Early Variations in White Matter Microstructure and Depression Outcome in Adolescents With Subthreshold Depression
Abstract
Objective:
Method:
Results:
Conclusions:
Method
Participants
Baseline Assessment
Follow-Up Assessment
Baseline | Follow-Up | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Characteristic | Subthreshold Depression Group (N=96) | Control Group (N=336) | Testa | Subthreshold Depression Group (N=81) | Control Group (N=284) | Testa | ||||||
Mean | SD | Mean | SD | F | p | Mean | SD | Mean | SD | F | p | |
Age (years) | 14.47 | 0.38 | 14.41 | 0.40 | 2.26 | 0.13 | 16.47 | 0.49 | 16.43 | 0.52 | 0.42 | 0.52 |
Pubertal Development Scale (0–5) | 3.03 | 0.52 | 2.95 | 0.54 | 0.90 | 0.34 | 3.45 | 0.40 | 3.41 | 0.40 | 0.34 | 0.56 |
N | % | N | % | χ2 | p | N | % | N | % | χ2 | p | |
Female | 62 | 64.58 | 217 | 64.58 | 0.00 | 1 | 52 | 64.20 | 182 | 64.08 | 0.00 | 1 |
Right-handed | 80 | 83.33 | 298 | 88.69 | 1.50 | 0.22 | 67 | 82.72 | 253 | 89.08 | 1.81 | 0.18 |
Parental history of depression | 8 | 8.33 | 24 | 7.14 | 0.03 | 0.86 | 6 | 7.41 | 19 | 6.69 | 0.00 | 0.98 |
Any parental psychiatric history | 15 | 15.63 | 46 | 13.69 | 0.12 | 0.73 | 12 | 13.38 | 38 | 14.81 | 0.02 | 0.88 |
Non-Caucasian ethnicity | 21 | 21.88 | 27 | 8.04 | 13.11 | <0.001 | 13 | 16.05 | 68 | 5.28 | 8.85 | 0.003 |
Adverse childhood experienceb | 12 | 12.50 | 30 | 8.93 | 0.77 | 0.38 | 4 | 4.94 | 28 | 9.86 | 1.34 | 0.25 |
Familial financial difficulties | 36 | 37.50 | 82 | 24.40 | 5.81 | 0.02 | 29 | 35.80 | 73 | 25.70 | 2.71 | 0.10 |
Subthreshold depression at age 16 | 22 | 27.16 | 29 | 10.21 | 13.69 | <0.001 | ||||||
Depression at age 16 | 8 | 9.88 | 7 | 2.46 | 7.01 | 0.008 | ||||||
Self-harm since age 14 | 24 | 29.63 | 24 | 8.51 | 22.65 | <0.001 | ||||||
Anxiety disorder at age 16c | 1 | 1.23 | 5 | 1.76 | 1 | |||||||
Externalizing disorder at age 16d | 1 | 1.23 | 1 | 0.35 | 0.40 | |||||||
Psychosis at age 16 | 0 | 0 | 0 | 0 | ||||||||
Mania at age 16 | 0 | 0 | 1 | 0.35 | 1 | |||||||
Monthly cannabis use at age 16 | 6 | 7.41 | 18 | 6.33 | 0.01 | 0.93 | ||||||
Alcohol abuse at age 16e | 15 | 23.81 | 26 | 12.38 | 4.10 | 0.04 | ||||||
Mean | SD | Mean | SD | U | p | Mean | SD | Mean | SD | U | p | |
NEO Five-Factor Inventory | ||||||||||||
Neuroticism | 29.11 | 7.46 | 20.97 | 6.76 | 6,802 | <0.001 | 27.16 | 6.42 | 20.67 | 7.28 | 5,483 | <0.001 |
Extraversion | 27.83 | 6.68 | 30.75 | 5.30 | 19,924 | <0.001 | 27.58 | 6.33 | 30.26 | 5.59 | 13,961 | <0.001 |
Openness | 26.47 | 6.55 | 26.30 | 5.57 | 16,070 | 0.96 | 28.21 | 6.47 | 27.46 | 6.03 | 10,610 | 0.47 |
Agreeableness | 26.44 | 5.67 | 30.91 | 5.07 | 23,380 | <0.001 | 27.31 | 5.11 | 31.03 | 5.55 | 15,633 | <0.001 |
Conscientiousness | 26.57 | 7.35 | 29.19 | 6.45 | 19,572 | 0.001 | 26.73 | 7.62 | 29.65 | 6.79 | 13,635 | 0.003 |
Substance Use Risk Profile Scale | ||||||||||||
Hopelessness | 14.89 | 3.93 | 12.42 | 2.54 | 10,079 | <0.001 | 14.18 | 3.98 | 12.44 | 3.06 | 8,174 | <0.001 |
Anxiety-sensitivity | 11.86 | 2.43 | 11.05 | 2.24 | 13,320 | 0.009 | 11.35 | 2.53 | 10.95 | 2.38 | 9,920 | 0.14 |
Impulsivity | 13.04 | 2.37 | 11.42 | 2.01 | 9,924 | <0.001 | 12.03 | 2.06 | 10.95 | 2.11 | 7,815 | <0.001 |
Sensation seeking | 16.21 | 3.03 | 15.58 | 3.13 | 14,362 | 0.10 | 13.83 | 2.61 | 13.80 | 2.80 | 11,306 | 0.82 |
Life Events Questionnaire score (−78 to +78) | –1.90 | 4.75 | –0.23 | 4.44 | 19,319 | 0.003 | 0.61 | 5.45 | 2.11 | 4.33 | 12,526 | 0.045 |
Diffusion MRI Acquisition and Preprocessing
Tract-Based Spatial Statistic
Probabilistic Diffusion Tractography
Statistical Analysis
Cross-sectional analyses.
