Background
Methods
Eligibility criteria
Report characteristics and information sources
Topic area | Pub Med Terms | |
---|---|---|
Population of interest
| Mood and anxiety syndrome or profile | Anxiety disorder OR anxiety OR depression OR depressive disorders OR depressive disorder [MeSH Terms] OR major depressive disorder OR MDD OR disorder, bipolar [MeSH Terms] OR bipolar disorder OR affective disorder OR mood disorder OR affective syndrome OR manic syndrome OR depressive syndrome OR anxious syndrome |
Youth | Adolescents OR young people OR adolescence OR adolescent [MeSH Terms] OR youth OR young adult | |
Functional domain
| Social and economic participation | Socio-occupational functioning OR functioning OR social functioning OR occupational participation OR economic participation |
Physical health | Physical health OR metabolic rate OR obesity OR blood pressure OR CVD OR fitness OR cardiovascular disease OR BMI or body mass index OR waist measurement OR blood glucose OR smoking rate OR physical activity OR cholesterol levels | |
Suicide and self-harm behaviours | Suicide [MeSH Terms] OR suicide ideation OR self-harm OR suicide risk | |
Alcohol and substance use | Substance use disorder [MeSH Terms] OR alcohol use OR drug use | |
Clinical syndrome | Illness progression OR syndrome progression OR symptom severity | |
Neurobiological parameter
| Neuropsychology | Neuropsychology OR neuropsychological test [MeSH Terms] |
Imaging | Brain imaging [MeSH Terms] OR imaging OR neuroimaging OR fMRI OR DTI OR MRI OR MRS | |
Sleep-wake and circadian biology | Actigraphy [MeSH Terms] OR melatonin secretion OR circadian rhythms OR DLMO OR sleep-wake and circadian biology | |
Neurophysiology | Neurophysiology OR EEG OR electroencephalography OR ERP OR event-related potentials | |
Metabolic | BMI OR waist measurement OR blood pressure OR cholesterol |
Study characteristics and selection
Identification of studies
Neurobiological parameter
| |||||
---|---|---|---|---|---|
Functional domain
| Neuropsychology | Imaging | Sleep-wake and circadian biology | Neurophysiology | Metabolic |
Social & economic participation | Beiderman (2011) | Perlman (2012) |
Abelson (1996)
|
Kaur (2013)
|
Taylor (2008)*
|
Fujii (2013)* |
Goodyer (1998)*
| ||||
Korhonen (2002) | Granger (1994) | ||||
Lee (2013c)
| |||||
Lee (2013a)
| |||||
Physical health | Bond (2011) | Jarworska (2011)* | Mannie (2013) | ||
Suicide & self-harm behaviours | Bridge (2012) | Ehrlich (2004) |
Coplan (2000)*
|
Ashton (1994)
| Apter (1999) |
Miranda (2012)
| Ehrlich (2005) |
Mathew (2003)
| Graae (1996) | De Berardis (2013) | |
Ohmann (2008) | Goodman (2011)* |
McCracken (1997)*
| Pechtel (2013) | Plana (2010) | |
Oldershaw (2009) | Pan (2011) | Soreni (1999) | |||
Pan (2013b)* | Pan (2013a) | Tyano (2006) | |||
Pan (2013b)* | |||||
Alcohol & substance use | Harvey (2007) |
Chitty (2013)
|
Chitty (2014)
| Goldstein (2008) | |
Hermens (2013a)
|
Cornelius (2010)
| Ehlers (2011) | |||
De Bellis (2005) | |||||
Jarvis (2008)
| |||||
Medina (2007) | |||||
Clinical syndrome | Andres (2007) | Adler (2007) | Adam (2010) |
Bakker (2011)
| Pine (2001) |
Andres (2008) | Aghajani (2013) | Ankers (2009) | Carrasco (2013a) | Taylor (2008)* | |
Basso (2001) | Bitter (2011) | Armitage (1997) | Carrasco (2013b) | ||
Cataldo (2005) | Chang (2008) |
Coplan (2000)*
|
Croarkin (2014)
| ||
Fleck (2008) | Chu (2013) | Doane (2013) | Dai (2012) | ||
Fujii (2013)* | Diler (2013) | Ellenbogen (2006) | El Badri (2001) | ||
Gunther (2004) | Forbes (2006) | Ellenbogen (2010) | Hajcak (2008) | ||
Han (2012) | Forbes (2010) |
Goodyer (1998)*
| Houston (2003) | ||
Kıvırcık (2003)* | Gabbay (2012) |
Harkness (2011)
| Jarworska (2011)* | ||
Klimkeit (2011) | Gabbay (2013) | Landsness (2011) | Jarworska (2013) | ||
Okasha (2000)* | Gao (2013) |
McCracken (1997)*
| Kıvırcık (2003)* | ||
Pavuluri (2010a) |
Gilbert (2000)
| Murray (2012) | Okasha (2000)* | ||
Schmid (2013)
| Gilbert (2009) |
Rao (1996)
| Stern (2010) | ||
Simons (2009)
| Goodman (2011)* | Rao (2008) | Vaidyanathan (2014) | ||
Torres (2010) | Gruner (2012) |
Robillard (2013a)
| |||
Wall (2013) |
Hatton (2012)
|
Robillard (2013b)
| |||
Henderson (2013) |
Scott (2014)
| ||||
Ho (2014) | |||||
Huang (2012)
| |||||
Huyser (2011)
| |||||
Huyser (2013) | |||||
Ladouceur (2011) | |||||
Lagopoulos (2012)
| |||||
Lagopoulos (2013a)
| |||||
Lagopoulos (2013b)
| |||||
Lazaro (2008)
| |||||
Lazaro (2012)
| |||||
Lisy (2011)
| |||||
MacMaster (2006) | |||||
MacMillian (2003) | |||||
McClure (2007) | |||||
Meng (2013) | |||||
Pannekoek (2014) | |||||
Patel (2008) | |||||
Pavuluri (2010b) | |||||
Pavuluri (2011) | |||||
Phan (2013) | |||||
Rauch (2002) | |||||
Reynolds (2014) | |||||
Rosenberg (1997) | |||||
Rosenberg (2000)
| |||||
Rosso (2005) | |||||
Schienle (2011) | |||||
Schneider (2012) | |||||
Strawn (2012) | |||||
Wegbreit (2011) | |||||
Yucel (2008) | |||||
Zarei (2011) | |||||
Zuo (2013) |
Synthesis of results
Outcome measure | Study | Age (mean ± SD) | Sample (N) | Aims | Key measures | Key findings |
---|---|---|---|---|---|---|
Social and economic participation
| [40] | HC: 13.6 ± 2.1, | HC (47M; 34F), | Evaluate the clinical impact of executive function deficits in youth with BPD-I disorder. | NΨ: Executive function deficits (CPT, CVLT-C, RCF, SCWT, WCST, WAIS-III- FFD) | BPD-I: ↓ executive function ~ ↓ social and economic participation |
HC-EFD: 13.9 ± 2.3, | HC-EFD (12M; 5F), | |||||
BPD-I: 13.7 ± 2.1, | BPD-I (52M; 24F), | |||||
BPD-I-EFD: 12.8 ± 2.4 | BPD-I-EFD (49M; 13F) | Functional: GAF, WRAT-III, placement in special class | ||||
[39]* | SAD: 23.9 ± 6.7; | SAD (20M; 10F) | Assess the neuropsychological function of SAD without co-morbidity | NΨ: Executive function (CPT, TMT-B, WCST), Processing speed (TMT-A), Verbal learning & memory (AVLT) | SAD: ↓ executive function ~ ↓ social and economic participation (and ↑ SAD severity) | |
HC: 25.6 ± 5.6 | HC (20M; 10F) | |||||
Functional: GAF | ||||||
[29] | MDD: 18.9 ± 2.0, | MDD (4M; 12F), | Investigate the association between cognitive performance and MDD. | NΨ: Executive function (SCWT, TMT-B), Verbal learning & memory (WMS-SR, LLT, RCF-3min), General intellect (WAIS-III-S & V), Attention (WAIS-III- DS, BD & DSp) | MDD: No significant ~ NΨ | |
HC: 16.9 ± 1.9 | HC (11M; 14F) | MDD: ↓ social and economic participation | ||||
