Bipolar Depression
Conditions
Keywords
Bipolar, depression
Brief summary
This study compared glutamate and other neurometabolites measured by proton magnetic resonance spectroscopy (1H-MRS) in bipolar I and II patients currently depressed with age-matched healthy controls. The study will also compare 1H-MRS of bipolar I and II patients before and after taking a 12-week course of lamotrigine. The goal of this study was to better understand the neurobiology of bipolar depression and how lamotrigine may therapeutically impact brain function and mood response. The hypothesis was that in comparison to non-remission participants, bipolar participants who achieve remission (defined as a Montgomery Asberg Depression Rating Scale (MADRS) score \<12 at week 12) associated with lamotrigine monotherapy will exhibit a greater decrease in glutamate (Glu) and an increase in N-acetyl aspartate (NAA), reported as a cerebrospinal fluid (CSF)-corrected absolute concentration percent change from baseline to endpoint in anterior cingulate (AC) and dorsolateral prefrontal cortex (DLPFC).
Detailed description
Depression is the predominant prevailing mood state in bipolar disorder and bipolar depression is associated with substantial morbidity and mortality. However, in comparison to acute mania, bipolar depression is understudied both from the standpoint of its pathophysiology as well as clinical trials which include FDA-approved treatments. Given this lack of evidence to base guidelines, clinicians and patients are limited as to how best to treat the depressive phase of the illness. Proton magnetic resonance spectroscopy (1H-MRS) is a valuable, non-invasive method to study in-vivo brain biochemistry. Of the novel imaging paradigms, MRS is uniquely positioned to investigate biochemical mechanism of drug action that is objectively measurable and clinically relevant. As there is increasing interest in glutamatergic dysregulation in mood disorders, this project will utilize 1H-MRS to study glutamate and glutamine levels in brain regions implicated in bipolar disorder (anterior cingulate and dorsolateral prefrontal cortex). This was a 5-year single-site study of bipolar depression utilizing 1H-MR spectroscopy before and after treatment with lamotrigine. At baseline bipolar depressed subjects and age-matched controls underwent a 1H-MRS at Mayo Clinic in Rochester, Minnesota. The bipolar depressed subjects were then be placed on 12-week, open evaluation of lamotrigine monotherapy. After 12 weeks, the bipolar subjects underwent a second 1H-MRS scan. Two different MRS sequences were used to measure the brain chemicals in a single 2 x 2 x 2 cm cube located in the center of anterior cingulate cortex: an intermediate echo-time PRESS sequence and a 2D J-resolved averaged PRESS sequence. Spectroscopic data were inspected for quality; subjects whose data were contaminated by artifact were excluded from the study. Spectra were then processed using LCModel to quantify brain chemical levels. Regular brain MRI images were segmented, yielding a map of the amount of CSF in the head. The MRS cube was overlaid onto the CSF map and the fraction of CSF within the cube measured. This measurement was used to remove the CSF from the MRS cube giving brain chemical concentrations. The concentrations were then used for statistical analysis. Note: All of the spectroscopy data are expressed in Institutional Units (IU).
Interventions
DRUGLamotrigine
12 week open trial: 25mg/day for 2 weeks, 50mg/day for 2 weeks, 100mg/day for 2 weeks, 200mg/day for 6 weeks. Flexible titration for early response and/or side effects.
