Biomedical subjects

Jana Wrase

Publications and source records attributed to Jana Wrase.

14 recordsLinked to original sources

PubMed2006

Serotonin transporter genotype (5-HTTLPR): effects of neutral and undefined conditions on amygdala activation.

BACKGROUND: A polymorphism of the human serotonin transporter gene (SCL6A4) has been associated with serotonin transporter expression and with processing of aversive stimuli in the amygdala. Functional imaging studies show that during the presentation of aversive versus neutral cues, healthy carriers of the short (s) allele showed stronger amygdala activation than long (l) carriers. However, a recent report suggested that this interaction is driven by amygdala deactivation during presentation of neutral stimuli in s carriers. METHODS: Functional MRI was used to assess amygdala activation during the presentation of a fixation cross or affectively aversive or neutral visual stimuli in 29 healthy men. RESULTS: Amygdala activation was increased in s carriers during undefined states such as the presentation of a fixation cross compared with emotionally neutral conditions. CONCLUSIONS: This finding suggests that s carriers show stronger amygdala reactivity to stimuli and contexts that are relatively uncertain, which we propose are stressful.

Adult↗

PubMed2006

Dysfunction of ventral striatal reward prediction in schizophrenic patients treated with typical, not atypical, neuroleptics.

RATIONALE: Clinical studies in patients with schizophrenia suggest that atypical neuroleptics are more effective than typical neuroleptics in reducing negative symptoms including apathy and anhedonia. Dysfunction of the dopaminergic reward system may contribute to negative symptoms in schizophrenia. OBJECTIVE: We used functional magnetic resonance imaging to assess the blood oxygen level dependency response in the ventral striatum of medicated schizophrenics and healthy control subjects during reward anticipation. METHODS: Twenty schizophrenics [ten medicated with typical (e.g., haloperidol) and ten with atypical (e.g., olanzapine and risperidone) neuroleptics] and ten age-matched healthy volunteers participated in an incentive monetary delay task in which visual cues predicted that a rapid response to a subsequent target stimulus would result either in monetary gain or no consequence. RESULTS: Healthy volunteers and schizophrenics treated with atypical neuroleptics showed ventral striatal activation in response to reward-indicating cues, but schizophrenics treated with typical neuroleptics did not. In patients treated with typical neuroleptics, decrease in activation of the left ventral striatum was correlated with the severity of negative symptoms. CONCLUSIONS: Failure to activate the ventral striatum during reward anticipation was previously associated with the severity of negative symptoms in schizophrenia and was also found in schizophrenics treated with typical neuroleptics in this study. Significant blunting of ventral striatal activation was not observed in patients treated with atypical neuroleptics, which may reflect the improved efficacy of these drugs in treating negative symptoms.

Adult↗

PubMed2006

Net influx of plasma 6-[18F]fluoro-L-DOPA (FDOPA) to the ventral striatum correlates with prefrontal processing of affective stimuli.

Dopaminergic neurotransmission in the ventral and dorsal striatum interact with central processing of rewarding and reward-indicating stimuli, and may affect frontocortical-striatal-thalamic circuits regulating goal-directed behaviour. Thirteen healthy male volunteers were investigated with multimodal imaging, using the radioligand 6-[(18)F]fluoro-l-DOPA (FDOPA) for positron emission tomography (PET) measurements of dopamine synthesis capacity, and also functional magnetic resonance imaging (fMRI) in a cognitive activation paradigm. We calculated the correlation between FDOPA net blood-brain influx (; ml/g/min) in the ventral and associative dorsal striatum and BOLD signal changes elicited by standardized affectively positive, negative and neutral visual stimuli. The magnitude of in the ventral striatum was positively correlated with BOLD signal increases in the left anterior cingulate cortex and right insular operculum elicited by positive vs. neutral stimuli, but not negative vs. neutral stimuli. In the dorsal striatum, the magnitude of was positively correlated with processing of positive and negative stimuli in the left dorsolateral prefrontal cortex. These findings suggest that dopamine synthesis capacity in the ventral striatum correlates with the attentional processing of rewarding positive stimuli in the anterior cingulate cortex of healthy subjects. Dopaminergic neurotransmission in the associative dorsal striatum has been associated previously with habit learning. The observed correlation between dopamine synthesis capacity in the dorsal striatum and BOLD signal changes in the dorsolateral prefrontal cortex suggests dopaminergic modulation of processing of emotional stimuli in brain areas associated with motor planning and executive behaviour control.

