Table 1:
STROBE Checklist of studies included in the meta-analysis
| Study | Region(s) examined | Objective and descriptive information |
Study Design | Statistical methods |
a) Summary of key results b) Limitations, sources of potential bias |
Source of Funding |
|---|---|---|---|---|---|---|
| FRONTAL LOBE | ||||||
| Pettegrew et al, Arch Gen Psychiatry, 48(6):563, 1991 (17) | Dorsal prefrontal cortex | To examine exaggerated synaptic pruning in the dorsal prefrontal cortex in SZ | Data collected on a 1.5 T Signa system with the spectroscopy research accessory 11 neuroleptic-naïve SZ patients (7 males and 4 females; mean age, 24.4 ±1.8 years) and 10 healthy controls (6 males and 4 females; mean age, 24.1±1.8 years). Duration of illness = 19.1 ±5.9 months |
Pooled variance t-test. Shapiro-Wilks test | a) SZ patients showed lower PME levels and higher PDE and β-ATP levels compared to controls. b) The findings were interpreted to be due to abnormal brain development c) First study to show MPL metabolite differences in first episode SZ |
NIMH grants AG05657 and AG08371 |
| Williamson et al, Arch Gen Psychiatry, 48(6):578, 1991 (24) | Dorsal PFC | Preliminary results of localized 31P MRS in chronic SZ patients and healthy controls | Data acquired on a 2 Tesla Siemens whole body imager using 5-cm transmit/receive surface dual tuned coil. Spectra were exponentially filtered, 0-fitted to 4096 data points, baseline corrected, and fitted with Lorentzian line shapes 10 SZ patients from outpatient (9M/1F; age: 33- 54 years). Mean CPZ equivalent dose=660±436 mg. Length of illness=15.9±5.2 years. 8 patients were on anticholinergic drug and two on a benzodiazepine. 7 controls matched for age and sex also examined. |
ANOVA | a) Lower PME levels in SZ as a U"trait" marker. No differences in PDEs. b) Lower PME may be observed early in the illness b) Small sample size; medicated patients |
Not Reported |
| Fujimoto et al, Acta Psychiatr Scand, 86(6): 455, 1992 (25)* | 10 regions that mainly consisted of frontal, temporal and parietal regions | To examine 31P MRS metabolites in chronic SZ | 16 medicated chronic male SZ patients (age=39±5 years, Mean illness duration=12 yrs), 20 controls (age=34±2 years, 15M/5F). Age of onset=22±4 years (range 18-30 years) Siemens-Asahi scanner at 2.0 Tesla. CSI with a voxel size of 36 cc |
Mann-Whitney U test | a) Elevated PDE levels on the left temporal lobe b) ATP and PCr levels were decreased |
None reported |
| Stanley et al, Schiz Res, 13(3):209, 1994 (8) | Left dorsal prefrontal cortex | Hypothesized that the increase in breakdown of membrane phospholipid metabolites will only be present early in the illness. | 5 cm diameter transmit/receive surface coil switchable between 1H and 31P frequencies on a 2 Tesla whole-body MRI using short pulse sequence repetition time 19 medicated SZ patients (age: 16-54 years; 16 were on anticholinergic medication for side effects) and 18 male controls (age: 18-53 years). The length of illness =1 to 24 years. |
ANOVA | a) Prefrontal PME levels in SZ lower than in controls, which was independent of the length of illness and medication status. PDE levels were increased in the newly diagnosed SZ b. Area of concern is the partial volume effect. CSF contamination could be different between the two groups. |
The Ontario Mental Health Foundation, London Upjohn Neurosciences Program, and Department of Psychiatry Research Trust |
| Deicken et al, Biol Psychiatry, 36(8):503, 1994 (35) | Frontal and parietal lobes | To examine MPL metabolite and high energy phosphate levels in the frontal and parietal lobes of SZ patients |
