Table 1.
Summary of characteristics of 35 neuroimaging studies included for investigation of resilience and recovery in alcohol dependence
| Study | Study Design | Method | Follow- Up Period |
Age | Study Sample |
Main Findings | ||
|---|---|---|---|---|---|---|---|---|
| Neuroimaging | Paradigm | Other Tests | ||||||
| Alhassoon et al. 2012 | prospective cohort study | MRI/DTI | none | none | 1 year | AD: mean 51.4 SD (6) Controls: mean 51.8 SD (7.4) | n male= 30 (detoxified alcohol dependent ↔healthy controls) | Low FA and high RD in corpus callosum of AD group compared to controls. Significant improvement at follow up in AD group. |
| Alvanzo et al. 2015 | cross-sectional | MRI/PET | none | Family Tree Questionnaire | none | FHP: mean 23.1 SD (2.98) FHN: mean 22.7 SD (3.21) | n male = 51 n female = 33 (family history of AD ↔ no family history of AD) | Baseline [11C]raclopride BPND was generally higher in FHP compared with FHN subjects across striatal regions. Negative subjective drug effects were more pronounced in FHP than in FHN subjects. In FHN correlation between BPND and positive drug effects. This correlation was less pronounced in FHP. |
| Beck et al. 2012 | prospective cohort study | fMRI/Biological Parametric Mapping/PPI | alcohol cues | none | 3 months | AD: mean 39.37 SD (7.72) controls: mean 40.37 SD (6.68) | n= 92(detoxified AD ↔ healthy controls) | Abstinence related to increased activation in midbrain and VS. Stronger functional connectivity midbrain-left amygdala and midbrain - left orbitofrontal cortex. Relapse associated with atrophy in bilateral orbitofrontal cortex, right medial PFC and ACC as well as increased activity in left medial PFC. |
| Burt et al. 2016 | cross sectional | MRI/VBM | none | ESPAD, SDQ, DAWBA, LEQ | none | Mean 14.56 SD (0.44) | n male = 906 n female = 964 (competent (C/a), resilient (C/A), maladaptive (c/A), vulnerable (c/a)) | C/a and C/A showed larger left OFC volume. C/a and c/A larger fusiform gyrus volume than c/a and C/A groups. C/A group showed increased volume relative to other groups in right superior frontal and right middle frontal regions; in the right superior frontal region |
| Cardenas et al. 2007 | cross sectional/prospective cohort study | MRI/DBM | none | LDH | 8 months (AD) 12 months (LD) | AD : mean 49 SD (14) Controls: mean 45 SD (8) | n male = 60 n female = 5 (AD ↔ LD; AD longitudinal ↔ LD) | Atrophy in frontal and temporal lobe in AD group. Abstainers show faster recovery in parietal and frontal tissue than LD. Temporal lobes, thalamus, brainstem, cerebellum, corpus callosum, anterior cingulate, insula, and subcortical white matter was increased in abstainers compared to relapsers. Recovery predicted by baseline gray matter volumes. |
| Cardenas et al. 2011 | Prospective cohort study | MRI/DBM | None | LDH | 7.8 months | AD: mean 50 SD (10) Controls: Mean 47 SD (8) | n male = 104 n female = 11 (AD< healthy control; relapsers ↔ abstainers) | Abstainers vs. controls had smaller volume in left hippocampus, entorhinal cortex, amygdala and right thalamus but larger volume in left orbitofrontal region. Relapsers vs. abstainers smaller volume in lateral OFC, left posterior middle/temporal gyry and supramarginal gyrus. Relapsers had different pattern of volume loss than abstainers. |
| Chanraud et al. 2013 | cross sectional | fMRI/PPI/Resting state functional connectivity | working-memory task | none | none | AD: mean 40.1 SD (10.9) controls: mean 47.7 SD (12.29) | n male= 30 (detoxified AD ↔ healthy controls) | Recovery related to recruitment of dorsolateral prefrontal cortex (DLPFC)-cerebellar VIII system during rest and DLPFC-cerebellar VI system during working memory task. |
| Charlet et al. 2014 | prospective cohort study | fMRI/Biological Parametric Mapping | n-back task | Alcohol Timeline Follow-back | 7 months | AD: mean 44.9 SD (11.4) controls: mean 44.1 SD (12) | n male = 60 n female = 20 (detoxified AD ↔ Healthy controls) | High resilience (low relapse risk in alcohol dependence) associated with neural activation in lateral/medial premotor cortex, rostral/ventrolateral prefrontal cortex during n-back working memory task. |