Adult↗

PubMed2006

Blockade of cue-induced brain activation of abstinent alcoholics by a single administration of amisulpride as measured with fMRI.

BACKGROUND: Once alcohol dependence is established, alcohol-associated cues may induce dopamine release in the reward system, which is accompanied by alcohol craving and may lead to relapse. In cocaine addicts, dopamine release in the thalamus was positively correlated with cocaine craving. We tested the effects of the atypical dopamine D(2/3) blocker amisulpride on cue-induced brain activation in a functional magnetic resonance imaging (fMRI) paradigm. METHODS: Alcohol-associated and neutral pictures were presented in a block design to 10 male abstinent alcoholics (1-3 weeks after detoxification) and 10 healthy men during fMRI. The fMRI scans were acquired before and 2 hours after the oral application of 400 mg amisulpride. Before and after each scan, alcohol craving was measured with visual analogue scales. RESULTS: Before the application of amisulpride, alcohol versus control cues elicited a higher blood oxygen level-dependent (BOLD) signal in the left frontal and orbitofrontal lobe, left cingulate gyrus, bilateral parietal lobe, and bilateral hippocampus in alcoholics compared with healthy controls. After amisulpride, alcoholics showed a reduced activation in the right thalamus compared with the first scan. Alcoholics no longer showed significant differences in their cue-elicited BOLD response after amisulpride medication compared with medication-free controls. Self-reported craving was not affected by amisulpride medication. CONCLUSIONS: Amisulpride medication was associated with reduced cue-induced activation of the thalamus, a brain region closely connected with frontostriatal circuits that regulate behavior and may influence relapse risk.

Adult↗

PubMed2006

Serotonergic dysfunction: brain imaging and behavioral correlates.

Identification of gene-environment and gene-gene interactions has become increasingly important in understanding psychiatric disorders. Dysfunction of central serotonergic neurotransmission has been implicated in alcoholism, depression, and anxiety. We review the literature on nonhuman primates that assesses the interaction between the genetic constitution of the regulatory region ofthe serotonin transporter (5-HTT) and environmental factors. Prospective studies in nonhuman primates that underwent social stress found a reduction of theserotonin turnover rate among carriers of one or two short alleles in a functional polymorphism of the 5-HTT promoter. In these primates, brain imaging studies showed a relative increase in the availability of raphe serotonin transporters. A low serotonin turnover rate and a high availability of serotonin transporters were associated with reduced response to excessive alcohol intake, anxiety, and impulsive aggression. Animal experiments point to a relationship between serotonergic dysfunction, negative mood states, and excessive alcohol intake, which may in part be mediated by reduced alcohol-induced sedation.

Aggression↗

PubMed2005

Dysfunction of ventral striatal reward prediction in schizophrenia.

BACKGROUND: Negative symptoms may be associated with dysfunction of the brain reward system in schizophrenia. We used functional magnetic resonance imaging (fMRI) to assess the BOLD response in the ventral striatum of unmedicated schizophrenics during presentation of reward-indicating and loss-indicating stimuli. METHODS: A total of 10 schizophrenic men (7 never medicated, 3 unmedicated for at least 2 years) and 10 age-matched healthy male volunteers participated in an incentive monetary delay task, in which visual cues predicted that a rapid response to a subsequent target stimulus would result either in monetary gain or loss or would have no consequence. RESULTS: Compared to healthy controls, unmedicated schizophrenics showed reduced ventral striatal activation during the presentation of reward-indicating cues. Decreased activation of the left ventral striatum was inversely correlated with the severity of negative (and trendwise positive) symptoms. DISCUSSION: Reduced activation in one of the central areas of the brain reward system, the ventral striatum, was correlated with the severity of negative symptoms in medication-free schizophrenics. In unmedicated schizophrenic patients, a high striatal dopamine turnover may increase the "noise" in the reward system, thus interfering with the neuronal processing of reward-predicting cues by phasic dopamine release. This, in turn, may contribute to negative symptoms as such as anhedonia, apathy, and loss of drive and motivation.

