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Andreas Heinz

Publications and source records attributed to Andreas Heinz.

52 records · Page 3Linked to original sources
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

Pharmacogenetic insights to monoaminergic dysfunction in alcohol dependence.

RATIONALE: Alcohol dependence is characterized by the development of tolerance, withdrawal symptoms, and craving for alcohol. Chronic alcohol consumption causes neuroadaptive changes in the central dopaminergic and serotonergic system, which are partially reversible after detoxification. The severity and time-course of recovery of these neuroadaptive changes may depend on the genetic constitution of monoamine transporters and receptors and contribute to the relapse risk of alcoholics. OBJECTIVES: To assess the interaction between the genetic constitution and the in vivo availability of dopamine and serotonin transporters and receptors, chronic alcohol intake, alcohol craving and withdrawal. METHODS: Review of brain imaging studies that assess the genotype and availability of dopamine and serotonin transporters in detoxified alcoholics and healthy control subjects. RESULTS: Chronic alcohol intake induced neuroadaptive reductions in striatal dopamine transporter (DAT) availability, which were reversible during early abstinence. A polymorphism of the DAT gene (SLC6A3) was associated with the in vivo transporter availability and with the severity of alcohol withdrawal. Neurotoxic reductions in 5-HTT protein expression were limited to homozygous carriers of the long allele in the 5-HTT gene (SCL6A4) regulatory region and correlated with negative mood states. CONCLUSION: Genetic constitution interacts with the in vivo availability of central dopamine and serotonin transporters during alcohol detoxification and may affect the severity of alcohol withdrawal and clinical depression.

Alcoholism↗
PubMed2004

[Genetic and pharmacological effects on prefrontal cortical function in schizophrenia].

Brain imaging studies with PET, SPECT, functional magnetic resonance imaging, and spectroscopy provide evidence of prefrontal dysfunction in schizophrenia. Dysfunction of the prefrontal cortex is associated with cognitive impairment and negative symptoms. Combined multimodal imaging shows that a developmentally early disturbance of frontotemporal-limbic neuronal networks is associated with a disinhibition of subcortical dopaminergic neurotransmission. Current studies imply genetic factors in the regulation of dopaminergic neurotransmission and their effects on prefrontal cortex function. Some studies also indicate that atypical neuroleptics may at least partially improve frontal cortex function. We review the literature and discuss genotype and medication effects on frontal dysfunction in schizophrenia. Molecular brain imaging combines imaging techniques with the assessment of genotype effects and represents a powerful tool for the understanding of neuropsychiatric disorders.

Antipsychotic Agents↗
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

Treatment of chronic hepatitis C in patients with drug dependence: time to change the rules?

AIMS: Approximately 170 million people world-wide are chronically infected with the hepatitis C virus (HCV). While the seroprevalence in the general population ranges between 0.2 and 2%, 50-90% of injection drug users are chronically HCV-infected. However, most patients who are drug abusers are still excluded from treatment of chronic HCV infection with interferon (IFN)-alpha. Due to the recent treatment advances resulting in sustained response rates between 50 and 80%, it becomes increasingly important to reflect the still existing contraindications and restrictions for IFN-alpha treatment, especially for patients with intravenous drug use (IDU) with or without psychiatric comorbidity. METHODS: We reviewed clinical trials that focus on the treatment of chronic hepatitis C in patients with drug addiction published between 1987 and 2003. FINDINGS: Only seven clinical trials investigating HCV treatment among drug users were found: four open prospective uncontrolled trials and three controlled trials. Thus far, no trials using pegylated IFN-alpha have been conducted. Data about sustained response and adherence in HCV-infected methadone substituted patients were either comparable to control groups or to representative clinically controlled trials using the same treatment regimen (IFN-alpha monotherapy or combined with ribavirin). Patients with former or present drug abuse seem more likely to discontinue treatment early. HCV-infected IDUs tended to be older with higher inflammatory activity and stage of fibrosis when interferon treatment was started. Psychiatric comorbidity did not negatively influence adherence or treatment outcome. CONCLUSIONS: There is no clinical evidence suggesting that HCV treatment with IFN-alpha should be limited to IDUs or methadone substituted patients. However, more prospective controlled trials on HCV treatment for patients with IDU are needed to establish and apply new rules and guidelines.

Antiviral Agents↗
PubMed2004

DASB -in vitro binding characteristics on human recombinant monoamine transporters with regard to its potential as positron emission tomography (PET) tracer.

