Dopaminergic function in depressed patients with affective flattening or with impulsivity: [18F]fluoro-L-dopa positron emission tomography study with voxel-based analysis.

A decreased striatal presynaptic dopaminergic function has been reported in depressed patients with affective flattening and psychomotor retardation, using (18)F-fluorodopa positron emission tomography and regions-of-interest. The present study aimed to investigate regional ;[(18)F]dopa uptake in mesolimbic and mesocortical dopaminergic projections with the hypothesis that there should be a decrease in mesolimbic [(18)F]dopa uptake associated with affective flattening and psychomotor retardation. [(18)F]Dopa-positron emission tomography and anatomical magnetic resonance imaging datasets from 12 screened depressed patients with either marked affective flattening and psychomotor retardation (n=6) or with marked impulsivity (n=6), and from eight healthy subjects, were analyzed using a voxel-based approach. Regional differences in [(18)F]dopa uptake rate constant (K(i)) values between the healthy group and the two depression subgroups were compared using both statistical parametric mapping and cluster-based regions-of-interest. Patients with affective flattening and psychomotor retardation had [(18)F]dopa K(i) decreases in the left caudate, bilateral putamen and nucleus accumbens, left parahippocampus and dorsal brainstem. Impulsive depressives had [(18)F]dopa K(i) decreases in the anterior cingulate and hypothalamus, and an increase in the right parahippocampal gyrus. These findings support distinct regional dysfunctions of monoamines depending on the depressive symptomatology.

Psychophysiological determinants and concomitants of deficient decision making in pathological gamblers.

Psychophysiological responses are considered to be a mediating factor in the development of pathological gambling (PG) and PG has been associated with differential arousal levels during gambling. Yet little is known about the specific psychophysiological responses to wins and losses in PG. This study investigated heart rate (HR) and skin conductance responses (SCRs) during the Iowa Gambling Task (IGT) in an adult PG group (n=46) and a normal control (NC) group (n=47). Anticipatory psychophysiological reactions to disadvantageous and advantageous choices during the IGT and psychophysiological responses to wins and losses were measured. The PG group performed worse than the NC group on the IGT and exhibited lower anticipatory SCRs and HR decreases when pondering choices of disadvantageous card decks during the IGT. The PG group showed a decrease in HR after losses and wins, whereas the NC group showed a decrease in HR after losses, but an increase in HR after wins. Reward and punishment sensitivity as measured by the self-report BIS/BAS scale influenced IGT performance and psychophysiological responses, but in general these effects were similar for the PG group and the NC group. Lower anticipatory psychophysiological responses to disadvantageous choices in PG suggest impaired risk assessment in this group. Absence of a HR increase after wins possibly implies that reward sensitivity is decreased in PG. Because levels of reward and punishment sensitivity were associated with differential anticipatory HR responses to advantageous and disadvantageous decks, it would be advisable to include this taxonomy in studies on psychophysiological responses to rewards and losses.

Disrupted sensory gating in pathological gambling.

BACKGROUND: Some neurochemical evidence as well as recent studies on molecular genetics suggest that pathologic gambling may be related to dysregulated dopamine neurotransmission. METHODS: The current study examined sensory (motor) gating in pathologic gamblers as a putative measure of endogenous brain dopamine activity with prepulse inhibition of the acoustic startle eye-blink response and the auditory P300 event-related potential. Seventeen pathologic gamblers and 21 age- and gender-matched healthy control subjects were assessed. Both prepulse inhibition measures were recorded under passive listening and two-tone prepulse discrimination conditions. RESULTS: Compared to the control group, pathologic gamblers exhibited disrupted sensory (motor) gating on all measures of prepulse inhibition. Sensory motor gating deficits of eye-blink responses were most profound at 120-millisecond prepulse lead intervals in the passive listening task and at 240-millisecond prepulse lead intervals in the two-tone prepulse discrimination task. Sensory gating of P300 was also impaired in pathologic gamblers, particularly at 500-millisecond lead intervals, when performing the discrimination task on the prepulse. CONCLUSIONS: In the context of preclinical studies on the disruptive effects of dopamine agonists on prepulse inhibition, our findings suggest increased endogenous brain dopamine activity in pathologic gambling in line with previous neurobiological findings.

Reduced prefrontal and increased subcortical brain functioning assessed using positron emission tomography in predatory and affective murderers.

There appear to be no brain imaging studies investigating which brain mechanisms subserve affective, impulsive violence versus planned, predatory violence. It was hypothesized that affectively violent offenders would have lower prefrontal activity, higher subcortical activity, and reduced prefrontal/subcortical ratios relative to controls, while predatory violent offenders would show relatively normal brain functioning. Glucose metabolism was assessed using positron emission tomography in 41 comparisons, 15 predatory murderers, and nine affective murderers in left and right hemisphere prefrontal (medial and lateral) and subcortical (amygdala, midbrain, hippocampus, and thalamus) regions. Affective murderers relative to comparisons had lower left and right prefrontal functioning, higher right hemisphere subcortical functioning, and lower right hemisphere prefrontal/subcortical ratios. In contrast, predatory murderers had prefrontal functioning that was more equivalent to comparisons, while also having excessively high right subcortical activity. Results support the hypothesis that emotional, unplanned impulsive murderers are less able to regulate and control aggressive impulses generated from subcortical structures due to deficient prefrontal regulation. It is hypothesized that excessive subcortical activity predisposes to aggressive behaviour, but that while predatory murderers have sufficiently good prefrontal functioning to regulate these aggressive impulses, the affective murderers lack such prefrontal control over emotion regulation.