31P MRSI over single volume MRS technique used in previous studies. 20 male SZ patients and 16 male controls (mean age = 40.3 ± 11.0 years). 6 patients were neuroleptic free. 7 patients on neuroleptics only. 3 on neuroleptic + diphenhydramine and 4 on neuroleptic + benztropine. BPRS, inter correlation coefficient was 0.91 |
Multivariate repeated measures analysis of variance and regression analysis | a) PDE and PCr levels were elevated in SZ patients in bilateral frontal lobes but not parietal lobes compared to controls. b) Higher PDE and PCr levels correlated with hostility-suspiciousness and anxiety-depression subscales of BPRS |
NARSAD YI Award; BRSG grant S07-RR05755 NIH; VA Career Scientist award; UCSF Individual Investigator award; Philips Medical Systems |
| Shioiri et al., Psychiatry Res, 55(4): 223, 1994 (26) | Frontal lobe regions | To examine frontal lobe regions for PME and PDE differences in SZ and controls, and to examine association of neuroleptics with metabolite levels | Data acquired on a 1.5-T SIGNA MR system using a surface coil and depth resolved surface coil spectroscopy (DRESS). VOI was 30 mm slice between the frontal pole and tip of the corpus callosum. 26 SZ inpatients (16 M/10 F; age=31.8±12.4 years; range: 15-63 years; duration of illness 8.7 ± 9.5 years). 6 SZ patients were neuroleptic free for ≥2 weeks. Mean CPZ equivalent dose: 747 ± 622 mg/day (range: 200 mg – 2150 mg). 10 patients were on benzodiazepines. 26 controls (16 M/10 F) matched with patients for age and sex (mean age=31.9 ± 12.4 years) participated in the study. | ANOVA, Pearson correlation coefficient, regression analysis and Studen’s t test | a) PME and PDE levels did not show differences between SZ and controls. b) Lower PME levels seen in high negative symptom-SZ patients compared to low negative symptom-SZ. Elevated β-ATP levels in high negative symptom SZ patients compared to low negative symptom SZ. Lower PDE levels in SZ with low negative symptoms compared to controls. c) PME levels and CPZ-equivalent antipsychotic dose were not correlated |
Grant-in-Aid from the Japanese Ministry of Education. |
| Deicken et al, Schiz Res 14(2): 177:1995 (43) | Frontal lobe | Examined whether decreased PME and elevated PDE levels in the frontal lobe would be associated with impaired performance on the WCST | Philips Gyroscan at 2 Tesla with multi-slice images. PME and PDE levels calculated for the left and right frontal lobe voxels (25 cc each) on 16 SZ patients and 13 male controls who were part of a larger cohort of 20 SZ and 16 controls. Duration of illness = 14.2 ±7.5 (range 1-27 years). 5 neuroleptic-free for ≥7 days; 9 patients were on neuroleptics only; and 2 patients were on neuroleptic + benztropine mesylate. Within 48 h of the MRSI study, all subjects were administered the WCST | ANOVA and Pearson correlation | a) Both left and right frontal PDE levels were elevated in SZ than in controls b) Left frontal PME levels positively correlated with number of categories completed and concept formation, and negatively correlated with total but not perseverative errors |
NARSAD YI Award; BRSG Grant (Divn of Research Resources, UCSF Academic Senate Individual Investigator Grant; VA Research Associate Career Development Award |
| Kato et al, Psychiatry Res, 61(3): 151, 1995 (27) | Left and right frontal lobes | Examined both the left and right frontal lobes simultaneously by 31P MRS in SZ patients using a onedimensional chemical shift imaging technique to evaluate for left-right differences | MRS data acquired on a Signa 1.5-Tesla MR system. 27 inpatients (mean age=30.1±10.4 years; 15 F/12 M; duration of illness = 6.8± 7.9 years). 10 patients were off neuroleptics for ≥1 week and never given depot neuroleptics. 15 on butyrophenones and remaining 2 required additional phenothiazines for agitation before MRS study. 26 healthy subjects (mean age = 34.2 ±12.9 years; 15 F/ 11 M) | Paired t-test for left-right, and t test for case-control differences. Spearman’s correlation test | a) Reduced PME levels in the frontal lobes of SZ patients. b) Metabolite ratio measures were used |
