higher TLS average was related to higher self-efficacy to resist alcohol use in contexts involving experience of physical issues and withdrawal/cravings and urges. These relationships were not mediated by PTSD symptomatology or duration of military service, age, education, time since military service, military branch, combat exposure, or current psychiatric diagnosis. Conclusions: The significant associations of perceived TLS during military service with anhedonic depression and alcohol use self-efficacy are clinically relevant because these measures are associated with relapse risk after AUD treatment. Further study of the implications of perceived TLS during military service for AUD and other substance use disorder treatment outcome is warranted in Veterans.
Language	English
Publishing date	2023-10-28
Publishing country	England
Document type	Journal Article
ZDB-ID	391061-1
ISSN	1930-613X ; 0026-4075
ISSN (online)	1930-613X
ISSN	0026-4075
DOI	10.1093/milmed/usad405
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Article ; Online: Regional cortical thickness recovery with extended abstinence after treatment in those with alcohol use disorder.

Durazzo, Timothy C / Stephens, Lauren H / Meyerhoff, Dieter J

Alcohol (Fayetteville, N.Y.)

2023 Volume 114, Page(s) 51–60

Abstract: Several cross-sectional investigations reported widespread cortical thinning in those with alcohol use disorder (AUD). The few longitudinal studies investigating cortical thickness changes during abstinence are limited to the first month of sobriety. ... ...

Abstract	Several cross-sectional investigations reported widespread cortical thinning in those with alcohol use disorder (AUD). The few longitudinal studies investigating cortical thickness changes during abstinence are limited to the first month of sobriety. Consequently, cortical thickness changes during extended abstinence in those with AUD is unclear. In this study, AUD participants were studied at approximately 1 week (n = 68), 1 month (n = 88), and 7.3 months (n = 40) of abstinence. Forty-five never-smoking controls (CON) completed a baseline study, and 15 were reassessed after approximately 9.6 months. Participants completed magnetic resonance imaging studies at 1.5T, and cortical thickness for 34 bilateral regions of interest (ROI) was quantitated with FreeSurfer. AUD participants demonstrated significant linear thickness increases in 25/34 ROI over 7.3 months of abstinence. The rate of change from 1 week to 1 month was greater than 1 month to 7.3 months in 19/34 ROIs. Proatherogenic conditions were associated with lower thickness recovery in anterior frontal, inferior parietal, and lateral/mesial temporal regions. After 7.3 months of abstinence, AUD participants were statistically equivalent to CON on cortical thickness in 24/34 ROIs; the cortical thickness differences between AUD and CON in the banks superior temporal gyrus, post central, posterior cingulate, superior parietal, supramarginal, and superior frontal cortices were driven by thinner cortices in AUD with proatherogenic conditions relative to CON. In actively smoking AUD, increasing pack-years was associated with decreasing thickness recovery primarily in the anterior frontal ROIs. Widespread bilateral cortical thickness recovery over 7.3 months of abstinence was the central finding for this AUD cohort. The longitudinal and cross-sectional findings for AUD with proatherogenic suggests alterations in perfusion or vascular integrity may relate to structural recovery in those with AUD. These results support the adaptive and beneficial effects of sustained sobriety on brain structural recovery in people with AUD.
MeSH term(s)	Humans ; Alcoholism/diagnostic imaging ; Alcoholism/therapy ; Cross-Sectional Studies ; Brain ; Longitudinal Studies ; Frontal Lobe ; Magnetic Resonance Imaging/methods ; Alcohol Abstinence ; Cerebral Cortex/diagnostic imaging
Language	English
Publishing date	2023-08-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	605912-0
ISSN	1873-6823 ; 0741-8329
ISSN (online)	1873-6823
ISSN	0741-8329
DOI	10.1016/j.alcohol.2023.08.011
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Article ; Online: Regional cortical brain volumes at treatment entry relates to post treatment WHO risk drinking levels in those with alcohol use disorder.

