Cross-sectional MRS studies of pediatric bipolar disorder
| Study | Sample | Methods (Device/FS/TR/TE/Sequence) | Region-of-Interest Voxel Size and Location | Findings |
|---|---|---|---|---|
| Castillo et al, 200066 | 10 Patients with BD, mood state not reported, unmedicated, (mean age, 8 yr), 10 non-aged-matched healthy volunteers | Not stated/1.5T/3000/30/PRESS | 8 mL or 27 mL in the left and right frontal lobe, 8 mL or 27 mL in the left and right temporal lobe | ↑ Glx/tCre in BD in the frontal lobe and basal ganglia; No significant difference in NAA/tCre or tChol/tCre |
| Davanzo et al, 200178 | 11 Patients with BD, mixed state (n = 9), manic state (n = 2), medicated (n = 9), unmedicated (n = 2), (mean age, 11.4 yr), 11 age- and gender-matched healthy volunteers | Signaa/1.5T/1500/135/PRESS | 8 mL in the anterior cingulate cortex | Trend (P = .054) toward ↑ mIns/tCre in BD |
| Moore and Galloway, 200250 | 9 Youth with BD with mean serum lithium level = −0.87 mEq/L, mood state not reported, (mean age, 13.4 yr), | Signaa/1.5T/25,000/not stated/1D-ISIS | 60-mm axial section centered on the superior edge of the ventricles | Mean brain lithium concentration = 0.52 mEq/L in pediatric patients with BD; |
| Lithium-7 MRS was used to measure brain lithium concentrations in vivo | mean brain lithium concentration = 0.92 mEq/L in adult patients with BD; | |||
| 18 adults with BD with mean serum lithium level = 0.78 mEq/L, mood state not reported, (mean age, 37.3 yr) | lower brain-to-serum concentration ratiosb in youth with BD compared with adults: 0.58 vs 0.92 (P < .02); | |||
| brain-to-serum concentration ratio correlated positively with age (r = 0.44; P < .02); | ||||
| formula for brain-to-serum lithium concentration ratiob; | ||||
| (brain lithium in mEq/L) / (serum lithium in mEq/L) | ||||
| Chang et al, 200370 | 15 Patients with BD with at least 1 parent with BD, mood state euthymic (n = 15), medicated (n = 14), unmedicated (n = 1), (mean age, 12.6 yr), 11 healthy volunteers (mean age, 12.6 yr) | Signaa/3T/2000/35/PRESS | 8 mL in left and right dorsolateral prefrontal cortices | ↓ NAA/tCre in BD in the right dorsolateral prefrontal cortex (P < .02) |
| Davanzo et al, 200375 | 10 Patients with BD, mood state manic (n = 2), mood state mixed (n = 8), medicated (n = 7), unmedicated (n = 3), (mean age, 9.8 yr), | Signaa/1.5T/3000/30/PRESS | 8 mL in the anterior cingulate cortex, | ↑ mIns and mIns/tCre in anterior cingulate in BD compared with both intermittent explosive disorder and healthy volunteers (P <0.02); |
| 10 patients with intermittent explosive disorder, (mean age, 9.6 yr), | 8 mL in the occipital cortex | ↓ tChol/tCre in anterior cingulate in BD compared with healthy volunteers (P = .05); | ||
| 13 healthy volunteers, (mean age, 11.7 yr) | no significant group differences in occipital cortex mIns, mIns/tCre, or tChol/tCre | |||
| Sassi et al, 200571 | 14 Patients with BD, mood state euthymic (n = 13), mood state depressed (n = 1), medicated (n = 13), unmedicated (n = 1), (mean age, 15.5 yr), | Signaa/1.5T/1500/20/STEAM | 8 mL in the left dorsolateral prefrontal cortex | ↓NAA in BD (P = .03); |
| 18 healthy volunteers, (mean age, 17.3 yr) | tChol was negatively correlated with the number of previous BD episodes (r = −0.86; P =.0001) | |||
| Moore et al, 200767 | 10 Unmedicated patients with BD mania, (mean age, 11.1 yr), | Signaa/1.5T/2000/30/Probe-P(PRESS) and MRSI; TR/TE not stated | 4.8 mL in the anterior cingulate cortex | ↓ Glx/tCre in BD mania compared with BD risperidone-treatment responders (P < .05) |
| 8 patients with BD on risperidone; mean dose = 2.09 mg; mean duration = 101 weeks (mean age, 10.9 yr) | ||||
| Moore et al, 200768 | 22 Patients with BD, euthymic state (n = 2), depressed state (n = 1), manic state (n = 10), mixed state (n = 9), medicated (n = 15), unmedicated (n = 7), (mean age, 12.6 yr), | Varianc 4T/2000/30/PRESS | 8 mL in the anterior cingulate cortex | ↓ Gln in unmedicated BD (n = 7; mean age, 12.9 yr) compared with both medicated BD (P = .003) and healthy volunteers (P = .027); |