Grant 5B-2-13 for Nervous and Mental Disorders from the Japanese Ministry of Health and Welfare. |
| Volz et al, Psychiatry Res: Neuroimaging, 76(2-3): 123, 1997 (28) | Dorsolateral Prefrontal Cortex | Examined changes in PDE and PCr levels linked to neuroleptic treatment and whether the reduced PDE levels are observed in neuroleptic-free patients | Image selected in vivo spectroscopy (ISIS)-sequence with double volume selection. Compared 50 medicated SZ patients (age=37.64±11.18 years; 31M/19F) with 10 SZ patients off neuroleptics for 3 days to 10 years (2 neuroleptic-naïve; age=33.60±13.29 years; 6M/4/F) and36 age-matched controls. | Kruskal Wallace H-test and Spearman correlation test | a) Decreased PDE levels in neuroleptic-free patients compared to controls. b) Resonance offset effects might have resulted in measuring signals from slightly different but overlapping VOIs |
BMBF |
| Hinsberger et al, Journal of psychiatry & neuroscience: JPN 22(2):111-117, 1997 (29) | Prefrontal lobe | Examined the relationship between 31P MRS data and left prefrontal gray and white matter volumes in SZ patients and controls predicting that previous findings of decreased PME levels in SZ patients compared to healthy subjects after controlling for gray and white volumes | Whole-body magnetic resonance imager at 2.0 T. The surface coil placed over the left dorsolateral prefrontal cortex. 10 patients and 10 controls were studied. 4 subjects were in their 1st episode and had not received antipsychotics prior to the study. One had received 1 mg of lorazepam in the 24 h before the study. The other SZ subjects received an average chlorpromazine-equivalent dose of 917±499 mg/d. 4 patients were taking an anticholinergic medication regularly. Mean duration of illness from the onset of positive symptoms was 12.2 ±8.6 years. | ANOVA | a) PME levels not correlated with left prefrontal grey matter volumes in either group or groups combines. b) Reduced PME levels might precede grey matter losses since patients showed reduced PME but not yet any volume loss. |
Canadian Psychiatric Research Foundation |
| Volz et al, Biol Psychiatry 44(6): 399-404, 1998 (30) | Dorsolateral prefrontal cortex | Examined MPL metabolites in a larger sample of SZ patients and controls since initial results were observed in smaller samples in the dorsolateral prefrontal region of SZ patients | Data acquired on a Philips Gyroscan ACS II system at 1.5 T. Each spectrum measured simultaneously in both VOIs was averaged over 768 measurements. The VOIs, located in both frontal brain areas, mainly in the DLPFC, had a mean volume of 28 × 28 × 50 mm3. 47 of the 50 patients were on stable neuroleptic medication of 10–15 mg haloperidol or equivalent. In this sample, the 13 SZ patients and 14 controls whose results were already reported as preliminary findings were also included. | Mann–Whitney U test with Bonferroni correction. Spearman correlation test and t test | a) Lower PDE and higher PME/PDE. b) PDE peak composed of glycerol-3-PC, glycerol-3-PE, and mobile phospholipids c) Spectra strongly T1-weighted; T1-weighted spin lattice relaxation times of PDE at 1.2–3.6 sec suggest that altered chemical/physical environment leading to T1 changes may have influenced measured peaks |
BMBF |