Functional: GAF | ||||||
FED: 22.00 ± 4.9 | FED (8M; 12F) | Assess the effectiveness of CR in patients with a first-episode of either major depression or psychosis | NΨ: Executive function (CANTAB-IED; -FAS, TMT-B), Processing speed (TMT-A, category fluency), Attention and working memory (LDSF, LDSB, CANTAB-SSP;-RVP, mental control), Immediate learning and memory (Logical Memory I, RAVLT- tot, CANTAB-PAL), Delayed learning and memory (LM-Ret, RCF-3min, RAVLT-Ret) | FED & FEP: CR ~ ↑ immediate learning and memory, and ↑ social and economic participation (mediated by ↑ delayed learning and memory) | ||
FEP: 23.30 ± 3.9 | FEP (20M; 13F) | |||||
Functional: SFS | ||||||
[24] | MHP: 21.6 ± 4.5 | MDD (34) | Identify cognitive markers that predict later socio-occupational functioning. | NΨ : Executive function (CANTAB-IED, TMT-B), Processing speed (TMT-A, CANTAB-FAS), Attention and working memory (CANTAB-RVP), Verbal learning & memory (LM-Ret, RAVLT-ret), Visual learning & memory (CANTAB- SSP;- PAL) | MHP: ↑ BL general NΨ ~ ↑ social and economic participation at FUP | |
BPD (29) | ||||||
PSD (30) | ||||||
(of the total 93, 52 % were male) | ||||||
Functional: SOFAS | ||||||
Suicide and self-harm
| [31] | SA: 15.5 ± 1.4 | SA (10M; 30F) | Examine decision-making processes in suicide attempters and never-suicidal comparison subjects | NΨ: Decision making (IGT) | SA: ↓ decision making ~ suicide attempt history |
PC: 15.6 ± 1.4 | PC (10M; 30F) | Functional: CSHF, PSIS | ||||
[32] | SA: 18.31 ± 0.63 | SA (1M; 12F) | Examine whether cognitive inflexibility can differentially and prospectively predict suicidal ideation. | NΨ: Executive function (WCST; perseverative errors) | SA: ↓ BL cognitive inflexibility ~ ↑ suicide ideation at 6-month FUP. | |
NSA: 18.31 ± 0.78 | NSA (9M; 23F) | |||||
Functional: BSS, SBS, SHBQ | ||||||
[35] | SIB: 15.5 ± 1.3 | SIB (99) | Investigate the neuropsychological differences between psychiatric patients with and without SIB. | NΨ: Executive function (SCWT, WCST) | Null findings | |
NSIB: 15.1 ± 1.4 | NSIB (77) | |||||
Functional: Clinical interview | ||||||
[33] | HC: 15.8 ± 1.5 | HC (11M; 46F) | Assess decision making and problem solving ability in adolescents with current or past self-harm | NΨ: Decision making (IGT, MEPS) | DSH: ↓ decision making ~ current, but not past DSH | |
PC: 15.7 + 1.3 | PC (2M; 20F) | Functional: Clinical interview | ||||
DSH: 15.8 + 1.5 | DSH (5M; 49F) | |||||
[34]* | SA: 16.20 ± 0.78 | SA (4M; 11F) | Measure neural activity during performance on the IGT in adolescents. | NΨ: Decision making (IGT-mod) | SA: ↑ decision making ~ suicide attempt history | |
PC: 15.79 ± 1.58 | PC (7M; 7F) | Functional: C-CASA, CSHF, SIQ, SIS | ||||
HC: 15.15 ± 1.46 | HC (8M; 5F) | |||||
Alcohol and substance use
| [164] | CU: 16.2 (13.5 – 18.4) | CU (28M; 42F) | Investigate the non-acute relationship between cannabis use and cognitive function | NΨ: Intelligence (WASI), Executive function (CANTAB-IED), (CANTAB-MS), Attention and working memory (CANTAB-RVP;-SWM; -SSP, DS, SDMT), Immediate learning and memory (RAVLT, CANTAB-PAL) | CU: ↓ attention, spatial working memory and learning. |
CU: was independent predictor of performance on the working memory and strategy measures | ||||||
Functional: TLFB | ||||||
[165] | HC-NB: 22.9 ± 3.1 | HC-NB (7M; 14F) | Compare the cognition in binge drinkers with depression to those with depression alone or binge drinking alone. | NΨ: Intelligence (WTAR), Psychomotor speed (TMT-A) Executive function (TMT-B), Verbal learning and memory (RAVLT), Attention (CANTAB- RVP), working memory (CANTAB-SSP, Visuospatial learning and memory (CANTAB-PAL) | MDD-B: ↓ visual learning & memory and overall pattern of ↓ NΨ functioning. | |
HC-B: 23.0 ± 2.5; | HC-B (13M; 11F) | |||||
MDD-NB: 21.7 ± 3.2 | MDD-NB (16M; 32F) | |||||
MDD-B: 21.8 ± 3.4 | MDD-B (24M; 19F) | |||||
Functional: AUDIT | ||||||
Clinical syndrome
| [50] | OCD: 13.84 ± 2.78 | OCD (18M; 17F) | Investigate the influence of clinical variables treatment on cognitive performance in OCD patients | NΨ: Intelligence (WISC-R: Vo), Visual organisation (WISC-R:-BD), Attention (WISC-R: -DS;-Co), Verbal learning and memory (WMS-III- LM1 & 2, RAVLT), Visual learning and memory (WMS-III: VR 1 & 2, RCFT), Processing speed (TMT-A), Cognitive flexibility (TMT-B, WCST, SCWT), Verbal fluency (COWAT) | OCD: ↓ verbal and visual memory and velocity. (Neuropsychological impairment was not related to obsessive-compulsive severity) |
HC: 13.81 ± 2.74 | HC (18M; 17F) | |||||
Clinical: CDI, Y-BOCS | ||||||
[51] | OCD: 13.46 ± 2.83 | OCD (16M; 13F) | Explore the evolution of cognitive dysfunction in children and adolescents with OCD after treatment | NΨ: Intelligence (WISC-R: Vo), Visual organisation (WISC-R:-BD), Attention (WISC-R: -DS;-Co), Verbal learning and memory (WMS-III- LM1 & 2, RAVLT), Visual learning and memory (WMS-III: VR 1 & 2, RCFT), Processing speed (TMT-A), Cognitive flexibility (TMT-B, WCST, SCWT), Verbal fluency (COWAT) | OCD: ↓ memory, speed of information processing and cognitive flexibility. (After treatment the cognitive profile of the OCD group was normalized) | |
HC: 13.06 ± 2.84 | HC (12M; 10F) | |||||
Clinical: Y-BOCS | ||||||
[53] | OCD: 29.70 ± 10.74 | OCD (12M; 8F) | Examine the impact of depression on executive function deficits in OCD | NΨ: VCAT, Verbal Fluency (COWAT), Processing speed (TMT-A), Cognitive flexibility (TMT-B, WCST) | OCD: cognitive flexibility deficits ~ co-morbid depression severity | |
HC: 30.06 ± 10.06 | HC (11M; 21F) | |||||
Clinical: MMPI-D | ||||||
[47] | HC: 12.5 ± 2.4 | HC (11M; 10F) | Compare impulsivity at the neuropsychological and behavioural level in young depressed patients and healthy controls. | NΨ: Cognitive style (MFFT), Verbal fluency (VFT), Decision making (WDWT), cognitive flexibility (SCWT), Impulsivity (CPT) | DD: ↑ symptom severity ~ ↑ reaction time, ↓ in commission errors. | |
DD: 11.7 ± 2.3 | DD (11M; 10) | |||||
DD: ↑ conservative response styles & attention problems, ↓ reaction times & response initiation | ||||||
Clinical: HDRS, CDI, CPRS-R:L | ||||||
[166] | HC: 28.2 ± 7.9 | HC (20M; 28F) | Investigate the effect of syndrome state or course on executive dysfunction | NΨ: Intelligence (NAART), Cognitive flexibility (WCST) | EUT: ↑ cognitive flexibility than MEM. Performed similarly to FEM | |
