Volumetric Prefrontal Cortex Alterations in Patients With Alcohol Dependence and the Involvement of Self-Control.

BACKGROUND: Aspects of self-control such as sensation seeking and impaired impulse control have been implicated in alcohol dependence (ALC). Conversely, sensation seeking has been ascribed a possible protective role in stress-related psychopathologies. We therefore examined gray matter (GM) morphology in individuals with ALC, focusing on differences in prefrontal regions that have been associated with self-control. Additionally, we accounted for differences in lifetime alcohol intake regarding self-control measures and cortical structures in ALC patients. METHODS: With voxel-based morphometry (VBM) focusing on prefrontal a priori defined regions of interest, we assessed a group of 62 detoxified ALC patients and 62 healthy controls (HC). ALC patients were subsequently divided into high (n = 9) and low consumers (n = 53). Self-control was assessed by use of the Barratt Impulsiveness Scale and the Sensation Seeking Scale. RESULTS: Compared to HC, ALC had significantly less GM volume in bilateral middle frontal gyrus (MFG) and right medial prefrontal cortex as well as in the right anterior cingulate. High-consuming ALC showed smaller GM in right orbitofrontal cortex as well as lower sensation seeking scores than low consumers. In low-consuming ALC, right MFG-GM was positively associated with magnitude of sensation seeking; particularly, larger MFG-GM correlated with greater thrill and adventure seeking. CONCLUSION: Thus, our findings (i) indicate deficient GM volume in prefrontal areas related to self-control and (ii) might accentuate the phenotypic divergence of ALC patients and emphasize the importance of the development of individual treatment options.

Association of the alcohol dehydrogenase gene polymorphism rs1789891 with gray matter brain volume, alcohol consumption, alcohol craving and relapse risk.

Alcohol metabolizing enzymes, such as the alcohol dehydrogenases and the aldehyde dehydrogenases, regulate the levels of acetaldehyde in the blood and play an important role in the development and maintenance of alcohol addiction. Recent genome-wide systematic searches found associations between a single nucleotide polymorphism (rs1789891, risk allele: A, protective allele: C) in the alcohol dehydrogenase gene cluster and the risk of alcohol dependence. The current study investigated the effect of this single nucleotide polymorphism on alcohol consumption, craving for alcohol, relapse risk and brain gray matter volume. Alcohol-dependent patients (n = 74) and controls (n = 43) were screened, genotyped and underwent magnetic resonance imaging scanning, and relapse data were collected during 3 months following the experiment. Alcohol-dependent A allele carriers reported increased alcohol craving and higher alcohol consumption compared with the group of alcohol-dependent individuals homozygous for the C allele, which displayed craving values similar to the control group. Further, follow-up data indicated that A allele carriers relapsed earlier to heavy drinking compared with individuals with two C alleles. Analyses of gray matter volume indicated a significant genotype difference in the patient group: individuals with two C alleles had reduced gray matter volume in the left and right superior, middle and inferior temporal gyri. Findings of the current study further support the relevance of genetic variants in alcohol metabolizing enzymes to addictive behavior, brain tissue volume and relapse risk. Genotype-dependent differences in acetaldehyde formation, implicated by earlier studies, might be the biological substrate of the genotype differences.

Frontal cortex gray matter volume alterations in pathological gambling occur independently from substance use disorder.

Neuroimaging in pathological gambling (PG) allows studying brain structure independent of pharmacological/neurotoxic effects occurring in substance addiction. Because of high comorbidity of PG with substance use disorder (SUD), first results on structural deficits in PG are controversial. The current investigation is the first to examine gray matter (GM) volume alterations in PG controlling for the impact of SUD by comparing non-comorbid (PGPURE ) and two comorbid (PGALCOHOL and PGPOLY ) groups. Two hundred and five individuals were included in the analysis: 107 patients diagnosed with PG and 98 healthy controls (HCs). We employed voxel-based morphometry to look for GM volume differences between the groups controlling for age, smoking and depression. GM decreases in the superior medial and orbital frontal cortex occur independently of substance use in PGPURE compared with HCs. The frontal pattern of GM decrease was comparable with PGALCOHOL group where additionally GM volume was decreased in the anterior cingulate but increased in the amygdala. Moreover, regions in PGALCOHOL + POLY with reduced GM volume were the medial frontal, anterior cingulate and occipital lobe regions. PGALCOHOL + POLY not only exhibited structural deficits in comparison with HCs but also relative to PGPURE in the precuneus and post-central gyrus. We demonstrated specific frontal cortex GM deficits in PG without SUD comorbidities. Whereas some target regions reported in earlier studies might result from comorbid substance abuse, there seems to be a core set of frontal alterations associated with addicted gambling behaviour independent of toxic substance effects.

The response to rapid infusion of fentanyl in the human brain measured using pulsed arterial spin labelling.