| Volz et al, Biol Psychiatry, 41(6):644, 1997 (36) | Dorsolateral prefrontal region | Pilot study, a volume selective 31P MRS technique was used allowing localization of the voxel in the prefrontal cortex | Image selected in vivo spectroscopy (ISIS)-sequence with double volume selection. Each spectrum was averaged over 768 measurements. 13 SZ inpatients and 14 age-matched controls were investigated. 10 SZ were on a neuroleptic, 3 of them on clozapine, and 3 received lithium | Mann-Whitney U-test | a) Decreased PDE levels in SZ compared to controls. PME/PDE ratio increased. b) No correlation between neuroleptic dose, duration of illness, BPRS, CGI, SANS or SAPS and PME and PDE levels |
BMBF |
| Potwarka et al, Biol Psychiatry 45(6): 687-693, 1999 (31) | Prefrontal, motor, and parieto-occipital regions. | Examined in vivo individual components of PME and PDE from prefrontal, motor and parieto-occipital cortex on both sides using 1H-decoupled 31P MRS 2-D chemical shift imaging to resolve elevated PDE in SZ to broad MPL peak. | Measurements performed on a Siemens Helicon SP4000 whole body imager at 1.5 T. Data acquired using a 2-dimensional chemical shift imaging sequence from a voxel of 50 cm3. This study examined 11 chronic medicated SZ patients on 461 ± 232 mg chlorpromazine equivalent and 11 healthy controls. 7 had taken an anticholinergic and 2 a benzodiazepine in the 24 hours before imaging. The average length of illness from the onset of positive symptoms was 20.6 ± 7.6 years. | 2-tailed t test, 2-factor MANCOVA, ANCOVA for the individual metabolite parameters. Pearson correlations | a) ↓ PC, and ↑ PDE and mobile phospholipid in SZ compared to controls in bilateral prefrontal cortex. b) No significant correlation with CPZ-equivalent medication dose. c) Metabolites were reported as a ratio to total phosphate signal. d) Not fully relaxed signal might have introduced partial saturation effects depending on T1 times; thus, measured metabolite level changes may be from T1 changes |
EJLB Foundation, The Medical Research Council of Canada (grant MT-12078), and NIMH |
| Riehemann et al., NMR Biomed 12(8):483-489. 1999 (32) | Frontal lobe | Investigated the influence of gender on the concentrations of MPL metabolites | 32 controls and 51 SZ inpatients (19 on stable meds) (50 men [19 controls, age=35.4± 12.5 years; 31 inpatients, age=37.5±12.4 years] and 33 women [13 controls, age=34.0±11.7 years; 20 inpatients, age=36.4±10.3 years]). ISIS on a 1.5 T scanner. 1024 data points from voxel of 28×28×50 mm3 | Mann–Whitney U-test with Bonferroni correction | a) The main results were increased Pi levels and decreased PCr levels in the brain of healthy females compared to healthy males b) Different spectrum analysis methodology used in studies |
German Ministry of Education, Science, Research, and Technology. BMBF |
| Shiryama et al, Eur J Neurosci 20(3): 749-756. 2004 (33) | Prefrontal cortex | Aim was to detect differences in MPL metabolite levels among medicated SZ patients | 11 male SZ outpatients (age: 28.6 ± 8.6 years) and 15 controls (28.4 ± 8.1 years). NMR measurements performed on a Philips Gyroscan S20MRI / MRS system at 2 Tesla. VOI 35 × 45 × 70 mm. Patients clinically stable for ≥1 year, receiving neuroleptics (CPZ equivalent dose, 317 ± 139 mg / day for 6.6±7.6 years) and anticholinergic medication. | Two-tailed Student’s t-tests for case-control differences | a) SZ patients showed an increased concentration of GPC but no other MPL metabolites such as GPE, PE and PC. b) Spectral quality was high with an SD of each MPL metabolite levels of < 15%. |
Ministry of Health and Welfare of Japan |
