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Neuropsychiatric Disorder in Young Adults with Down Syndrome
We propose to consecutively enroll new patients presenting to our clinic for initial clinical evaluation of neuropsychiatric and behavioral problems. Our goal is to 1) quantify psychiatric and behavioral symptomatology using standardized measures, 2) obtain a detailed family mental health history and pedigree, and 3) obtain follow-up data regarding the subject’s clinical course and response to treatment.
Down syndrome (DS) is associated with an increased incidence of congenital anomalies, neurodevelopmental impairment and accelerated ageing. Approximately 15% of children (< 21yr) with Down syndrome also have a behavioral or psychiatric condition (e.g. autistic spectrum disorders, stereotypy movement disorder, disruptive disorder, ADHD etc.) [Myers, 1991]. In some children there appears to be a high degree of behavioral comorbidity and confusion regarding the primary diagnosis. Other than clinical descriptions of reported prevalence rates, there is little information available regarding criteria used for diagnostic classification, associated risk-factors, outcomes or use of available treatments to ameliorate symptoms.
The prevalence of certain disorders also increases with age among persons with DS. Overall, about 25% of DS adults (> 21yr) have a psychiatric diagnosis [Myers, 1991]. The rates of depression, obsessive-compulsive disorder and dementia are significantly increased in this population compared to cognitively impaired control subjects [Collacott, 1992;Prasher, 1995]. Several features appear to be characteristic of depressive disorder in DS including , 1) often of sudden onset, 2) co-morbid cognitive and social-adaptive regression, 3) increased prevalence of associated obsessive-compulsive, anxious or psychotic features, 4) ocassionally a movement disorder is seen (characterized by bradykinesia, rigidity and difficulty initiating movements) and, 5) poor response to anti-depressant or other psychotrophic medications [Cooper, 1993; Collacott, 1992; Geldmacher, 1997]. Clinically, it is sometimes difficult to determine the most debilitating aspect of the presenting illness (depression, compulsions, cognitive regression, anxiety or movement disorder). Perhaps some cases of complex or treatment-resistant depression are related to vulnerability of subcortical projections (e.g. serotonergic, cholinergic or dopaminergic systems), related to 1) the increased risk for earlier-onset AD, 2) genetic/psychiatric risk-factors within the family, or 3) other neurobiologic or medical risk- factors specific to DS individuals.
During the past 6 years, our group has been impressed by the unexpectedly high prevalence of new-onset psychiatric disorder in adolescents between the ages of 13-21 yr. Nearly 50% of subjects presenting to our clinic for initial evaluation of depression or other mood disorder, obsessive-compulsive disorder, anxiety, psychosis or movement disorder are adolescents or young adults between 13-21 yr. We believe that the biological impact(s) of puberty places some adolescents at increased risk for these psychiatric conditions; thus we wish to be able to recruit and study this age group in greater numbers. Additionally, the role of primary sleep disturbances and obstructive sleep apnea syndrome are increasingly being recognized as significant risk-factors for cognitive and behavioral deterioration in persons with DS at all ages.
The importance of this research is that it will allow us to better characterize and subtype these disorders, which will become the basis for future studies of outcome and the effects of treatment.
A case-control design will be used whereby each DS subject who meets criteria for inclusion into our study will be paired with an age- and gender-matched case-control also with DS but without symptoms of psychiatric or serious behavioral dysfunction.
Subjects will be required to make at least one visit to KKI for the initial clinical evaluation. The research component of the evaluation consists of reviewing the questionnaires, getting written authorization to obtain medical records and assuring that consent/assent for this study is obtained. We will use the medical information obtained at that visit and any supporting medical records obtained by written consent, to support our diagnostic formulation. Upon obtaining informed consent, parents or caretakers will be given a battery of behavioral questionnaires pertaining to their child to complete and return to us by mail. A family medical and psychiatric history and pedigree will be obtained. At 6 and 12 months after the initial evaluation, parents/caretakers will be recontacted by telephone and sent several standardized questionnaires to complete.