EUT: 30.0 ± 7.2 | EUT (11M; 14F) | |||||
FEM: 25.7 ± 9.2 | FEM (11M; 10F) | Clinical: YMRS, HDRS | ||||
MEM: 28.2 8.6 | MEM (16M; 18F) | |||||
[39]* | SAD: 23.9 ± 6.7; | SAD (20M; 10F) | Assess the neuropsychological function of SAD without co-morbidity | NΨ: Executive function (CPT, TMT-B, WCST), Processing speed (TMT-A), Verbal learning & memory (AVLT) | SAD: ↓ executive function ~ ↑ SAD severity | |
HC: 25.6 ± 5.6 | HC (20M; 10F) | |||||
Clinical: GAF | ||||||
[44] | HC: 12.8 ± 2.5 | HC (15M; 18F) | Examine basic performance neuropsychological performance in children and adolescents with anxiety disorder or depressive disorder and in healthy subjects under drug-free condition | NΨ: Intelligence (WISC-III), Verbal learning and memory (RAVLT), Attention (go-no go task) | DD: ↓ verbal learning and memory compared to HC and ANX. | |
ANX: 12.4 ± 2.3 | ANX (19M; 15F) | |||||
DD: 13.5 ± 2.6 | DD (17M; 14F) | |||||
Clinical: CDI | ||||||
[48] | HC: 17.46 ± 1.59, MDD: 17.32 ± 1.59 | HC (14M, 16F) MDD (12M, 19F) | Investigate whether major depression in adolescence is characterized by neurocognitive deficits in attention, affective decision making, and cognitive control of emotion processing | NΨ: Inhibitory control (CPT, go-no go task), Attention (ANT), Decision making (IGT), Verbal learning and memory (RAVLT), Attention (go-no go task) | MDD: ↑ depression symptom severity ~ ↓ cognitive control of emotion processing | |
Clinical: BDI | ||||||
[167]* | OCD: 27 ± 9.8 | OCD (15M; 16F) | Characterize the cognitive functions of the patients with OCD by utilizing ERPs and neuropsychological tests | NΨ: cognitive flexibility (SCWT, TMT-B), Processing speed (TMT-A), Design fluency test, Verbal fluency (CWAT) | Null findings for neuropsychological tests. | |
HC: 27.4 ± 9.1 | HC (14M; 16F) | |||||
Clinical: HDRS | ||||||
[49] | MDD: 15.3 ± 1.6 | MDD (5M; 17F) | Investigate verbal fluency, cognitive speed, motor speed, and executive functions in adolescents with unipolar depression. | NΨ: Verbal fluency (COWAT), Processing speed (Inspection time task), Working memory (Serial choice reaction time task), Set shifting (Local-global task) Clinical: | DD: ↓ WM & VF. MDD: ↓WM & processing speed | |
DD: 15.6 ± 1.5 | DD (6M; 6F) | |||||
HC: 15.8 ± 1.2 | HC (9M; 24F) | |||||
[52] | OCD: 24.06 ± 5 | OCD (21M; 9F) | Assess the relationship between cognitive dysfunction, clinical status and severity in OCD. | NΨ: Intelligence (WAIS-BD; -S), Cognitive flexibility (WCST) | Results showed a defective visuospatial recognition, which worsens with chronicity, deteriorated set-shifting abilities, overfocused attention to irrelevant stimuli and delayed selective attention to relevant tasks. Mild cases showed better selective attention than severe cases. Obsessive cases had a defective visual memory, while compulsive cases had delayed perception of task relevant stimuli. Mixed cases showed disturbed information-processing both early and late. | |
HC: Matched | HC (21M; 9F) | |||||
Clinical: YBOCS | ||||||
[55] | HC: 12.4 ± 3.3, | HC (15M; 9F) | Examine the treatment impact of lamotrigine on the neurocognitive profile of patients with pediatric bipolar disorder | NΨ: Attention (TMT-A, CPT), cognitive flexibility (TMT-B), Verbal fluency (COWT), Working memory (WMS; DS, SS), Verbal memory (CVLT) | BPD: ↑ Working memory and verbal memory following treatment (to levels similar to HC) | |
BPD: 13 ± 3.1 | BPD (18M; 16F) | |||||
Clinical: YMRS | ||||||
[168] | MDD: 26.93 ± 5.33 | MDD (14M; 14F) | Assess the association between executive function and relapse | NΨ: cognitive flexibility (CWIT, TMT-B), Verbal fluency (VFT), Processing speed (TMT-A), | MDD: Poor BL inhibition and switching ~ ↑ relapse at FU | |
HC: 26.93 ± 5.18 | HC (14M; 14F) | |||||
Clinical: MADRS | ||||||
[45] | CS: 28 ± 7.9 | CS (642) | Examine whether cognitive deficits predict current and/or follow-up (sub)clinical depressive symptoms in the general population | NΨ: Information processing (SCWT, CST, LDST), Episodic memory (AVLT) | CS: Poor BL episodic memory ~ ↑ depressive symptoms at FUP | |
Clinical: SCL-90 | ||||||
[169] | BD: 22.2 ± 3.9 | BD (23M; 22F) | Determine whether neuropsychological impairments are present in clinically stable patients with bipolar disorder shortly after resolution of their first manic episode | NΨ: Intelligence (NAART), Visual spatial reasoning (K-BIT), Attention/processing speed (TMT-A, CANTAB-RVP, CVLT), Learning and memory (CVLT- recall, CANTAB-SRM;-PRM;-PAL), cognitive flexibility (TMT-B, CANTAB-IED;-SWM), Verbal fluency (COWT), | BPD: ↓ learning/memory, spatial/nonverbal reasoning, executive function, and some aspects of attention | |
HC: 22.5 ± 4.8 | HC (12M; 13F) | |||||
Clinical: PANSS, HDRS, BPRS, GAF, YMRS | ||||||
[56] | MDD: 16.2 ± 1.1 | MDD (7M; 11F) | Investigate the neurocognitive outcome in adolescents who were treated with TMS | NΨ: Verbal learning and memory (CAVLT), Cognitive flexibility (D-KEFS, TMT) | MDD: ↓ Depressive symptoms were associated with ↑ in immediate and delayed verbal memory. | |
Clinical: CDRS-R |
Outcome measure | Study | Age (mean ± SD) | Sample (N) | Aims | Key measures | Key findings |
---|---|---|---|---|---|---|
Social and economic participation
| [57] | MDD: 15.7 ± 1.5; | MDD (8M; 6F) | Assess amygdala activation and connectivity during an emotional regulation task. | Imaging: fMRI | MDD: ↓ amygdala–seeded connectivities ~ ↓ social and economic participation |
HC: 15.1 ± 1.6 | HC (8M; 6F) | Functional: CGAS | ||||
Physical health
| [58] | BPD-O: 23.8 ± 4.5 | BPD-O (9M; 11F) | Examine the relationship between BMI and brain volumes in mania. | Imaging: sMRI | BPD: ↑ BMI ~ ↓ WMV and TLV |
BPD-N: 22.2 ± 4.4 | BPD-N (19M; 18F) | Functional: BMI | HC: ↑ BMI ~ ↓ TBV and GMV. | |||
HC-O: 22.0 ± 3.8 | HC-O (12M; 5F) | |||||
HC-N: 22.3 ± 3.5 | HC-N (19M; 19F) | |||||
Suicide and self-harm
| [170] | MHP: 14.6 ± 3.4 | PSD (18M; 5F) | Compare WMH in psychiatrically hospitalized youth with and without a history of suicide attempt | Imaging: sMRI | MDD: ↑ WMH ~ suicide attempt history, but not ideation |
BPD (26M; 9F) MDD (33M; 15F) | Functional: PRS | |||||
PC (34M; 12F) | ||||||
[171] | MDD: 26.7 ± 5.5 | MDD (34M; 68F) | Compare the prevalence and location of WMH in young MDD inpatients with and without histories of suicide attempts | Imaging: sMRI | MDD: ↑ PVH, not DWMH, ~ suicide attempt history, but not ideation | |
