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Genetic and Environmental Determinants of Comorbid Medical Conditions in Major Psychiatric Disorders: The Med-Psych Study

Final Report Summary - MEDPSYCH (Genetic and Environmental Determinants of Comorbid Medical Conditions in Major Psychiatric Disorders: The Med-Psych Study)

Final Publishable Summary Report:
People with major psychiatric disorders (MPD) (major depressive disorder, bipolar disorder, schizophrenia), particularly with mood disorders, have higher prevalence of comorbid medical conditions, such as obesity, diabetes and cardiovascular diseases. It is well documented that people with MPD have an excess mortality rates, being two to more than three times as high as the rate in the general population. Concomitantly, people with MPD has a high prevalence of obesity, nearly twice that of the overall population. There is also evidence that people with MPD are less likely to receive standard levels of care for most of the comorbid medical conditions.
The relationship between MPD and medical conditions is complex and bidirectional. There are many factors leading this comorbidity, such as psychotropic medication, individual lifestyle choices, socioeconomic factors, psychosocial stress, disparities in health care, as well as biological factors, including genetic risk factors.
The aim of the proposed work was to investigate genetic and environmental factors that contribute to the comorbidity between medical conditions, specifically obesity, and major psychiatric disorders.
The proposed project capitalises of an ongoing epidemiological study (PISMA-ep) at the University of Granada and University Hospital San Cecilio (Spain) lead by Professor Cervilla. This study includes a population-based cohort (n=5,309) representative of the Spanish general population, containing a wealth of detailed data collected on medical conditions, clinical, psychosocial, sociodemographic, anthropometric measures and environmental variables, as well as a biological sample.
We first examined and determined the prevalence and characteristics of a list of 21 self-reported medical conditions in the Pisma-ep cohort. Lifetime prevalence of medical disorders was significantly higher in the MPD group compared to psychiatrically healthy controls in the vast majority of the diseases.
Specifically, 19 medical disorders were significantly more frequent in the MPD group. The highest significant differences were found for chronic pain, asthma, migraine, vertigo, rhinitis and arthritis. There were also differences between both groups in cancer, chronic bronchitis, diabetes, stomach ulcer, chronic allergy, hypercholesterolemia, thyroid problems, renal and liver difficulties, embolism, tinnitus and anaemia. This initial result highlights the importance of addressing medical conditions in people with MPD, specifically depression.
Then we aimed to investigate genetic variation in two candidate genes for obesity and mental disorders (BDNF, FTO) genotyping two well-known polymorphisms (rs6265, rs9939609) in these genes, respectively.
We found a significant association between body mass index (BMI) and depression. Individuals with depression had significantly higher BMI values compared to controls, confirming findings reported from previous studies.
Results with the BDNF rs6265 polymorphism did not show a significant association between this variant and BMI, neither in the whole sample nor when depression cases and controls were analyzed separately. Besides, no significant interaction between the rs6265 polymorphism and depression in relation to BMI was found. We tried to replicate our results in a larger and independent sample from the RADIANT study. We found the same results; there was no evidence of association between BMI and the BDNF rs6265 polymorphism in depression cases and controls. In conclusion, these findings do not support the implication of the BDNF rs6265 polymorphism in the reported relationship between higher BMI values and depression.
We initially planned to genotype the rest of candidate SNPs identified by GWAS in relationship to BMI (n=30) with TaqMan® OpenArrayTM Genotyping System. But during the course of the project and thanks to the collaboration with the Psychiatric Genomics Consortium (PGC), it has been possible to carry out a genome-wide analysis using the Psych-Chip, jointly developed by Illumina and the PGC. The chip contains information for approximately 50,000 variants and the genetic information will be available shortly to perform the statistical analyses. We expect to identify new risk loci for the comorbidity between obesity-related disorders and depression. We also expect that genetic variation at candidate genes for obesity-related disorders may increase the risk to suffer comorbid medical conditions in MPD. We hope to replicate our most significant findings in independent samples. It is worth mentioning that our sample will be part of the PGC and will be also included in futures meta and mega analyses carried out by the Consortium.

Psychiatric disorders and medical conditions, specifically obesity-related disorders, often coexist and both have major public health, clinical, economical, personal and social implications worldwide.
There is need for more research on this area as there are a limited number of cross-national studies on comorbid mental and medical conditions.
Identifying genetic and environmental risk factors that are involved in the development of these disorders may help to design new therapeutic targets and more efficient treatments. They also may help to inform public programs to reduce their prevalence and potentially will improve prevention, management and treatment programmes.