Table 3.

Mental and Emotional Health Findings by Construct and Instrument

Construct (# Studies)	Instrument (# Studies, type of control groups) Score range/Cutoff	Mean±SD, % Above Cutoff	Caregiver Mental Health Comparisons or Associations (comparisons with control groups listed first where reported)
Psychological Adjustment
Distress (18 studies)	SCL-90-R Global Severity Index (7 studies, 30,48,49,52,58,61,66 1 with a control group30) Cutoff: T score>63 (90th percentile=high distress)	• 51.0±11.766 to 56.6±14.152 • Above cutoff: 30%49 to 47%30	• Distress of caregivers of youth with SCD did not differ from that of caregivers of children without a chronic condition. 30 • Association between caregiver distress and child SCD coping strategies mixed: significantly correlated; 48,58 not correlated. 61 • Association between caregiver distress and perception of child symptom severity mixed: significantly correlated; 66 not correlated. 52
	BSI-GSI (2 studies, 38,50 1 with normative sample comparisons38) Cutoff: T score >63 (90th percentile)	• 52.8±11.050 • Above cutoff: 19.7%50	• SCD caregiver distress did not differ from the BSI normative sample. 38 • Distress negatively associated with caregiver child concordance regarding child’s health-related quality of life. 50
	GHQ-12 (2 studies, 36,391 study with control group36) Cutoff: ≥2, 36 ≥339	• Mean NR • Above cutoff: 43.8%39 to 62.2%36	• Caregivers of children with SCD hospitalized more frequently reported emotional distress. 39  Compared to caregivers of children without a chronic condition, more mothers of children with SCD reported distress (62.2% versus 35.6%) but distress similar compared to mothers of children with T1DM (53.3%).36
	Distress Thermometer (1 study) 60 Range: 0–10; higher score=greater distress	• 3.6±3.1 • Cutoff NR	• Not tested
	SF-36 (1 study with a control group) 29 Range: 0–100; lower scores = worse health	• 74.9±36.6 • Cutoff NR	• Caregivers of children with SCD had greater distress compared to caregivers of children without a chronic condition (74.9±36.6 versus 100.0±0).
	Stressful Life Events Questionnaire (1 study) 65 Range: 0–9; higher score=greater distress	• 2.9±2.0 • Cutoff NR	• Not tested
	SRQ (1 study with 2 control groups) 32 Cutoff: ≥5=psychiatric morbidity	• Mean NR • 28%	• Psychiatric morbidity of SCD caregivers (28%) did not differ from caregivers of children with either asthma (20%) or acute medical illness (25%).  No association between SCD caregiver psychiatric morbidity and child clinic visits in past 6 months or previous hospitalizations.
	Investigator developed scale (2 studies) 40,46 Range: 0–340, higher scores=greater distress	• 2.3±0.5040 to 2.4 (Median) 46 • Cutoff NR	• Greater distress reported by caregivers of children with >3 painful crises. 46
	Depression, Anxiety, Stress Scale-21 (1 study with a control group) 35 Range: 0–21; higher scores-greater distress	• Moderate and higher: 32.4%	• Proportion with at least moderate levels of distress not significantly different that caregivers of children with diabetes.
Anxiety/Depressive Symptoms
Anxiety (7 studies)	BAI (1 study) 41 Range: 0–63 Cutoff: 0–7=minimal; 8–15=mild; 16–25=moderate; 26–63=severe anxiety	• Mean NR • Above cutoff: 13% moderate and 8% severe anxiety	• Not tested
	GAD-7 (2 studies) 12,55 Range: 0–21 Cutoffs: 8–15=mild; 16–25= moderate; 26–63= severe anxiety	• Mean Range: 4.7±0.312 to 4.7±4.955 • Cutoff NR in either study	• Caregiver anxiety symptoms related to increased child pain intensity and functional disability; child chronic pain did not moderate this relationship. 12  Not tested55
	SCL-90-R Anxiety subscale (1 study) 49 Cutoff: T score>63 (90th percentile)	• Mean NR • Cutoff NR	• Caregiver55 anxiety not associated with child’s disease severity.
	STAI (1 study) 64 Range 20–80 Cutoff: >39–40=clinically significant anxiety	• 30.6±9.6 • Cutoff NR	• Caregiver anxiety not associated with child’s pain.