Functional: Clinical records | ||||||
[59]* | HC: 16.2 ± 0.8 | HC (4M; 9F) | Evaluate the ACC volumes of MDD/borderline personality patients with and without a suicide attempt history | Imaging: sMRI | MDDx: ↓ BA24 volumes ~ ↑ number of suicide attempts (and ↑ borderline severity, but not depression) | |
MDDx: 15.8 ± 1.1 | MDDx (2M; 11F) | Functional: Clinical interview | ||||
[62] | SA: 16.20 ± 0.78 PC: 15.87 ± 1.55 HC: 15.21 ± 1.42 | SA (4M; 11F) | Evaluate the association between neural activity during performance of the go no-go task and suicide history. | Imaging: fMRI | PC: ↑ activity in right ACG compared to SA (but SA not different from HC) | |
PC (7M; 8F) | Functional: CSHF | |||||
HC (8M; 6F) | ||||||
[60] | SA: 16.21 ± 0.80 | SA (4M; 10) | Measure neural activity during processing of emotional faces in adolescents with a history of depression and suicide attempt | Imaging: fMRI | SA: ↑ dorsal ACG activity when viewing angry faces, and ↓ visual, sensory, prefrontal, ACG activity to intense happy and neutral faces ~ suicide attempt history. | |
PC: 15.87 ± 1.55 | PC (7M; 8F) | Clinical: C-CASA, CSHF, SIQ, SIS | ||||
HC: 15.27 ± 1.39 | HC (8M; 7F) | |||||
[34]* | SA: 16.20 ± 0.78 | SA (4M; 11F) | Measure neural activity during performance on the IGT in adolescents. | Imaging: fMRI | PC: ↑ hippocampal activity compared to HC. (HC and SA did not differ, evidence of ↓ activation) | |
PC: 15.79 ± 1.58 | PC (7M; 7F) | Functional: C-CASA, CSHF, SIQ, SIS | ||||
HC: 15.15 ± 1.46 | HC (8M; 5F) | |||||
Alcohol and substance use
| [172] | BPD-L: 23.7 ± 3.6 | BPD-L (14M; 5F) | Assess the effects of alcohol use on GSH in young people with BPD. | Imaging: MRS | BPD-H: ↓ GSH |
BPD-H: 23.4 ± 3.1 | BPD-H (12M; 2F) | Functional: AUDIT | ||||
HC: 23.6 ± 2.8 | HC (13M; 4F) | |||||
[65] | MDD: 21.7 ± 2.0 | MDD (5M; 1F) | Examine the effect of cannabis use on threat-related amygdala reactivity. | Imaging: fMRI | MDD: ↑ CU ~ ↓amygdala reactivity | |
Functional: SCID (presence of dependence) | ||||||
[66] | AUD: 17 ± 2.1 | AUD (8M; 6F) | Compare prefrontal-thalamic-cerebellar measures of adolescents and young adults with adolescent-onset alcohol use disorders | Imaging: sMRI | AUD: ↓ PFC & PFC WMV. | |
HC: 16.9 ± 2.3 | HC (16M; 12F) | Fucntional: ACQ, LHAUI, SCID | AUD: ↓ PFC GM ~ ↑ alcohol consumption | |||
AUD(M): ↓ CV | ||||||
PFC volume variables ~ measures of alcohol consumption | ||||||
[64] | BPD: 16 ± 2, | BPD (5M; 9F) | Compare brain morphometry in bipolar adolescents with co-occurring substance and alcohol disorders | Imaging: sMRI | BPD: CUD ~ ↓ LFG GMV & ↑ RC, PCG GMV | |
Functional: ASI, SCID, SAC | ||||||
[63] | CU: 18 ± 0.7 | CU (12M; 4F) | Examine the relationship between brain volumes, depression and cannabis use. | Imaging: sMRI | CU: ↓ WMV ~ ↑ depressive symptoms | |
HC: 18 ± 0.9 | HC (11M; 5F) | Functional: BDI, CDDR, HDRS, TLFB, | ||||
Clinical syndrome
| [173] | BPD: 19.9 ± 7.9 | BPD (15M; 18F) | Explore structural brain changes in first-episode bipolar patients | Imaging: VBM | BPD: ↑ volume in left thalamus and fusiform and cerebellum bilaterally. ↑ AC, PPS GMD. ↑ middle/superior temporal and posterior cingulate gyri, GMV & GMD. |
HC: 21.5 ± 4.3 | HC (19M; 14F) | Clinical: SCID, KSADS | ||||
[90] | DD: 15.6 ± 1.4, | DD (4M; 21F) | Investigate WM microstructure in a sample of clinically depressed adolescents relative to matched controls. | Imaging: DTI | DD: ↓ FA and ↑ RD, MD in corpus callosum. ↑ FA & AD, and ↓ RD in uncinate fasciculus. | |
HC: 14.7 ± 1.6 | HC (3M; 18F) | Clinical: ADIS, CDI, CBCL, RCADS, YSRS | ||||
[46] | BPD: 15.8 ± 1.8 | BPD (6M; 11F) | Compare amygdala neurodevelopment among BPD, ADHD, and healthy adolescents | Imaging: sMRI | BPD: ↑ BL amygdala volumes ~ symptomatic recover compared to those who did not achieve recovery. No increase in amygdala volume over time. | |
ADHD: 16.3 ± 1.7 | ADHD (13M; 11F) | Clinical: KSADS, LIFE, YMRS, HDRS | ||||
HC: 16.3 ± 1.8 | HC (13M; 10F) | |||||
[85] | BPD: 15.9 ± 1.4 | BPD (4M; 4F) | Evaluate the effect of lamotrigine treatment on amygdalar activation | Imaging: fMRI | BPD: clinical improvement ~ ↓ right amygdalar activation | |
Clinical: CDRS | ||||||
[99] | BPD: 25 ± 9 | BPD (7M; 14F) | Investigate the distribution of lactate in bipolar and healthy brains | Imaging: MRS | BPD: ↑ Lac/NAA & Lac/Cr ratio | |
HC: 25 ± 6 | HC (5M, 5F) | Clinical: SCID | ||||
[174] | BPD: 15.6 ± 0.9 | BPD (2M; 8F) | Explore the neural correlates of depression at baseline and after 6 weeks of open as usual treatment | Imaging: fMRI | BPD: After treatment, ↓ left occipital cortex activity in the intense fearful experiment, but ↑ left insula, left cerebellum, and right ventrolateral PFC in the intense happy experiment. ↑ improvement in depression ~ ↑ BL activity in ventral ACC to mild happy faces | |
HC: 15.6 ± 1.2 | HC (2M; 8F) | Clinical: KSADS, CDRS, SCARED, YMRS | ||||
[175] | MDD: 14.73 ± 1.49 | MDD (3M; 11F) | Examine behavioral and neural responses to reward in young people with depressive disorders using a reward decision-making task | Imaging: fMRI | MDD: ↓ activation in the ACC, bilateral caudate, and inferior OFC bilaterally during reward decision/anticipation and reward outcome. | |
HC: 14.45 ± 1.79 | HC (7M; 10F) | Clinical: KSADS, CBCL, SCARED, CDI, BDI | ||||
[176] | MDD: 12.9 ± 2.3 | MDD (4M; 9F) | Evaluate reward-related brain function as a predictor of treatment response in adolescents with MDD | Imaging: fMRI | MDD: severity, anxiety and depression symptoms ↓ following treatment. ↑ reward related striatal function before treatment ~ ↑ clinical severity, ↓ anxiety symptoms and faster improvement in anxiety symptoms after treatment. ↑ mPFC function before ~ slower improvements in anxiety symptoms. | |
Clinical: KSADS, MFQ, SCARED, CGI | ||||||
[68] | MDD: 16.7 ± 2.7 | MDD (9M; 12F) | Test whether ACC GABA levels are decreased in adolescents with MDD | Imaging: MRS, sMRI | MDD & HC: ↑ ACC GABA ~ ↓ anhedonia scores. | |
HC: 16.2 ± 1.6 | HC (6M; 15F) | Clinical: KSADS, CDRS-R, BDI | ||||
MDD: ↓ ACC GABA, ↓ ACC WM | ||||||
