SUPPLEMENTARY INFORMATION
Glutamate normalization with ECT treatment response in major depression
Jingjing Zhang, MS1; Katherine L. Narr, PhD2; Roger P. Woods, MD1, Owen R. Phillips, BS2,
Jeffry R. Alger, PhD1, Randall T. Espinoza, MD, MPH3
Ahmanson-Lovelace Brain Mapping Center1 and Laboratory of Neuro Imaging2, Department of
Neurology and Jane and Terry Semel Institute for Neuroscience and Human Behavior,
Department of Psychiatry3, Geffen School of Medicine at the University of California at Los
Angeles
Correspondence: Dr. Katherine L. Narr, Laboratory of Neuro Imaging, Department of Neurology,
Geffen School of Medicine at UCLA, 635 Charles Young Drive South, Suite 225, Los Angeles,
CA 90095-7334; Phone: 310.206.2101; Fax: 310.206.5518; email: narr@loni.ucla.edu
SUPPLEMENTARY SUBJECTS AND METHODS
Clinical Characteristics of Patients
Subjects included 10 patients with major depressive disorder (MDD) scheduled to receive ECT
as part of their standard clinical care at the UCLA Resnick Neuropsychiatric Hospital and 10
demographically similar healthy control subjects recruited from the surrounding community.
Patients were assessed at three time points, prior to their first ECT (baseline) and after their 2nd
and 6th ECT sessions, corresponding to approximately 48 hrs and 2 weeks following treatment
onset. Controls were assessed at two time points approximately 2-weeks apart. At baseline,
diagnosis was determined by clinical interview using DSM-IV TR criteria. Ratings ≥18 on the
Hamilton Depression Rating Scale (HAMD) and ≥20 on the Montgomery-Asberg Depression
Rating Scale (MADRS) and onset before age 50 years served as inclusion criteria for patients
(mean baseline HAMD: 25.5, 4.9 SD; mean baseline MADRS: 38.9, 10.59 SD). Comorbid
primary psychotic, active substance use or dependence, somatoform, cognitive, personality and
mood disorders due to a general medical condition and dementia served as exclusionary
criteria. Patients were also screened to exclude first episode depression (mean number of prior
depressive episodes at baseline: 3.4, 1.4 SD; mean duration of the index episode (months):
17.0, 13.07 SD). All antidepressant medications were tapered and stopped prior to beginning
the index ECT series and to obtaining the baseline scan. A minimum of 72 hours but more often
at least 1 week passed between stopping medication and beginning ECT or obtaining baseline
scan. Supplementary Table 1 lists the clinical details for each patient separately.
ECT Treatment
ECT was administered using the seizure threshold (ST) titration method. At the first ECT
treatment, individual seizure thresholds were determined using established stimulus dosing
techniques. For 8 patients, ECT included right unilateral (RUL) D’Elia lead placement. For 2
patients, bilateral (BL) ECT with bitemporal lead placement was used. After seizure threshold
was determined at the first ECT session, subsequent treatments were delivered at energy
settings 5x ST for RUL ECT and at 1.5x ST for BL ECT. Clinical mood assessment and imaging
data were collected within 24hrs of the 2nd and 6th ECT sessions. After the 6th ECT session,
some subjects were assessed to have achieved remission, but others not, and all continued to
receive further ECT treatment as clinically warranted. Supplementary Table 1 lists the lead
placements used for each patient and the HAMD and MADRS scores obtained at each study
time points for patients.
MRS Voxel Placement
Voxels of interest (20 ×18 ×12 mm) were placed in dorsal ACC gray matter at midline using the
T1-weighted images reconstructed in 3D [see Fig 1]. A trained anatomist (K.N.) performed voxel
placement for each subject at each time point. In the sagittal plane, the long axis of the voxel
was positioned as parallel to the cingulate sulcus, encompassing the maximal amount of gray
matter on the inferior and superior banks of the cingulate gyrus. The anterior edge of the voxel
was positioned to be in line with the most anterior point (rostrum) of the corpus callosum. In the
coronal plane, the center of the voxel was positioned at midline and tilted if necessary to
accommodate left-right asymmetries in the trajectory of the cingulate gyrus. For each follow-up
scan, images showing voxel placement from the baseline scan were reloaded on the scanner
console to further ensure reliable placement of ACC voxels. In post-processing procedures,
each MRS voxel was mapped back to the structural image on which it was prescribed. The
proportion of CSF-content within each voxel was computed following scanner field
inhomogeneity correction, scalp editing and tissue classification. Each metabolite was
subsequently adjusted for the proportion of CSF content within each voxel.
Acknowledgements
This work was supported by Award Number R01 MH092301 from the NIMH, and intramural
support from the UCLA Integrative Mood Disorders Center, Brain Mapping Medical Research
Organization and a UCLA Various Donor Fund (Dr. Espinoza).
Supplementary Table 1. Baseline Clinical Features, ECT Treatment Characteristics and Mood Scores
Baseline Clinical Features
Age (yrs), DSM-IV TR Diagnosisa
Sex
43, F
MDD, rec, severe without
psychosis
51, M
MDD, rec, severe with
psychosis
33, M
MDD, rec, severe with
psychosis
43, F
MDD, rec, severe without
psychosis
37, F
MDD, rec, severe with
psychosis; OCD
42, F
MDD, rec, severe without
psychosis; OCD; Bulimia
37, F* Bipolar, depressed, rec,
severe without psychosis
61, F
MDD, rec, severe without
psychosis
50, M
MDD, rec, severe without
psychosis; Dysthymia
44, M
MDD, rec, severe without
psychosis
a
# Prior
Episodes
3
HAMD
Duration of Index # Failed Drug Trialsb
Episode (mos)
18
6
MADRS
ECT Lead
Placement
RUL
Pre
ECT2 ECT6 Pre ECT2 ECT6
28
19
9
40
26
12
1
8
2
BL
26
23
12
42
36
12
1
4
2
RUL
34
21
13
52
46
22
3
48
6
RUL
20
19
13
32
30
19
4
8
4
RUL
27
28
18
44
44
28
4
12
3
RUL
22
22
8
40
36
6
3
6
4
RUL
32
30
-
56
52
-
5
18
8
RUL
22
16
11
35
30
14
3
24
4
RUL
19
20
15
24
24
20
5
24
3
BL
25
16
7
24
24
14
DSM-IV TR diagnosis achieved after clinical interview. bFailed trials counted during index episode. MDD= major depressive
disorder, rec=recurrent, RUL = right unilateral, BL = bilateral, bitemporal lead placement used for BL ECT. * data point missing for 3rd
ECT.