K. Mann

Alcohol-associated stimuli activate the ventral striatum in abstinent alcoholics.

Summary. Alcohol-associated cues may act as conditioned stimuli that activate the brain reward system and motivate alcohol intake in alcoholics. Alcohol-associated visual stimuli were presented during functional magnetic resonance imaging. An activation of the ventral putamen was observed in alcoholics but not in control subjects. Patients with a strong activation of the ventral putamen relapsed during the next three months. This observation supports the hypothesis that alcohol use affects areas involved in brain reward circuits and that their stimulus-induced activation may be associated with an increased risk for relapse.

Gene–gene effects on central processing of aversive stimuli

Emotional reactivity and regulation are fundamental to human behavior. As inter-individual behavioral variation is affected by a multitude of different genes, there is intense interest to investigate gene–gene effects. Functional sequence variation at two genes has been associated with response and resiliency to emotionally unpleasant stimuli. These genes are the catechol-O-methyltransferase gene (COMT Val158Met) and the regulatory region (5-HTTLPR) of the serotonin transporter gene. Recently, it has been proposed that 5-HTT expression is not only affected by the common S/L variant of 5-HTTLPR but also by an A to G substitution. Using functional magnetic resonance imaging, we assessed the effects of COMT Val158Met and both 5-HTT genotypes on brain activation by standardized affective visual stimuli (unpleasant, pleasant, and neutral) in 48 healthy subjects. Based on previous studies, the analysis of genotype effects was restricted to limbic brain areas. To determine allele-dose effects, the number of COMT Met158 alleles (i.e., lower activity of COMT) and the number of 5-HTT low expressing alleles (S and G) was correlated with the blood oxygen level-dependent (BOLD) response to pleasant or unpleasant stimuli compared to neutral stimuli. We observed an additive effect of COMT and both 5-HTT polymorphisms, accounting for 40% of the inter-individual variance in the averaged BOLD response of amygdala, hippocampal and limbic cortical regions elicited by unpleasant stimuli. Effects of 5-HTT and COMT genotypes did not affect brain processing of pleasant stimuli. These data indicate that functional brain imaging may be used to assess the interaction of multiple genes on the function of neuronal networks.

Development of alcohol-associated cues and cue-induced brain activation in alcoholics

The objective of this study was to develop new standardized alcohol-associated cues and assess their effects on brain activation with functional magnetic resonance imaging (fMRI). Pictures of alcoholic and neutral beverages and affectively neutral pictures were presented to 44 abstinent alcoholics and 37 age-matched healthy control subjects. We assessed the skin conductance response, and the elicited arousal and valence. Alcoholics and control subjects did not differ in arousal, valence or skin conductance response evoked by alcohol-associated and affectively neutral stimuli, while nonalcoholic beverages were rated as more unpleasant and arousing by alcoholics compared with control subjects. In the fMRI pilot study, alcohol and abstract pictures were presented to six abstinent alcoholics and induced a significant activation of brain areas associated with visual emotional processes such as the fusiform gyrus, parts of the brain reward system (basal ganglia and orbitofrontal gyrus) and further brain regions in the frontal and parietal cortices associated with the attention network. These observations suggest that standardized pictures of alcoholic beverages can be used to assess brain circuits involved in the processing and evaluation of alcohol cues.

Midbrain serotonin transporter binding potential measured with [11C]DASB is affected by serotonin transporter genotype.

SummaryBackground. Homozygote carriers of two long (L) alleles of the serotonin transporter (5-HTT) regulatory region displayed in vitro a twofold increase in 5-HTT expression compared with carriers of one or two short (S) alleles. However, in vivo imaging studies yielded contradictory results. Recently, an A > G exchange leading to differential transcriptional activation of 5-HTT mRNA in lymphobalstoid cell lines was discovered in the 5-HTT regulatory region. In vitro and in vivo evidence suggests that [11C]DASB, a new 5-HTT ligand offers some advantages over the ligands used in previous studies in measuring 5-HTT density independent of synaptic levels of serotonin. Method. We assessed 5-HTT binding potential (BP2) in the midbrain of 19 healthy subjects with positron emission tomography and [11C]DASB. Accounting for the hypothesized functional similarity of LG and S in driving 5-HTT transcription, we assessed whether LALA homozygotes display increased midbrain BP2 compared with carriers of at least one S allele. Results. BP2 in the midbrain was significantly increased in LALA homozygotes compared with carriers of at least one S allele. Interestingly, the genotype effect on the midbrain was significantly different from that on the thalamus and the amygdala where no group differences were detected. Conclusions. This in vivo study provides further evidence that subjects homozygous for the LA allele display increased expression of 5-HTT in the midbrain, the origin of central serotonergic projections.