Longitudinal analyses.
Post hoc analyses.
Results
Demographic and Clinical Characteristics
DTI Whole Brain Analyses
Subthreshold Depression Group (N=96) | Control Group (N=336) | Test | ||||
---|---|---|---|---|---|---|
Characteristic | Mean | SD | Mean | SD | F (df=1, 425) | p |
DTI global measures | ||||||
Global FA values (×10–1) | 4.47 | 0.17 | 4.50 | 0.20 | 3.96 | 0.047 |
Global MD values (×10–4) | 7.35 | 0.24 | 7.26 | 0.20 | 2.38 | 0.12 |
Global AD values (×10–3) | 1.13 | 0.34 | 1.12 | 0.29 | 0.28 | 0.60 |
Global RD values (×10–4) | 5.40 | 0.23 | 5.31 | 0.22 | 3.89 | 0.049 |
DTI measures within the cluster region identified in voxel-wise comparisonb | ||||||
FA values (×10–1) | 6.23 | 0.38 | 6.39 | 0.39 | 19.41 | <0.001 |
RD values (×10–4) | 5.38 | 0.24 | 5.20 | 0.24 | 30.84 | <0.001 |
Tractography analysesc | ||||||
Tracts spanning from the anterior corpus callosum cluster to the anterior cingulate cortex | ||||||
FA values (×10–1) | 4.51 | 0.31 | 4.60 | 0.34 | 10.06 | 0.01 |
MD values (×10–4) | 8.04 | 0.46 | 7.85 | 0.36 | 8.56 | 0.03 |
AD values (×10–3) | 1.24 | 0.06 | 1.22 | 0.05 | 1.58 | 0.21 |
RD values (×10–4) | 5.85 | 0.49 | 5.66 | 0.42 | 10.93 | 0.001 |
Right cingulum bundle | ||||||
FA values (×10–1) | 3.45 | 0.34 | 3.59 | 0.39 | 9.13 | 0.03 |
MD values (×10–4) | 8.16 | 0.54 | 7.98 | 0.45 | 0.01 | 1 |
AD values (×10–3) | 1.13 | 0.07 | 1.12 | 0.06 | 0.02 | 0.88 |
RD values (×10–4) | 6.60 | 0.54 | 6.40 | 0.48 | 7.29 | 0.007 |
Left cingulum bundle | ||||||
FA values (×10–1) | 3.71 | 0.39 | 3.80 | 0.41 | 5.17 | 0.24 |
MD values (×10–4) | 8.24 | 0.54 | 8.08 | 0.45 | 2.39 | 1 |
Right uncinate bundle | ||||||
FA values (×10–1) | 3.99 | 0.39 | 3.99 | 0.35 | 0.02 | 1 |
MD values (×10–4) | 7.85 | 0.40 | 7.73 | 0.29 | 0.45 | 1 |
Left uncinate bundle | ||||||
FA values (×10–1) | 4.01 | 0.49 | 3.99 | 0.48 | 0.42 | 1 |
MD values (×10–4) | 8.01 | 0.47 | 7.88 | 0.29 | 0.12 | 1 |
Tractography Analysis
Longitudinal Analyses
Effect Type | Point Estimate | 95% CI | p |
---|---|---|---|
Mediator variable: FA values | |||
Mediation effect (subthreshold depression at age 14–FA–depression at age 16) | 0.018 | 0.004, 0.044 | 0.01 |
Direct effect (subthreshold depression at age 14–depression at age 16) | 0.067 | –0.001, 0.162 | 0.06 |
Total effect | 0.085 | 0.016, 0.184 | 0.01 |
Proportion of total effect via mediation | 0.206 | 0.042, 0.902 | |
Mediator variable: MD values | |||
Mediation effect (subthreshold depression at age 14–MD–depression at age 16) | 0.010 | 0.000,0.027 | 0.06 |
Direct effect (subthreshold depression at age 14–depression at age 16) | 0.073 | 0.008, 0.016 | 0.02 |
Total effect | 0.083 | 0.016, 0.177 | 0.01 |
Proportion of total effect via mediation | 0.017 | –0.002, 0.512 |
Post Hoc Analyses
Discussion
Acknowledgments
Footnotes
Supplementary Material
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