Effects of depressive symptoms and peripheral DAT methylation on neural reactivity to alcohol cues in alcoholism.

In alcohol-dependent (AD) patients, alcohol cues induce strong activations in brain areas associated with alcohol craving and relapse, such as the nucleus accumbens (NAc) and amygdala. However, little is known about the influence of depressive symptoms, which are common in AD patients, on the brain's reactivity to alcohol cues. The methylation state of the dopamine transporter gene (DAT) has been associated with alcohol dependence, craving and depression, but its influence on neural alcohol cue reactivity has not been tested. Here, we compared brain reactivity to alcohol cues in 38 AD patients and 17 healthy controls (HCs) using functional magnetic resonance imaging and assessed the influence of depressive symptoms and peripheral DAT methylation in these responses. We show that alcoholics with low Beck's Depression Inventory scores (n=29) had higher cue-induced reactivity in NAc and amygdala than those with mild/moderate depression scores (n=9), though subjective perception of craving was higher in those with mild/moderate depression scores. We corroborated a higher DAT methylation in AD patients than HCs, and showed higher DAT methylation in AD patients with mild/moderate than low depression scores. Within the AD cohort, higher methylation predicted craving and, at trend level (P=0.095), relapse 1 year after abstinence. Finally, we show that amygdala cue reactivity correlated with craving and DAT methylation only in AD patients with low depression scores. These findings suggest that depressive symptoms and DAT methylation are associated with alcohol craving and associated brain processes in alcohol dependence, which may have important consequences for treatment. Moreover, peripheral DAT methylation may be a clinically relevant biomarker in AD patients.

[Rehabilitee-management-categories (RMK)--results of the development phase and of the first clinical implementation in alcohol rehabilitation centres]. / Rehabilitanden-Management-Kategorien (RMK)--Entwicklungsprozess und ausgewählte Ergebnisse am Beispiel der Suchtrehabilitation.

BACKGROUND: Due to the introduction of lump sum reimbursement systems for acute-care settings (DRGs), patient classification systems have been developed in Germany during the last 15 years to adapt a case-based lump sum system to the field of medical rehabilitation. The concept of Rehabilitee-Management-Categories (RMK), developed by the Charité - Universitätsmedizin Berlin, classifies rehabilitees primarily by their relevant impairments of activity and participation, as these factors mainly determine treatment needs and resources required in rehabilitation. It can, inter alia, be used to optimize the demand-related allocation of treatment services in the rehabilitation centres as well as lead to more transparency in the allocation process. RMK results are reported on the example of inpatient rehabilitation of alcohol dependence. METHODS: Utilizing internationally established assessments, an RMK-assessment was developed that allows the assessment of rehab treatment needs of patients undergoing alcohol dependence rehabilitation. The RMK-assessment was completed by n=731 rehabilitees. Latent class analysis was applied to find groups of cases. To facilitate the RMK-patient classification a software-based algorithm was developed and implemented in 12 rehabilitation centres (implementation study). To validate the results of the first study phase, the data collected during implementation (n=1,533) was again analyzed using latent class analysis. Combined standardized and qualitative user surveys were conducted at the end of the implementation study. RESULTS: On the basis of 15 needs-related patient characteristics, 4 comparable case groups (AL-1 to AL-4) each were identified in 2 independent samples, groups that differed significantly in their degree of dependence-related, psychological and social impairment. The user survey confirmed the basic clinical plausibility of the 4 different case groups as well as the feasibility of the instruments applied in a rehabilitation setting. CONCLUSIONS: The RMK-concept offers a new approach for a demand-related patient classification in medical rehabilitation. The RMK-instruments allow a standardized initial assessment of impairment and treatment needs in alcohol rehabilitation and can hence be used for objective comparisons between rehabilitation centres. The results of the RMK-assessment provide relevant information about demand-related treatment requirements, which is a matter of great interest in the context of limited resources. Appropriate treatment requirements for the 4 RMK-case groups will be defined and verified in the next step of the RMK-concept. A financial evaluation of the RMK is possible in principal, will however require more extensive development, not least in order to model and evaluate the health-economic implications involved.