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Table 5 Sleep-wake and circadian biology studies evaluating the five functional domains in young people (12-30 yrs) with a mood and/or anxiety disorder

From: The underlying neurobiology of key functional domains in young people with mood and anxiety disorders: a systematic review

Outcome measure Study Age (mean ± SD) Sample (N) Aims Key measures Key findings
Social and economic participation [103] PD: 30.6 ± 6.1 PD (8M; 12F) Determine whether HPA activity can predict FUP functional status. SWC: 24-hour cortisol samples, ACTH profiles, CRH stimulation test PD: ↑ cortisol secretion pre-treatment ~ ↓ social and economic participation (better than pre-treatment clinical severity)
Functional: SDS
  [102]* MDD (M): 12.8 ± 2.6, MDD (F): 13.6 ± 1.9 MDD (22M; 33F) Investigate whether diurnal changes in cortisol and DHEA levels are associated with the occurrence of undesirable life events. SWC: Cortisol/DHEA ratio, MDD: ↑ cortisol/DHEA ratios at BL ~ ↓ social and economic participation at FUP.
Functional: Semi-structured interview
  [104] MHP: 12.1 (7 – 17.9 years) MHP (62M; 40F) Investigate whether cortisol reactivity is associated with internalizing problem behaviour SWC: Cortisol level MHP: ↑ cortisol secretion during the social interaction task ~ ↓ social and economic participation
Functional: CBCL, SASC, CDI
Suicide and self-harm [105]* MDD: 25.19 ± 2.42 MDD (33M; 23F) Examine baseline neuroendocrine predictors of follow up clinical features SWC: Sleep EEG, GH secretion, blood cortisol MDD: ↑ BL GH secretion during first 4 hours of sleep ~ a suicide attempt during FUP
HC: 25.92 ± 2.16 HC (10M; 11F)
Functional: Clinical interview
  [106] MDD: 25.19 ± 2.42 MDD (33M; 23F) Assess whether any premorbid cortisol abnormalities were associated with depressive course of illness SWC: Sleep EEG, GH secretion, blood cortisol MDD: ↑ BL cortisol secretion in the late evening hours ~ suicide attempts during FUP
HC: 25.92 ± 2.16 HC (10M; 11F)
Functional: Clinical interview
  [107]* MDD: 16 ± 0.3 MDD (6M; 14F) Compare sleep EEG profiles of a sample of outpatient adolescents SWC: Sleep EEG, blood samples MDD: ↓ Delta sleep variable ~ ↑ suicidality (and depression severity).
HC: 15.6 ± 0.6 HC (7M; 6F)
Functional: HDRS
Clinical syndrome [108] CS: 17.04 ± 0.36 CS (57M; 173F) Examine whether individual differences in the CAR serve as a premorbid risk factor for MDD SWC: Salivary cortisol CS: ↑ cortisol after waking at BL ~ ↑ risk of developing MDD at FUP
Clinical: SCID, LSI
  [118] HYP: 20.91 ± 3.72 HYP (8M; 23F) Assess circadian activity and sleep in individuals at behavioral high-risk of hypomania/bipolar disorders SWC: Actigraphy HYP: ↑ variability in duration, fragmentation and efficiency of sleep, ↓ sleep duration and later more variable be times.