| Charlet et al. 2014 | prospective cohort study | fMRI/Biological Parametric Mapping | Hariri faces task (modified) | LDH | none | AD: mean 44.8 SD (9.8) controls: mean 46.1 SD (9.8) | n male = 50 n female = 16 (detoxified AD ↔ healthy controls) | Increased ACC response to affective faces correlated to abstinence and less retrospective alcohol intake in alcohol dependent patients. |
| Chung et al. 2011 | cross sectional | event-related fMRI | antisaccade reward task | none | none | SUD: mean 17.0 SD (0.9) control: mean 16.9 SD (0.9) | n male/female = 12 (SUD [marijuana, alcohol, other] ↔ healthy controls) | During response preparation SUD showed increased activation in oculomotor control regions (FEF, SEF), DLPFC, regions in the parietal lobe, and areas in the frontal gyrus. |
| Deshmukh et al. 2005 | cross sectional | MRI/Volumetric data | none | none | none | AD: mean 49.4 SD (10.9) Controls: mean 45.2SD (13.9) Schizophrenia: mean 44.7 SD (8.6) Comorbid: mean 41.0 SD (7.5) | n male = 122 (AD detoxified ↔ schizophrenia ↔ AD/schizophrenia ↔ healthy controls) | Putamen and nucleus accumbens decrease greater in schizophrenia than AD, comorbid group fell between these groups. Schizophrenic patients treated with atypical medication showed greater volume decreases in putamen than those treated with typical medication. Recently sober (< 3 weeks) alcoholics had greater deficits in nucleus accumbens than AD with long-term sobriety. |
| Durazzo et al. 2015 | Prospective cohort study | MRI/Volumetric data | none | LDH, nerurocognitive battery | 7,5 months | AD smoking: mean 49 SD (9) AD non-smoking: mean 52 SD (11) Controls: Mean 47 SD (9) | n male = 103 n female = 11 | AD: volume increases in all GM and WM regions at FU; no significant predictors of regional volume change. Rates of GM gain greatest in first month. sAD showed less volume gain nsAD in frontal and total cortical GM. Improvement Processing Speed associated with increased volumes in nsAD, but not in sAD. After 7.5-months of abstinence, nsAD and sAD equal to controls on frontal GM volume |
| Gazdzinski et al. 2005 | cross sectional/prospective cohort study | MRI/Boundary Shift Integral | none | LDH | up to 12 months | AD: mean 50.6 SD (9.3) Controls: mean 45.0 SD (6.8) | n male = 37 n female = 3 (AD detoxified/longitudinal ↔ healthy controls) | Most tissue gain during the first abstinent month. Fastest volume recovery patients with greatest baseline brain shrinkage and drinking severity. Reversal of volume increases in non-abstinent individuals (modulated by duration of abstinence and non-abstinence periods, as well as recency of non-abstinence). |
| Gazdzinski et al. 2008 | cross sectional/prospective cohort study | MRI/short echo proton spectroscopy | none | BVMT | 1 month | smoking alcohol dependent: Mean 50.7 SD (9.0) Non-smoking alcohol dependent: Mean 50.2 SD (9.1) Non-Smoking controls: Mean 47.3 SD (8.2) | n male = 38 (smoking AD ↔ non-smoking AD ↔ non-smoking LD) | N-acetyl-aspartate normalized in the MTL of non-smoking AD group, remained low in the MTL of smoking AD group. Changes in both groups associated with improvements in visuospatial memory. Hippocampal volumes increased in both groups during abstinence, but increasing volumes correlated with visuospatial memory improvements only in non-smoking AD. |
| Gazdzinski et al. 2010 | prospective cohort study | MRI/DTI/spectroscopy | none | none | 1 year | smoking alcohol dependent: Mean 47.7 SD (9.5) Non-smoking alcohol dependent: Mean 51.5 SD (10.3) Non-smoking controls: Mean 48.3 SD (8.4) | n male = 53 n female = 5 (smoking AD ↔ non-smoking AD ↔ non-smoking LD) | Higher mean diffusivity in AD (smoking: frontal; non-smoking: parietal, frontal, temporal). Lower concentrations of N-acetyl-aspartate in AD (smoking: frontal; non-smoking: parietal). In non-smoking alcohol-dependent individuals increase in FA and decreases in mean diffusivity over 1 month of abstinence. White matter volume increase in frontal and temporal lobes in smoking AD group. |