Durazzo, Timothy C / Stephens, Lauren H / Kraybill, Eric P / May, April C / Meyerhoff, Dieter J

Drug and alcohol dependence

2024 Volume 255, Page(s) 111082

Abstract: Background: Abstinence following treatment for alcohol use disorder (AUD) is associated with significant improvements in psychiatric and physical health, however, recent studies suggest resumption of low risk levels of alcohol use can also be beneficial. ...

Abstract	Background: Abstinence following treatment for alcohol use disorder (AUD) is associated with significant improvements in psychiatric and physical health, however, recent studies suggest resumption of low risk levels of alcohol use can also be beneficial. The present study assessed whether post-treatment levels of alcohol use were associated with cortical brain volumedifferences at treatment entry. Methods: Individuals seeking treatment for AUD (n=75) and light/non-drinking controls (LN, n=51) underwent 1.5T magnetic resonance imaging. The volumes of 34 bilateral cortical regions of interest (ROIs) were quantitated via FreeSurfer. Individuals with AUD were classified according to post-treatment alcohol consumption using the WHO risk drinking levels (abstainers: AB; low risk: RL; or higher risk: RH). Regional volumes for AB, RL and RH, at treatment entry, were compared to LN. Results: Relative to LN, AB demonstrated smaller volumes in 18/68 (26%), RL in 24/68 (35%) and RH in 34/68 (50%) ROIs with the largest magnitude volume differences observed between RH and LN. RH and RL reported a higher frequency of depressive disorders than AB. Among RH and RL, level of depressive and anxiety symptomatology were associated with daily number of drinks consumed after treatment. Conclusions: Volumetric differences, at treatment entry, in brain regions implicated in executive function and salience networks corresponded with post-treatment alcohol consumption levels suggesting that pre-existing differences in neural integrity may contribute to treatment outcomes. Depressive and anxiety symptomatology was also associated with brain morphometrics and alcohol use patterns, highlighting the importance of effectively targeting these conditions during AUD treatment.
MeSH term(s)	Humans ; Alcoholism/diagnostic imaging ; Alcoholism/therapy ; Alcohol Drinking/psychology ; Brain/diagnostic imaging ; Brain/pathology ; Magnetic Resonance Imaging/methods ; World Health Organization
Language	English
Publishing date	2024-01-05
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	519918-9
ISSN	1879-0046 ; 0376-8716
ISSN (online)	1879-0046
ISSN	0376-8716
DOI	10.1016/j.drugalcdep.2024.111082
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Article ; Online: GABA concentrations in the anterior cingulate and dorsolateral prefrontal cortices: Associations with chronic cigarette smoking, neurocognition, and decision making.

Durazzo, Timothy C / Meyerhoff, Dieter J

Addiction biology

2020 Volume 26, Issue 3, Page(s) e12948

Abstract: Chronic cigarette smoking is associated with regional metabolite abnormalities in choline-containing compounds, creatine-containing compounds, glutamate, and N-acetylaspartate. The effects of cigarette smoking on anterior frontal cortical gamma- ... ...