The neural basis of video gaming

Video game playing is a frequent recreational activity. Previous studies have reported an involvement of dopamine-related ventral striatum. However, structural brain correlates of video game playing have not been investigated. On magnetic resonance imaging scans of 154 14-year-olds, we computed voxel-based morphometry to explore differences between frequent and infrequent video game players. Moreover, we assessed the Monetary Incentive Delay (MID) task during functional magnetic resonance imaging and the Cambridge Gambling Task (CGT). We found higher left striatal grey matter volume when comparing frequent against infrequent video game players that was negatively correlated with deliberation time in CGT. Within the same region, we found an activity difference in MID task: frequent compared with infrequent video game players showed enhanced activity during feedback of loss compared with no loss. This activity was likewise negatively correlated with deliberation time. The association of video game playing with higher left ventral striatum volume could reflect altered reward processing and represent adaptive neural plasticity.

Anxiety is associated with reduced central serotonin transporter availability in unmedicated patients with unipolar major depression : a [11C]DASB PET study

Serotonergic dysfunction may contribute to negative mood states in affective disorders. Some in vivo imaging studies showed reduced availability of serotonin transporters (5-HTT) in the brainstem and thalamus of patients with major depression. We tested the hypothesis that 5-HTT availability is reduced in unmedicated unipolar patients with major depression compared to healthy control subjects matched for gender, age, genotype and smoking status. Availability of 5-HTT was measured in vivo with positron emission tomography and [11C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB) in the midbrain, thalamus and amygdala. DASB binding was correlated with the severity of depression (Becks Depression Inventory), anxiety (Spielbergers State-Trait Anxiety Inventory) and personality traits (Temperament and Character Inventory). Patients with major depression displayed reduced 5-HTT availability in the thalamus (P=0.005). In patients, low serotonin transporter availability correlated with high anxiety (thalamus: r=−0.78, P=0.004; midbrain: r=−0.78, P=0.004; amygdala: r=−0.80, P=0.003). Correlations with severity of depression were weaker and did not survive correction for multiple testing. These results support the hypothesis that central serotonergic dysfunction is associated with negative mood states in affective disorders. In the thalamus, a low serotonin reuptake capacity may interfere with thalamic control of cortical excitability and contribute to anxiety rather than depression per se in major depression.

Impairment of inhibitory control in response to food-associated cues and attentional bias of obese participants and normal-weight controls

Objective:Starting from a model of impaired response inhibition and salience attribution for addictive behaviour we investigated whether obese participants show a greater impairment of inhibitory control in response to food-associated cues compared with neutral stimuli and whether this is seen in normal-weight control subjects. In addition, we questioned whether an attentional bias towards food-associated cues can be observed in an early stage of information processing.Design:Control-group study including the administration of behavioural tasks (that is, go/no-go task with food-associated and neutral words, visual dot probe task with food-associated and neutral pictures) and self-reported measures of eating behaviour and impulsivity.Results:Although self-reported measures indicated disinhibition of eating behaviour of obese patients, we found that food-associated stimuli induced an impairment of inhibitory control in both obese participants as well as normal-weight controls. Results from the visual dot-probe task indicated that food-associated cues did not modulate attention allocation in a very early stage of information processing, which suggests that the incentive salience of food-associated stimuli might be lower than that of drug-associated cues.Conclusion:These findings are not in line with hypotheses derived from models of addictive behaviour and call into question that an impairment of inhibitory control in response to food-associated cues and salience attribution might be at the core of obesity. Future studies using larger sample sizes and refined experimental procedures are warranted to further investigate mechanisms controlling food intake in obesity.