[177] | MDD: 17.1 ± 2.5 | MDD (9M; 12F) | Assess striatum-based circuitry in relation to categorical diagnosis of MDD and anhedonia severity | Imaging: fMRI | MDD: ↑ iFC between all striatal regions bilaterally and DmPFC, RVC and ACC. MDD severity ~ iFC between the striatum and the precuneus, posterior cingulate cortex and dmPFC. Anhedonia severity ~ Pregenual ACC, subgenual ACC, supplementary motor area, and supramarginal gyrus iFC. | |
HC: 16.3 ± 1.4 | HC (9M; 12F) | Clinical: KSADS, CDRS-R, BDI | ||||
[178] | BPD: 15.1 ± 1.81 | BPD (6M; 12F) | Investigate the brain structural changes in BPD children and adolescents | Imaging: DTI | BPD: ↓ GMV in left hippocampus. ↓ FA value in rACC. | |
HC: 14.1 ± 1.61 | HC (6M; 12F) | Clinical: KSADS, YMRS, MFQ | ||||
↓ hippocampal volume ~ ↑ YMRS score | ||||||
[91] | OCD: 12.35 ± 2.93 | OCD (7M; 14F) | Measure neuroanatomical changes in the thalamus of patients with OCD near the onset of illness, and before and after treatment. | Imaging: MRI | OCD: ↑ thalamic volumes in treatment naïve patients. ↓ thalamic volumes (to comparable levels with controls) ~ paroxetine monotherapy. | |
HC: 12.47 ± 8.33 | HC (7M; 14F) | Clinical: KSADS, YBOCS, HDRS | ||||
↓ thalamic volumes ~ ↓ OCD symptom severity | ||||||
[179] | OCD: 13.1 ± 2.5 | OCD (11M; 7F) | Examine whether overlapping but symptom dimension-specific neural activity patterns in adults are apparent in youths | Imaging: fMRI | OCD: ↓ activity in right insula, putamen, thalamus, dorsolateral prefrontal cortex and left orbitofrontal cortex, and right thalamus and right insula. ↑ OCD symptom related measures were significantly predictive of ↓ neural activity in the right dorsolateral prefrontal cortex during the contamination experiment. | |
HC: 13.6 ± 2.4 | HC (11M; 7F) | Clinical: YBOCS | ||||
[59]* | HC: 16.2 ± 0.8 | HC (4M; 9F) | Evaluate the ACC volumes of MDD/borderline personality patients with and without a suicide attempt history | Imaging: sMRI | MDDx: ↓ BA24 volumes ~ ↑ borderline severity, but not depression | |
MDDx: 15.8 ± 1.1 | MDDx (2M; 11F) | Clinical: Clinical interview | ||||
[94] | OCD: 14.3 ± 2.1 | OCD (13M; 10F) | Investigate white matter abnormalities in pediatric obsessive-compulsive disorder. | Imaging: DTI | ODD: ↑ FA in splenium ~ ↑ obsession severity | |
HC: 14.2 ± 2.2 | HC (12M; 11F) | Clinical: YBOCS, KSADS | ||||
[180] | MHP: 22.3 ± 3.7 | MHP (50M; 83F) | Examine the relationship between anterior insula GMV, clinical symptom severity and neuropsychological performance. | Imaging: sMRI | MHP: ↓ GMV in left anterior insula. Changes (↑ or ↓) in right anterior insula GMV ~ ↑ symptom severity. | |
HC: 23.8 ± 2.4 | HC (13M; 26F) | Clinical: BPRS, HDRS, SOFAS | ||||
[95] | MDD: 16.8 ± 2.2 | MDD (9M; 8F) | Investigate WM microstructure in MDD using diffusion tensor imaging | Imaging: DTI | MDD: ↓ WM integrity in the genu of corpus callosum, anterior thalamic radiation, anterior cingulum and sagittal stratum ~ ↑ depression severity. | |
HC: 16.4 ± 1.4 | HC (6M; 10F) | Clinical: KSADS, BDI, CDRS-R, MASC | ||||
[181] | MDD: 15.8 ± 1.4 | MDD (8M; 11F) | Investigate sgACC FC in adolescent depression during negative emotional processing. | Imaging: fMRI | MDD: ↑ sgACC- amygdala Functional connectivity and ↓ sgACC-fusiform gyrus, sgACC-precuneus, sgACC-insula, and sgACC-middle frontal gyrus functional connectivity. ↓ sgACC-precuneus functional connectivity ~ ↑ depression severity. | |
HC: 16.1 ± 1.2 | HC (8M; 11F) | Clinical: BDI | ||||
[93] | HC: 16 ± 2.74 | HC (6M; 7F) | Evaluate whether the observed WM disruptions are associated with increased vulnerability to psychopathology during prospective follow-up | Imaging: DTI | MDD at FUP ~ ↓ FA in the superior longitudinal fasciculi & the right cingulum-hippocampal Projection. SUD at FUP ~ ↓ FA in the right cingulum-hippocampal projection. | |
MT: 15.89 ± 2.79 | MT (5M; 14F) | Clinical: KSADS, FH-RDC, CDRS-R, HDRS, CGAS, BDI DUSI | ||||
[182] | OCD: 13.95 ± 2.52 | OCD (9M; 16F) | Investigate the development of the ACC and its associations with psychopathology. | Imaging: fMRI | OCD: ↑ ACC activity during error responses in bilateral insular cortex during high conflict tasks | |
HC: 13.71 ± 2.85 | HC (9M; 16F) | Clinical: YBOCS, ADIS, CDI, STAI-C, CBCL | ||||
[81] | OCD: 13.78 ± 2.58 | OCD (11M; 18F) | Identify differences in regional brain volume between medication-free pediatric OCD patients and controls and examine changes after cognitive behavioural therapy | Imaging: VBM | OCD: ↑ Orbitofrontal GMV after treatment ~ ↑ symptom improvement | |
HC: 13.6 ± 2.73 | HC (11M; 18F) | Clinical: YBOCS, ADIS, CDI, STAI-C, CBCL | ||||
[183] | BPD-I: 14.57 ± 1.98 | BPD-I (11M; 7F) | Examine patterns of activity and connectivity in youth with BPD. | Imaging: fMRI | BP-I: ↑ activity in amygdala and VMPFC regulation regions to happy faces and reduced DLPFC activity to fearful faces compared to HC. BPD-NOS: ↓ PFC activity to neural faces compared to HC. | |
BPD-NOS: 12.59 ± 2.27 | BPD-NOS (11M; 7F) | Clinical: KSADS, MFQ, SCARED, CALS | ||||
HC: 13.67 ± 2.55 | HC (7M; 11F) | |||||
[71] | HC: 23.9 ± 2.3 | HC (12M; 21F) | Evaluate patterns of grey matter changes very early in the course of affective illness compared to those with discrete disorders and/or illness persistence | Imaging: sMRI | ST-2/3: ↓ GMV in frontal brain regions | |
ST-1: 20.4 ± 5.2 | ST-1 (8M; 15F) | Clinical: HDRS, SOFAS, BPRS | ||||
ST-2/3: 23.5 ± 3.5 | ST-2/3 (14M; 10F) | |||||
[96] | HC: 23.82 ± 2.52 | HC (15M; 24F) | Examine the association between microstructural WM changes and different stages of psychiatric illness. | Imaging: DTI | ST-2/3: ↓ FA within the left anterior corona radiata compared to HC. | |
ST-1B: 21.36 ± 3.51 | ST-1B (24M; 49F) | Clinical: HDRS, BPRS, SOFAS | ||||
ST-1B: pattern of ↓ FA within the left anterior corona radiate (less WM involvement than ST-2/3) | ||||||
ST-2/3: 22.45 ± 4.35 | ST-2/3 (37M; 32) | |||||
[92] | BPD: 23.03 ± 5.04 | BPD (23M; 35F) | Examine WM microstructural changes in BPD. | Imaging: DTI | BPD: ↓ FA in the genu, body and splenium of the corpus callosum as well as the superior and anterior corona radiata. ↑ radial diffusivity. | |
HC: 24.05 ± 2.92 | HC (12M; 28F) | Clinical: HDRS, YMRS, SOFAS, BPRS | ||||
