Towards precision medicine in ADHD and depression: a genetic approach

Research project description

A PhD position is available at the Group of Psychiatry, Mental Health and Addictions of the Institut de Recerca Vall d’Hebron under the supervision of Marta Ribasés (geneticist) and Maria Soler (mathematician). The successful candidate will be enrolled in the Genetics doctoral programme at the Universitat Autònoma de Barcelona (UAB) in the framework of the TOUCH project. TOUCH (“Towards the next generatiOn of excellent yoUng doctoral researchers on mental health by developing an intersectoral & transdisciplinary approaCH”) is a new excellent doctoral programme co-funded by the Marie Skłodowska-Curie (MSCA) Actions of the European Commission and led by the UAB for the recruitment and training of 24 doctoral candidates in the field of mental health and wellbeing.

Background: attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with a prevalence of around 5% in childhood, which persists into adulthood in two-thirds of cases. It is characterized by a persistent pattern of inattentive, hyperactive, and impulsive behaviours. In addition to these primary symptoms, comorbid conditions in ADHD cause significant functional and psychosocial impairments, worsening symptom progression, the course of the disorder, and its outcomes. The pattern of comorbidity in ADHD is highly heterogeneous and changes substantially throughout life. There is increasing recognition that ADHD is associated with depression, which generally manifests later, with estimates showing a 6.5-fold increase in the risk of developing depression within the first year following an ADHD diagnosis. ADHD has a strong genetic component, with a heritability estimate from twin studies of 0.74. In the most recent genome-wide association study on ADHD, in which we actively participated, 27 loci were identified, highlighting 76 genes expressed during the early stages of brain development. Most ADHD comorbidities are also highly heritable, with genetic risk factors involved not only in their individual aetiology but also in their co-occurrence. However, the causal pathways and precise mechanisms explaining this relationship remain unclear.

Hypothesis: there is a strong genetic background underlying the comorbidity between ADHD and depression.

Objective:

1. To study the genetic overlap between ADHD and depression.
2. Identify pleiotropic genetic variants (i.e., with effects on multiple disorders) and provide insights into the biological mechanisms underlying this comorbidity.
3. Assess whether genetic susceptibility to ADHD is associated with a higher risk of depression.
4. Infer if there is a causal relationship between ADHD and depression and if this relationship may be mediated by intermediate phenotypes.

Impact: the project will significantly advance understanding of the genetic and biological underpinnings of comorbidity patterns in ADHD, specifically identifying patient subgroups at elevated risk for depression based on genetic profiles and risk factors. This research is expected to lead to actionable insights for targeted prevention strategies and inform the development of individualized treatment approaches.

Academic background / Skills

The candidates must fulfil the following eligibility criteria from the EC: Mobility rule: candidates must not have resided or carried out their main activity (work, studies, etc.) in Spain for more than 12 months in the 36 months immediately preceding the deadline for the programme call. Experience rule: researchers must be doctoral candidates at the date of recruitment, that is not already in possession of a doctoral degree at the deadline of the open calls. Researchers who have successfully defended their doctoral thesis but have not yet formally awarded the doctoral degree will not be considered eligible. Candidates must hold a degree that allows admission to the official doctoral programme at UAB.

The Group of Psychiatry, Mental Health and Addictions is seeking a PhD student with experience in statistical genetics, computational biology or similar field to work on mental health.

Education and qualifications:

• Degree in Biological, Health or Basic sciences (Biology, Genetics, Mathematics, etc.).
• Master’s Degree in Bioinformatics or Biosciences.

Experience and knowledge:

Desired experience in Genetics and Genomics, Statistical Genetics, Biostatistics, Computational Biology, Bioinformatics or similar field and programming skills (particularly R, Unix/ Linux).

Main responsibilities and duties:

Responsibilities will include genetic association analyses of clinical features across mental disorders, application of the novel methods described, manuscript writing, and oral presentations at lab meetings, consortium calls, and scientific conferences.

The candidate will also engage in regular collaborative meetings with teams of scientists locally and internationally, including the Psychiatric Genomics Consortium.

There will also be training opportunities for subject-specific and generic research skills, aiming to help the candidate to enhance his/her employability.

Research group/s description

Our multidisciplinary research team has skills and expertise in epidemiology, psychiatry, psychology, genetics, bioinformatics and biostatistics.

Our main objective is to break the stigma associated with mental disorders and to show that they are biological conditions by using -omics data and multiple approaches, that include GWAS and omics profiling.

Our main contribution to the field has been to identify a) genes involved in mental disorders; b) shared and specific genetic background for comorbid conditions and c) biomarkers for disease, with the final aim to use genetic information to understand the disease mechanism, to predict risk and to improve patients’ classification and diagnostic procedures.

In the last 5 years our group has published more than 190 articles (Science, Cell, Nature Genetics, Molecular Psychiatry, …) This activity has also been awarded with Human Resources competitive contracts (Miguel Servet, Ramón y Cajal, AGAUR, PFIS, Juan de la Cierva, Sara Borrell or Marie Curie ITN).