PROCEDURE1H-MR
Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
Sponsors
National Institute of Mental Health (NIMH)
Mayo Clinic
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Bipolar Group Inclusion Criteria: * Diagnosis of Bipolar Type I or II disorder depress phase (SCID confirmed) * Moderate depression as confirmed by Montgomery Asberg Depression Rating Scale greater than or equal to 20 * Negative urine toxicology screen * Negative urine pregnancy test * No clinically significant lab abnormalities for complete blood count (CBC), Thyroid stimulating hormone (TSH), Sodium (Na+), Potassium (K+), Chlorine (Cl-), Carbon dioxide (CO2), creatinine (CREA), blood urea nitrogen (BUN), Glucose, hepatic panel. Bipolar Group
Exclusion criteria
* Inability to provide informed consent * Any current Axis I diagnosis other than anxiety disorders needing concurrent antidepressant therapy * History of active substance abuse/dependence within the last 3 months * History of claustrophobia * History of adverse reaction to Lamotrigine * Fluoxetine and decanoate antipsychotic therapy * Unwilling or unable to taper current sub-optimal psychotropic medications other than a stable dosage of Lithium, Depakote, or an Atypical Antipsychotic approved by study personnel * Unstable active medical illness * Pregnancy or breast-feeding * Male/ Female not practicing a reliable form of birth control (condom, Intrauterine Device (IUD), depo injection) * Female wishing to commence oral contraceptive therapy within 3 months of enrollment date (stable oral contraceptive therapy exception) * Active suicidal ideation with plan * History of major head trauma with loss of consciousness \> 5 minutes or skull fracture * History of previous neurological event (epilepsy, stroke, transient ischemic attack) * Implanted metal objects (i.e., pacemakers, aneurysm clips, metal prostheses, joints, rods) * Inability to speak English * Prominent Axis II disorder \[This will be assessed by the principal investigator, who has \>10 years clinical experience with this population. Hospital discharge summaries and outpatient medical records will be reviewed for evidence that Axis II pathology is the primary psychiatric disturbance (i.e., adequate trials of mood stabilizing treatments with minimal to no response, prominent self injurious behavior in the absence of significant mood symptomatology, or atypical cycle patterns)\]. Healthy Control Group Inclusion Criteria: * Negative urine toxicology screen * Negative urine pregnancy test * Normal blood values for thyroid stimulating hormone (TSH) Healthy Control Group
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Montgomery-Åsberg Depression Rating Scale (MADRS) Score at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | baseline, 12 weeks | The MADRS is a 10-item observer rating scale assessing symptoms of depression. The score ranges from 0 (no depression) to 60 (very depressed). A score of less than 12 is considered clinical remission of depression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glutamate+Glutamine (GLX) Measured in Mid Anterior Cingulate Cortex (MACC) & Left Dorsal Lateral Prefrontal Cortex (LDLPC) Using Long TE PRESS MRS Technique at Baseline for Both Groups; After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | baseline, after 12 weeks | Two different MRS sequences were used to measure the brain chemicals in in anterior cingulate and left dorsal lateral prefrontal cortex : an intermediate echo-time PRESS sequence and a 2D J-resolved averaged PRESS sequence. (Note: The intermediate echo-time PRESS sequence was used for this outcome measure.) Spectroscopic data were inspected for quality; subjects whose data were contaminated by artifact were excluded from the study. Spectra were then processed using LCModel to quantify brain chemical levels. Regular brain MRI images were segmented, yielding a map of the amount of cerebrospinal fluid (CSF); the MRS voxel was overlaid onto the CSF map and the fraction of CSF was measured. This CSF corrected measurement was used for statistical analysis. |
| N-acetylaspartic Acid (NAA) Measured in the MACC and LDLPC Using the Long TE (TE80) PRESS MRS Technique at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar (BP) Group and BP Responders and Non-responders | baseline, 12 weeks | Two different MRS sequences were used to measure the brain chemicals in a single 2 x 2 x 2 cm cube located in the center of anterior cingulate cortex: an intermediate echo-time PRESS sequence and a 2D J-resolved averaged PRESS sequence. (Note: The intermediate echo-time PRESS sequence was used for this outcome measure.) Spectroscopic data were inspected for quality; subjects whose data were contaminated by artifact were excluded from the study. Spectra were then processed using LCModel to quantify brain chemical levels. Regular brain MRI images were segmented, yielding a map of the amount of CSF in the head. The MRS voxel was overlaid onto the CSF map and the fraction of CSF within the voxel measured. This CSF-corrected measurement was used for statistical analysis. |
| Mean Glutamate (GLU) Measured in the MACC and LDLPC Using the ProFit MRS Technique at Baseline for Both Groups, After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | baseline, 12 weeks | Two different MRS sequences were used to measure the brain chemicals in a single 2 x 2 x 2 cm cube located in the center of anterior cingulate cortex: an intermediate echo-time PRESS sequence and a 2D J-resolved averaged PRESS sequence. (Note: The 2D J-resolved averaged PRESS sequence was used for this outcome measure.) Spectroscopic data were inspected for quality; subjects whose data were contaminated by artifact were excluded from the study. Spectra were then processed using LCModel to quantify brain chemical levels. Regular brain MRI images were segmented, yielding a map of the amount of CSF in the head. The MRS voxel was overlaid onto the CSF map and the fraction of CSF within the voxel measured. This CSF-corrected measurement was then used for statistical analysis. |
| Glutamine/Glutamate Ratio Measured in the LDLPC at Baseline Using the ProFit Magnetic Resonance Spectroscopy (MRS) Technique | baseline | Two different MRS sequences were used to measure the brain chemicals in a single 2 x 2 x 2 cm cube located in the center of anterior cingulate cortex: an intermediate echo-time PRESS sequence and a 2D J-resolved averaged PRESS sequence. (Note: The 2D J-resolved averaged PRESS sequence was used for this outcome measure.) Spectroscopic data were inspected for quality; subjects whose data were contaminated by artifact were excluded from the study. Spectra were then processed using LCModel to quantify brain chemical levels. Regular brain MRI images were segmented, yielding a map of the amount of CSF in the head. The MRS voxel was overlaid onto the CSF map and the fraction of CSF within the voxel measured. This CSF-corrected measurement was then used for statistical analysis. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the Mayo Clinic in Rochester, Minnesota.