Adult↗

PubMed2005

Catechol-O-methyltransferase val158met genotype affects processing of emotional stimuli in the amygdala and prefrontal cortex.

Catechol-O-methyltransferase (COMT) degrades the catecholamine neurotransmitters dopamine, epinephrine, and norepinephrine. A functional polymorphism in the COMT gene (val158met) accounts for a fourfold variation in enzyme activity. The low-activity met158 allele has been associated with improved working memory but with higher risk for anxiety-related behaviors. Using functional magnetic resonance imaging, we assessed the effects of COMT genotype on brain activation by standardized affective visual stimuli (unpleasant, pleasant, and neutral) in 35 healthy subjects. The analysis of genotype effects was restricted to brain areas with robust activation by the task. To determine genedose effects, the number of met158 alleles (0, 1, or 2) was correlated with the blood oxygen level-dependent (BOLD) response elicited by pleasant or unpleasant stimuli compared with neutral stimuli. COMT genotype had no significant impact on brain activation by pleasant stimuli but was related to the neural response to unpleasant stimuli: reactivity to unpleasant stimuli was significantly positively correlated with the number of met158 alleles in the limbic system (left hippocampus, right amygdala, right thalamus), connected prefrontal areas (bilateral ventrolateral prefrontal cortex, right dorsolateral prefrontal cortex), and the visuospatial attention system (bilateral fusiform gyrus, left inferior parietal lobule). Genotype explained up to 38% of interindividual variance in BOLD response elicited by unpleasant stimuli. We conclude that (1) genetic variations can account for a substantial part of interindividual variance in task-related brain activation and that (2) increased limbic and prefrontal activation elicited by unpleasant stimuli in subjects with more met158 alleles might contribute to the observed lower emotional resilience against negative mood states.

Adult↗

PubMed2005

Correlation of stable elevations in striatal mu-opioid receptor availability in detoxified alcoholic patients with alcohol craving: a positron emission tomography study using carbon 11-labeled carfentanil.

BACKGROUND: The pleasant effects of food and alcohol intake are partially mediated by mu-opiate receptors in the ventral striatum, a central area of the brain reward system. Blockade of mu-opiate receptors with naltrexone reduces the relapse risk among some but not all alcoholic individuals. OBJECTIVE: To test the hypothesis that alcohol craving is pronounced among alcoholic individuals with a high availability of mu-opiate receptors in the brain reward system. DESIGN: Patients and comparison sample. The availability of central mu-opiate receptors was measured in vivo with positron emission tomography (PET) and the radioligand carbon 11-labeled carfentanil in the ventral striatum and compared with the severity of alcohol craving as assessed by the Obsessive Compulsive Drinking Scale (OCDS). SETTING: Hospitalized care. PARTICIPANTS: Volunteer sample of 25 male alcohol-dependent inpatients assessed after detoxification of whom 12 underwent PET again 5 weeks later. Control group of 10 healthy men. MAIN OUTCOME MEASURES: After 1 to 3 weeks of abstinence, the availability of mu-opiate receptors in the ventral striatum, including the nucleus accumbens, was significantly elevated in alcoholic patients compared with healthy controls and remained elevated when 12 alcoholic patients had these levels measured 5 weeks later (P<.05 corrected for multiple testing). Higher availability of mu-opiate receptors in this brain area correlated significantly with the intensity of alcohol craving as assessed by the OCDS. CONCLUSIONS: Abstinent alcoholic patients displayed an increase in mu-opiate receptors in the ventral striatum, including the nucleus accumbens, which correlated with the severity of alcohol craving. These findings point to a neuronal correlate of alcohol urges.

Adult↗

PubMed2005

Correlation of alcohol craving with striatal dopamine synthesis capacity and D2/3 receptor availability: a combined [18F]DOPA and [18F]DMFP PET study in detoxified alcoholic patients.

