Down syndrome: Systematic review of the prevalence

and nature of presentation of unipolar depression

Dr Catherine Walton CT3, Cwm Taf University Health Board, Wales

Supervised by: Professor Michael Kerr Clinical Professor, Institute of Psychological Medicine

and Clinical Neurosciences, Cardiff University

Case • AB, male in mid-late 30’s with DS (severe ID).

– Lived all his life with his parents. – No previous contact with MH services – Father passed away, G stays with mother, seemingly settled – Some months later:

• change in behaviour at work and at home: destructive, distressed: crying day and night, oversensitive to small changes in daily routine.

• GP review: some issues with physical health • Continued problems, mother elderly and having difficulty in coping • Moved to supported accommodation – further worsening

presentation • Finally…. referral to MH services: at this point requiring inpatient care.

• Timely recognition of a MH problem? – Easier to spot on a timeline (!)

Depression

• Most common MH problem diagnosed in community samples

– Morbidity

• Diagnosis not always straightforward

– General population

– ID population

• Communication of innermost thoughts and feelings

• Diagnostic overshadowing

• The consequence of impaired detection?

NCCMH (2010) Depression: The NICE Guideline on the Treatment and Management of Depression in Adults (Updated edition). Matson et al (1999) Characteristics of Depression as Assessed by the Diagnostic Assessment for the Severely Handicapped-II (Dash-II). Research in Developmental Disabilities. 20(4), 305-313.

DS and depression

• DS most common chromosomal abnormality leading to ID

• Research has highlighted

– suggested vulnerability to depression

– possible link between signs and symptoms of depression and the development Alzheimer’s disease (‘prodrome’)

Walker, J.C., Dosen, A., Buitalaar, J.K., & Janzing, J.G.E. (2011) Depression in Down Syndrome: A review of the literature. Research in Developmental Disabilities. 32, 1432-1440 Dykens, E.M. (2007) Psychiatric and Behavioural Disorders in Persons with Down Syndrome. Mental Retardation and Developmental Disabilities Research Reviews. 13, 272-278

AIM

• Assess for the PREVALENCE and NATURE of presentation of unipolar depression in DS.

– Systematic review

Methods

• PRISMA (2009) checklist followed where possible

Eligibility criteria

• Participants – Individuals with DS

– No limitations for age or gender

• Intervention – Primary research investigating the prevalence and nature

of presentation of symptoms of depression in DS.

– Exclude challenging behaviour

– Exclude studies pertaining to AD.

– Exclude bipolar affective disorder.

– Exclude studies pre-dating 1990

– Exclude studies not in the English language

• Comparison

– The aim is to complete a systematic review analysis of the studies found.

• Outcome

– Data for the prevalence of unipolar depression in DS and the nature of its presentation.

• Study design

– Primary research excluding individual case studies.

Information sources

• Cardiff University’s Electronic Portal of databases – Medline – Embase – PsychInfo – Web of Science – CINAHL.

• English language, peer reviewed journals • Published between 1st January 1990 and 30th

September 2013 • Relevant journals, review articles and bibliographies

hand searched

Search strategy

• Terms kept broad:

• Down Syndrome combined with: • Psychopathology

• Depression

• Mood disorder

• Or Affective disorder

Summary methods Item Criteria Score

Number of participants >100 >30-100 <30

2 1 0

Characteristics of participants Group representing target population of the instrument (screening for depression)

0/1

Psychopathology of the participants >20-50% of participants had depression 10-20% or >50-90% had depression <10% or >90% of the participants had depression Unclear

2 1 1 0

Gold standard Clinical diagnosis by a psychiatrist or psychologist based on standard diagnostic system Clinical diagnosis by a psychiatrist or psychologist Other depression screening instrument used as reference standard All other Not applicable

2 1 1 0 0

Report on measures of validity Standard deviation or standard error, or confidence interval is reported.

0/1

Hermans, H. & Evenhuis, H.M. (2010) Characteristics of instruments screening for depression in adults with intellectual disabilities: Systematic Review. Research in Developmental Disabilities. 31 1109-1120.