| Du et al, JAMA Psychiatry 71(1): 19-27, 2014 (34) | Frontal Lobe | To investigate cerebral bioenergetics in SZ via measurement of creatine kinase activity using in vivo 31P magnetization transfer spectroscopy. | Cross-sectional case-control study. most acquired signal comes from a 6 × 6 × 4 cc region in the frontal lobes. 26 participants with chronic SZ and 26 age-matched and sex-matched healthy controls (14 males and 12 females, 31.9± 8.9 years old) and 26 SZ patients (13 males and 13 females, 34.5 ± 8.4 years old). |
SPSS version 17; SPSS, Inc | a) A substantial (22%) and statistically significant reduction in creatine kinase kf in SZ. PCr/ATP, Pi /ATP, and PME/ATP ratios were not altered in SZ, but PDE/ATP ratio was reduced. SZ and schizoaffective disorder did not differ. b) To minimize low SNR, collected data from a large brain region. Most SZ patients were on medication. Results may be secondary to medications. |
NIH and the Shervert Frazier Research Institute at McLean Hospital |
| Prasad et al, Biological Psychiatry: Cognitive Neuroscience & Neuroimaging 1(6): 528-538, 2016 (21)* | a. Cross Sectional b. Multiple brain regions |
Examined MPL metabolite levels using whole-brain multi-voxel 3D CSI 31P MRS in early-course SZ and controls, and their relationship with IL-6 and CRP levels, performance on sustained attention, executive function and verbal memory tasks, and psychopathology scores | Data acquired on Siemens Tim Trio at 3 Tesla from 12 unique brain regions. Examined MPL metabolites and their cognitive, clinical and immunologic correlates among 28 early-course SZ patients (M:F=18/10; age=25.15±8.03 years; illness duration 1.99±1.33 years; antipsychotic-naïve=18; mean antipsychotic CPZ equivalent dose=317.53±270.20 mg) and 21 controls (M:F=5/16; age=25.24±6.25 years) | Generalized linear mixed models including bilateral VOI controlling for age, sex and GM fraction, and partial correlation with multiple test corrections | a) Higher PDE levels in thalamus and hippocampus but lower levels in the DLPFC and inferior frontal cortex in SZ. b) Higher PME levels in SZ compared to controls in the hippocampus and anterior cingulate but lower in inferior frontal and parietal lobule c) Antipsychotic dose did not correlate with PDE or PME levels. d) The left thalamus PDE correlated negatively with sustained attention. e) PDE levels positively correlated with IL-6 levels in the thalamus in SZ |
NIMH MH72995 and MH93540 |
| TEMPORAL LOBE | ||||||
| O’Callaghan et al, Biol Psychiatry, 29(11):1149, 1991 (37) | Temporo-parietal cortex | To examine the 31P MRS metabolites in SZ patients and controls | 18 medicated SZ patients (age=31 years, ll M/7 F, Illness duration=10 years), 10 controls (age=36 years, 6 M/4 F) Used surface coil on 1.5 T scanner |
Multiple regression | a) PME and PDE were not elevated b) pH was elevated in SZ compared to controls |
St John of God Order |
| Calabrese et al, Biol Psychiatry, 32(1):26, 1992 (38) | Temporal lobes | To examine PME metabolites, ATP and PCr in the temporal lobes of SZ patients | 11 SZ patients (2 neuroleptic-free, 9 medicated, age=39 years, lO M/l F), 9 male controls (age=35 years) Used ISIS, voxel size=87 cc on a 2 Tesla scanner |
MANOVA | a) SZ patients showed elevated PDE in the left temporal lobe b) β-ATP and PCr elevations inversely correlated with thought disorder severity c) PCr/β-ATP and PCr/Pi effects reflected higher ratios on the right side in SZ; percentage of β-ATP reflected higher relative concentrations in the left temporal lobe SZ |
R01DK33293, Philips Medical Systems, VA Medical Research Service, VA Psychiatrist Research Training Program, BRSG Grant S07-RR05755 |