OBJECTIVE: In abstinent alcoholic patients, a low availability of dopamine D2/3 receptors in the ventral striatum and adjacent putamen was associated with a high level of craving for alcohol. Alcohol craving may also depend on presynaptic dysfunction of striatal dopamine production, which may contribute to the risk of relapse. In this study, positron emission tomography (PET) was used to compare dopamine synthesis capacity in the striatum in alcoholic patients and healthy comparison subjects. METHOD: Positron emission tomography (PET) was used to map the net blood-brain clearance of the dopa decarboxylase substrate 6-[18F]fluoro-l-dopa, an index of dopamine synthesis capacity, in the striatum of 12 detoxified male alcoholic patients and 13 age-matched healthy men. The parametric maps were correlated with results of an earlier [18F]desmethoxyfallypride PET study of dopamine D2/3 receptor availability in the same 12 alcoholic patients and in 12 of the healthy volunteers. Alcohol craving was measured with the Alcohol Craving Questionnaire. Patients were followed for 6 months, and alcohol intake was recorded. RESULTS: The magnitude of net blood-brain clearance in the striatum did not differ significantly between detoxified alcoholic patients and the comparison subjects. However, a voxel-wise correlation analysis of net blood-brain clearance in the alcoholic patients linked low levels of dopamine synthesis capacity in the bilateral putamen with high levels of alcohol craving. After normalization of net blood-brain clearance maps to the voxel-wise estimates of dopamine D2/3 receptor availability, there was still a negative correlation with alcohol craving. Alcohol craving at the time of scanning was associated with high level of alcohol intake in the 6-month follow-up period. CONCLUSIONS: Simultaneous assay by PET of pre- and postsynaptic markers of dopamine neurotransmission indicated that a striatal dopamine deficit correlated with alcohol craving, which was associated with a high relapse risk.

Adult↗

PubMed2004

Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter.

Major depression is conditionally linked to a polymorphism of the human serotonin transporter gene (SLC6A4). During the presentation of aversive, but not pleasant, pictures, healthy carriers of the SLC6A4 short (s) allele showed stronger activation of the amygdala on functional magnetic resonance imaging. s carriers also showed greater coupling between the amygdala and the ventromedial prefrontal cortex, which may contribute to the abnormally high activity in the amygdala and medial prefrontal cortex seen in major depression.

Aged↗

PubMed2004

Cue-induced activation of the striatum and medial prefrontal cortex is associated with subsequent relapse in abstinent alcoholics.

RATIONALE: Animal experiments have provided evidence that the striatum and medial prefrontal cortex play a predominant role in the acquisition and maintenance of drug-seeking behavior. OBJECTIVES: Alcohol-associated stimuli that were regularly paired with alcohol intake may become conditioned cues and elicit a motivational response that triggers relapse in alcohol-dependent patients. METHODS: We used functional magnetic resonance imaging and visual alcohol-associated and control cues to assess brain activation in ten abstinent alcoholics and control subjects. Patients were followed for 3 months, and alcohol intake was recorded. RESULTS: Alcohol-related versus neutral visual stimuli activated the putamen, anterior cingulate and adjacent medial prefrontal cortex in alcoholics compared with healthy controls. Cue-induced activation of these brain areas was pronounced in the five alcoholics who subsequently relapsed during the observation period. A multiple regression analysis showed that, in alcoholics, the amount of subsequent alcohol intake was associated with the intensity of cue-induced brain activation but not the severity of alcohol craving, amount of previous alcohol intake or duration of abstinence before scanning. CONCLUSIONS: This pilot study showed that cue-induced activation of the anterior cingulate, medial prefrontal cortex and striatum may play a role in the attribution of incentive salience to alcohol-associated stimuli, thus increasing the motivational value and attentional processing of alcohol cues. Functional brain imaging may help to identify a group of alcoholics with an otherwise undetected high risk of relapse.

Adult↗

PubMed2004

Correlation between dopamine D(2) receptors in the ventral striatum and central processing of alcohol cues and craving.

