ABSTRACT
The A1 allele of TaqI A restriction fragment length polymorphism (RFLP) in the D2 receptor (DRD2) gene locus has been suggested to be associated with low D2 receptor density in man. Striatal dopamine transporter (DAT) densities were studied with [(123)I]2-beta-carbometoxy-3beta(4-iodophenyl)tropane and single-photon emission tomography in 29 detoxified alcoholics, who were also genotyped for the two alleles of TaqI A RFLP at the DRD2 receptor gene locus. Alcoholics with the A1/A2 genotypes (n = 10) had statistically significantly higher DAT densities than subjects with the A2/A2 genotypes [n = 19; 8.0 +/- 1.2 (mean +/- SD) vs 6.9 +/- 1.1, P = 0.035]. We suggest that the TaqI A RFLP is in linkage disequilibrium with a gene variant modifying DAT density in alcoholics.
Subject(s)
Alcoholism/genetics , Carrier Proteins/genetics , Membrane Glycoproteins , Membrane Transport Proteins , Nerve Tissue Proteins , Receptors, Dopamine D2/genetics , Adult , Aged , Alcoholism/metabolism , Alcoholism/psychology , Alleles , DNA/genetics , DNA/isolation & purification , Depression/psychology , Dopamine Plasma Membrane Transport Proteins , Female , Genotype , Humans , Male , Middle Aged , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length , Taq PolymeraseABSTRACT
OBJECTIVE: The aim of this study was to investigate a putative association between the personality trait of novelty seeking (NS) and dopaminergic neuronal activity in the human brain. METHOD: We studied the striatal dopamine transporter (DAT) density of 30 (18 early and 12 late-onset) alcoholics and 26 healthy controls with beta-CIT ([123I]-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane) and SPET (Single Photon Emission Tomography); personality traits were assessed with the Tridimensional Personality Questionnaire (TPQ). RESULTS: DAT density correlated significantly with both NS (r = 0.46, p = 0.011) and age (r = -0.50, p = 0.005) in the alcoholics, generally. NS scores were higher in alcoholics with antisocial personality disorder (p = 0.004) than among other alcoholics. CONCLUSION: Among alcoholics, NS correlated positively with DAT density, which is in line with Cloninger's theory concerning personality and character.
Subject(s)
Alcoholism/metabolism , Corpus Striatum/metabolism , Exploratory Behavior , Membrane Glycoproteins , Membrane Transport Proteins/analysis , Nerve Tissue Proteins , Adult , Aged , Alcoholism/genetics , Alcoholism/psychology , Dopamine Plasma Membrane Transport Proteins , Exploratory Behavior/physiology , Female , Finland , Humans , Male , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , Middle Aged , Psychiatric Status Rating Scales , Tomography, Emission-Computed, Single-PhotonABSTRACT
Alcohol-related temporary depressive symptoms are hypothesized to be related to dopaminergic dysfunction. The aim of this study was to investigate whether or not depressive symptoms correlate with reduced dopamine transporter (DAT) availability. We studied the DAT availability in 28 alcoholic subjects with beta-CIT ([123-iodium]-2-betacarbomethoxy-3-beta-(4-iodophenyl)-tropa ne) single photon emission tomography (SPET) and found a reduction in DAT availability during withdrawal that subsequently showed a significant increase during sobriety. The relationship between DAT availability and Montgomery-Asberg Depression Rating scale scores, both during withdrawal and after sobriety, was assessed. The main finding was a statistically significant correlation between DAT variances and depressive symptom scores during both states. The findings indicate a possible dopaminergic etiology for depressive symptoms in alcohol withdrawal, which suggests that dopaminergic antidepressants might be beneficial in the treatment of alcohol withdrawal.
Subject(s)
Alcohol Withdrawal Delirium/metabolism , Brain/metabolism , Carrier Proteins/metabolism , Depression/etiology , Depression/metabolism , Membrane Glycoproteins , Membrane Transport Proteins , Nerve Tissue Proteins/metabolism , Adult , Aged , Alcohol Withdrawal Delirium/diagnostic imaging , Alcohol Withdrawal Delirium/psychology , Brain/diagnostic imaging , Cocaine/analogs & derivatives , Depression/diagnostic imaging , Depression/psychology , Dopamine Plasma Membrane Transport Proteins , Female , Follow-Up Studies , Humans , Iodine Radioisotopes , Male , Middle Aged , Prospective Studies , Psychiatric Status Rating Scales , Tomography, Emission-Computed, Single-Photon/methodsABSTRACT
Dopaminergic transmission has been suggested to be a main mechanism mediating reinforcement, withdrawal and craving associated with alcohol addiction. We measured here striatal dopamine (DA) transporter binding from 27 alcoholics within 4 days after cessation of prolonged heavy drinking and after a 4-week period of abstinence with single photon emission computed tomography (SPECT) using a cocaine analogue, iodine-123-beta-CIT. Controls were 29 healthy volunteers. Blind quantitative analyses of the SPECT data revealed markedly lower DA transporter binding in alcoholics on admission for detoxification than in the non-alcoholic controls. After a 4-week period of abstinence DA transporter binding increased significantly in the alcoholics (P<0.0001) reaching the levels of the healthy controls. The most substantial recovery in DA transporter binding occurred during the first 4 days of abstinence. The data indicate that prolonged heavy drinking decreases DA transporter binding and disturbs synaptic dopamine transport. This may sensitize alcoholics to dopaminergic transmission, which may lead to early relapse after ethanol withdrawal.
Subject(s)
Alcoholism/metabolism , Carrier Proteins/metabolism , Corpus Striatum/diagnostic imaging , Corpus Striatum/metabolism , Membrane Glycoproteins , Membrane Transport Proteins , Nerve Tissue Proteins , Tomography, Emission-Computed, Single-Photon/methods , Adult , Aged , Alcoholism/diagnostic imaging , Carrier Proteins/analysis , Cocaine/analogs & derivatives , Cocaine/pharmacokinetics , Dopamine Plasma Membrane Transport Proteins , Female , Humans , Iodine Radioisotopes/pharmacokinetics , Male , Middle Aged , Reference Values , Substance Withdrawal Syndrome/diagnostic imaging , Substance Withdrawal Syndrome/metabolism , Temperance , Time FactorsABSTRACT
Ten years ago Chile successfully privatized its social security system, beginning a worldwide trend to solve the problem of an increasing burden on government-supported social security programs. Contributing factors include an aging population, fewer workers to support retirees, government budget deficits and the influence of politics.