	Investigator developed scale (1 study) 57 Range: 3–12; higher scores=greater anxiety	• 4.9 • Cutoff NR	• Caregiver anxiety greater for those of children with severe disease severity compared to children with mild and moderate disease severity.
	Depression, Anxiety, Stress Scale-21 (1 study) 35 Range: 0–21; higher scores=greater anxiety	• Moderate and higher: 26.5%	• Proportion with at least moderate anxiety symptoms not significantly different that caregivers of children with diabetes.
Depressive symptoms (12 studies)	BDI (2 studies) 41,43 Range 0–63 Cutoff: 21–30=moderate; 31–40= severe; >40=extreme depression	• 7.9±4.4 to 17.0±1.443 • Above cutoff: 13% moderate; 8% severe41	• No differences in caregiver depression by number of painful crises. 43
	CES-D (1 study) 44 Range 0–60 Cutoff: ≥16=depression	• 16.6±12.0 • Cutoff NR	• Not tested
	CESD-R-10 (2 studies) 12,55 Range: 0–30 Cutoff: ≥10=depression	• Mean range: 8.4±0.312 to 8.4±6.3. 55 • Cutoff NR	• Caregiver depressive symptoms associated with increased child pain intensity and functional disability; child chronic pain did not moderate relationship. 12 • Not tested. 55
	SCL-90-R Depression subscale (2 studies, 30,49 1 with a control group30) Cutoff: T score>63 (90th percentile)	• 53.5±14.049 • Above cutoff: 22%30	• Caregiver depression not associated with child’s disease severity. 49 • No differences in depression between caregivers of children with SCD and a comparison group of community caregivers of children matched on sex and race as the child with SCD. 30
	IPAT Depression Inventory (1 study with 2 control groups) 37	• 6.0±1.9 • Cutoff NR	• No differences in depression between caregivers of children with SCD, caregivers of children with T1DM and without a chronic condition.
	PHQ-2 (1 study) 45 Cutoff: Score ≥3	• 3.7±2.0 • Cutoff NR	• Caregiver depressive symptoms not associated with number of child pain crises in past 12 months.
	PROMIS Depression Scale (2 studies) 54 Cutoff: T score 55–60=mild; 60–70= moderate; >70=severe depression	• Above cutoff: 15.8%	• Not tested
	TAAQoL – Depressive Mood subscale (1 study with a normative sample comparisons31) Range: 0–100; lower score=greater depression	• Median (IQR) 58 (33, 66)	• Compared to caregivers of children without a chronic condition (67 [50, 88]) and to Dutch normative sample (83 [75, 92]), SCD caregivers had more severe depressive symptoms (p=0.02).
	Depression, Anxiety, Stress Scale-21 (1 study) 35 Range: 0–21; higher scores-greater depression	• Moderate and higher: 34.7%	• Proportion with at least moderate depressive symptoms not significantly different that caregivers of children with diabetes.
	Investigator developed scale (1 study) 57 Range: 4–16; higher scores=greater depression	• 9.5 • Cutoff NR	• Caregiver depression not associated with child illness severity.
Combined (1 study)	Family Symptom Inventory (1 study with 2 control groups) 33 Caregiver internalizing symptoms subscale (i.e., anxiety and depressive symptoms combined) Range 0 (never/rare)-3 (most days)	• 0.6±0.5 • Cutoff NR	• Caregivers of children with SCD reported fewer internalizing symptoms (0.6±0.5) compared to caregivers of children with cancer (0.9±0.8) and other hematological conditions (1.1±0.7, p<0.05). • Caregiver internalizing symptoms did not moderate association between child sleep and pain.