Abstract	Chronic cigarette smoking is associated with regional metabolite abnormalities in choline-containing compounds, creatine-containing compounds, glutamate, and N-acetylaspartate. The effects of cigarette smoking on anterior frontal cortical gamma-aminobutyric acid (GABA) concentration are unknown. This study compared chronic smokers (n = 33) and nonsmokers (n = 31) on anterior cingulate cortex (ACC) and right dorsolateral prefrontal cortex (DLPFC) GABA+ (the sum of GABA and coedited macromolecules) concentrations and associations of GABA+ levels in these regions with seven neurocognitive domains of functioning, decision making, and impulsivity measures. Smokers had significantly lower right DLPFC GABA+ concentration than nonsmokers, but groups were equivalent on ACC GABA+ level. Across groups, greater number of days since end of menstrual cycle was related to higher GABA+ level in the ACC but not right DLPFC GABA+ concentration. In exploratory correlation analyses, higher ACC and right DLPFC GABA+ levels were associated with faster processing speed and better auditory-verbal memory, respectively, in the combined group of smokers and nonsmokers; in smokers only, higher ACC GABA+ was related to better decision making and auditory-verbal learning. This study contributes additional novel data on the adverse effects of chronic cigarette smoking on the adult human brain and demonstrated ACC and DLPFC GABA+ concentrations were associated with neurocognition and decision making/impulsivity in active cigarette smokers. Longitudinal studies on the effects of smoking cessation on regional brain GABA levels, with a greater number of female participants, are required to determine if the observed metabolite abnormalities are persistent or normalize with smoking cessation.
MeSH term(s)	Adult ; Case-Control Studies ; Cigarette Smoking/metabolism ; Cigarette Smoking/psychology ; Cognition/physiology ; Decision Making/physiology ; Female ; Gyrus Cinguli/metabolism ; Humans ; Impulsive Behavior/physiology ; Magnetic Resonance Imaging ; Male ; Memory ; Middle Aged ; Prefrontal Cortex/metabolism ; gamma-Aminobutyric Acid/metabolism
Chemical Substances	gamma-Aminobutyric Acid (56-12-2)
Language	English
Publishing date	2020-08-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1324314-7
ISSN	1369-1600 ; 1355-6215
ISSN (online)	1369-1600
ISSN	1355-6215
DOI	10.1111/adb.12948
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Zs.A 4586: Show issues

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Article ; Online: Cigarette smoking history is associated with poorer recovery in multiple neurocognitive domains following treatment for an alcohol use disorder.

Durazzo, Timothy C / Meyerhoff, Dieter J

Alcohol (Fayetteville, N.Y.)

2020 Volume 85, Page(s) 135–143

Abstract: Cigarette smoking is associated with neurocognitive dysfunction in various populations, including those seeking treatment for an alcohol use disorder (AUD). This study compared the rate and extent of recovery on measures of processing speed, executive ... ...

Abstract	Cigarette smoking is associated with neurocognitive dysfunction in various populations, including those seeking treatment for an alcohol use disorder (AUD). This study compared the rate and extent of recovery on measures of processing speed, executive functions, general intelligence, visuospatial skills and working memory in treatment-seeking alcohol dependent individuals (ALC) who were never-smokers (nvsALC), former-smoker (fsALC), and active smokers (asALC), over approximately 8 months of abstinence from alcohol. Methods: ALC participants were evaluated at approximately 1 month of abstinence (AP1; n = 132) and reassessed after 8 months of sobriety (AP2; n = 54). Never-smoking controls (CON; n = 33) completed a baseline and follow-up (n = 19) assessment approximately 9 months later. Domains evaluated were executive functions, general intelligence, processing speed, visuospatial skills and working memory; a domain composite was formed from the arithmetic average of the foregoing domains. nvsALC showed greater improvement than fsALC, asALC and CON on most domains over the AP1-AP2 interval. fsALC demonstrated greater recovery than asALC on all domains except visuospatial skills; fsALC also showed greater improvements than CON on general intelligence, working memory and domain composite. asALC did not show significant improvement on any domain over the AP1-AP2 interval. At 8 months of abstinence, asALC were inferior to CON and nvsALC on multiple domains, fsALC performed worse than nvsALC on several domains, but nvsALC were not different from CON on any domain. Our results provide robust evidence that smoking status influenced the rate and extent of neurocognitive recovery between 1 and 8 months of abstinence in this ALC cohort. Chronic smoking in AUD likely contributes to the considerable heterogeneity observed in neurocognitive recovery during extended abstinence. The findings provide additional strong support for the benefits of smoking cessation and the increasing clinical movement to offer smoking cessation resources concurrent with treatment for AUD.
MeSH term(s)	Adult ; Aged ; Alcohol Abstinence/psychology ; Alcoholism/psychology ; Cigarette Smoking/psychology ; Cognition/physiology ; Cohort Studies ; Cross-Sectional Studies ; Executive Function ; Female ; Humans ; Longitudinal Studies ; Male ; Memory, Short-Term ; Middle Aged ; Neuropsychological Tests ; Recovery of Function/physiology
Language	English
Publishing date	2020-01-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	605912-0
ISSN	1873-6823 ; 0741-8329
ISSN (online)	1873-6823
ISSN	0741-8329
DOI	10.1016/j.alcohol.2019.12.003
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Article ; Online: Changes of frontal cortical subregion volumes in alcohol dependent individuals during early abstinence: associations with treatment outcome.