The efficiency of serotonergic signal transduction is controlled by the density of serotonegic synapses and by the activity of the serotonin transporter (SERT), which selectively clears the synaptic cleft of the neurotransmitter. SERT is located in axons, where it is concentrated in varicosities and terminal boutons and thus is an exquisite marker for serotonergic synapses. This finding has been taken advantage of for neuroimaging serotonergic synaptic contact sites. Previous positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies were often carried out using radioligands that bind with high affinity to SERTs in the brainstem but also exhibit high affinity for dopamine and norepinephrine transporters and therefore did not allow quantification of serotonergic innervations in brain regions also containing dopaminergic or noradrenergic terminals. In order to visualize SERT availability more selectively, in recent years new tracers have been developed, one of which is [11C]DASB (N,N-dimethyl-2-2-amino-4-cyanophenylthiobenzylamine). Here, we have performed a detailed pharmacological characterization of unlabelled as well as radioactive DASB on recombinant human monoamine transporter proteins. Our results show that DASB selectively binds to SERT with high affinity (KD = 3.5 nm) to a site distinct from the serotonin (5-HT) recognition/translocation site. 5-HT inhibits DASB binding to SERT with more than one order of magnitude lower affinity than that of DASB binding (IC50 = 82.4 nm). These findings suggest DASB to be a highly selective PET tracer to visualize the density of serotonergic synapses in human brain.

Adrenergic Uptake Inhibitors↗
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

[The alcoholic patient in the daily routine].

Chronic alcohol abuse is of significant clinical and economic relevance. A major part of internal medical pathology is associated with chronic alcoholism. 50% of all accidents with subsequent traumatic injuries are related to alcohol intake. Patients who are chronic alcohol abusers have prolonged hospital stays and substantial increases in postoperative morbidity. A sophisticated diagnosis of alcoholism within standard clinical routine is often difficult, and in most cases the treatment of alcohol-related diseases and complications is protracted and requires increased energy expenditure by the treating physicians. In surgical patients, chronic alcohol abuse is associated with a 3- to 4-fold risk of infections, sepsis, cardiac and bleeding complications. Therefore, the patients themselves, along with the general practitioner and an in-hospital interdisciplinary team should cooperate in medical and operative treatment in order to attain better clinical outcome. Each patient history should include a detailed assessment of the quantity of daily alcohol intake. Alcoholic diagnostic regimens including questionnaires (i.e. CAGE, AUDIT) in combination with specific laboratory markers (CDT, GGT, MCV), if implemented, could prove valuable, especially in cases where major surgical procedures are considered. Strict abstinence by alcoholic patients with organ pathology in medical and elective surgical settings as well as the prophylactic treatment of pre-operative alcohol withdrawal appear to be useful strategies to reduce the risk of complications. Short-term interventions are associated with reduced alcohol intake and decreased incidence of re-trauma. Considering the clinical relevance of alcohol abuse, sufficient screening, interventions, and open approaches to address alcohol problems should be important components of the daily clinical routine in outpatient clinics, emergency rooms, in GPs' offices and in general hospitals.

Acute Disease↗
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↗
PubMed2003

Therapy and supportive care of alcoholics: guidelines for practitioners.

Alcohol dependence is one of the most pervasive diseases of the Western world. However, less than 5% of all patients receive proper treatment. Each year, about 30% of all alcohol-dependent patients are admitted to general hospitals, usually to treat alcohol-related physical diseases. The alcohol dependence itself, however, is often not diagnosed or is ignored. This chapter describes current neurobiological findings, which help in the diagnosis and understanding of the development of alcohol tolerance, withdrawal and craving. It also discusses evidence-based treatment options that include brief interventions, outpatient programmes, self-help groups and medication to reduce the relapse risk. The state-of-the-art would be to develop a therapeutical network that offers a menu of treatment options for alcohol-dependent patients. If adequate treatment is available, relapse rates were as low as 50% in those follow-up studies that examined treatment periods of up to 2 years, so that there is no justification for therapeutic nihilism.

Alcohol-Related Disorders↗
PubMed2003

Lithium augmentation therapy in refractory depression: clinical evidence and neurobiological mechanisms.

