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Table 4 Imaging studies evaluating the five functional domains 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 [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
  1. Note. Sample: ADHD attention deficit hyperactivity disorder, ANX anxiety disorder, AUD alcohol use disorder, BPD bipolar disorder, BPD-I bipolar disorder I, BPD-O bipolar disorder with obesity, BPD-L bipolar disorder with low alcohol use, BPD-H bipolar disorder with high alcohol use, BPD-N bipolar disorder without obesity, BPD-NOS bipolar disorder not otherwise specified, BPD-R bipolar disorder remitters, BPD-NR bipolar disorder non remitters, BPD-RE bipolar disorder responders to pharmacotherapy, BPD-NRE bipolar disorder non responders to pharmacotherapy, DD depressive disorder, CU cannabis user, GAD generalised anxiety disorder, gSP generalised social phobia, HC healthy controls, HC-O healthy controls with obesity, HC-N healthy controls without obesity, MDD major depression disorder, MDDx major depression disorder with borderline personality disorder, MHP mental health patients (mixed diagnosis sample), MT childhood maltreatment, OCD obsessive compulsive disorder, PC psychiatric control (i.e. psychiatric diagnosis but no suicide attempt), PSD psychotic spectrum disorder, SA suicide attempters, ST stage of illness; 1B, 2, & 3, SAD social anxiety disorder
  2. Measures: AAS anxiety analogue scale, ACQ alcohol consumption questionnaire, ADIS anxiety disorders interview schedule, ASI addictions severity index, AUDIT alcohol use disorder identification test, BDI beck depression inventory, BMI body mass index, PRS brief psychiatric rating scale, CALS child affect liability scale, CBCL child behaviour checklist, CDI children’s depression inventory, CDRS children’s depression rating scale; R revised, CGAS children’s global assessment scale, CGI clinical global impression scale, ChIPS children’s interview for psychiatric syndromes, CDDR customary drinking and drug use record, CGAS child global assessment scale, C-CASA Columbia Classification Algorithm of Suicide Assessment, CSHF Colombia Suicide History Form, DTI diffuse tensor imaging, DUSI drug use screening inventory, FH-RDC family history-research diagnostic criteria, fMRI functional magnetic resonance imaging, GAF global assessment of functioning, HAMA Hamilton anxiety rating scale, HDRS Hamilton depression rating scale, K-SADS kiddie schedule for affective disorders and schizophrenia, LHAUD lifetime history of alcohol use disorder, LIFE modified longitudinal interval follow-up examination, LOI-CV Leyton Obsessive Inventory-Child Version, LSAS Liebowitz social anxiety scale, MASC multidimensional anxiety scale for children, MCQ meta cognition questionnaire, MFQ Mood frequencies questionnaire, MRS magnetic resonance spectroscopy, PET positron emission tomography, PRS Pfeffer rating scale, OCDAS obsessive compulsive disorder analogue scale, RCADS the revised child anxiety and depression scale, SAC substance abuse course-modified life II, SCARED screen for child anxiety related disorders, SCID structured clinical interview for DSM, SIQ suicide ideation questionnaire, SIS suicide intent scale, SOFAS social and occupational functioning assessment scale, sMRI structural magnetic resonance imaging, STAI-C state- trait anxiety inventory – child version, TLFB time-line followback, VBM voxel-based morphometry, Y-BOCS Yale–Brown obsessive-compulsive scale, YMRS young mania rating scale, YSRS the youth self-report scale
  3. Findings: ↑ = Increased, Improved or Higher, ↓ = Decreased, Reduced or Lower, ~ = ‘is associated with’, ACC anterior cingulate cortex, AD Axial diffusivity, ACG Anterior Cingulate Gyrus, BA Broadman Area -24, BL baseline, CV cerebellar vermis, DmPFC dorsomedial prefrontal cortex, DWMH deep white matter hyperintensities, FA fractional anisotropy, GABA gamma-aminobutyric acid, GM grey matter, GMV grey matter volumes, GSH glutathione, iFC intrinsic functional connectivity, LFG left fusiform gyrus, MD mean diffusivity, MFG middle frontal gyus, MPFC medial prefrontal cortex, OFC orbitofrontal cortex, RD radial diffusivity, PVH periventricular hyperintensities, PCG precentral Gyrus, PFC prefrontal cortex, TBV total brain volumes, TLV temporal lobe volume, VMPFC ventromedial prefrontal cortex, WMH white matter hyperintensities, WMV White Matter Volumes
  4. *indicates that the study features more than once in the data synthesis