OBJECTIVE: We evaluated the sensitivity of pulsed Arterial Spin Labelling (pASL) for the detection of changes in regional cerebral blood perfusion (CBP) during and after intra-venous (i.v.) infusion of an opioid agonist (fentanyl) and an opioid antagonist (naloxone). MATERIALS AND METHODS: Twenty-three subjects were scanned four times, receiving i.v. infusion of fentanyl, naloxone, placebo and a second fentanyl administration, in four separate scanning sessions in randomised order. End-tidal CO(2), respiration rate and heart rate were recorded continuously throughout each scan. pASL time series were collected using single shot EPI for 15 min (including 5 min of baseline prior to infusion). RESULTS: Significant increases in CBP were detected during and after administration of fentanyl, (when compared to placebo and naloxone), in most areas of high concentration of mu-opioid receptors (thalamus, lingual gyrus, para-hippocampal gyrus, and insula); near-significant increases were also observed in the insula. No increases in perfusion were observed during or after naloxone infusion. No correlation was found between regional rCBF changes and end-tidal CO(2), respiration rate or heart rate. Good reliability was found between the first and second fentanyl sessions but the regions of high reliability did not overlap completely with those of highest perfusion change. CONCLUSION: pASL is a suitable method for examining rapid, dynamic effects of opioid administration on brain physiology.

GATA4 variant interaction with brain limbic structure and relapse risk: A voxel-based morphometry study.

Atrial natriuretic peptide (ANP) receptors are highly expressed in the amygdala, caudate and hypothalamus. GATA4 gene encodes a transcription factor of ANP associated with the pathophysiology of alcohol dependence. We have previously demonstrated that the GATA4 single nucleotide polymorphism (SNP) rs13273672 revealed stronger alcohol-specific amygdala activation associated with lowered relapse risk to heavy drinking at 90 days in the AA-homozygotes. Our understanding however with respect to GATA4 variation on gray matter (GM) regional amygdala, caudate and hypothalamus volume is limited. We investigated GM differences specific to GATA4 and hypothesized that GM alterations will be predictive of heavy relapse. Eighty-three recently detoxified alcohol dependent patients were included. Neuroimaging data was analyzed using Voxel Based Morphometry (VBM). The main effects of GM volume and genotype as well as their interaction effect on time to heavy relapse (60 and 90 days) were analyzed using cox regression. Significant higher GM volume was found for the AA-genotype group compared with AG/GG-genotype in the hypothalamus and caudate. A significant interaction was revealed between caudate and amygdala GM volume and GATA4 genotype on time to heavy relapse. The interaction was expressed by means of higher GM in the AA genotype group to be associated with reduced risk to relapse whereas in the AG/GG group higher GM was associated with increased risk to relapse. This is the first report on GM regional volume alterations specific to GATA4 genotype [(SNP) rs13273672] and its association with relapse in alcohol dependence. Current findings further support the role of GATA4 in alcoholism.

Insula and striatum activity in effort-related monetary reward processing in gambling disorder: the role of depressive symptomatology.

The neurobiological underpinnings of effort-related monetary reward processing of gambling disorder have not been previously studied. To date neuroimaging studies lack in large sample sizes and as a consequence less attention has been given to brain reward processing that could potentially be attributed to comorbid conditions such as depressive mood state. We assessed monetary reward processing using an effort-dependent task during 3 tesla functional magnetic resonance imaging. We investigated a large sample of male, right-handed, slot-machine-playing disordered gamblers (DGs; N = 80) as well as age- and smoking-matched male healthy controls (HCs; N = 89). Depressive symptoms were assessed using the Beck Depression Inventory (BDI). DGs and HCs were divided into subgroups ("high" and "low") based on their BDI scores. Effort-related monetary reward processing did not differ between the complete groups of HCs and DGs. Brain activation during receipt of monetary reward though revealed a significant Group × BDI interaction: DGs with higher BDI scores compared to DGs with lower BDI scores showed greater brain activity in the right insula cortex and dorsal striatum while no differences were observed for HCs with higher versus lower BDI scores. Our results suggest that effort-related aspects of monetary motivation, i.e. when monetary output is tied to performance, are not altered in DG. Additionally, our findings strengthen the need for subgroup comparisons in future investigations of the disorder as part of a personalized medicine approach.

Decision-making deficits in patients diagnosed with disordered gambling using the Cambridge Gambling task: the effects of substance use disorder comorbidity.

BACKGROUND: Disordered gambling (DG) has often been associated with impaired decision-making abilities, suggesting a dysfunction in the ventromedial prefrontal cortex (vmPFC). AIMS: To our knowledge, no previous study has accurately considered the effect of substance use disorder (SUD) comorbidity (including nicotine dependence) on decision-making impairments in DG. METHODS AND MATERIALS: We employed the Cambridge Gambling Task (CGT) to assess a big cohort of patients diagnosed with DG (N = 80) against matched healthy controls (HCs) (N = 108). The cohort included DG patients with nicotine and alcohol dependence, alcohol dependence only and 12 "pure" nonsmokers with only DG diagnosis. RESULTS: Pure nonsmoking, nicotine dependent as well as alcoholic DGs with current nicotine dependence, demonstrated a decision making profile, characterized by poor decision-making abilities and failure to make right choices (rational), closely resembling that of patients with vmPFC damage. DISCUSSION: This suggests that DGs with and without SUD comorbidity are equally affected in that domain of decision making abilities. Additionally, gambling diagnosis combined with alcohol and nicotine dependence involves a group of gambling patients with a relatively riskier decision making profile, showing that these patients apart from making irrational decisions take also more risks. Our findings highlight the importance of accounting for SUD comorbidities with useful implications for future research and therapy. Limitations of the current investigation are discussed.