Positron emission tomography imaging of the serotonin transporter in subjects with a history of alcoholism

BACKGROUND Our purpose was to investigate the serotonin transporter (SERT) in various brain regions of alcoholics using positron emission tomography and C-11 McN5652. METHOD Thirty-two adult subjects were involved, 17 social drinkers as control subjects and 15 subjects who were abstinent or recovering alcoholics. Concomitant psychiatric diseases were ruled out based on DSM-IV criteria. The majority of subjects were men. Radioligand binding in 11 brain areas was expressed as the total distribution volume (DV), distribution volume of specific binding (DV(spec)), and distribution volume ratio (DVR). The cerebellum was used as reference tissue for calculation of DV(spec) and DVR. RESULTS In subjects with a history of alcoholism, DV was lower in all brain regions, with significant differences in the midbrain, thalamus, amygdala, pons, cingulate gyrus, frontal cortex, and cerebellum. Additionally, DV(spec) was lower in all brain regions, but differences were only significant in the midbrain; DVR was lower in nine regions but the differences did not reach statistical significance. CONCLUSIONS These studies demonstrate lower binding of [(11)C](+)McN5652 to the SERT in the brain of abstinent or recovering alcoholics compared with control subjects. Differences in the radioligand distribution volumes are more significant before than after correction for nonspecific binding of the radioligand.

[1]  D. Marquardt An Algorithm for Least-Squares Estimation of Nonlinear Parameters , 1963 .

[2]  A. Beck,et al.  Internal consistencies of the original and revised Beck Depression Inventory. , 1984, Journal of clinical psychology.

[3]  M. Kraut,et al.  Kinetic Analysis of [11C]McN5652: A Serotonin Transporter Radioligand , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[4]  J. Balldin,et al.  Six-month open trial with Zimelidine in alcohol-dependent patients: reduction in days of alcohol intake. , 1994, Drug and alcohol dependence.

[5]  D. W. Goodwin,et al.  Blood platelet uptake of serotonin in men alcoholics. , 1985, Journal of studies on alcohol.

[6]  W. Mcbride,et al.  Serotonin and dopamine systems regulating alcohol intake. , 1991, Alcohol and alcoholism (Oxford, Oxfordshire). Supplement.

[7]  M. Thase,et al.  Comorbid alcoholism and depression: treatment issues. , 2001, The Journal of clinical psychiatry.

[8]  Jerry L. Prince,et al.  Adaptive fuzzy segmentation of magnetic resonance images , 1999, IEEE Transactions on Medical Imaging.

[9]  M. Schuckit,et al.  Substance use and mental health problems among sons of alcoholics and controls. , 1987, Journal of studies on alcohol.

[10]  Karl Fagerstrom,et al.  Measuring nicotine dependence: A review of the Fagerstrom Tolerance Questionnaire , 1989, Journal of Behavioral Medicine.

[11]  J. Rice,et al.  Comparison of direct interview and family history diagnoses of alcohol dependence. , 1995, Alcoholism, clinical and experimental research.

[12]  K O Lim,et al.  Brain gray and white matter volume loss accelerates with aging in chronic alcoholics: a quantitative MRI study. , 1992, Alcoholism, clinical and experimental research.

[13]  John Hilton,et al.  Comparison of (+)-11C-McN5652 and 11C-DASB as Serotonin Transporter Radioligands Under Various Experimental Conditions , 2002 .

[14]  A. Beck,et al.  An inventory for measuring depression. , 1961, Archives of general psychiatry.

[15]  K. Fagerström [Measuring nicotine dependence]. , 2001, Italian heart journal : official journal of the Italian Federation of Cardiology.

[16]  M. Linnoila,et al.  A nonhuman primate model of type II excessive alcohol consumption? Part 1. Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations and diminished social competence correlate with excessive alcohol consumption. , 1996, Alcoholism, clinical and experimental research.

[17]  K. Mann,et al.  Neuroimaging in alcoholism: CT and MRI results and clinical correlates , 2005, Journal of Neural Transmission / General Section JNT.