Results

634recordsiden fiedthroughdatabase

searches

2recordsiden fiedthroughhandsearching

reviewar cles

636recordsscreened

10fulltextar clesscreenedforeligibility

8studiesincludedinqualita vesynthesis

9excluded

2excluded

19abstractsscreenedforeligibility

Results of search strategy as per PRISMA Guidance (Moher, 2009)

Study Design (n.b. not

scored)

n Characteristics Measure (Gold

standard)

Report on

measures of

variability (if

applicable)

Quality

score /6 Frequency of

depression in

sample

Collacott et al

(1992) Cross-

sectional

study

371 DS Community sample

ICD-9 Chi Square 6 42/371 (11.3%)

Cooper &

Collacott

(1994)

Cross-

sectional

study

378 DS Community sample

DCR-ICD-10

and DSM-III-

R

- 5 42 / 378 (11.1%)

Capone et al

(2011) Cross-

sectional

study

56 DS Patients presenting to a

university-level

medical clinic

DSM-IV-R Confidence

interval 5 11/117 (9.4%)

MDE* 9/117 (7.7%)

MDE* & psychotic

features Myers &

Pueschel

(1991)

Cross-

sectional

study

497 DS 425 university clinic &

72 residential care

DSM-III-R Chi square 6 10/497 (2%)

Myers &

Pueschel

(1995)

Cross-

sectional

study

164 DS Regular attendees to a

university-affiliated

DS clinic

DSM-III-R - 5 9/164 (5.5%)

Mantry et al

(2008) Cohort T1

186 T2

134

DS Community sample

DC-LD, ICD-

10, DCR-

ICD-10,

DSM-IV-TR

Confidence

interval 6 T1 5/166 (2.7%)

T2 7/134 (5.2%)

Prasher

(1995) Cross-

sectional

study

201 DS (age 16 or above) Community sample

DCR-ICD-10 - 5 10/215 (5%)

McCarthy &

Boyd (2001) Cohort T1

193 T2

52

DS register –

community sample ICD-10 Pearson’s

correlation

coefficient,

5 7/52 (13%)

Quality assessment (modified version) based on Hermans, H. & Evenhuis, H.M. (2010) Characteristics of instruments screening for depression in adults with intellectual disabilities: Systematic Review. Research in Developmental Disabilities. 31 1109-1120.

Prevalence and incidence of depression in DS

• Patterns did emerge – Despite difference in populations sampled and study designs

• Depression is the most common psychiatric condition – Exclude dementia – Myers & Pueschel (1991), Mantry et al (2008), Prasher (1995), McCarthy &

Boyd (2001)

• Studies that investigated both mental ill health and depression suggested that: – Depression is more common in DS in comparison to general ID

population – Mental ill health (all causes) less common in DS population in

comparison to general ID population – Collacott et al (1992), Mantry et al (2008)

Prevalence and incidence of depression in DS

• Depression frequency

– 5-13% (university / healthcare samples) » Exclude children

– 2.7- 13% (community sample)

• Age groups

• Level of ID

Study Frequency of

depression Source of subjects Age Level of ID

Collacott et al (1992) 11.3% Health service &

community records 16-78 years Not differentiated

Cooper & Collacott

(1994) 11.1% Health service and

community records 11-50 years Not differentiated

Capone et al (2011) 11/117 (9.4%) MDE* 9/117 (7.7%) MDE*

with psychotic features 8/117 (6.8%) ‘deficit syndrome’

University based clinic

for DS 13-35 years Not differentiated

Myers & Pueschel

(1991) 10/497 (2%) 10 / 164 subjects over

20 years had depression

(6.1%)

University clinic for

DS, and a local state

school

-261subjects <20 years -164 subjects >20 years -72 subjects between

29-72 years

Not differentiated

Myers & Pueschel

(1995) 9/164 (5.5%)

University affiliated

outpatient clinic 21 – 44 years 6 of 9 moderate ID

2 severe ID Mantry et al (2008) T1 5/166 (2.7%)

T2 7/134 (5.2%) Community sample 16-74 years 41.1% mild ID,

26.9% moderate ID,

18.3% severe, 13.4%

profound ID Prasher (1995) 10/215 (5%) Hospital and

community samples 16-76 years 21% mild ID, 66.7%

moderate ID 13.4% severe ID.

McCarthy & Boyd

(2001) 7/52 (13%) adult sample 1/193 (0.5%) child

sample

Community Child 6-17 years Adult 22-33 years

Not differentiated

Frequencies of depression and demographic characteristics for Down syndrome

Presentation of depression

• Symptoms highlighted did not fit neatly into different categories (i.e. biological, objective) – Most common: reduced interest/pleasure (91%),

depressed affect (88%), psychomotor retardation (59%), loss of energy (57%), and appetite/weight disturbance (55%).

– Least common: constipation (13%), obsessions/compulsions (13%) and mood congruent delusions or hallucinations (5%).

» Cooper & Collacott (1994), n=378

Presentation of depression

• Certain more common symptoms: – Observed ‘vegetative’ as opposed to verbal / symptoms of self-

expression – 4 of the 9 subjects reported hallucinations

» Myers & Pueschel (1995) n=9

• Major Depressive Episode symptoms described included: – Anhedonia and depressed mood, plus, biological symptoms such as

disturbed sleep, reduced attention and psychomotor slowing. – ‘deficit syndrome’ possible atypical depression or psychosis

• Within same study a group diagnosed with MDE with psychotic features – Met criteria for both MDE and schizophreniform disorder – 7.7% of the study population – No details of the symptoms of psychosis were available.

