Table 2:

Longitudinal MRS studies of pediatric bipolar disorder and youth at risk for bipolar disorder

Study	Sample	Methods (Device/FS/TR/TE/Sequence)	Region-of-Interest Voxel Size and Location	Findings
Davanzo et al, 2001⁷⁸	11 Patients with BD mania, medicated (n = 9), unmedicated (n = 2), (mean age, 11.4 yr),	Signa^{^a}/1.5T/3000/30/PRESS	8 mL in the anterior cingulate cortex	↓ mIns/tCre was associated with acute lithium treatment (P = .047);
				↓ mIns/tCre in lithium responders (P < .012);
				mIns/tCre was not significantly different in lithium nonresponders (P < .655);
				NAA/tCre was the metabolite least affected by lithium
	Treatment with lithium for 1 week (mean lithium level = 0.64 mEq/L),
	Scans obtained at baseline and day 7
DelBello et al, 2006⁸¹	19 Unmedicated manic or mixed patients with BD treated with olanzapine, 10–20 mg/day for 4 weeks,	Signa/1.5T/2000/35/PRESS	8 mL in the medial ventral prefrontal cortex,	↑ tChol in medial ventral prefrontal cortex (P = .0001) associated with olanzapine treatment;
	(mean age, 14.7 yr),		8 mL in the left and right ventral lateral prefrontal cortices,	↑ baseline tChol in the medial ventral prefrontal cortex associated with remission at 4 weeks (P = .001);
	10 healthy volunteers, (mean age, 15 yr),		Scans obtained at baseline, day 7, and day 28	↑ NAA for 4 weeks in the medial ventral prefrontal cortex in olanzapine remitters (n = 11) vs ↓ NAA in nonremitters (n = 8) (P = .006);
	10 healthy volunteers, (mean age, 15 yr),		Scans obtained at baseline, day 7, and day 28	↑ NAA for 4 weeks was associated with reduction in YMRS scores (r = 0.68; P = .004)
Patel et al, 2006⁷⁹	28 Unmedicated depressed patients with BD, (mean age, 15.5 yr),	Signa/1.5T/2000/35/PRESS	8 mL in the medial prefrontal cortex,	mIns in medial prefrontal cortex did not significantly differ among baseline, day 7, or day 42;
			8 mL in the left and right lateral prefrontal cortices,	↓ baseline mIns in medial prefrontal cortex in lithium remitters (n = 8) vs non-remitters (n = 20) (P = .003)
	Treatment with lithium for 42 days, titrated to serum levels of 1.0–1.2 mEq/L		Scans obtained at baseline, day 7, and day 42
Chang et al, 2009⁸³	10 Offspring of BD parents with mood symptoms but not BD, medicated (n = 3), unmedicated (n = 7), (mean age, 11.3 yr),	Signa/3T/2000/35/ PRESS	8 mL in the left and right dorsolateral prefrontal cortices,	No significant difference in NAA in the left (P = .88) or right (P = .13) dorsolateral prefrontal cortex associated with 12 weeks of divalproex treatment;
			Scans obtained at baseline and 12 weeks	Effect size for decreased NAA = 0.94 for the right dorsolateral prefrontal cortex;
				Exploratory analyses showed no significant differences in tChol or mIns
	Treatment with divalproex for 12 weeks; mean serum VPA level = 82 μg/mL
Strawn et al, 2012⁷⁶	25 Unmedicated manic or mixed patients with BD (mean age, 14.5),	Varian^{^b}/4T/3000/23/PRESS	8 mL in the anterior cingulate cortex (gray matter),	↓ Glx at baseline in the left ventrolateral prefrontal cortex in treatment remitters (P = .01);
			8 mL in left and right ventrolateral prefrontal cortices (white matter),	In divalproex treatment remitters, change in Glu in the left ventrolateral prefrontal cortex correlated with change in YMRS score (r = 0.82; P = .03)
	Treatment with divalproex for 28 days, titrated to a serum VPA level of 85–125 μg/mL		Scans obtained at baseline, day 7, and day 28
Chang et al, 2012⁸²	26 Unmedicated depressed patients with BD,	Signa/3T/2000/26/ PRESS	8 mL in the anterior cingulate cortex,	↓ Posttreatment mIns in the ACC in quetiapine responders (5 of 16 patients);
	Treatment with either quetiapine (n = 16) or placebo (n = 10) for 8 weeks,	and	8 mL in the left dorsolateral prefrontal cortex,	no significant change in NAA between the quetiapine and placebo groups
	(mean age, 15.6 yr)	Varian/4T/2000/26/PRESS	8 mL in the right dorsolateral prefrontal cortex

Note:—TR and TE are expressed in milliseconds. FS indicates field strength; PRESS, point-resolved spectroscopic sequence; ↓, decreased; ↑, increased; tCre, total creatine; VPA, valproic acid; YMRS, Young Mania Rating Scale.
↵a GE Healthcare, Milwaukee, Wisconsin.
↵b Varian, Palo Alto, California.