[18]  R Coppola,et al.  Reduced central serotonin transporters in alcoholism. , 1998, The American journal of psychiatry.

[19]  L. Derogatis,et al.  The Brief Symptom Inventory: an introductory report , 1983, Psychological Medicine.

[20]  D. Caine,et al.  Brainstem Serotonergic Neurons in Chronic Alcoholics With and Without the Memory Impairment of Korsakoff's Psychosis , 1993, Journal of neuropathology and experimental neurology.

[21]  Ralph Buchert,et al.  Long-term effects of "ecstasy" use on serotonin transporters of the brain investigated by PET. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[22]  M F Huque,et al.  Some comments on frequently used multiple endpoint adjustment methods in clinical trials. , 1997, Statistics in medicine.

[23]  H N Wagner,et al.  [11C](+)McN5652 as a radiotracer for imaging serotonin uptake sites with PET. , 1993, Life sciences.

[24]  J. Turkkan,et al.  Alcohol and drug use by college males as a function of family alcoholism history. , 1990, Alcoholism, clinical and experimental research.

[25]  H. Kranzler,et al.  Fluoxetine treatment seems to reduce the beneficial effects of cognitive-behavioral therapy in type B alcoholics. , 1996, Alcoholism, clinical and experimental research.

[26]  E. Reyes,et al.  Adolescent Males, Impulsive/Aggressive Behavior, and Alcohol Abuse: Biological Correlates. , 1998 .

[27]  E H Cook,et al.  Cocaine, ethanol, and genotype effects on human midbrain serotonin transporter binding sites and mRNA levels. , 1998, The American journal of psychiatry.

[28]  M. Eckardt,et al.  Early-onset alcoholics have lower cerebrospinal fluid 5-hydroxyindoleacetic acid levels than late-onset alcoholics. , 1996, Archives of general psychiatry.

[29]  R. Pihl,et al.  Men at high risk for alcoholism: the effect of alcohol on cardiovascular response to unavoidable shock. , 1987, Journal of abnormal psychology.

[30]  J. Kleinman,et al.  3H-paroxetine binding in brains of alcoholics , 1991, Psychiatry Research.

[31]  M. Meaney,et al.  Different pituitary beta-endorphin and adrenal cortisol response to ethanol in individuals with high and low risk for future development of alcoholism. , 1989, Life sciences.

[32]  A. Beck,et al.  An inventory for measuring clinical anxiety: psychometric properties. , 1988, Journal of consulting and clinical psychology.

[33]  G. Fein,et al.  Brain atrophy and cognitive function in older abstinent alcoholic men. , 1995, Alcoholism, clinical and experimental research.

[34]  J. Nurnberger,et al.  A new, semi-structured psychiatric interview for use in genetic linkage studies: a report on the reliability of the SSAGA. , 1994, Journal of studies on alcohol.

[35]  H. Kranzler,et al.  Determination of fluvoxamine concentration in plasma by reversed-phase liquid chromatography. , 1994, Biomedical chromatography : BMC.

[36]  J. Turkkan,et al.  Familial density of alcoholism: effects on psychophysiological responses to ethanol. , 1991, Alcohol.

[37]  Robert A Zucker,et al.  Serotonin transporter promoter polymorphism, peripheral indexes of serotonin function, and personality measures in families with alcoholism. , 2002, American journal of medical genetics.

[38]  Andreas Heinz,et al.  A relationship between serotonin transporter genotype and in vivo protein expression and alcohol neurotoxicity , 2000, Biological Psychiatry.

[39]  John Hilton,et al.  as Serotonin Transporter Radioligands Under Various Experimental Conditions , 2002 .

[40]  M. E. Charness,et al.  Brain lesions in alcoholics. , 1993, Alcoholism, clinical and experimental research.

[41]  D. Wong,et al.  Column-switching HPLC for the analysis of plasma in PET imaging studies. , 2000, Nuclear medicine and biology.