Cortical thickness of superior frontal cortex predicts impulsiveness and perceptual reasoning in adolescence

Impulsiveness is a pivotal personality trait representing a core domain in all major personality inventories. Recently, impulsiveness has been identified as an important modulator of cognitive processing, particularly in tasks that require the processing of large amounts of information. Although brain imaging studies have implicated the prefrontal cortex to be a common underlying representation of impulsiveness and related cognitive functioning, to date a fine-grain and detailed morphometric analysis has not been carried out. On the basis of ahigh-resolution magnetic resonance scans acquired in 1620 healthy adolescents (IMAGEN), the individual cortical thickness (CT) was estimated. Correlations between Cloningers impulsiveness and CT were studied in an entire cortex analysis. The cluster identified was tested for associations with performance in perceptual reasoning tasks of the Wechsler Intelligence Scale for Children (WISC IV). We observed a significant inverse correlation between trait impulsiveness and CT of the left superior frontal cortex (SFC; Monte Carlo Simulation P<0.01). CT within this cluster correlated with perceptual reasoning scores (Bonferroni corrected) of the WISC IV. On the basis of a large sample of adolescents, we identified an extended area in the SFC as a correlate of impulsiveness, which appears to be in line with the trait character of this prominent personality facet. The association of SFC thickness with perceptual reasoning argues for a common neurobiological basis of personality and specific cognitive domains comprising attention, spatial reasoning and response selection. The results may facilitate the understanding of the role of impulsiveness in several psychiatric disorders associated with prefrontal dysfunctions and cognitive deficits.

Konzept der Verhaltenssüchte und Grenzen des Suchtbegriffs

ZusammenfassungDie Zahl von Betroffenen mit „Verhaltenssüchten“ nimmt vor allem bei Jugendlichen und jungen Erwachsenen deutlich zu. Psychiater und Psychotherapeuten erwarten Hinweise zur diagnostischen Einordnung und zum therapeutischen Vorgehen. Wir diskutieren nosologische Aspekte und empfehlen Glücksspiel und exzessiven Computer- und Internetgebrauch als Verhaltenssüchte zu behandeln. In Einzelfällen kann das Suchtmodell auch bei pathologischem Kaufen, exzessivem Sexualverhalten und Adipositas therapeutisch genutzt werden.SummaryThe numbers of persons with a prevalence for behavioral addiction are rising especially among the young. Psychiatrists and psychotherapists are still awaiting indications for diagnostic classification and treatment approaches. We discuss the nosological aspects and suggest categorizing gambling and excessive computer and internet use as behavioral addictions. In specific cases the addiction model can also be applied for excessive sexual behavior, compulsive buying and obesity.The numbers of persons with a prevalence for behavioral addiction are rising especially among the young. Psychiatrists and psychotherapists are still awaiting indications for diagnostic classification and treatment approaches. We discuss the nosological aspects and suggest categorizing gambling and excessive computer and internet use as behavioral addictions. In specific cases the addiction model can also be applied for excessive sexual behavior, compulsive buying and obesity.

The concept of behavioral addiction and limits of the term addiction

ZusammenfassungDie Zahl von Betroffenen mit „Verhaltenssüchten“ nimmt vor allem bei Jugendlichen und jungen Erwachsenen deutlich zu. Psychiater und Psychotherapeuten erwarten Hinweise zur diagnostischen Einordnung und zum therapeutischen Vorgehen. Wir diskutieren nosologische Aspekte und empfehlen Glücksspiel und exzessiven Computer- und Internetgebrauch als Verhaltenssüchte zu behandeln. In Einzelfällen kann das Suchtmodell auch bei pathologischem Kaufen, exzessivem Sexualverhalten und Adipositas therapeutisch genutzt werden.SummaryThe numbers of persons with a prevalence for behavioral addiction are rising especially among the young. Psychiatrists and psychotherapists are still awaiting indications for diagnostic classification and treatment approaches. We discuss the nosological aspects and suggest categorizing gambling and excessive computer and internet use as behavioral addictions. In specific cases the addiction model can also be applied for excessive sexual behavior, compulsive buying and obesity.The numbers of persons with a prevalence for behavioral addiction are rising especially among the young. Psychiatrists and psychotherapists are still awaiting indications for diagnostic classification and treatment approaches. We discuss the nosological aspects and suggest categorizing gambling and excessive computer and internet use as behavioral addictions. In specific cases the addiction model can also be applied for excessive sexual behavior, compulsive buying and obesity.