| Fujimoto et al, Acta Psychiatr Scand, 86(6): 455, 1992 (25)* | 10 regions that mainly consisted of frontal, temporal and parietal regions | To examine 31P MRS metabolites in chronic SZ | 16 medicated chronic male SZ patients (age=39±5 years, Mean illness duration=12 yrs), 20 controls (age=34±2 years, 15M/5F). Age of onset=22±4 years (range 18-30 years) Siemens-Asahi scanner at 2.0 Tesla. CSI with a voxel size of 36 cc |
Mann-Whitney U test | a) Elevated PDE levels on the left temporal lobe b) ATP and PCr levels were decreased |
None reported |
| Fukuzako et al, Eur Arch Psychiatr Clin Neurosci, 244(5): 236, 1994 (39) | Temporal lobes; Also examined frontal and parietal lobes | Selected a relatively homogeneous group of neuroleptic-resistant SZ patients. | Data acquired on a 2.0 Tesla MR system. Voxel size=36 cc (3 ×3× 4 cm). Peak areas were automatically calculated by means of a Lorentzian curve fitting after baseline correction. SZ patients with persistent positive symptoms such as auditory hallucinations and delusions for > 2 years despite neuroleptic treatment were enrolled (n=16; 8 men and 8 women; mean age 39.6±8.1 years | Wilks-Shapiro test, MANOVA Pearson and Kendall’s rank-order correlation test | a) Observed elevated PDE in the bilateral medial temporal lobes of SZ patients compared to controls. b) No significant correlation between the PDE levels and daily dose of neuroleptics or anticholinergics. |
National Center of Psychiatry and Neurology of the Ministry of Health and Welfare; Japan Ministry of Education, Science and Culture |
| Deicken et al, Biol Psychiatry, 38(5):279, 1995 (40) | Temporal Lobes | To replicate and extend initial findings using new samples of patients and controls. Aim to test the hypothesis of metabolic asymmetry in the temporal lobes of SZ patients compared to healthy controls. | MRSI studies performed on a Philips Gyroscan system at 2 Tesla. MRSI raw data volume consisted of 1728 phase-encoded half-echo time signals, each with 256 samples and a bandwidth of 3 kHz. 18 male SZ patients (age =39.4 ± 6.0 years) and 14 male control subjects (age = 39.0 ± 5.2 years). 5 patients were neuroleptic-free; 8 on neuroleptics only; 3 were on neuroleptic plus diphenhydramine and 2 patients on a neuroleptic plus benztropine | MANOVA and Regression analysis | a) PME and PDE did not differ between SZ and controls b) PCr/Pi and PCr/ β-ATP showed significant group × side interaction c) Negative correlation between left temporal lobe PCr and the thinking disturbance on the BPRS. Degree of PCr asymmetry positively correlated with thinking disturbance on the BPRS. |
NARSAD YI Award: BRSG Grant of the Division of Research Resources, Academic Senate Individual Investigator Grant, A Research Associable Career Development Award |
| Fukuzako et al, Prog Neuropsychop harmacol & Biol Psychiatr, 20(4):629, 1996 (41) | Temporal lobes | Prior study did not investigate the relationship between MRS abnormalities and clinical characteristics. | Spectroscopy was performed on a Siemens-Asahi Meditec MR system at 2.0 tesla. Voxel size: 36 cc (3×3×4 cm3). 31 medicated patients (22 men, 9 women; mean age: 38.7±7.8 years; mean daily CPZ-equivalent dose of neuroleptics=481.8±374.6 mg) and 31 controls (22 men and 9 women; age=40.3±9.4 years) | MANOVA; Kendall’s correlation coefficient test | a) Increased PDE levels and decreased β-ATP in bilateral temporal lobe of SZ patients, especially on the left side. b) PDE levels positively correlated with BPRS positive symptom severity c) Daily neuroleptic dose did not correlate with PME or PDE. |
Ministry of Science, Culture, and Education; National Center of Psychiatry and Neurology of Ministry of Health and Welfare, Japan |