HC: 22.12 ± 2.83 HC (8M; 16F) Clinical: SCID, HPS, HIQ, ISS
  [120] MDD: 12 ± 1.9 MDD (2M; 4F) Explore the effects of fluoxetine on sleep EEG SWC: Sleep EEG MDD: ↑ stage 1 sleep, arousals and REM density ~ fluoxetine treatment
Clinical: K-SADS, CDRS, BDI, WSAS
  [105]* MDD: 25.19 ± 2.42 MDD (33M; 23F) Examine baseline neuroendocrine predictors of follow up clinical features SWC: Sleep EEG, GH secretion, blood cortisol MDD: Premorbidly, earlier and more steep GH secretion at sleep onset
HC: 25.92 ± 2.16 HC (10M; 11F)
Clinical: Clinical interview
  [114] MDD: 17.04 ± 0.35 MDD (4M; 7F) Examine the associations between MDD and anxiety disorders, and HPA- axis functioning SWC: Salivary cortisol P-MDD & MDD/ANX: flatter diurnal cortisol slopes
ANX: 17.04 ± 0.37 ANX (8M; 21F) Clinical: MASQ, LSI
MDD/ANX: 16.85 ± 0.21 MDD-ANX (4M; 8F)
P-MDD: 17.13 ± 0.37 P-MDD (11M; 45F)
P-ANX: 17.02 ± 0.38 P-ANX (6M; 2F)
  [109] HR: 16.8 ± 1.7 HR (14M; 15F) Examine the cortisol increase after awakening and basal cortisol levels hypothesis that high-risk offspring are more reactive to psychosocial stress than low-risk offspring SWC: Salivary cortisol HR: ↑ daytime cortisol in their natural environment.
LR: 16.6 ± 2.1 LR (14M; 15F) Clinical: CDI, CBCL, PANAS
  [110] HR: 18.3 ± 2.6 HR (12M; 12F) Determine whether HR individuals exhibit elevated cortisol levels relative to LR individuals during two weeks of daily sampling SWC: Salivary cortisol HR: ↑ afternoon cortisol levels in their natural environment
LR: 18.0 ± 2.3 LR (11M; 11F) Clinical: BDI, CDI, PSWQ, CBCL, RLEQ
  [102]* MDD (M): 12.8 ± 2.6 MDD (22M; 33F) Investigate whether diurnal changes in cortisol and DHEA levels are associated with the occurrence of undesirable life events. SWC: Cortisol/DHEA ratio, MDD: ↑ cortisol/DHEA ratios at BL ~ persistent major depression at FUP
MDD (F): 13.6 ± 1.9 Clinical: Semi-structured interview
  [113] Mild: 14.73 ± 2.30 Moderate: 15.69 ± 1.58 Mild (10M; 20F) Moderate (7M; 9F) Examine cortisol reactivity to a psychological stress challenge in depressed adolescents. SWC: Salivary cortisol Moderate/severe depression: ↓ cortisol response regardless of child maltreatment history
Clinical: CECA, BDI-II, K-SADS
Severe: 16.00 ± 2.00 Severe (6M; 19F)
  [119] MDD: 23.94 ± 2.31 MDD (8M; 9F) Investigate the effect of reducing slow waves during sleep on depression symptomology SWC: Sleep EEG MDD: ↑ overnight dissipation of SWA predicted ↓ in depressive symptoms.
Clinical: QIDS, HDRS
  [107]* MDD: 16 ± 0.3 MDD (6M; 14F) Compare sleep EEG profiles of a sample of outpatient adolescents SWC: Sleep EEG, blood samples MDD: ↓ Delta sleep variable ~ ↑ depression severity.
HC: 15.6 ± 0.6 HC (7M; 6F)
Clinical: HDRS
  [117] DD: 15.35 ± 1.85 DD (18M; 28F) Assess sleep disturbances pain and pubertal development in adolescent depressive disorders SWC: Actigraphy DD: ↓ sleep efficiency and total time asleep, ↑ time awake after sleep onset. ↑ pain intensity and depressive symptoms predicted worse sleep quality
HC: 14.83 ± 1.76 HC (17M; 43F) Clinical: K-SADS, PDS, CES-D, BPD
  [111] MDD: 22.4 ± 1.5 MDD (9M; 17F) Examine the relationship between longitudinal clinical course, sleep and cortisol in adolescent depression SWC: Sleep EEG MDD: recurrent illness ~ ↑ plasma cortisol near sleep onset at BL.