[184] | OCD: 13.1 ± 2.7 | OCD (7M; 5F) | Investigate possible regional brain dysfunction in premotor cortico-striatal activity, correlate brain activation with severity of obsessive-compulsive symptomatology; And, detect possible changes in brain activity after pharmacological treatment | Imaging: fMRI | OCD: ↑ activation bilaterally in the middle frontal gyrus. Clinical improvement following pharmacological treatment ~ ↓ activation in left insula and left putamen | |
HC: 13.7 ± 2.8 | HC (7M; 5F) | Clinical: ChIPS, Y-BOCS, CDI, STAI-C, LOI-CV | ||||
[98] | OCD: 12.5 ± 2.9 | OCD (6M; 5F) | Measure neurometabolite concentrations in anterior cingulate-medial frontal cortex and right and left striatum of drug naïve children and adolescents with OCD | Imaging: MRS | OCD: ↓ total Cho in left striatum (this ↓ did not change over time and persisted at follow-up Assessment) | |
HC: 14.5 ± 2.8 | HC (5M; 7F) | Clinical: Y-BOCS, CDI, STAI-C, LOI-CV | ||||
[185] | BPD: 27 ± 10 | BPD (26M; 32F) | Assess changes in GMV in BPD. | Imaging: sMRI | BPD: ↑ GMV in portions of the VLPFC and hippocamps complex. ↑ GMV in amygdala proper and caudate. ↑ number of depressive episodes ~ ↑ GMV in the right cingulate gyrus bilaterally and right thalamus and bilateral lenticulate nuclei, and left cerebellar vermis. ↑ illness duration ~ ↓ GMV in left cerebellar vermis. | |
HC 27 ± 10 | HC (21M; 27F) | Clinical: SCID, KSADS | ||||
[83] | OCD: 12.79 ± 2.64 | OCD (10M; 21F) | Measure pituitary gland volume in OCD | Imaging: MRI | OCD: ↓ pituitary gland volume ~ ↑ compulsive symptom severity (more pronounced in males). | |
HC: 12.89 ± 2.66 | HC (10M; 21F) | Clinical: YBOCS, HAMA, HDRS | ||||
[74] | MDD: 8 – 17years | MDD (10M; 13F) | Examine temporal lobe anatomy in pediatric patients with MDD near the onset of illness before treatment | Imaging: MRI | MDD: ↑ left and right amygdala: hippocampus volume ratios ~ ↑ severity of anxiety (but not ↑ depression severity or duration of illness) | |
HC: 8–17 years | HC (10M; 13F) | Clinical: CDRS-R, HAMA | ||||
[87] | ANX: 11.8 ± 1.8 | ANX (6M; 6F) | Examine the relationships between pretreatment amygdala activity and treatment response in a sample of anxious children and adolescents | Imaging: fMRI | ANX: ↑ left amygdala activation pre-treatment ~ treatment response to CBT or medication. (no association between pre-treatment symptom severity and pre-treatment amygdala activity) | |
Clinical: KSADS, CGI | ||||||
[78] | SAD: 21.80 ± 3.68 | SAD (14M; 6F) | Explore the GMD deficits in drug-naïve adult SAD patients | Imaging: VBM | SAD: ↓ GMD in bilateral thalami, right amygdala, and right precuneus. ↓ right amygdala GMD ~ ↑ disease duration and ↓ age of onset. | |
HC: 21.58 ± 3.72 | HC (13M; 6F) | Clinical: HAMA, HDRS, LSAS, SCID | ||||
[69] | DD: 15.4 ± 1.5 | DD (3M; 23F) | Examine GMV in brain areas putatively involved in affective psychopathology. | Imaging: VBM | DD: ↓ bilateral dorsal ACC volume. No association with clinical severity of depression or anxiety. | |
HC: 14.7 ± 1.5 | HC (3M; 23F) | Clinical: ADIS, CDI, RCADS, YSR, CBCL | ||||
[100] | BPD: 15.5 ± 1.5, | BPD (5M; 23F) | Compare in vivo neurometabolite concentrations in bipolar adolescents with a depressed episode | Imaging: MRS | BPD: ↑ NAA in the ACC and VLPFC. ↑ Cho and Cr in the VLPFC. | |
HC: 14.6 ± 1.8 | HC (4M; 6F) | Clinical: KSADS, CDRS-R | ||||
[186] | BPD: 14.3 ± 1.1 | BPD (6M; 11F) | Investigate the effects of pharmacotherapy on brain function underlying affect dysregulation and cognitive function in pediatric bipolar disorder. | Imaging: fMRI | BPD: YMRS improvement ~ ↓ VMPFC activity. Normalization of activity in the inferior frontal gyrus following pharmacological treatment. | |
HC: 14.1 ± 2.4 | HC (7M; 7F) | Clinical: YMRS, KSADS, CDI, CDRS-R | ||||
[187] | BPD: | BPD (16M; 8F) | Determine the relative effects of risperidone and divalproex on brain function in pediatric mania | Imaging: fMRI | BPD: Divalproex treatment ~ ↑ activity in left MPFC relative and modulation of positive emotions to risperidone. ↑ pre-treatment right amygdala activity with negative and positive condition in the risperidone group, and left amygdala with positive condition in divalproex group predicted poor response on YMRS. | |
HC: 13.9 ± 3.4 | HC (7M; 7F) | Clinical: KSADS, CDRS, YMRS | ||||
[86] | gSP: 25.91 ± 5.50 | gSP (8M; 13F) | Examine the change in amygdala-insula-medial frontal function during perception of social threat cues before and after SSRI treatment | Imaging: fMRI | gSP: SSRI treatment ~ ↓ amygdala reactivity to fearful faces (which was ↑ pre-treatment) and ↑ ventral MPF activity to angry faces (which was ↓ Pre-treatment treatment). No correlations with symptom improvement. | |
HC: 26.95 ± 8.11 | HC (10M; 9F) | Clinical: SCID, LSAS, HDRS, BDI, STAI | ||||
[188] | OCD: 28.8 ± 8.2 | OCD (4M; 5F) | Identify neuroimaging predictors of medication response in contamination-related obsessive compulsive disorder OCD | Imaging: PET | OCD: ↓ rCBF in OFC and ↑ rCBF values in PCC predicted better fluvoxamine treatment response. | |
Clinical: AAS, OCDAS | ||||||
[70] | HC: 17.19 ± 1.87 | HC (7M; 9F) | Investigate the role of dysregulation of frontal-limbic circuits in the symptomology of this disorder | Imaging: sMRI | MDD: ↑ right and left rostral MFG, and left caudal anterior cingulate cortex thickness. ↑ age ~ ↓ left MFG thickness. | |
MDD: 16.89 ± 2.01 | MDD (9M; 21F) | Clinical: CDRS, KSADS, BDI | ||||
[84] | OCD: 12.70 ± 3.11 | OCD (13M; 8F) | Investigate the regional morphology of the CC in OCD. | Imaging: sMRI | OCD: ↑ corpus callosum (except the isthmus). ↑ CC area, genu, anterior body, posterior body, isthmus and anterior splenium ~ ↑ compulsive symptom severity | |
HC: 12.74 ± 3.12 | HC (13M; 8F) | Clinical: YBOCS, HAMA, HDRS, KSADS | ||||
[79] | OCD: 12.89 ± 3.23 | OCD (5M; 6F) | Evaluate neuroanatomic changes in the thalamus of OCD patients near illness onset before and after cognitive behavioral therapy | Imaging: sMRI | OCD: No significant change in thalamic volume after CBT | |
Clinical: YBOCS, HDRS, HAMA, KSADS | ||||||
[73] | MDD: 15.35 ± .34, | MDD (3M; 17F) | Examine amygdala and hippocampus volumes in pediatric MDD. | Imaging: sMRI | MDD: ↓ left and right amygdala volumes. No correlations with symptom severity, age of onset or illness duration. | |
HC: 14.08 ± .31 | HC (8M; 16F) | Clinical: HDRS, FH-RDC, KSADS | ||||
[75] | GAD: 22.9 ± 4.1, | GAD (16F) | Investigate the neural substrates associated with excessive and persistent worrying in GAD | Imaging: sMRI | GAD: ↑ amygdala and DMPFC volumes. ↑ symptom severity ~ ↑ DMPFC and ACC volumes | |