| Heinz et al. 2004 | cross sectional | fMRI/PET | alcohol cues | Alcohol craving questionnaire | none | AD: mean 44.5 SD (6.5) controls: mean 43.2 SD (9.5) | n male = 24 (detoxified AD ↔ healthy controls) | In alcohol-dependent subjects higher activation of the medial pre-frontal cortex and striatum related to 1. less availability of D2-like receptors in VS, 2. Higher craving severity. |
| Heitzeg et al. 2008 | cross-sectional | fMRI | lexical emotional stimuli | YSR, Drinking and Drug History Form for Children | none | COAs resilient: mean 18.4 SD (1) COAs vulnerable : mean 17.5 SD (1.3) controls: mean 17.2 SD (1.6) | n male = 15 n female = 13 (COAs resilient ↔ COAS vulnerable↔ controls) | In response to emotional stimuli: Activation of orbital frontal gyrus and left insula/putamen greater in resilient than control and vulnerable groups. Vulnerable group had more activation of dorsomedial PFC and less activation of VS and extended amygdala. Increased dorsomedial prefrontal activation and decreased VS and amygdala activation correlated pos. with externalizing behaviors. |
| Hoefer et al. 2014 | cross sectional/pro spective cohort study | MRI/Volumetric data | none | LDH; Taqman genotyping assay; WAIS III; BVMT; AMNART | 7 months | smoking alcohol dependent: Mean 49.6 SD (9) Non-smoking alcohol dependent: Mean 53.6 (10.5) Non-smoking controls: Mean 45.6 SD (9.9) | n male = 144 n female = 12 (smoking alcohol dependent ↔ non-smoking alcohol dependent ↔ non-smoking controls) | AD had smaller hippocampi than healthy controls at all time points. Hippocampal volume at 1 month of abstinence correlated with lower visuospatial function. Smoking status did not influence volume or recovery. BDNF Val homozygotes had hippocampal volume increases over 7 months of abstinence, and Val homozygotes had significantly larger hippocampi than Met carriers at 7 months of abstinence. |
| Johnson-Greene et al. 1997 | pilot study | PET | none | neuropsych ological battery | up to 32 months | AD mean: 48.6 SD (10.2) | n male = 6 (AD longitudinal) | Abstinent group showed partial recovery of ICMRglc in two of three divisions of the frontal lobes and improvement on neuropsychological tests of general cognitive and executive functioning, whereas the patients who relapsed had further declines in these areas. |
| Kühn et al. 2014 | cross sectional/prospective cohort study | MRI/Volumetric data | none | LDH | 2 weeks | AD: mean 42.1 SD (11.6) Controls: mean 40.8 SD (3.4) | n male = 53 n female = 21 (AD detoxified ↔ healthy controls) | AD group had lower CA2+3 baseline volume and significant normalization of gray matter volume 2 weeks later. Neg. correlation between baseline CA2+3 volume and alcohol consumption and alcohol-withdrawal symptoms. AD patients with stronger withdrawal symptoms displayed the largest volume increase of CA2+3. |
| Mon et al. 2011 | prospective cohort study | MRI/Volumetric data/mathematical predictions | none | none | 222 days | AD: mean 50.7 SD (11.9) | n male = 13 n female = 3 | The data predicted from the formula were very similar to the experimentally measured data for all lobes and for both gray and white matter (intra-class correlation coefficients ↔ 0.95). |
| Mon et al. 2013 | cross sectional/pro spective cohort study | MRI/Volumetric data | none | LDH; Taqman genotyping assay; WAIS III | 5 weeks | AD: mean 50.8 SD (10.6) controls: mean 47.9 SD (7) | n male= 70 N female = 9 (AD detoxified/longitudinal ↔ LD) | VAL homozygote in AD group related to gray matter increase. VAL/MET heterozygote associated with white matter increases. Gray matter volume increases pos. correlated to neurocognitive measure increases. |