| Fukuzako et al, Neuropsychop harmacology 21(4): 542-549, 1999 (42) | Temporal Lobes | Longitudinal 31P MRS to investigate metabolite changes in the temporal lobes of SZ patients after 12-week haloperidol treatment | Data acquired on a Siemens-Asahi Meditec MR system at 2 Tesla. Voxel size 36 cc containing mainly the temporal lobes and small part of the frontal and parietal lobes. 25 first-episode, drug-naive Japanese SZ outpatients (14/11 men/women aged 16-32 years; mean 23.1) and 13 controls (15-31 years, mean 22.2 years). 16 SZ patients completed MRS scans before and after haloperidol; data on 13 patients and 13 controls reported | 2-way ANOVA; RMANOVA followed by Scheffé multiple-comparison method. | a) Significant effect of scan and side on PME and PDE in SZ but not in controls b) Significant diagnosis effect on PME and PDE c) PDE elevated on both sides in drug-naïve patients d) Haloperidol reduced the excess PDE after 12 weeks e) Large voxel size |
Ministry of Science, Culture, and Education; National Center of Psychiatry and Neurology of the Ministry of Health and Welfare of Japan |
| Fukuzako et al, Am J Psychiatry 156(8): 1205-1208, 1999 (44) | Temporal lobes | To examine 31P MRS metabolite changes in the temporal lobes of medication-naive SZ patients. | MRS data acquired on Siemens-Asahi Meditec MR system at 2.0 T. FOV=24 cm with an 8×8 data matrix and a 4-cm section thickness. 17 first-episode, drug-naive Japanese SZ patients (10/7 men/7 women; mean age=23.1 years) from outpatient clinics. Illness Duration: 6.6±6.2 months. 17 age and sex-matched controls (age=22.5 years) |
ANOVA | a) Elevated PDE levels and decreased PME levels in bilateral temporal lobes. b) Results were not corrected for multiple tests because of small n and exploratory nature of the study. c) Metabolites were modeled as single spectral peaks |
Ministry of Science, Culture & Education; National Center of Psychiatry and Neurology, Ministry of Health and Welfare, Japan |
| Prasad et al, Biological Psychiatry: Cognitive Neuroscience & Neuroimaging 1(6): 528-538, 2016 (21)* | a. Cross Sectional b. Multiple brain regions |
Examined MPL metabolite levels using whole-brain multi-voxel 3D CSI 31P MRS in early-course SZ and controls, and their relationship with IL-6 and CRP levels, performance on sustained attention, executive function and verbal memory tasks, and psychopathology scores | Data acquired on Siemens Tim Trio at 3 Tesla from 12 unique brain regions. Examined MPL metabolites and their cognitive, clinical and immunologic correlates among 28 early-course SZ patients (M:F=18/10; age=25.15±8.03 years; illness duration 1.99±1.33 years; antipsychotic-naïve=18; mean antipsychotic CPZ equivalent dose=317.53±270.20 mg) and 21 controls (M:F=5/16; age=25.24±6.25 years) | Generalized linear mixed models including bilateral VOI as repeated measures controlling for age, sex and GM fraction, and partial correlation with multiple test corrections | a) PDE levels elevated in the thalamus and hippocampus but reduced in the DLPFC and inferior frontal cortex in SZ compared to controls. b) PME levels elevated in SZ compared to controls in the hippo-campus and anterior cingulate but reduced in inferior frontal and parietal lobule c) Antipsychotic dose did not correlate with PDE or PME levels. d) The left thalamus PDE levels correlated negatively with sustained attention. e) PDE levels positively correlated with IL-6 levels in the thalamus in SZ |
NIMH MH72995 and MH93540 |
*
These studies examined both frontal and temporal lobes and hence are included in both groups. Total number of studies are the same as in the CONSORT diagram