HC: 23.7 ± 3.7 | HC (15F) | Clinical: SCID, BDI, MCQ | ||||
[189] | BPD: 14.6 ± 2.2 | BPD (11M; 12F) | Examine the neurofunctional effects of ziprasidone in manic adolescents | Imaging: fMRI | BPD: Ziprasidone treatment ~ ↑ in right BA 11 and 47 activation. No association with symptom improvement. ↓ BL right BA 47 activation ~ ↑ improvement of YMRS score. | |
HC: 15.0 ± 1.8 | HC (6M; 4F) | Clinical: YMRS, CGI, KSADS | ||||
[101] | BPD-R: 15.4 ± 1 | BPD-R (4M; 3F) | Evaluate the in vivo effects of extended-release divalproex sodium on the glutamatergic system in adolescents with BPD and neurochemical predictors of clinical remission. | Imaging: MRS | BPD-r: ↓ BL Glx in LVLPFC. Change in LVLPFC Glu ~ change in YMRS score | |
BPD-NR: 14.1 ± 2.2 | BPD-NR (6M; 1F) | Clinical: KSADS, CDRS, CGI, YMRS | ||||
HC: 14.4 ± 1.6 | HC (6M; 9F) | |||||
[88] | BPD-RE: 13.5 ± 2.4 | BPD-RE (13M; 9F) | Determine functional connectivity among patients with pediatric BPD who are responders to pharmacotherapy and those who are nonresponders, | Imaging: fMRI | BPD-RE: ↑ connectivity of the amygdala before and after treatment compared to BPD-NRE. ↑ right amygdala functional connectivity after treatment ~ ↑ improvement in mania symptoms | |
BPD-NRE: 13.3 ± 2.0 | BPD-NRE (6M; 6F) | Clinical: KSADS, YMRS, CDRS-R | ||||
HC: 14.2 ± 3.1 | HC (7M; 7F) | |||||
[72] | MDD: 28.8 ± 10.7 | MDD (35M; 30F) | Evaluate the early effects of antidepressant therapy, as well as of key clinical variables, on ACC volume | Imaging: sMRI | MDD: >3 untreated depressive episodes ~ ↓ subcallosal gyrus volumes compared to HC. | |
HC: 28.4 ± 10.7 | HC (37M; 56F) | Clinical: YMRS, GAF, HDRS, SCID | ||||
[82] | OCD: 16.6 ± 1.5 | OCD (14M; 12F) | Identify structural GM and WM microstructure changes in pediatric OCD | Imaging: sMRI, DTI | OCD: ↑ symptom severity ~ ↑ GM volume in right insula, posterior orbitofrontal cortex, brainstem and cerebellum, | |
HC: 16.5 ± 1.4 | HC (14M; 12F) | Clinical: YBOCS | ||||
[80] | OCD: 22.0 ± 5.2 | OCD (3M; 5F) | Evaluated resting brain metabolism and treatment response in OCD patients. | Imaging: PET, MRI | OCD: ↑ clinical improvement ~ ↑ changes in bilateral dosal ACC and in the right middle occipital gyrus | |
HC: 21.5 ± 5.9 | HC (8F) | Clinical: YBOCS, HDRS |
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) |
Outcome measure | Study | Age (mean ± SD) | Sample (N) | Aims | Key measures | Key findings |
---|---|---|---|---|---|---|
Social and economic participation
| [190] | MHP: 22.1 ± 4.0 | BPD (18) | Determine the longitudinal relationship between MMN/P3a and functional outcomes in patients. | Nα: MMN | BPD & PSD: ↑ BL MMN ~ ↑ social and economic participation at FUP |
PSD (13) | Functional: SOFAS, WHO-DAS-II | |||||
Physical health
| [191]* | MDD: 17.1 ± 0.6 | MDD (8F) | Investigate the effect of nicotine on resting EEG activity and affect. | Nα: EEG | MDD: ↓ rPR theta & ↓ smoking withdrawal, craving and physical symptoms ~ acute nicotine administration. |
Functional: HONC | ||||||
Suicide and self-harm
| [122] | SA: 29.5 ± 13.3, HC: 34 ± 13.3 | SA (24M; 16F) | Investigate the trait predisposing to DSH by examining EEG and peripheral monoamine activity. | Nα: EEG and blood samples | SA: ↓ CNV and whole blood 5-HT ~ multiple episodes of self-harm. |
HC (13M; 14F) | Functional: HLS, MADRS, SIS | |||||
[123] | SA: 14 (12 – 17yrs) | SA (16F) | Examine EEG alpha asymmetry among high-risk adolescents | Nα: EEG alpha asymmetry | SA: ↑ posterior alpha asymmetry ~ suicidal intent (not depression severity) | |
HC: 14 (12 – 17yrs) | HC (22F) | Functional: HASS, SIS | ||||
[124] | rMDD + CSA: 31.60 ± 10.98 | rMDD + CSA (15F) | Examine the association between CSA, MDD and maladaptive behaviour. | Nα: EEG | rMDD + CSA: ↑ subgenual ACC activation during reward based decision making, ↓ reaction time during incentive-based trials ~ ↑ frequency of self harm/suicidal behaviours. | |
rMDD: 24.81 ± 3.94 | rMDD: (16F) | Functional: YRBS (adult version) | ||||
HC: 30.44 ± 10.78 | HC (18F) | |||||
Alcohol and substance use
| [192] | BPD-L: 21.8 ± 3.9 | BPD-L (5M; 11F) | Investigate the effects of alcohol use on MMN in BP. | Nα: MMN | BPD-H: ↓ temporal MMN |
BPD-H: 22.6 ± 3.4 | BPD-H (9M; 17F) | Functional: AUDIT | ||||
HC-L: 22.4 ± 2.6 | HC-L (6M; 14F) | |||||
HC-H: 23.4 ± 3.2 | HC-H (6M; 8F) | |||||
[193] | AD: 24 ± 3.77 | AD (44M; 47F) | Explore the use of a startle paradigm and its association with alcohol use. | Nα: Startle, ERP | AD: ↑ facilitation, ↓ inhibition of the N4S component by pre pulse stimuli. | |
BD: 24.6 ± 5.76 | BD (23M; 18F) | Functional: SSAGA, FHAM | ||||
AFF: 22.9 ± 3.94 | AFF (32M; 65F) | |||||
DD: 23.5 ± 3.17 | DD (51M; 61F) | |||||
Clinical syndrome
| [128] | ANX : 12.9 ± 2.6 | ANX (7M; 13F) | Examine the relationship between ASR, symptom reduction and treatment success. | Nα: Multiple muscle ASR | ANX: ↓ in multiple muscle ASR ~ ↓ in anxiety symptoms. |
HC: 12.0 ± 2.5 | HC (10M; 15F) | Clinical: ADIS-C/P, SCAS | ||||
ANX: ↑ multiple muscle ASR predicted CBT treatment response | ||||||
[133] | OCD: 13.9 ± 2.4 | OCD (18M; 22F) | Assess ERN as a biomarker for OCD | Nα: ERN | OCD & SIB: ↑ ERN at Cz (independent of symptom severity, current diagnostic status and treatment effects). | |
SIB: 13.9 ± 2.4 | SIB (13M; 6F) | Clinical: Y-BOCS, CBCL, MASC, CDI | ||||
HC: 13.8 ± 2.3 | HC (20M; 20F) | |||||
[134] | ANX: 11.8 ± 2.3 | ANX (3M; 10F) | Demonstrate ERN amplitude is increased in young anxiety patients. | Nα: ERN | ANX & OCD: ↑ ERN at Cz (independent of symptom severity, current diagnostic status and treatment effects). | |
OCD: 12.7 ± 2.2 | OCD (8M; 18F) | Clinical: Y-BOCS, CBCL, MASC, CDI | ||||
HC: 12.4 ± 2.2 | HC (14M; 13F) | |||||
[194] | RES: 14.1 ± 2.8 | RES (2M; 6F) | Examine the relationship between TMS with subsequent treatment response | Nα: TMS | NoRES: ↑ deficits in pre-treatment LICI | |
NoRES: 13.1 ± 1.6 | NoRES (5M; 3F) | Clinical: CDRS-R, QIDS, CGI-severity scale | ||||
[195] | HC: 25.54 ± 3.41 | HC (28M; 16F) | Investigate the intensity evaluation of social stimuli in depression | Nα: ERP (N170, P1, P2) | MDD: ↑ intensity scores for sad faces compared with HC, ↑ reaction times for all faces and ↑ P1 & P2 amplitude for sad faces | |