HC: 21.9 ± 1.7 HC (13M; 20F) Clinical: K-SADS
HC: high density REM and ↓ REM latency at BL ~ the development of depression a FUP
  [112] MDD: 15.6 ± 1.4 MDD (6M; 10F) Examine EEG sleep and HPA changes during MDD episodes and recovery SWC: NUFC, sleep EEG MDD: ↓ NUFC excretion during remission
HC: 15.8 ± 1.9 HC (7M; 9F) Clinical: PRS, HDRS, K-SADS
  [115] UPD: 21.8 ± 4.3 UPD (5M; 13F) Evaluate the potential of circadian measures as early markers of mood disorders subtypes SWC: Actigraphy, DLMO BPD:↓ and later onset of melatonin secretion
BPD: 22.8 ± 4.8 BPD (3M; 11F) Clinical: Psychiatric interview (DSM-IV criteria), BDI
  [116] HC: 24.8 ± 2.5 HC (8M; 12F) Investigate objectively the 24-h sleep–wake cycle in adolescents and young adults with mood disorders SWC: Actigraphy BPD: 62 % had delayed sleep (during a depressive phase), and later sleep offset compared to UPD and HC
UPD: 20.1 ± 4.7 UPD and BPD (28M; 47F) Clinical: Psychiatric interview (DSM-IV criteria)
BPD: 23.2 ± 4.3
UPD: 30 % had delayed sleep
HC: 10 % had delayed sleep
  [121] Stage 1a: 17.6 ± 4.0 Stage 1a (7M; 11F) Determine if disturbed sleep–wake cycle patterns in young people with emerging mental disorder are associated with stages of illness SWC: Actigraphy Stage 1b & 2: ↑ delayed sleep schedule, especially on weeknights
Stage 1b: 19.1 ± 4.1 Stage 1b (44M; 38F) Clinical: Psychiatric interview (DSM-IV criteria)
Stage 2+: 22.4 ± 4.3 Stage 2+ (27M; 27F) Stage 1a & 2+: ↓ sleep efficiency
HC: 24.4 ± 3.1 HC (11M; 12F)
  1. Note. Sample: ANX anxiety disorder, BPD bipolar disorder, CS community sample, DD depressive disorder, HC healthy controls, HR high risk participants (offspring of parents with bipolar disorder), HYP hypomanic participants, LR low risk participants (offspring of parents without a mental disorder), MDD-ANX comorbid Major depressive disorder and anxiety disorder, MDD major depression disorder, MHP mental health patients (mixed diagnosis sample), P-MDD past major depressive disorder, P-ANX past anxiety disorder, PD panic disorder
  2. Measures: ACTH adrenocorticotropic hormone, BDI beck depression inventory, BPD body pain diagram, CBCL child behaviour checklist, CDI children’s depression inventory, CDRS children’s depression rating scale, CECA childhood experience of case and abuse contextual semi-structured interview and rating system, CES-D Center for Epidemiologic Studies Depression, CRH corticotropin-releasing hormone, DHEA dehydroepiandrosterone, DLMO dim light melatonin onset, DSM-IV diagnostic and statistical manual of mental disorders IV, EEG electroencephalography, GH growth hormone, HDRS Hamilton depression rating scale, HPS hypomanic personality scale, HIQ hypomanic interpretations questionnaire, ISS internal state scale, K-SADS schedule for affective disorders and schizophrenia for school age children, LSI life stress interview, MASQ mood and anxiety symptom questionnaire, NUFC nocturnal urinary free cortisol, PANAS positive and negative affect scale, PDS pubertal developmental scale, PRS Pfeffer rating scale, PSWQ Penn state worry questionnaire, QIDS quick inventory of depressive symptomatology, RLEQ recent life events questionnaire, SASC social anxiety scale for children, SCID structured clinical interview for DSM, SDS Sheehan disability scale, SWC sleep-wake and circadian biology, WSAS work and social adjustment scale
  3. Findings: ↑ = Increased, Improved or Higher, ↓ = Decreased, Reduced or Lower, ~ = ‘is associated with’, BL baseline, FUP follow-up, NUFC nocturnal urinary free cortisol, REM rapid eye movement, SWA slow wave activity
  4. *indicates that the study features more than once in the data synthesis