Table 1.

Diffusion tensor imaging (DTI) studies of children and adolescents with bipolar disorder and/or at-risk for bipolar disorder.

Authors and Year	Subjects	Mean Age	Age Range (years)	DTI Measures	Analysis Type	Regions of Interest	Findings and Overall Significance Levels
		(year ± SD)
Studies of children and adolescents at-risk for BD
Versace et al. 2010 [101]	20 AR-BD 25 HC	13.2 ± 2.5 13.9 ± 2.6	8–17	FA, RD, L1	TBSS	Whole brain	AR-BD > HC: FA in left CC body, L1 in right ILF
							AR-BD < HC: RD in left CC body, right ILF
							Significant group-by-age interaction:
							HC: FA increases/RD decreases with age in left CC body; RD decreases with age in right ILF; L1 increases with age in right ILF
							AR-BD: FA decreases/RD increases with age in left CC body; RD no relation with age in right ILF; L1 decreases with age in right ILF
							AlphaSim corrected p < 0.05
Studies of children and adolescents both with BD and at-risk for BD
Frazier et al. 2007 [102]	7 AR-BD 10 BD 8 HC	8.9 ± 3.0 9.2 ± 3.0 9.2 ± 2.4	4–12	FA	Voxel-based	A priori CPC and SLF, and whole brain	BD < HC: FA in bilateral CPC and SLF, right CC body, left OF WM
							AR-BD < HC: FA in bilateral SLF
							BD < AR-BD: FA in bilateral CPC
							p < 0.05 Bonferroni corrected
Studies of children and adolescents with BD
Adler et al. 2006 [103]	11 BD 17 HC	14 ± 2	10–18	FA, trace ADC	ROI	Frontal and posterior regions	BD < HC: FA in bilateral superior frontal WM tracts
							p < 0.01 uncorrected
Kafantaris et al. 2009 [104]	26 BD 26 HC	16.0 ± 1.5 15.3 ± 1.5		FA, ADC	Voxel-based	Whole brain	BD < HC: FA in right OF WM, bilateral temporal lobes, left occipital lobe
							BD > HC: ADC in bilateral subgenual region, bilateral precuneus, left postcentral gyrus, left temporal and right occipital lobes
							p < 0.005 uncorrected, cluster size ≥100
Pavuluri et al. 2009 [105]	13 BD 13 ADHD 15 HC	14.8 ± 2.5 13.4 ± 3.0 13.7 ± 2.7		FA, ADC, r-FCI	ROI and voxel-based	ACR, ALIC, CB, CC (splenium), ILF, PLIC, SLF, SRI	BD and ADHD < HC: FA in ACR, r-FCI in CC splenium
							BD and ADHD > HC: ADC in CC splenium
							p < 0.05 uncorrected
Barnea-Goraly et al. 2009 [106]	21 BD 18 HC	16.1 ± 2.7 14.5 ± 2.7	9–18	FA, trace values (average diffusivity), ADC	TBSS	Whole brain	BD < HC: FA in CC, PCR, left mid-posterior CB, fornix, fibers from fornix to thalamus
							p < 0.05 corrected
Gönenç et al. 2010 [107]	10 BD (8 in study) 10 HC (8 in study)	3M: 16.6 ± 4.87 F: 11.8 ± 4.5 6M: 10.6 ± 4.0 4F: 14.3 ± 1.9	6–18	FA, trace diffusivity, RD, AD	ROI	Bilateral CPC	BD < HC: FA left CPC
							BD > HC: left and right trace and left RD in CPC
							p < 0.05 uncorrected
Saxena et al. 2012 [108]	10 BD 10 HC	13.9 ± 3.6 13.6 ± 3.6	7–17	FA	TBSS	5 CC	BD < HC: FA genu CC and AC
						subdivisions, AC	p < 0.001 uncorrected, p < 0.05 small-volume FDR correction
Gao et al. 2013 [109]	18 BD 18 HC	15.1 ± 1.8 14.1 ± 1.6	10–18	FA	TBSS	Whole brain	BD < HC: FA right anterior CB
							p < 0.05 FDR correction
Abbreviations
							PCR	Posterior corona radiate
AC	Anterior commissure			CPC	Cingulate-paracingulate		PLIC	Posterior limb of the internal capsule
ACR	Anterior corona radiate			DTI	Diffusion tensor imaging		OF	Orbitofrontal
AD	Axial diffusivity			F	Female		r-FCI	Regional fiber coherence index
ADC	Apparent diffusion coefficient			FA	Fractional anisotropy		RD	Radial diffusivity
ADHD	Attention deficit hyperactivity disorder			FDR	False discovery rate		ROI	Region of interest
ALIC	Anterior limb of the internal capsule			HC	Healthy comparison		SD	Standard deviation
AR-BD	At-risk for BD, i.e., having a first-degree relative with BD			ILF	Inferior longitudinal fasciculus		SLF	Superior longitudinal fasciculus
BD	Bipolar disorder			L1	Longitudinal diffusivity		SRI	Superior region of the internal capsule
CB	Cingulum bundle region			M	Male		TBSS	Tract-based spatial statistics
CC	Corpus callosum						WM	White matter