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Neuroimmunology of depression and alcohol use disorders (The DARCY Studies) (completed)

Substance use and depression constitute close to a half of all disease burden associated with neuropsychiatric conditions. Alcohol use disorder and major depression frequently occur in the same individual, either simultaneously or sequentially.

In the context of alcohol use disorder, depressive symptoms can occur alongside heavy drinking as part of alcohol-induced deterioration of mood symptoms, but in some cases depressive symptoms may last long after cessation of drinking. Recent evidence suggests that depression and alcohol use disorders are, among other psychiatric conditions, accompanied by dysregulated neuro-immune system, particularly the innate immunity. This tantalizing concept has emerged as a new field of science, referred to as Psychoneuroimmunology. Psychoneuroimmunology challenges the conventional thinking of mental disorders and embodies various interactions between processes in the brain and the body's immune response as underlying mechanisms for mood and behavioral disorders. The DARCY project incorporates several studies investigating the role of neuroimmune functions, and thereby of its derangement, in the emergence and progression of major depression and alcohol use disorders.

About the project

The first wave of the DARCY studies was launched in 2009, and included two cross-sectional studies in multiple treatment institutions in Norway and Nepal. These studies characterized treatment seeking populations with alcohol use disorders in the two culturally and ethnically different settings. Neuroimmune correlates of, along with several biochemical alterations in depression in alcohol use disorder were examined. The epidemiological evidence for the associations between depression and alcohol use disorders were examined in a large nationally representative dataset from the Health Study in Oppland and Hedmark (OPPHED) and the Oslo Health Study (HUBRO) which suggested an interaction of socioeconomic status in the comorbidity between alcohol use disorder and major depression.

The second wave of the DARCY studies includes several longitudinal studies on clinical samples. A longitudinal study of inpatients at a psychiatric treatment institution in Norway (Modum Bad) has been carried out with data from multiple primary psychiatric diagnoses with neuroimmune parameters and clinical evaluation followed up through treatment. These data will help disentangle relationships between alterations in neuroimmune parameters and clinical outcomes. Clinical interventions trials will constitute the third wave for the DARCY studies.

The completed and ongoing DARCY studies received funding from the University of Oslo and Innlandet Hospital Trust. For conducting prospective studies on alcohol treatment sample, funding has been secured from the Research Council of Norway and South-East Regional Health Authority. Preparations for these studies are underway.

Publications from this project

Neupane SP, Neuroimmune factors related to depression in alcohol-use disorders: A cross-sectional study of Nepalese patients undergoing treatment for alcohol-use disorders (2015). PhD dissertation (University of Oslo). ISBN 978-82-8333-037-3
Martinez P, Neupane SP, Perlestenbakken B, Toutoungi C & Bramness JG. (2015) The association between alcohol use and depressive symptoms across socioeconomic status among 40- and 45-year-old Norwegian adults. BMC Public Health. Nov 19;15(1):1146. doi: 10.1186/s12889-015-2479-6
Neupane SP, Lien L, Ueland T, Mollnes TE, Aukrust P, Bramness JG (2015) Serum brain-derived neurotrophic factor levels in relation to comorbid depression and cytokine levels in Nepalese men with alcohol-use disorders. Alcohol. doi:10.1016/j.alcohol.2015.01.012
Neupane SP, Lien L, Martinez P, Hestad K, Bramness JG (2015) The relationship of alcohol-use disorders and depressive symptoms to tryptophan metabolism: cross-sectional data from a Nepalese alcohol treatment sample Alcoholism: Clinical and Experimental Research 3:514–521. doi:10.1111/acer.12651
Neupane SP, Bramness JG (2014) Who seeks treatment for alcohol problems? Demography and alcohol-use characteristics of patients in taboo and non-taboo drinking groups attending professional alcohol services in Nepal. Asian J Psychiatr 12:82-87.
Neupane SP, Lien L, Martinez P, Aukrust P, Ueland T, Mollnes TE, Hestad K, Bramness JG (2014) High Frequency and Intensity of Drinking may Attenuate Increased Inflammatory Cytokine Levels of Major Depression in Alcohol-use Disorders. CNS Neuroscience & Therapeutics 20:898-904.
Neupane, SP & Bramness, JG (2013). Prevalence and correlates of major depression among Nepalese patients in treatment for alcohol-use disorders. Drug and Alcohol Review. 32(2), 170- 177. doi: 10.1111/j.1465-3362.2012.00487.x
Neupane, SP; Lien, L; Hilberg, T & Bramness, JG (2013). Vitamin D deficiency in alcohol-use disorders and its relationship to comorbid major depression: A cross-sectional study of inpatients in Nepal. Drug And Alcohol Dependence. 133(2), 480- 485. doi:10.1016/j.drugalcdep.2013.07.006
Neupane, SP (2011). Prevalence and correlates of major depression and anxiety disorders among patients with alcohol-use disorders in Nepal. MPhil Dissertation. University of Oslo, http://urn.nb.no/URN:NBN:no-29755.

Conference papers

Toft HP. (Sept 2016). Associations between immune status and depression with and without alcohol use. Innlandskonferensen, Hamar, Norway
Bramness JG. (Sept 2016). Cytokine level changes following acute ethanol intoxication in healthy men: a cross-over study. World Congress on Alcohol and Alcoholism (ISBRA/ESBRA). Berlin, Germany.
Neupane SP. (June 2016). Cytokine level changes following acute ethanol intoxication in healthy men: a cross-over study. Psychoneuroimmunological Research Society’s 21^st annual meeting, Brighton, UK.
Martinez P. (Mar 2016). Cytokine levels, depression and psychological distress among people with substance use disorders. Behavior, Biology, and Chemistry Conference. San Antonio, TX, USA.
Neupane SP. (June 2014). Alteration of circulatory cytokine levels in alcohol-use disorder patients with or without comorbid major depression. College on Problems of Drug Dependence annual conference. San Juan, Puerto Rico.
Neupane SP. (Sept 2011) Depression and anxiety among Nepalese patients with alcohol use disorders. International Society of Addiction Medicine annual conference (ISAM), Oslo, Norway.