Durazzo, Timothy C / Meyerhoff, Dieter J

Brain imaging and behavior

2019 Volume 14, Issue 5, Page(s) 1588–1599

Abstract: We previously reported that at 1-and-4 weeks of sobriety, those who relapsed after treatment demonstrated significantly smaller total frontal cortical volume than individuals who maintained abstinence for at least 12 months post treatment. The ... ...

Abstract	We previously reported that at 1-and-4 weeks of sobriety, those who relapsed after treatment demonstrated significantly smaller total frontal cortical volume than individuals who maintained abstinence for at least 12 months post treatment. The segmentation method employed did not permit examination of frontal subregions that serve as nodes of the executive, salience and emotional regulation networks; structural abnormalities in these circuits are associated with relapse in those seeking treatment for alcohol use disorders (AUD). The primary goal of this study was to determine if frontal cortical subregion volume recovery during early abstinence is associated with long-term abstinence from alcohol. We compared bilateral components of the dorsal prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex and insula volumes, at 1 and 4 weeks of abstinence, between individuals who resumed drinking within 12 months of treatment (Relapsers) those who showed sustained abstinence over 12 months following treatment (Abstainers) and healthy Controls. At 1 and 4 weeks of sobriety, Relapsers demonstrated significantly smaller volumes than Controls in 15 of 20 regions of interest, while Abstainers only had smaller volumes than Controls in 5 of 20 regions. In Relapsers, increasing volumes over 1 month in multiple frontal subregions and the insula were associated with longer duration of abstinence after treatment. The persistent bilateral frontal and insula volume deficits in Relapsers over 4 weeks from last alcohol use may have implications for neurostimulation methods targeting anterior frontal/insula regions, and represent an endophenotype that differentiates those who respond more favorably to available psychosocial and pharmacological interventions.
MeSH term(s)	Alcoholism/diagnostic imaging ; Alcoholism/therapy ; Cerebral Cortex/diagnostic imaging ; Frontal Lobe/diagnostic imaging ; Humans ; Magnetic Resonance Imaging ; Treatment Outcome
Language	English
Publishing date	2019-06-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2377165-3
ISSN	1931-7565 ; 1931-7557
ISSN (online)	1931-7565
ISSN	1931-7557
DOI	10.1007/s11682-019-00089-5
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Article ; Online: Medical Conditions Linked to Atherosclerosis Are Associated With Magnified Cortical Thinning in Individuals With Alcohol Use Disorders.

Durazzo, Timothy C / Nguyen, Linh-Chi / Meyerhoff, Dieter J

Alcohol and alcoholism (Oxford, Oxfordshire)

2020 Volume 55, Issue 4, Page(s) 382–390

Abstract: ... such as hypertension, type 2 diabetes mellitus, hepatitis C seropositivity and hyperlipidemia on cortical thickness ...

