High-risk Participant Studies

High-risk participant studies are research studies in which subjects may be at high risk for a psychological disorder or disease under investigation. Such studies can provide useful information about the etiology of disorders, but they also present special problems.

High-risk participant studies are very useful for examining relatively rare disorders or negative outcomes. In the absence of subjects at relatively high risk for developing the disorder or experiencing a negative outcome, it can be difficult to achieve statistically significant results without recruiting an unrealistically large pool of participants. By studying high-risk populations, researchers can limit the number of participants and may be able to identify vulnerabilities or processes that are important for the development of mental disorders and for the design of effective interventions to prevent their development. High-risk participant studies may or may not include control participants who are at low or average risk for the disorder under investigation.

High-risk participant studies originated in the “diathesis-stress” model of the development of psychopathologies. Diathesis-stress psychological theory attempts to explain behaviors based on a combination of vulnerability or predisposition and stress. Diathesis-stress models of psychopathology emphasize the influence of external stress factors on individuals with vulnerabilities, predisposition, or susceptibility. The predisposition may be due to psychological factors, hereditary or other biological factors, lifestyle factors, or life situations.

As an example of a high-risk participant study, research published in 2013 attempted to determine whether cognitive functioning measures could predict the development of affective disorder (mood disorders such as major depression or bipolar disorder) in healthy twins who were at high risk or low risk because of hereditary factors. The participants were studied at six-month intervals for up to nine years. Over the course of the study, 36 of 234 participants (15.4%) developed psychiatric illnesses—almost all affective or anxiety disorders. These future developments were predicted based on tests of executive function and attention. Without the utilization of high-risk participants, it is doubtful that such a study could have produced statistically significant results.


As useful as high-risk participant studies can be, they can present unique problems. To be successful, they often must recruit a higher number of subjects than is typical in psychological research since, by definition, the participants are at relatively high risk for developing disorders or experiencing adverse outcomes. Furthermore, it can be difficult to convince potential high-risk subjects to participate in studies, and they often have high attrition rates, with so many participants dropping out part way through that the significance of the results is jeopardized. This is a particular problem because many high-risk participant studies are longitudinal, prospective projects, meaning that the subjects are followed over a relatively long period to measure future outcomes. Finally, high-risk participant studies sometimes involve unique ethical concerns.

Improving participation and retention

Recruiting and retaining subjects is a major impediment to high-risk participant studies, and unequal participation and retention can bias findings. One study set out to define socio-demographic and functional features related to non-collaboration in a mental health study of high-risk children aged 9–13. Factors that increased the risk of initial nonparticipation were lower socioeconomic status, families that were unemployed or receiving Social Security benefits, minority culture, and poor school performance. Participants who were at risk for dropping out of the study included adolescents and those needing extra help at school, in poor health, experiencing more life events, receiving professional help for mental problems, or diagnosed with more psychopathologies at previous assessments. The study concluded that special measures are required to reduce initial refusals and attrition in mental health studies of highrisk children and adolescents.

A 2005 study examined predictors of participation and retention in a study of barrier contraception by woman at high risk for sexually transmitted diseases (STDs). Factors associated with agreeing to participate in the study included:

Young age was associated with both participation in the study and early attrition. Other factors associated with attrition included:

A 2012 study examined strategies for retaining high-risk participants and recovering participants who had dropped out. This maternal lifestyle study was researching the effects of prenatal exposure to cocaine or opiates on children from birth through age 15. Such longitudinal, prospective studies are especially difficult to conduct with high-risk participants—those for whom the results are most relevant. However, after 15 years, the study had a retention rate of 76%. Factors that encouraged retention or re-participation included:

A clinical smoking-cessation treatment trial with high-risk, vulnerable, low-income participants with serious mental illnesses had an initial follow-up rate at three months of less than 40%. Therefore, the researchers developed effective, proactive strategies that increased retention rates up to almost 93% at 12 months. The strategies included:


Participant withdrawal from a research study.
Diathesis-stress model—
A psychological theory that explains behavior based on vulnerability and life stresses; often the basis for high-risk participant studies.
Individuals who are considered at significantly increased risk for developing a disorder, disease, or behavior due to hereditary, environmental, or lifestyle factors.
Longitudinal study—
A research method for examining changes that occur over time.
Prospective study—
A research method that follows participants over time.
Sexually transmitted diseases (STDs)—
Diseases transmitted by sexual contact, including gonorrhea, chlamydia, HIV/AIDS, genital herpes, syphilis, and genital warts.



Graziotti, Ann L., et al. “Maintaining Participation and Momentum in Longitudinal Research Involving HighRisk Families.” Journal of Nursing Scholarship 44, no. 2 (June 2012): 120–6.

Romina, Kim, et al. “Maximizing Retention With High Risk Participants in a Clinical Trial.” American Journal of Health Promotion 28, no. 4 (March/April 2014): 268–74.

Vinberg, Maj, Kamilla W. Miskowiak, and Lars Vedel Kessing. “Impairment of Executive Function and Attention Predicts Onset of Affective Disorder in Healthy High-Risk Twins.” Journal of Clinical Psychiatry 74, no. 8 (2013): e747–53.


Eunice Kennedy Shriver National Institute of Child Health and Human Development, NICHD Information Resource Center, PO Box 3006, Rockville, MD, 20847, (800) 370-2943, Fax: (866) 760-5947, NICHDInformationResourceCenter@mail.nih.gov, http://www.nichd.nih.gov .

UCL Institute of Education, University College London, 20 Bedford Way, London, UK, WC1H 0AL, +44 20 7612 6000, enquiries@ioe.ac.uk, http://www.ioe.ac.uk .