DEP: 25.96 ± 4.58 | DEP (9M; 15F) | Clinical: SCID, BDI, HDRS, BAI | ||||
MDD: 26.58 ± 4.16 | MDD (10M; 14F) | |||||
DEP: ↓ scores for happy and neutral faces, ↑ reactions times and ↑ P1 & P2 amplitude for happy faces compared to sad faces. | ||||||
[196] | HC: 27.7 ± 7.0 | HC (14M; 12F) | Assess brain function impairments in bipolar patients. | Nα: Resting EEG | BPD: ↑ power in all wave bands. Marked increases in right temporal theta and left occipital beta. | |
BPD: 30.7 ± 6.1 | BPD (10M; 19F) | Clinical: BDI | ||||
[135] | OCD: 13.3 ± 2.8, | OCD (13M; 5F) | Examine ERN in paediatric patients with OCD | Nα: ERN | OCD: ↑ ERN pre-treatment and after treatment. No relationship with symptom severity or changes in symptom severity | |
HC: 11.9 ± 2.6 | HC (8M; 10F) | Clinical : Y-BOCS | ||||
[197] | HC: 17 ± 1.6 | HC (43F) | Evaluate the effects of depression and a family history of alcohol or substance dependence on P300. | Nα: ERP (P300) | DD: ↓ P300 amplitude. No effect of family history of alcohol or drug dependence. | |
HC-FHA: 16.5 ± 1.3 | HC-FHA (31F) | Clinical: SSAGA, MAST, PANAS | ||||
HC-FHD: 16.1 ± 1.5 | HC-FHD (27F) | |||||
DEP: 17.2 ± 1.4 | DD (12F) | |||||
DEP-FHA: 17.3 ± 1.5 | DD-FHA (9F) | |||||
DEP-FHD: 16.3 ± 1.3 | DD-FHD (8F) | |||||
[191]* | MDD: 17.1 ± 0.6 | MDD (8F) | Investigate the effect of acute nicotine administration on resting EEG activity and affect | Nα: EEG | MDD: Nicotine ↓ theta amplitude in right parietal region. No associations with mood. | |
Clinical: BDI, HONC, PANAS | ||||||
[129] | MDD: 30.4 ± 11.8 | MDD (28M; 23F) | Assess the utility of baseline LDAEP predicting response to antidepressants. | Nα: LDAEP | MDD: steep N1 sLORETA-LDAEP at BL ~ treatment response. ↑ P2 sLORETA-LDAEP slope at week 1 ~ treatment response. | |
Clinical: HDRS, MADRS | ||||||
[167]* | OCD: 27 ± 9.8 | OCD (15M; 16F) | Characterize the cognitive functions of the patients with OCD by utilizing ERPs and neuropsychological tests | Nα: ERP (P300) | OCD: ↓ P300 duration. ↓ stroop duration ~ ↑ P300 amplitude in occipital, parietal and temporal anterior regions. | |
HC: 27.4 ± 9.1 | HC (14M; 16F) | Clinical: HDRS | ||||
[52]* | OCD: 24.06 ± 5 | OCD (21M; 9F) | Assess the relationship between cognitive dysfunction, clinical status and severity in OCD. | Nα: ERP (N100, P200, N200, P300) | OCD: ↑ P200 amplitude, unrelated to neither severity nor chronicity of illness. ↓ N200 amplitude (worsens with ↑ severity). ↓ N100 and P200 ~ ↑ chronicity | |
HC: Matched | HC (21M; 9F) | |||||
Clinical: YBOCS | ||||||
[136] | OCD-U: 25 ± 8.0 | OCD-U (9M; 10F) | Examine the effects of chronic medication on error responses in OCD. | Nα: ERN | OCD: ↑ ERN, irrespective of medication use. | |
OCD-M: 30.8 ± 9.5 | OCD-M (9M; 10F) | Clinical: HDRS, HAMA, YBOCS | ||||
PC-M: 31.7 ± 10.6 | PC-M (8M; 11F) | HC & PC: ↑ anxiety and depression ~ ↑ ERN amplitude | ||||
HC: 25.3 ± 7.5 | HC (11M; 10F) | |||||
[127] | DEP: 20.9 ± 0.55 | DEP (515) | Examine whether recurrent major depression is associated with abnormal startle | Nα: ASR | DEP: ↑ ASR was associated with multiple (more than 1) depressive episode. | |
Clinical: SCID |
Outcome measure | Study | Age (mean ± SD) | Sample (N) | Aims | Key measures | Key findings |
---|---|---|---|---|---|---|
Social and participation
| [140]* | MHP: 28.74 ± 10.38 | MHP (38M; 28F) | Identify changes in the rates of obesity in never-treated patients with mood disorder over 4 years of follow-up. | Metabolic: BMI | MHP: ↑ BMI ~ ↑ social and economic participation |
(40 MDD, 26 BPD) | Functional: GAF | |||||
Physical health
| [198] | FH+: 18.9 ± 1.0 | FH+ (32M, 53F) | Determine whether young people with a family history of depression have altered metabolic markers. | Metabolic/Functional: glucose, lipids and high-sensitivity CRP. BP, arterial stiffness and waking cortisol concentration. | FH+: ↑ peripheral and central BP, arterial stiffness and ↓ insulin sensitivity |
HC: 19.1 ± 0.1 | HC (27M; 42F) | |||||
Suicide and self-harm
| [138] | SUC: 15.93 ± 1.48 | SUC (15M; 32F) | Examine the relationship between serum cholesterol levels and suicidal behaviours | Metabolic: blood serum samples | SUC: ↑ cholesterol ~ current suicide behaviour (within the SUC group, ↑ serum cholesterol ~ ↓ severity of SUC, but not ~ symptom severity) |
PC: 16.22 ± 1.95 | PC (58M; 47F) | Functional: SPI | ||||
PD: 25.3 ± 3.3 | PD (37M; 35F) | Elucidate the relationships between alexithymia, suicide ideation and serum lipid levels. | Metabolic: BMI, blood serum samples | PD: ↓ HDL-C and ↑ VLDL-C ~ higher suicide ideation | ||
Functional: SSI | ||||||
[137] | SA: 15.44 ± 1.99 | SA (17M; 49F) | Explore the associations between cholesterol and suicidal behaviour | Metabolic: blood serum samples | SA: ↓ cholesterol levels ~ attempted suicide history | |
PC: 15.19 ± 1.68 | PC (15M; 39F) | Functional: hospital records | ||||
[199] | SA: 16.8 SEM = .74 | SA (3M; 6F) | Investigate platelet PBR density in suicidal teens | Metabolic: blood serum samples | SA: ↓ platelet PBR density | |
PC: 16.5 SEM = .5 | PC (7M; 3F) | Functional: hospital records, SPI, SRS | ||||
[155] | SA: 15.87 ± 1.56 | SA(10M; 25F) | Evaluate the relationship between plasma serotonin levels and psychometric measures in suicidal adolescents | Metabolic: blood serum samples | SA: ↓ plasma 5-HT level ~ ↑ suicidality. (5-HT did not discriminate between the psychiatric diagnostic categories) | |
PC: 16.29 1.81 | PC (19M; 11F) | Functional: hospital records, SPI | ||||
ER: 16.91 2.47 | ER (13M; 38F) | |||||
HC: 15.26 1.41 | HC (45M; 50F) | |||||
Alcohol and substance use
| [200] | BPD-O: 12.9 ± 3.1 | BPD-O (77M; 68F) | Investigate obesity in paediatric bipolar patients and notable correlates | Metabolic: BMI | BPD: SUD ~ 2.8 fold increased prevalence of BPD-OB. |
BPD-NO: 13.3 ± 3.0 | BPD-NO (108M; 95F) | Functional: K-SADS-P | ||||
Clinical syndrome
| [162] | MDD: 24.1 ± 3.2 | MDD (45M; 44F) | Examine the association between MDD in childhood and BMI in adulthood | Metabolic: BMI | MDD: ↑ BMI at FUP (in adulthood) |
HC: 22.2 ± 2.9 | HC (43M; 45F) | Clinical: KSADS, | ||||
[140]* | MHP: 28.74 ± 10.38 | MHP (38M; 28F) | Identify changes in the rates of obesity in never-treated patients with mood disorder over 4 years of follow-up. | Metabolic: BMI | MHP: clinical improvement ~ ↑ BMI | |
(40 MDD, 26 BPD) | Clinical: HAMD |