Abstract	Aims: Magnetic resonance imaging (MRI) studies report widespread cortical thinning in individuals with alcohol use disorder (AUD), but did not consider potential effects of pro-atherogenic conditions such as hypertension, type 2 diabetes mellitus, hepatitis C seropositivity and hyperlipidemia on cortical thickness. The conditions are associated with regional cortical thinning in those without AUD. We predicted that individuals with concurrent AUD and pro-atherogenic conditions demonstrate the greatest regional cortical thinning in areas most vulnerable to decreased perfusion. Methods: Treatment-seeking individuals with AUD (n = 126) and healthy controls (CON; n = 49) completed a 1.5 T MRI study. Regional cortical thickness was quantitated via FreeSurfer. Individuals with AUD and pro-atherogenic conditions (Atherogenic+), AUD without pro-atherogenic conditions (Atherogenic-) and CON were compared on regional cortical thickness. Results: Individuals with AUD showed significant bilateral cortical thinning compared to CON, but Atherogenic+ demonstrated the most widespread and greatest magnitude of regional thinning, while Atherogenic- had reduced thickness primarily in anterior frontal and posterior parietal lobes. Atherogenic+ also showed a thinner cortex than Atherogenic- in lateral orbitofrontal and dorso/dorsolateral frontal cortex, mesial and lateral temporal and inferior parietal regions. Conclusions: Our results demonstrate significant bilateral cortical thinning in individuals with AUD relative to CON, but the distribution and magnitude were influenced by comorbid pro-atherogenic conditions. The magnitude of cortical thinning in Atherogenic+ strongly corresponded to cortical watershed areas susceptible to decreased perfusion, which may result in morphometric abnormalities. The findings indicate that pro-atherogenic conditions may contribute to cortical thinning in those seeking treatment for AUD.
MeSH term(s)	Adult ; Aged ; Alcoholism/complications ; Atherosclerosis/diagnostic imaging ; Case-Control Studies ; Cerebral Cortical Thinning/diagnostic imaging ; Cerebral Cortical Thinning/etiology ; Diabetes Mellitus, Type 2/complications ; Female ; Hepatitis C/complications ; Humans ; Hyperlipidemias/complications ; Hypertension/complications ; Magnetic Resonance Imaging/methods ; Male ; Middle Aged ; Risk Factors
Language	English
Publishing date	2020-05-22
Publishing country	England
Document type	Journal Article
ZDB-ID	604956-4
ISSN	1464-3502 ; 0309-1635 ; 0735-0414
ISSN (online)	1464-3502
ISSN	0309-1635 ; 0735-0414
DOI	10.1093/alcalc/agaa034
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Article ; Online: BDNF rs6265 Met carriers with alcohol use disorder show greater age-related decline of N-acetylaspartate in left dorsolateral prefrontal cortex.

Durazzo, Timothy C / McNerney, M Windy / Hansen, Annika M / Gu, Meng / Sacchet, Matthew D / Padula, Claudia B

Drug and alcohol dependence

2023 Volume 248, Page(s) 109901

Abstract: Background: Brain-derived neurotrophic factor (BDNF) is implicated in neuronal and glial cell growth and differentiation, synaptic plasticity, and apoptotic mechanisms. A single-nucleotide polymorphism of the BDNF rs6265 gene may contribute to the ... ...

Abstract	Background: Brain-derived neurotrophic factor (BDNF) is implicated in neuronal and glial cell growth and differentiation, synaptic plasticity, and apoptotic mechanisms. A single-nucleotide polymorphism of the BDNF rs6265 gene may contribute to the pattern and magnitude of brain metabolite abnormalities apparent in those with an Alcohol Use Disorder (AUD). We predicted that methionine (Met) carriers would demonstrate lower magnetic resonance spectroscopy (MRS) measures of N-acetylaspartate level (NAA) and greater age-related decline in NAA than valine (Val) homozygotes. Methods: Veterans with AUD (n=95; 46±12 years of age, min = 25, max = 71) were recruited from VA Palo Alto residential treatment centers. Single voxel MRS, at 3 Tesla, was used to obtain NAA, choline (Cho) and creatine (Cr) containing compounds from the left dorsolateral prefrontal cortex (DLPFC). Metabolite spectra were fit with LC Model and NAA and Cho were standardized to total Cr level and NAA was also standardized to Cho. Results: Val/Met (n=35) showed markedly greater age-related decline in left DLPFC NAA/Cr level than Val/Val (n=60); no differences in mean metabolite levels were observed between Val/Met and Val/Val. Val/Met demonstrated greater frequency of history of MDD and higher frequency of cannabis use disorder over 12 months prior to study. Conclusions: The greater age-related decline in left DLPFC NAA/Cr and the higher frequency of MDD history and Cannabis Use disorder in BDNF rs6265 Met carriers with AUD are novel and may have implications for non-invasive brain stimulation targeting the left DLFPC and other psychosocial interventions typically utilized in the treatment of AUD.
MeSH term(s)	Humans ; Methionine/genetics ; Dorsolateral Prefrontal Cortex ; Brain-Derived Neurotrophic Factor/genetics ; Brain-Derived Neurotrophic Factor/metabolism ; Alcoholism/genetics ; Marijuana Abuse ; Racemethionine ; Creatine/metabolism
Chemical Substances	Methionine (AE28F7PNPL) ; Brain-Derived Neurotrophic Factor ; N-acetylaspartate (997-55-7) ; Racemethionine (73JWT2K6T3) ; Creatine (MU72812GK0)
Language	English
Publishing date	2023-04-28
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	519918-9
ISSN	1879-0046 ; 0376-8716
ISSN (online)	1879-0046
ISSN	0376-8716
DOI	10.1016/j.drugalcdep.2023.109901
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Article ; Online: A pilot, randomized clinical trial: Left dorsolateral prefrontal cortex intermittent theta burst stimulation improves treatment outcomes in veterans with alcohol use disorder.

