Perspectives on current directions in the neurobiology of addiction disorders relevant to genetic risk factors.

Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.
CNS spectrums (Impact Factor: 1.3). 12/2006; 11(11):855-62.
Source: PubMed

ABSTRACT There is a significant heritability of drug addiction disorders, but potential genes that may underlie such vulnerability have not been clearly identified. Common neurobiological candidates for drug abuse include genes related to dopamine, opioid neuropeptide, and glutamate transmission that play important roles in drug reward and inhibitory control. This article provides an overview of genetic polymorphisms linked to these neurobiological systems, particularly in relation to psychostimulant- and opioid-addiction vulnerability.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Obesity is typically associated with abnormal eating behaviors. Brain imaging studies in humans implicate the involvement of dopamine (DA)-modulated circuits in pathologic eating behavior(s). Food cues increase striatal extracellular DA, providing evidence for the involvement of DA in the nonhedonic motivational properties of food. Food cues also increase metabolism in the orbitofrontal cortex indicating the association of this region with the motivation for food consumption. Similar to drug-addicted subjects, striatal DA D2 receptor availability is reduced in obese subjects, which may predispose obese subjects to seek food as a means to temporarily compensate for understimulated reward circuits. Decreased DA D2 receptors in the obese subjects are also associated with decreased metabolism in prefrontal regions involved in inhibitory control, which may underlie their inability to control food intake. Gastric stimulation in obese subjects activates cortical and limbic regions involved with self-control, motivation, and memory. These brain regions are also activated during drug craving in drug-addicted subjects. Obese subjects have increased metabolism in the somatosensory cortex, which suggests an enhanced sensitivity to the sensory properties of food. The reduction in DA D2 receptors in obese subjects coupled with the enhanced sensitivity to food palatability could make food their most salient reinforcer putting them at risk for compulsive eating and obesity. The results from these studies suggest that multiple but similar brain circuits are disrupted in obesity and drug addiction and suggest that strategies aimed at improving DA function might be beneficial in the treatment and prevention of obesity.
    Journal of Addiction Medicine 03/2009; 3(1):8-18. DOI:10.1097/ADM.0b013e31819a86f7 · 1.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Besides the ventral tegmental area and the nucleus accumbens as the most investigated brain reward structures, several reports about the relation between volume and activity of the amygdala and drug-seeking behavior have emphasized the central role of the amygdala in the etiology of addiction. Considering its proposed important role and the limited number of human protein expression studies with amygdala in drug addiction, we performed a human postmortem proteomic analysis of amygdala tissue obtained from 8 opiate addicts and 7 control individuals. Results were validated by Western blot in an independent postmortem replication sample from 12 opiate addicts compared to 12 controls and 12 suicide victims, as a second "control sample". Applying 2D-electrophoresis and MALDI-TOF-MS analysis, we detected alterations of beta-tubulin expression and decreased levels of the heat-shock protein HSP60 in drug addicts. Western blot analysis in the additional sample demonstrated significantly increased alpha- and beta-tubulin concentrations in the amygdala of drug abusers versus controls (P = 0.021, 0.029) and to suicide victims (P = 0.006, 0.002). Our results suggest that cytoskeletal alterations in the amygdala determined by tubulin seem to be involved in the pathophysiology of drug addiction, probably via a relation to neurotransmission and cellular signaling. Moreover, the loss of neuroprotection against stressors by chaperons as HSP60 might also contribute to structural alteration in the brain of drug addicts. Although further studies have to confirm our results, this might be a possible pathway that may increase our understanding of drug addiction.
    European Archives of Psychiatry and Clinical Neuroscience 03/2011; 261(2):121-31. DOI:10.1007/s00406-010-0129-7 · 3.36 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: In 1987, Cloninger proposed a clinical description and classification of different personality traits genetically defined and independent from each other. Moreover, he elaborated a specific test the TCI to investigate these traits/states. The study of craving in Alcohol Use Disorder (AUD) assumed a greater significance, since ever more data seems to suggest a direct correlation between high levels of craving and a higher risk of relapse in alcoholics. Thus, our study aim is to explore the possible correlations among TCI linked molecular neurobiological pattern (s), craving and alcohol addiction severity measures in a sample of Italian alcoholics. Materials and Methods: 191 alcoholics were recruited in a Day Hospital (DH) setting at the Alcohol Addiction Program Latium Region Referral Center, Sapienza University of Rome. After 7 days detoxification treatment a psychodiagnostic protocol was administered, including TCI, VAS-C, ASI and SADQ. All patients signed an Institutional Review Board (IRB) approved informed consent. Results: Principally, we detected a significant positive correlation between HA-scale scores and the VAS scale: increasing in HA-scale corresponds to an increase in craving perception for both intensity (r=0.310; p ≤ 0.001) and frequency (r=0.246; p ≤ 0.001). Moreover, perception of dependence severity, measured with SADQ was also found to be significantly associated positively to both HA-scale (r=0.246; p ≤ 0.001) and NS-scale (r=0.224; p ≤ 0.01). While, for character scales, Persistence (r=-0.195; p=.008) and Self-directedness (r=-0.294; p ≤ 0.001) was negatively associated with ASI linked to alcohol problems. Self-directedness was also negatively correlated with ASI linked to family and social problems (r=-0.349; p ≤ 0.001), employment and support problems (r=-0.220; p=0.003) and psychiatric problems (r=-0.358; p ≤ 0.001). Cooperativeness was a negative correlate with Legal Problems (r=-0.173; p=0.019). and Self- Transcendence was positive correlated with Medical Problems (r=0.276; p ≤ 0.001) Conclusions: In view of recent addiction neurobiological theories, such as the “Reward Deficiency Syndrome (RDS)” and the Koob model, our data could suggest that our cohort of patients could possibly be in a particular stage of the course of their addiction history. Thus, if our hypothesis will be confirmed, the TCI-based assessment of alcoholics would allow an optimization of the treatment. Clinicians understanding these newer concepts will be able to translate this information to their patients and potentially enhance clinical outcome (s), because it could suggest a functional hypothesis of neurotransmitter circuits that helps to frame the patient in his/her history of addiction.