| 10 healthy volunteers, (mean age, 12.3 yr) | no significant difference in Glu among the 3 groups | |||
| Olvera et al, 200772 | 35 Patients with BD, (mean age, 13.2 yr), mood state not reported, medicated (n = 24), unmedicated (n = 11), | Interab/1.5T/6000/30/PRESS | 8 mL in the left dorsolateral prefrontal cortex | ↓ NAA in BD (P = .04); |
| 36 healthy volunteers, (mean age, 13.7 yr) | no significant difference in Glu, tCre, tChol, or mIns | |||
| Patel et al, 200874 | 28 Unmedicated depressed patients with BD, (mean age, 15.5 yr), | Signaa/1.5T/2000/35/Probe-P(PRESS) | 8 mL in the anterior cingulate cortex, and the left and right ventral lateral prefrontal cortices | ↑ NAA in BD in the anterior cingulate cortex, (P = .0002) and the left (P = .0008) and right (P = .002) ventral lateral prefrontal cortices; |
| 10 healthy volunteers, (mean age, 14.6 yr) | ↑ tChol in BD in the left (P = .001) and right (P = .01) ventral lateral prefrontal cortices; | |||
| ↑ mIns in BD in the right (P = .002) ventral lateral prefrontal cortex; | ||||
| in general, patients with BD had higher neurometabolite concentrations than healthy volunteers | ||||
| Caetano et al, 201173 | 43 Patients with BD, euthymic state (n = 8), depressed state (n = 11), manic state (n = 12), mixed state (n = 12), medicated (n = 31), unmedicated (n = 12), (mean age, 13.2 yr), | Interb/1.5T/1500/272/MRSI | 8 mL in bilateral medial prefrontal cortex, dorsolateral prefrontal cortex, anterior and posterior cingulate cortices, and occipital lobe | ↓ NAA in BD in the left (P = .002) and right (P = .004) medial prefrontal cortices; |
| ↓ GPC+PC in BD in left (P = .006) and right (P = .002) right) medial prefrontal cortices; | ||||
| ↓ PCr+Cr in BD in the left medial prefrontal cortex (P = .005); | ||||
| 38 healthy volunteers, (mean age, 13.9 yr) | ↓ NAA in BD in the left dorsolateral prefrontal cortex (P = .013); | |||
| ↓ PCr+Cr in BD (P = .011) in the left dorsolateral prefrontal cortex | ||||
| Shi et al, 201253 | 14 Depressed patients with BD, medicated (n = 6), unmedicated (n = 8), (mean age, 15.6 yr), | Triod/3T/3000/2.3/31P-MRSI; No 1H decoupling; dual-tuned 1H and 31P head coil | 15.625 mL in the frontal lobe | ↓ Pi/TP in unmedicated BD vs healthy controls; |
| 24 healthy volunteers, (mean age, 15.7 yr) | ↑ PCr/Pi ratio in unmedicated BD compared with healthy volunteers (24%; P = .013) and with medicated BD (39%; P = .002) | |||
| Sikoglu et al, 201354 | 8 Patients with BD, mood state euthymic (n = 3), mood state mixed, manic, or depressed (n = 5), medicated (n = 8), unmedicated (n = 0), (mean age, 16.9 yr), | Varianc/4T/3000/1.2/31P-MRSI; no 1H decoupling; dual-tuned 1H and 31P head coil | 540 mL global sagittal whole-brain slab, | ↓ Global Pi/TP in BD (P= .021); |
| 8 healthy volunteers, (mean age, 15.5 yr) | 108 mL in the frontal lobe | ↑ PCr/Pi global ratio in BD (P= .05); | ||
| Frontal pHi increased with age in BD (Spearman ρ = 0.64) | ||||
| Weber et al, 201355 | 19 Unmedicated patients with manic BD, | Varianc/4T/500/not stated/31P-MRSI | 11-mL effective voxel size in the anterior cingulate cortex | ↓ pHi in manic BD vs HC (P = .03); |
| (mean age, 15.5 yr), | and | ↓ ADP in manic BD vs HC (P = .01) | ||
| 14 unmedicated patients with euthymic BD, | Varianc/4T/2000/23/PRESS; | |||
| (mean age, 16.1 yr), | no 1H decoupling; dual-tuned 1H and 31P head coil | |||
| 20 healthy volunteers, | ||||
| (mean age, 15.4 yr) |
Note:—TR and TE are expressed in milliseconds. FS indicates field strength; 1D-ISIS, adiabatic 1D image-selected in vivo spectroscopy; PRESS, point-resolved spectroscopic sequence; Probe-P(PRESS), proton brain examination single-voxel PRESS; MRSI, multivoxel MRS imaging; 31P-MRSI, multivoxel phosphorus MRS imaging; ↓, decreased; ↑, increased; 31P-MRS, phosphorus 31 MRS; ADP, adenosine diphosphate; GPC, glycerophosphocholine; PC, phosphocholine; pHi, intracellular pH; tCre, total creatine; TP, total 31P signal.
↵a GE Healthcare, Milwaukee, Wisconsin.
↵b Philips Healthcare, Best, the Netherlands.
↵c Varian, Palo Alto, California.
↵d Siemens, Erlangen, Germany.