Depression and Sleep Disorders in Adolescents and Young Adults with Down Syndrome

Principal Investigator: George Capone

Persons with Down syndrome (DS) are known to exhibit adolescent and adult-onset psychopathology such as depression, anxiety, obsessive-compulsive and schizophreniform disorders. Many also have medical conditions which increase their risk for developing sleep-related breathing disorders (SRBD). Additional neurobiological risk-factors render them vulnerable to cognitive decline, with executive dysfunction in conjunction with chronic sleep disruption throughout adolescence and adulthood.

In clinical practice this population frequently requires a modified approach to establishing sleep and mental health diagnoses, prioritizing treatment intervention and measuring the outcome of standard therapies. Complex cognitive, executive, mental health and medical co-morbidities are difficult to sort out in a traditional outpatient setting which requires multiple referrals and unacceptably long delays. A comprehensive clinical research evaluation requires both a specialized multidisciplinary team and a dedicated research environment such as the General Clinical Research Center, (GCRC) or Pediatric Clinical Research Unit, (PCRU).

Currently, there is a very poor understanding of the temporal sequence by which chronic sleep impairment results in cognitive/mental decline in vulnerable individuals. It is hypothesized that disturbance in the neuroregulatory control of frontal-subcortical-limbic function plays a central role in psychiatric and cognitive-executive symptoms; while neuroendocrine and neurobiological responses to chronic sleep-fragmentation and hypoxemia may be additional factors which determine symptom severity and the potential reversibility of cognitive or psychiatric symptoms once established.

It has proven difficult to discern the chain of causal mechanisms resulting in functional decline and cognitive-executive dysfunction in young persons with DS. Biological and physiological relationships remain largely unexplored in part because the clinical symptomatology has been poorly characterized and no unifying research model suitable for hypothesis testing has ever been advanced.

We suspect that the duration and severity of SRBD, rather than its mere presence or absence, along with individual biological vulnerabilities modulates the expression of cognitive-executive dysfunction and psychopathology in persons with DS, although the topic is virtually unexplored. Reversibility of clinical symptoms may vary with the duration of undiagnosed SRBD due to temporal delay in both symptom recognition and commencing with effective treatment for the respiratory, sleep, and psychiatric symptoms. Pre-morbid level of cognitive/executive function and the presence of co-morbid medical factors (i.e. cardiopulmonary function, hypothyroidism, obesity and airway anatomy) are also important considerations.

Based on our preliminary clinical data this study proposes to test our three main hypotheses constructed to examine the association between SRBD, a specific type of psychopathology (depression with functional decline) and presumptive biological factors which mediate the pathophysiological response.