Psychobiological research projects

Psychobiological research projects

1. Children of alcoholics: Predictors of the development of psychopathology and addiction
Goal of the study:
To identify the predictors of the development of psychopathology and addiction in the children of alcoholics. This Ph.D. project has psychopathological, biochemical, and biological components.

Research questions:
The psychopathological component of the study is descriptive and aimed at assessing the influence of gender, parental psychiatric comorbidity, and family history of alcoholism on the presence of psychopathology in the children of alcoholics.
The biochemical component examines the activity of adenylate cyclase in blood platelets. Such activity has been reported to be lower in the blood cells of alcoholics and abstinent alcoholics when compared to controls. In addition, dysregulation of adenylate cyclase in the CNS of animals appears to be involved in drug-seeking behavior.
The molecular biological component examines a possible association between the A1 allele of the dopamine D2 receptor gene and the P300. The P300 is an evoked response potential and a trait marker for alcoholism.

Results:
The results of the biochemical part of the study show that the Gs-protein stimulated cAMP production induced by NaF, unlike that induced by direct stimulation of adenylyl cyclase with forskolin, to be profoundly lower in the platelet membranes of the children of alcoholics than in the platelet membranes of control children. A reduction of Gs-protein stimulated adenylyl cyclase activity in platelets may thus be a sensitive and gender-independent trait marker of a disposition towards alcoholism.

References:
Not available as yet.

2. Pathological gambling and deficient self-regulation: A neuropsychological approach
Goal of the study:
Pathological gambling is viewed as resulting from a deficient self-regulation. Various cognitive processes are hypothesized to be involved in deficient self-regulation. In this research inhibition and executive functioning in pathological gambling will be investigated. To examine the specificity of impaired self-regulation in pathological gambling, subjects with other impulse control disorders (adult ADHD and Tourette syndrome) and subjects with an addictive disorder (alcohol) will be assessed as well. Comparison of cognitive functioning of pathological gamblers and patients with other psychopathology may help in resolving the controversy regarding the conceptualization of pathological gambling as an impulse control disorder or an addiction.

At a basal cognitive level of functioning, deficient self-regulation may be due to a mild dysfunction of the limbic system, where the septo-hippocampal system is involved in self-regulation concerning responses to reward and punishment. Dysfunctioning of this system causes impulsive or disinhibited behavior (Gray, 1987). On the more complex level of executive functioning, pathological gambling may be due to an impaired response modulation or impairments in strategic planning.

The purpose of this study is to examine which processes of self-regulation are impaired in pathological gamblers. Reward and punishment will be employed to investigate their influence on task performance in pathological gamblers. Experimental tasks, assessing both levels of self-regulation will be used. Nonspecific autonomic arousal is an important mediator variable for the effects of reward and punishment on inhibition and response modulation. Therefore arousal level will be continuously monitored, using electrodermal activity and heart rate variability measures.

Research questions:
Two hypotheses regarding the deficient self-regulation of pathological gamblers will be tested:
Deficient self-regulation due to higher order cognitive dysfunction , such as poor judgment or poor planning (prefrontal cortex), and
deficient self-regulation due to lower level cognitive dysfunction, such as a lack of momentary inhibitory control under reward or punishment conditions (limbic system).

Results:
Not available as yet.

References:
Not available as yet.

3. The neurobiology, psychophysiology, and clinical characteristics of distinct pathways to craving in alcoholics
Goal of the study:
The primary objective of this study is to examine the role of 1) opioidergic and glutamatergic/GABAergic neurotransmission and 2) psychophysiological cue reactivity in two distinct pathways to craving. A secondary objective is to identify clinical indicators of pathways that may be used for prediction and treatment matching.

Research questions:
Do prototypical reward cravers and prototypical relief cravers show a reduction of cue-induced craving in response to naltrexone (opiate antagonist) and/or acamprosate (glutamate antagonist and/or GABA agonist)?
Do prototypical reward cravers and/or prototypical relief cravers show psychophysiological reactivity in response to alcohol cue exposure and, if so, is this reactivity affected by naltrexone and/or acamprosate?
Are changes (if any) in the cue-induced craving as a result of the drug challenges associated with specific characteristics of the cues?

Results:
Results: Not available as yet.

References:
Not available as yet.