Characterizing Depression and Coexisting Sleep Disorders in Adolescents & Adults with Down Syndrome

George T Capone, MD Director, Down Syndrome Center Kennedy Krieger Institute Baltimore, Maryland www.kennedykrieger.org

Down Syndrome & Mental Health

AAP Health Supervision Guidelines for Children (2011) Healthcare Guidelines for Adults? Depression, anxiety, other MH concerns

Mental Health Concerns in Adolescents & Adults

A 9me for concerned paren9ng Life Events: psychosocial stressors, rela9onships, transi9ons Social: self-awareness, keeping up at work-school, the big pond Lifestyle: social rela9onships, exercise, ac9vity level Puberty: hormones & re-organiza9on of brain connec9ons Medical condi9ons: appe9te-weight, sleep, general health Trisomy 21: con9nuing impact on brain func9on throughout life?

Challenges Managing Mental Health Disorders

Discomfort with Mental Health Issues in DS/ID Limited resources for Mental Health and ID Diagnos9c overshadowing (DS or AD) Diagnos9c uncertainty - complex symptom presenta9on Therapeu9c uncertainty -

Depression & Down Syndrome

Mood, anxiety, compulsive disorders increase post-puberty (10-15%) Grief, bereavement or adjustment reac9on? Is NOT Major Depression Depression may seem to appear unexpectedly Is age associated with risk of Major Depression? Most common between 15-25yr Male = Female Does NOT appear to show a linear increase with age Demen9a prodrome vs other risk-factors?

Major Depressive Episode & Down Syndrome

Warren et al. (1989) reported on young adults Dis9nguished major depression from AD-type demen9a Symptom-complex including: Apathy, social withdrawal Func9onal decline in cogni9ve-adap9ve skills Psychomotor slowing Conrmatory reports:
Cooper & Collaco` (1990s), Myers & Pueschel (1995), Prasher (1996) Khan et al (2002), Walker et al (2011) for reviews

Deteriora9on from an established baseline

 Case-Control Study: DS + Major Depression Recruited through DS Clinic at KKI

Diagnos(c Groups DS Subjects N=19 N=9 21.0 + 5 12.8 + 9.1 N=9 19.8 + 7.1 Func(onal decline 13 (68%) 6 (66%) Major Depressive Episode (MDE) MDE + Psychosis Age at evalua(on (years) Symptom dura(on (months) Mentally Healthy DS (Controls) Age at evalua(on (years)

Thyroid Func9on
MDE Thyroid Status Thyroid supplement Euthyroid (TSH 0.5-5.5 uIU/ml) Compensated (TSH > 5.5uIU/ml; normal T4) Hypothyroid (low T4) N=28 11/28 (39%) 27 (96%) 1 0 Controls N=9 4/9 (44%) 9 (100%) 0 0

Psychiatric Symptom Screener: Reiss Scales of Childrens Dual Diagnosis

MDE Controls N=9 1.7 2.8 0.2 0.4 0.8 1.0 0.1 0.3 0.4 1.0 0.7 1.4 1.0 1.3 0.3 0.7 1.2 2.1 0.9 1.4 1.0 1.9 8.4 8.5 Subscale score N=28 2.2 1.7 2.4 2.0 2.2 1.6 2.5 1.8 0.6 0.8 4.6 2.0 1.4 1.9 4.3 2.2 1.2 1.5 5.8 2.4 2.9 1.9 30.4 10.9 t-test NS < .0001 < .01 < .0001 NS < .0001 NS < .0001 NS < .0001 .01 < .0001

Anger Anxiety AQen(on Au(sm Conduct Depression Poor Self-Esteem Psychosis Somatoform Withdrawn Other Behavior Reiss Total

Reiss Scales of Childrens Dual Diagnosis

"Spider-Graph" Composite MDE vs Controls
Anger
6 5 4

MDE
Anxiety

Controls

Other Behavior

Withdrawn

3 2 1 0

A`en9on

Somatoform

Au9sm

Psychosis

Conduct

Self-Esteem

Depression

Is There an Associa9on between Depression and Sleep Apnea?

Neuroanatomy of Sleep Apnea in Adults

Brain MRI Red = significantly increased gray matter loss
Macey, et al 2002 Lal, et al 2012

Sleep Apnea: Severity & Tonsillectomy Status

Mental Health Diagnosis % with Sleep Apnea Mod- Severe Apnea N=16 Mild Apnea N=12 No Apnea N=9 Previous tonsil removal N=15

Major depressive episode (MDE) N=28 No mental health diagnosis N=9

86% 44%

15 (54%) 1 (11%)

9 (32%) 3 (33%)

4 (14%) 5 (55%)

12 (43%) 3 (33%)

Respiratory Events & Oxygena9on Data

Respiratory Events Apnea/Hypopnea Index (n/hr) REM-Apnea/Hypopnea Index (n/hr) Respiratory Disturbance Index (n/hr) Central Apneas (n/TST) Oxygena(on Mean Sa02 during sleep (%) Sa02 nadir during sleep (%) Sa02 < 90% (TST%) [- outlier]

MDE
N=28 18.8 14.7 35.8 35.9 24.3 24.6 4.9 16.0 95.1 1.4 83.7 8.4 3.7 5.2

Controls
N=9 4.5 3.8 11.9 10.2 7.3 7.3 2.3 4.0 96.3 2.7 92.0 6.7 3.9 11.6 [0.0]

t-test .001 .01 < .01 NS NS < .01 NS [001]

Sleep Arousal Data

Arousals Total Arousal Index Respiratory Arousal Index Limb Movement Arousal Index Spontaneous Arousal Index Awakening Index MDE N= 28 22.4 20.1 14.9 17.9 1.9 3.9 11.5 10.8 3.8 5.3 Controls N=9 16.4 15.7 2.7 3.1 0.4 0.8 15.5 13.4 3.0 2.6 t-test NS < .01 .05 NS NS

Sleep Stage Data

Sleep Architecture Sleep Eciency (%) N1 (TST%) N2 (TST%) N3 (TST%) REM (TST%) REM latency (min) MDE N= 28 70.5 20.3 6.0 7.2 58.5 20.3 25.0 16.7 8.3 7.5 187.5 106.2 Controls N=9 77.3 16.2 6.5 5.9 58.9 12.5 21.2 5.0 12.1 6.4 227.1 65.0 t-test NS NS NS NS .15 t NS

Limita9ons of this Study

Syndrome of Co-exis9ng Depression + OSA (not characterized) Delay in presenta9on-diagnosis (symptom severity- reversibility) Dura9on of sleep-respiratory symptoms (chronic stress) Medica9on eects on sleep pa`ern Other psychosocial stressors (triggers?) Demen9a prodrome (amyloid, monoamines)? Case-control design does not address causality Carefully matched controls

Further Research on Sleep Apnea & Depression

Causality or Co-Morbidity ? Research sleep studies: mul9ple nights, medica9on nave subjects Characterize and measure: Psychiatric symptoms and cogni9ve func9on Social-adap9ve skills, func9onal decline Life events, impact on caretakers Biomarkers: for depression & OSA Biological psychological vulnerability (individual risk factors) Clinical interven9on studies: Standard of care treatments: medica9ons, weight loss, CPAP or ENT airway management

Thank You