» Capone et al (2011) n=56

Methodological concerns & bias

• 6/8 cross-sectional studies: – Concerns regarding methodology (or lack of clarity) mean

that conclusions not drawn with confidence

– Unclear from the methods whether data relates to ‘life-to-date’ prevalence or point/period prevalence

» Myers & Pueschel (1991), Collacott (1992), Cooper & Collacott (1995)

• 7/8 retrospective case note analyses – Observer bias

• Low participant numbers in some studies – Impossible to stratify with any accuracy for age or level of

ID

Conclusions

• Does this study alter the ‘stereotypical’ phenotype? – DS prone to depressive episodes – Perhaps more so than general ID population – (also evidence to contrary – Lund, 1988)

• Course of depression in DS – Suggestion of shorter episodes

» Cooper & Collacott, 1994

– One study showed 2-year incidence higher than point prevalence – would support this

» Mantry et al, 2008

• Increased frequency of depression in adult samples in comparison to children

» McCarthy & Boyd (2001), Myers & Pueschel (1991)

• Difficult to form firm conclusions regarding ‘nature’ of depressive illness from current evidence – Biological symptoms

– Psychosis

– Deficit syndrome and possible links to dementia or simple schizophrenia

• Which diagnostic tools do we use?

Clinical practice

• Review has demonstrated need for high index of suspicion when assessing individual with DS

– Depression relatively high frequency event

– Has varied presentation

– Requires education of carers, allied health professionals and teachers for recognition

• Allow for timely diagnosis and management, therefore reduced distress for all concerned

Future directions

• Large-scale cohort studies may give more indication of the nature and course of depression in DS

• Clearer methodology of cross-sectional studies will give more meaningful results

Limitations of this review

• Limitations related to search criteria: – Excluded challenging behaviour

– Excluded Alzheimer's dementia

– Both important in terms of the characterisation of the nature and symptoms of depression in DS

• Limitations of systematic review: – Unable to perform further statistical analysis due to

the heterogeneous aims and objectives of each of the studies. Also due to the lack of clarity regarding the frequencies quoted in some studies.

Thanks for listening!

• Any questions?

Main references • Walker, J.C., Dosen, A., Buitalaar, J.K., & Janzing, J.G.E. (2011) Depression in Down Syndrome: A review of

the literature. Research in Developmental Disabilities. 32, 1432-1440 • Dykens, E.M. (2007) Psychiatric and Behavioural Disorders in Persons with Down Syndrome. Mental

Retardation and Developmental Disabilities Research Reviews. 13, 272-278 • Matson, J.L., Rush, K.S., Hamilton, M., Anderson, S.J., Bamburg, J.W. & Baglio, C.S. (1999) Characteristics of

Depression as Assessed by the Diagnostic Assessment for the Severely Handicapped-II (Dash-II). Research in Developmental Disabilities. 20(4), 305-313.

• Collacott, R.A., Cooper, S., McGrother, C. (1992) Differential Rates of Psychiatric Disorders in Adults with Down’s Syndrome Compared with Other Mentally Handicapped Adults. British Journal of Psychiatry. 161 671-674.

• Cooper, S.A. & Collacott, R.A. (1994) Clinical Features and Diagnostic Criteria of Depression in Down’s Syndrome. British Journal of Psychiatry. 165(3) 399-403

• Capone, G.T., Aidikoff, J.N., & Goyal, P. (2011) Adolescents and Young Adults with Down Syndrome Presenting to a Medical Clinic with Depression: Phenomenology and Characterization Using the Reiss Scales and Aberrant Behaviour Checklist. Journal of Mental Health Research in Intellectual Disabilities. 4 244-264.

• Myers, B.A. & Pueschel, S.M. (1991) Psychiatric Disorders in Persons with Down Syndrome. The Journal of Nervous and Mental Disease. 179(10) 609-613.

• Myers, B.A. & Pueschel, S.M. (1995) Major Depression in a Small Group of Adults with Down Syndrome. Research in Developmental Disabilities. 16(4) 285-299.

• Prasher, V.P. (1995) Prevalence of Psychiatric Disorders in Adults with Down Syndrome. European Journal of Psychiatry. 9(2) 77-82.

• McCarthy, J. & Boyd, J. (2001) Psychopathology and young people with Down’s syndrome: childhood predictors and adult outcome of disorder. Journal of Intellectual Disability Research. 45(2) 99-105.

• Please get in touch for full list of references