| Pfefferbaum et al. 1995 | prospective cohort study | MRI/Volumetric data | none | none | up to 12 months | AD: mean 45.0 SD (10.9) controls: mean 45.3 SD (14.2) | n male = 116 (AD detoxified/longitudinal ↔ controls) | From 1. to 2. scan, AD group showed declines in CSF volumes of lateral ventricles and posterior cortical sulci, and an increase in anterior cortical gray matter volume. From 2. to 3. scan third ventricular volumes decreased in the abstainers relative to the relapsers and controls; cortical white matter volume decreased in the relapsers. In the relapsers alcohol consumption predicted later vulnerability to white matter volume decline and third ventricular enlargement with relapse. |
| Pfefferbaum et al. 2001 | cross sectional | MRI/Volumetric data | none | LDH | none | AD male: mean 43.4 SD (8.4) AD female: mean 41.7 SD (9.5) Controls male: mean 44.6 SD (11.4) Controls female: mean42.9 SD (13.4) | n male = 92 n female = 79 (AD detoxified male/female ↔ healthy controls male/female) | Less brain shrinkage was found among alcoholic women than among alcoholic men. |
| Pfefferbaum et al. 2014 | Prospective cohort study | MRI/DTI/TBSS | None | Self-reported drinking histories | Up to 8 years | AD: mean 44.3 SD (9.2) Controls: mean 43.0 SD (10.1) | N male = 52 N female = 51 | FA of AD lower than that of healthy controls. Relapsing AD showed continued worsening, whereas abstaining AD showed improvement in fiber integrity. FA trajectories of relapsers exhibited faster aging relative to controls, whereas the trajectories of abstainers showed improvement toward normality |
| Ruiz et al. 2013 | cross sectional | MRI/Volumetric data | none | none | none | AD: mean 53.9 SD (11) Controls: mean 53.9 SD (12.4) | N = 44 N = 44 (AD detoxified male/female ↔ healthy controls male/female) | Female AD showed stronger positive associations between sobriety duration and white matter volume than men in first year of abstinence. Men showed this association more so than women after 1 year of abstinence. |
| Sameti et al. 2011 | cross sectional | MRI/Volumetric data | none | C-DIS | none | Long-term abstinent AD: mean 46.6 SD (6.7) Controls: mean 45.6 SD (6.5) | n male = 53 N female = 47 (long-term abstinent AD ↔ healthy controls) | Minimal differences in subcortical structure volumes between long-term abstinent AD and controls. In AD group differences in volume associated with current or lifetime psychiatric diagnosis. |
| Segobin et al. 2014 | cross sectional/prospective cohort study | MRI/Tensor-based Morphometry | none | none | 6 months | AD patients: mean 44.4 SD (6.07) Controls: mean 46.7 SD (4.25) | n male = 37 N female = 2 (AD ↔ healthy controls; AD/longitudinal) | Reduced thalamus volume associated with relapse. Recovery of cerebellum, striatum and cingulate gyrus even in AD patients with moderate alcohol intake but neg. correlated to amount of alcohol consumed over 6 months in AD group. |
| van Eijk et al. 2013 | cross sectional/prospective cohort study | MRI/VBM | none | none | 2 weeks | AD: mean 47.0 SD (10.1) Controls: mean 45.3 SD (11.9) | n male = 82 N female = 22 (AD detoxified/longitudinal ↔ healthy controls) | Gray matter volume (cingulate gyrus, middle and precentral prefrontal gyri, cerebellum, insula) smaller in AD compared with control group at baseline. Significant recovery after 2 weeks of abstinence. |
| Volkow et al. 1994 | prospective cohort study | PET | none | none | up to 2 months | AD: mean 41.0 SD (8) controls: mean 38.4 SD (3) | n male = 20 (AD detoxified/longitudinal ↔ healthy controls) | Metabolism increased predominantly in first 30 days of abstinence. Increases mainly in prefrontal regions. Metabolism negatively correlated to alcohol use. |