OBJECTIVE: Alcohol and other drugs of abuse stimulate dopamine release in the ventral striatum, which includes the nucleus accumbens, a core region of the brain reward system, and reinforce substance intake. Chronic alcohol intake is associated with down-regulation of central dopamine D(2) receptors, and delayed recovery of D(2) receptor sensitivity after detoxification is positively correlated with high risk for relapse. Prolonged D(2) receptor dysfunction in the ventral striatum may interfere with a dopamine-dependent error detection signal and bias the brain reward system toward excessive attribution of incentive salience to alcohol-associated stimuli. METHOD: Multimodal imaging, with the radioligand [(18)F]desmethoxyfallypride and positron emission tomography as well as functional magnetic resonance imaging (fMRI), was used to compare 11 detoxified male alcoholics with 13 healthy men. The authors measured the association of D(2)-like dopamine receptors in the ventral striatum with alcohol craving and central processing of alcohol cues. RESULTS: Activation of the medial prefrontal cortex and striatum by alcohol-associated stimuli, relative to activation by neutral visual stimuli, was greater in the detoxified alcoholics than in the healthy men. The alcoholics displayed less availability of D(2)-like receptors in the ventral striatum, which was associated with alcohol craving severity and with greater cue-induced activation of the medial prefrontal cortex and anterior cingulate as assessed with fMRI. DISCUSSION: In alcoholics, dopaminergic dysfunction in the ventral striatum may attribute incentive salience to alcohol-associated stimuli, so that alcohol cues elicit craving and excessive activation of neural networks associated with attention and behavior control.

Adult↗

PubMed2003

Gender differences in the processing of standardized emotional visual stimuli in humans: a functional magnetic resonance imaging study.

Pictures from the International Affective Picture System were used in a functional magnetic resonance imaging study to assess gender differences in brain activation in ten male and ten female volunteers. The affectively positive, negative and neutral pictures were presented for 750 ms in a single event design and were carefully matched for arousal, valence and stimulus content. Men and women showed no significant difference in valence, arousal, skin conductance response and startle modulation. Only in men was amygdala activation observed in the pleasant condition. Furthermore, men showed a stronger brain activity for positive visual stimuli than women in the frontal lobe (inferior and medial frontal gyrus). In women, stronger brain activation for affectively negative pictures was observed in the anterior and medial cingulate gyrus. These results indicate that it is crucial to take gender differences into account when emotional paradigms are used in functional brain imaging.

Adult↗

PubMedDate not supplied

Reward craving and withdrawal relief craving: assessment of different motivational pathways to alcohol intake.

AIMS: Craving for the rewarding effects of alcohol may be evoked by conditioned alcohol-like effects whereas conditioned compensatory responses may induce withdrawal relief craving. We tested the hypothesis that drinking in positive emotional states is associated with appetitive reactions to alcohol-associated cues and contributes to reward craving, while conditioned withdrawal is associated with drinking in negative situations and distressful, obsessive preoccupations with alcohol. METHODS: In 38 detoxified alcoholics, the Obsessive Compulsive Drinking Scale was used to assess the craving factors 'impaired control', 'interference with social functioning' and 'obsession'. Affective responses to alcohol-associated visual stimuli were measured with the affect-modulated eyeblink startle reflex, positive and negative drinking situations with the Inventory of Drinking Situations (IDS) and withdrawal-like symptoms preceding alcohol intake with the revised Clinical Institute Assessment for Alcohol Scale (CIWA-Ar). RESULTS: Appetitive reactions to alcohol-associated cues correlated positively with drinking in positive situations and contributed significantly to the craving factor 'interference' with social and work functioning. The severity of withdrawal-like symptoms preceding alcohol intake contributed to the craving factor 'obsession'; however, contrary to our hypothesis, this measure of conditioned withdrawal correlated with drinking not only in negative but also in positive situations. CONCLUSIONS: Drinking in positive and negative situations, appetitive reactions to alcohol and withdrawal-like symptoms contributed differentially to the craving factors 'obsession' and 'interference', supporting the notion of different craving factors with separate underlying mechanisms.

Adult↗