Padula, Claudia B / McCalley, Daniel M / Tenekedjieva, Lea-Tereza / MacNiven, Kelly / Rauch, Andrew / Morales, Jairelisse Morales / Knutson, Brian / Humphreys, Keith / Williams, Leanne M / Durazzo, Timothy C

Alcohol, clinical & experimental research

2024 Volume 48, Issue 1, Page(s) 164–177

Abstract: Background: Transcranial magnetic stimulation (TMS) offers a promising treatment avenue to modulate brain function in alcohol use disorder (AUD). To the best of our knowledge, this pilot study is the first randomized, double-blind, sham-controlled trial ...

Abstract	Background: Transcranial magnetic stimulation (TMS) offers a promising treatment avenue to modulate brain function in alcohol use disorder (AUD). To the best of our knowledge, this pilot study is the first randomized, double-blind, sham-controlled trial to deliver intermittent theta burst stimulation to the left dorsolateral prefrontal cortex (DLPFC) among US veterans with AUD. We hypothesized that 20 sessions of real TMS are tolerable and feasible. As a secondary line of inquiry, we hypothesized that, relative to sham TMS, individuals receiving real TMS would experience greater reductions in 6-month relapse rates, anhedonia, and alcohol cue-reactivity. Methods: Veterans (n = 17, one woman) were enrolled in a double-blind, sham-controlled trial (2-3 sessions/day; 7-10 days; 600 pulses/session; 20 sessions). Pre- and posttreatment assessments included responses to self-report questionnaires and functional magnetic resonance imaging measures of alcohol cue-reactivity. Alcohol consumption was assessed for 6 months. Linear mixed-effects models were constructed to predict posttreatment craving, mood, and cue-reactivity. Results: Individuals who received active iTBS (n = 8) were less likely to relapse within 3 months after treatment than the sham-treated group (n = 9) (OR = 12.0). Greater reductions in anhedonia were observed following active iTBS (Cohen's d = -0.59), relative to sham (d = -0.25). Alcohol cue-reactivity was reduced following active iTBS and increased following sham within the left insula (d = -0.19 vs. 0.51), left thalamus (d = -0.28 vs. 0.77), right insula (d = 0.18 vs. 0.52), and right thalamus (d = -0.06 vs. 0.62). Conclusions: Relative to sham, we demonstrate that 20 sessions of real left DLPFC iTBS reduced the likelihood of relapse for at least 3 months. The potential utility of this approach is underscored by observed decreases in anhedonia and alcohol cue-reactivity-strong predictors of relapse among veterans. These initial data offer a valuable set of effect sizes to inform future clinical trials in this patient population.
Language	English
Publishing date	2024-01-10
Publishing country	United States
Document type	Journal Article
ISSN	2993-7175
ISSN (online)	2993-7175
DOI	10.1111/acer.15224
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Inter-library loan at ZB MED