| Volkow et al. 2006 | Cross sectional | PET | None | Multidimensional Personality Questionnaire | none | FHP: mean 24 SD (3) FHN: mean 26 SD (4) | N male = 28 N female = 2 | FHP group had significantly higher measures of D2 receptor availability in caudate and VS. FHP subjects had lower metabolism in hippocampal gyrus, temporal pole and cerebellum. Metabolism in prefrontal cortex increased in FHP. Positive correlation between striatal D2 receptor availability and metabolism in OFC, ventral cingulate gyrus and PFC. D2 receptor and metabolism in left OFC was positively correlated to positive emotionality. |
| Wang et al. 2016 | Prospective cohort study | MRI/Volumetric data (CT, SA) | none | none | 14 days | AD: mean 47.02 SD (10) Controls: mean 46.65 SD (12.37) | N male = 47 N female = 12 (AD ↔ controls) | Lower subcortical volumes in AD in putamen, NA, amygdala and hippocampus. No subcortical volume regain at FU. Cortical volume recovery driven by an increase in CT. More CT reduction and recovery in sulci compared to gyri. |
| Weiland et al. 2012 | cross sectional | fMRI/PPI | n-back task | California Child Q-Sort | none | mean 20.2 SD (1.2) | N male = 43 N female = 24 (parental alcoholism ↔ no parental alcoholism) | High resilience: neg. correlated to STN, pallidum activation; pos. correlated to lower levels of substance use, fewer alcohol problems and better working memory performance. |
| Yau et al. 2012 | cross sectional | fMRI | MID task | Drinking and Drug History | none | COAs: mean 20.12 SD (1.2) control: mean 20.1 SD (1.3) | n male = 24 n female = 16 (COAs ↔ controls) | Resilience related to reduced ventral striatum activation in COAs. |
| Zakiniaeiz et al. 2016 | Prospective cohort study | fMRI/ICD | Individualized imagery paradigm | none | 90 days | Study 1 AD: mean 37.73 SD (1.16) Study 2 AD: mean 35.97 SE (0.08) Controls: mean 34.47 SE (1.55) | Study 1 N male = 35 N female = 10 Study 2 N male = 43 N female = 17 | AD showed decreased cingulate connectivity in responses to alcohol and stress cues compared to neutral cues. Weaker connectivity in ACC and MCC during neutral cue exposure related to longer abstinence. PCC connectivity during alcohol cues compared to stress cue conditions positively correlated to longer time to relapse. Cingulate connectivity significantly different between groups. AD showed reduced cingulate connectivity during alcohol and stress cues and increased cingulate connectivity during neutral cues. AD more similar to controls in cingulate connectivity had longer abstinence and better recovery. |
MRI = magnetic resonance imaging; DTI = diffusion tensor imaging; AD = alcohol dependent; SD = standard deviation; ↔ = versus; FA = fractional anisotropy; RD = radial diffusivity; PET = positron emission tomography; FHP = family history positive; FHN = family history negative; BPND = binding potential; FDG = 18F-fluorodeoxyglucose; fMRI = functional magnetic resonance imaging; PPI = psychophysiological interaction analysis; PFC = prefrontal cortex; ESPAD = european school survey project on alcohol and other drugs; SDQ = strengths and difficulties questionnaire; DAWBA = development and well-being assessment, LEQ = life events questionnaire; ACC = anterior cingulate cortex; DBM = deformation-based morphometry; LDH = lifetime drinking history; LD = light drinkers; OFC = orbitofrontal cortex; DLPFC = dorsolateral prefrontal cortex; SUD = substance use disorder; FEF = frontal eye field; SEF = supplementary eye field; GM = gray matter; WM = white matter; sAD = smoking alcohol dependent; nsAD = non-smoking alcohol dependent; BVTM = brief visuospatial memory test; MTL = medial temporal lobe; YSR = youth self-report; COA = children of alcoholics; VS = ventral striatum; pos. = positively; WAIS III = Wechsler adult intelligence scale; AMNART = American national adult reading test; BDNF = brain-derived neurotropic factor; ICMRGLC = regional cerebral glucose uptake; neg. = negative; c-DIS = computerized diagnostic interview schedule; FU = follow-up; CT = cortical thickness; STN = subthalamic nucleus; MID = monetary incentive delay; PCC = posterior cingulate gyrus; MCC = midcingulate cortex; ICD = intrinsic connectivity distribution