Clinical trial NCT02910193: Alcohol Addiction: A Systems-oriented Approach
Official title: Alcohol Addiction: A Systems-oriented Approach; Functional Validation II: Neuroimaging x Genetics
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Alcoholism
Keywords: alcoholism
genetics
functional MRI
structural MRI
first-degree relatives
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Central Institute of Mental Health, Mannheim
First posted: 2016-09-21
Enrollment: 159
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: primary care clinic and community sample

Brief summary: The goal of the multicenter subproject (SP) 10 of the eMED Alcohol Addiction Consortium - A Systems-Oriented Approach is to study neuroimaging x genetics predictions in an existing sample (NGFNplus) of tightly endophenotyped and genome-wide genotyped alcohol dependent subjects (N=240) and controls (N=240); (ii) to translate the results of neuroimaging and genetic analyses from an adolescent risk sample (IMAGEN) to adult disease (NGFNplus sample) by examining related MRI-paradigms tagging the same functional brain systems in both samples (e.g. reward system, inhibitory control system, emotion processing, working memory); (iii) to conduct a follow-up neuroimaging study on the NGFNplus sample validating the neurobehavioral risk profiles predictive for juvenile harmful alcohol use in adult patients with alcohol addiction, (iv) to expand the NGFNplus sample by including a new set of healthy subjects with high genetic risk (1st degree relatives of patients with alcohol addiction). The investigators will do so by using elaborate imaging genetic methods that are already available and successfully used in other multicenter studies by the investigator's research group (e.g. univariate analyses, functional and effective connectivity analyses, polygenetic scores, network topology) as well as by using complex computational algorithms and mathematical models, in particular advanced machine learning methods, developed in SP 6. The investigator's approach aims in the long to predict and characterize longitudinal outcomes in patients with alcohol addiction (5 years following our index session) and to complement the NGFN-sample with an add-on study with 1st degree relatives that will allow the investigators to test the generalizability of the identified predictive risk profiles for early risk identification.

Detailed description: The overall research goal of this project is (i) to study neuroimaging x genetics predictions in an existing sample (NGFNplus) of tightly endophenotyped and genome-wide genotyped alcohol dependent subjects (N=240) and controls (N=240); (ii) to translate the results of neuroimaging x genetic analyses from an adolescent risk sample (IMAGEN) to adult disease (NGFNplus sample) by examining related paradigms tagging the same functional systems in both samples; (iii) to conduct a follow-up neuroimaging study on the NGFNplus sample validating the neurobehavioral risk profiles predictive for harmful alcohol use in adolescents in adult patients with alcohol addiction (iv) to expand the NGFNplus sample by including a new set of healthy subjects with high genetic risk (1st degree relatives of patients with alcohol addiction). The investigators will do so by using imaging genetic methods that are already available and used in other multicenter studies by the investigator's research group (e.g. univariate analyses, functional and effective connectivity analyses, polygenetic scores, network topology) as well as by using computational algorithms and mathematical models, in particular advanced machine learning methods, developed in other sub projects (SPs) of the consortium in particular of SP4 and SP6. The investigator's approach will enable the researchers to characterize outcome longitudinal in patients with alcohol addiction (5 years following our index session) and to complement the NGFN-sample with an add-on study with 1st degree relatives that will allow the investigators to test the generalizability of the identified predictive risk profiles for early risk identification.

Eligibility criteria: Inclusion Criteria:

* written informed consent
* right handedness
* no psychiatric disorders according to the International Classification of Diseases, Version 10 (ICD-10) (in patients: other than nicotine and alcohol dependence)
* no use of psychotropic substances during previous 3 months

Exclusion Criteria:

* severe illnesses (e.g. neurological diseases)
* MR-contraindications (e.g. pacemaker, metal or electronic implants, metal splinters)
* no psychiatric axis I-disorders according to the International Classification of Diseases, Version 10 (ICD-10) (in patients: other than nicotine and alcohol dependence)
* no use of psychotropic substances during previous 3 months
* insufficient language knowledge
* claustrophobia
* pregnancy in women

Primary outcomes:
measure: Functional brain imaging assessed using a Siemens Magnetom TimTrio, 3 Tesla
timeFrame: 3 year
measure: Structural brain imaging assessed using a Siemens Magnetom TimTrio, 3 Tesla
timeFrame: 3 year
Secondary outcomes:
measure: Assessment of genetic candidate markers and epigenetic markers of alcohol use disorders
timeFrame: 3 years
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charite - Universitätsmedizin Berlin
Study officials:
References:
citation: Spanagel R, Durstewitz D, Hansson A, Heinz A, Kiefer F, Kohr G, Matthaus F, Nothen MM, Noori HR, Obermayer K, Rietschel M, Schloss P, Scholz H, Schumann G, Smolka M, Sommer W, Vengeliene V, Walter H, Wurst W, Zimmermann US; Addiction GWAS Resource Group; Stringer S, Smits Y, Derks EM. A systems medicine research approach for studying alcohol addiction. Addict Biol. 2013 Nov;18(6):883-96. doi: 10.1111/adb.12109.