OBJECTIVE: This systematic review examines the evidence and discusses the clinical relevance of lithium augmentation as a treatment strategy for refractory major depressive episodes. It also examines hypotheses on the mode of action of lithium augmentation, with a focus on serotonin (5-HT) and neuroendocrine systems, and proposes recommendations for future research. METHOD: We searched the Medline computer database and the Cochrane Library for relevant original studies published in English from January 1966 to February 2003. The key words were as follows: lithium, augmentation strategies, lithium augmentation, major depression, refractory depression, treatment-resistant depression, neuroendocrinology, and serotonin. RESULTS: Of 27 prospective clinical studies published since 1981, 10 were double-blind, placebo-controlled trials, 4 were randomized comparator trials, and 13 were open-label trials. Five of 9 acute-phase placebo-controlled trials demonstrated that lithium augmentation had substantial efficacy. In the acute-treatment trials, the average response rate in the lithium group was 45%, and in the placebo group, 18% (P < 0.001). One placebo-controlled trial showed the efficacy of lithium augmentation in the continuation-phase treatment. Summarizing the open and controlled data, approximately 50% of patients responded to lithium augmentation within 2 to 6 weeks. Animal studies offer robust evidence that lithium augmentation increases 5-HT neurotransmission, possibly by a synergistic action of lithium and the antidepressant on brain 5-HT pathways. CONCLUSIONS: Augmentation of antidepressants with lithium is the best-documented augmentation therapy in the treatment of refractory depression. Emerging data from animal studies suggest that the 5-HTergic system is involved in the augmentatory effect of lithium.

Animals↗
PubMed2002

Effects of acute psychological stress on adhesion molecules, interleukins and sex hormones: implications for coronary heart disease.

RATIONALE: Subjects with high levels of daily stress suffer from an increased risk of coronary heart disease. Increased concentrations of the intercellular adhesion molecule-1 (ICAM-1) contribute to atherosclerosis. Cell adhesion molecules may be activated by psychological stress exposure, depending on their interaction with the interleukin network, sex hormones and cortisol secretion. OBJECTIVES: To assess effects of acute psychological stress on the interaction between cell adhesion molecules, interleukins, sex hormones and cortisol in healthy male subjects. METHODS: Cell adhesion molecules, interleukin-1 beta (IL-1beta), IL-2, IL-6, sex hormones and cortisol levels of 18 healthy male physicians were measured before and after an academic oral presentation and on a control day. RESULTS: The oral presentation was perceived as a stressful event and was accompanied by a significant increase in cortisol secretion in all volunteers. Soluble ICAM-1 and IL-1beta also increased in all subjects after psychological stress exposure. The stress-associated increase in IL-2 concentrations approached statistical significance and correlated negatively with luteinizing hormone plasma levels. Estradiol concentrations correlated positively with IL-6 levels. CONCLUSIONS: Subjective ratings and the increase in cortisol plasma concentrations support the validity of the chosen stress model. Acute stress exposure was followed by an increase in IL-1beta, IL-2 and soluble ICAM-1 plasma concentrations, which can contribute to coronary heart disease and immunological disorders.

Adult↗
PubMed2002

Dysregulation of the hypothalamic-pituitary-thyroid axis in alcoholism.

Thyroid dysfunction is a prominent finding in alcoholism. Subclinical and clinical hypothyroidism have been associated with clinical depression and cognitive impairment and may increase the relapse risk among alcoholics. In spite of these important clinical associations, there is no consensus on thyroid dysfunction in alcoholism in the literature. In this paper, we present a review of the literature and develop a hypothesis that may explain dysfunction of the hypothalamic-pituitary-thyroid axis in alcoholism. Based on a Medline research of the years 1980-2001 we found 33 empirical studies that assessed thyroid function in alcoholism. The most consistent findings were a reduction in total thyroxine and total and free triiodothyronine concentrations during early abstinence. About one-third of all alcoholics also displayed a blunted thyroid stimulation hormone (TSH) response in the thyrotrophin-releasing hormone test (TRH-test). Blunting was observed frequently during detoxification, but was also present in some alcoholics after several weeks of abstinence. We suggest that a reduction in peripheral thyroid hormones may be caused by a direct toxic effect of alcohol on the thyroid gland, which induces a central compensatory activation of the hypothalamic-pituitary axis with an increased TRH release. The TRH release induces a downregulation of pituitary TRH receptors, which manifest as a blunted TSH response to the TRH test. We discuss further additional effects of alcohol on thyroid-hormone metabolizing deiodinases and on monoaminergic systems, which may interact directly with mood states among abstinent alcoholics.

Alcoholism↗
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↗