CoCA — Aktiivsus-tähelepanuhäirega koosesinevad haigused ja tervisehäired / Comorbid Conditions of Attention Deficit/Hyperactive Disorders

Permanent URI for this collectionhttps://hdl.handle.net/10062/63786

CoCA kodulehekülg.

Psychiatric disorders are highly co-morbid, both with somatic and other mental disorders, and are one of the last areas of medicine where disease classifications are driven by phenomenology rather than pathophysiology. Here, we will study the comorbidity between the most frequent psychiatric conditions, attention-deficit/hyperactivity disorder (ADHD), mood and anxiety disorders, substance use disorders (SUD), and a highly prevalent somatic disorder, i.e. obesity. In this project, the CoCA consortium will:
• specify the population prevalence and sex-specificity of comorbidity of ADHD’s comorbidity with mood and anxiety disorders, SUD, and obesity across the lifespan (WP1)
• determine the socioeconomic impact of ADHD in conjunction with its common comorbid disorders (WP1)
• specify the genetic and environmental contributions to the overlap among the disorders (WP2)
• determine the biological mechanisms underlying ADHD and its comorbid disorders (mood and anxiety disorders, SUD, obesity) (WP2,3,4):
o Sleep and the circadian rhythm system (CIRCA system) (WP2,3)
o Reward processing system and dopaminergic neurotransmission therein (DA system) (WP2,4)
o Additional, currently unknown biological pathways derived from genetic big data studies (WP2)
• test biomarkers from candidate systems (CIRCA, DA) and identify novel ones (WP2,3,4)
• develop algorithms to predict the development of ADHD’s comorbidities based on epidemiological/genetic data as well as the CIRCA/DA systems (WP7)
• improve the diagnosis of ADHD-related comorbidity in adolescence / early adulthood through mobile healthcare (mHealth) approaches (WP5)
• develop an mHealth approach to support patients in daily life (mHealth-based monitoring and coaching) (WP5,6)
• establish effect sizes of non-pharmacologic treatments for ADHD with comorbid obesity and depression by targeting the CIRCA/DA systems with chronobiological approaches, physical exercise and mHealth-based coaching (WP6)
• explore targets for novel pharmacologic treatment strategies for ADHD and its comorbid disorders (WP8)
• disseminate results to the public, emphasizing the role of life-style modifications for prevention (WP9)
• educate and train a new generation of inter- and transdisciplinary researchers and clinicians (WP10)

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    Interactive effects of DRD2 rs6277 polymorphism, environment and sex on impulsivity in a population-representative study
    (Elsevier, 2021-04) Klaus, K.; Vaht, M.; Pennington, K.; Harro, J.
    Previous research has shown that dopaminergic dysregulation and early life stress interact to impact on aspects of impulse control. This study aimed to explore the potentially interactive effects of the rs6277 polymorphism of the dopamine D2 receptor gene (DRD2), stressful or supportive environment and sex on behavioural and self-reported measures of impulsivity, as well as alcohol use – a condition characterised by a deficit in impulse control. The sample consisted of the younger cohort (n=583) of the longitudinal Estonian Children Personality, Behaviour and Health Study. The results showed that the CC homozygotes (suggested to have decreased striatal D2 receptor availability) who had experienced stressful life events (SLE) or maltreatment in the family prior to age 15 showed higher self-reported maladaptive impulsivity at age 15. The genotype-SLE interaction and further association with sex was also evident in the frequency of alcohol use at age 15. Lack of warmth in the family contributed to significantly higher levels of thoughtlessness and more frequent alcohol use in CC carriers at age 25, whereas family support was associated with lower thoughtlessness scores in CC males, which may suggest a protective effect of supportive family environment in this group. Together the findings suggest that DRD2 rs6277 polymorphism, in interaction with environmental factors experienced in childhood and youth may affect facets of impulsivity. Future work should aim to further clarify the sex and age-specific effects of stressful and supportive environment on the development of neuronal systems that are compromised in disorders characterised by deficits in impulse control.