Parenting Stress
Parenting Stress (15 studies)	PIP (11 studies) 12,41,44,47,51,53,55,59,62,63,65 Range: 40–210 for Total Frequency and Total Difficulty	• Mean Range: • Frequency = 67.4±12.0344 to 114.9±32.541 • Difficulty = 71.4±18.7 44to 100.5±32.247 • Cutoff NR	• Caregiver perception of child’s pain burden mediated relationship between PIP score and ED visits. 62 • Higher scores associated with higher routine and urgent service use. 65 • Total score associated with caregiver perception of child’s SCD pain and ED visits. 62 • Total frequency negatively associated with child health-related quality of life. 59 • Total frequency associated with higher health care utilization. 51 • Total frequency and difficulty not associated with reported adherence; stratified by child age group, total difficulty associated with adherence for older youth only. 63 • Total frequency and difficulty higher among caregivers of youth who reported chronic pain versus episodic pain; neither score associated with hospital admissions in the prior year. 55
	Parent Stress Index (2 studies, 37,38 1 with 2 control groups, 37 1 with normative sample comparisons38)	• Mean NR • Cutoff NR	• Caregivers of children with SCD in 2 parent families had less stress around social isolation and relationships with spouse compared to caregivers of children with T1DM and non-disease controls. 37 • In single parent families, there were no differences in stress of caregivers of SCD compared to caregivers of children with type 1 diabetes and caregivers of children without a chronic condition. 37 • Compared to a normative sample, caregivers of children with SCD reported higher levels of situational/demographic life stress and stress due to child distractibility/hyperactivity. 38 • Caregivers of children with more severe genotypes reported higher levels on PSI subdomain of depression and isolation compared to those of children with milder genotypes. 38
	Parental Stress Scale (1 study) 67 Range 18–90; higher scores=greater stress	• 39.6±9.9 • Cutoff NR	• Increased parenting stress associated with worse child health-related quality of life.
	Investigator developed scale (1 study) 57 Range: 1 (never)-4 (almost all the time)	• 2.08 • Cutoff NR	• Caregivers of children with severe illness severity had more stress because of the SCD than those of children with mild and moderate illness severity.
Other
PTSD (3 studies)	SCID IV PTSD module (1 study) 42	• Mean NR • Prevalence: 40%	• Not tested
	Impact of Events Scale-R (1 study with 2 control groups) 34 Cutoff: ≥30 suggestive of PTSD	• 14.5±18.3 • Above cutoff: 0%	• Compared to caregivers of pediatric transplant candidates, caregivers of children with SCD had less traumatic stress symptoms; similar traumatic stress to caregivers of children with HIV.
	PCL-C-6 (1 study) 60 Range: 6–30 Cutoff: ≥14=positive PTSD screen	• 10.0±5.2 • Cutoff NR	• Not tested
Reaction to illness (4 studies)	PECI – Guilt and worry; Unresolved sorrow and anger subscales (2 studies) 45,62 Range: 0–4; higher scores=worse mental health	• Guilt and worry:1.6±0.862 to 2.2±0.745 • Unresolved sorrow/anger: 1.0±0.662 to 2.0±0.945	• Caregiver reaction to child’s pain not associated with frequency of pain crises during past year. 45 • Caregiver reaction to illness associated with perception of child’s SCD pain burden but not associated with ED visits. 62
	Investigator developed scale - Anger (1 study) 57 Range: 0–3; higher scores=greater anger	• 1.4 • Cutoff NR	• Caregivers of SCD children with severe illness had more anger than caregivers of children with mild and moderate illness severity.
	Pain Catastrophizing Scale (1 study) 56 13 items, 5-point scale Range 0–52; higher scores=higher levels of catastrophizing Cutoff: >30=clinically relevant level of catastrophizing	• 26.8±11.1 • Cutoff NR	• Caregiver catastrophizing associated with child pain intensity and frequency and functional disability.

Abbreviations: SD=standard deviation; SCL-90-R=Symptom Checklist-90-Revised; SCD=sickle cell disease; BSI-GSI= Brief Symptom Inventory, Global Severity Index; GHQ-12=General Health Questionnaire; NR=not reported; SF-36=Medical Outcomes Study 36 - Item Short-Form Health Survey; SRQ Self-Reporting Questionnaire; BAI=Beck Anxiety Inventory; GAD-7=Generalized Anxiety Disorder Scale; STAI=State Trait Anxiety Inventory; BDI=Beck Depression Inventory; CES-D= Center for Epidemiologic Studies Depression Scale; CESD-R-10= Center for Epidemiologic Studies Depression Scale Revised; PHQ-2=Patient Health Questionnaire; PROMIS= Patient-Reported Outcomes Measurement Information System; TAAQoL=TNO-AZL Adult Quality of Life Questionnaire; PIP=Pediatric Inventory for Parents; SCID IV= SCID IV= Structured Clinical Interview for DSM-IV; PCL-C-6= Post-Traumatic Checklist – 6 Item Civilian Version; PECI=Parent Experience of Child Illness