Pre-assignment details
39 subjects signed informed consent for the Bipolar Group, but 9 were screen failures, and one subject signed consent but did not start the study. 33 subjects signed informed consent for the Healthy Control group, and all of these subjects completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Bipolar Group Subjects underwent proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC) before and after treatment with Lamotrigine.
Lamotrigine: 12 week open trial: 25mg/day for 2 weeks, 50mg/day for 2 weeks, 100mg/day for 2 weeks, 200mg/day for 6 weeks. Flexible titration for early response and/or side effects.
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC). | 29 |
| Control Group Subjects underwent proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
1H-MR: Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC). | 33 |
| Total | 62 |
Baseline characteristics
| Characteristic | Bipolar Group | Control Group | Total |
|---|---|---|---|
| Age, Continuous | 36.10 years STANDARD_DEVIATION 13.44 | 35.18 years STANDARD_DEVIATION 10.1 | 35.61 years STANDARD_DEVIATION 11.69 |
| Region of Enrollment United States | 29 participants | 33 participants | 62 participants |
| Sex: Female, Male Female | 17 Participants | 15 Participants | 32 Participants |
| Sex: Female, Male Male | 12 Participants | 18 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 29 | 0 / 33 |
| serious Total, serious adverse events | 5 / 29 | 0 / 33 |
Outcome results
Primary
Mean Montgomery-Åsberg Depression Rating Scale (MADRS) Score at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group
The MADRS is a 10-item observer rating scale assessing symptoms of depression. The score ranges from 0 (no depression) to 60 (very depressed). A score of less than 12 is considered clinical remission of depression.
Time frame: baseline, 12 weeks
Population: The control group only did the MADRS depression rating scale at baseline. 25 participants in the Bipolar group took the MADRS depression rating scale at 12 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bipolar Group | Mean Montgomery-Åsberg Depression Rating Scale (MADRS) Score at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | Baseline | 27.79 units on a scale | Standard Deviation 5.8 |
| Bipolar Group | Mean Montgomery-Åsberg Depression Rating Scale (MADRS) Score at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | 12 weeks | 14.28 units on a scale | Standard Deviation 11.67 |
| Control Group | Mean Montgomery-Åsberg Depression Rating Scale (MADRS) Score at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | Baseline | 0.30 units on a scale | Standard Deviation 0.64 |
| Control Group | Mean Montgomery-Åsberg Depression Rating Scale (MADRS) Score at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | 12 weeks | NA units on a scale | — |
Secondary
Glutamate+Glutamine (GLX) Measured in Mid Anterior Cingulate Cortex (MACC) & Left Dorsal Lateral Prefrontal Cortex (LDLPC) Using Long TE PRESS MRS Technique at Baseline for Both Groups; After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group
Two different MRS sequences were used to measure the brain chemicals in in anterior cingulate and left dorsal lateral prefrontal cortex : an intermediate echo-time PRESS sequence and a 2D J-resolved averaged PRESS sequence. (Note: The intermediate echo-time PRESS sequence was used for this outcome measure.) Spectroscopic data were inspected for quality; subjects whose data were contaminated by artifact were excluded from the study. Spectra were then processed using LCModel to quantify brain chemical levels. Regular brain MRI images were segmented, yielding a map of the amount of cerebrospinal fluid (CSF); the MRS voxel was overlaid onto the CSF map and the fraction of CSF was measured. This CSF corrected measurement was used for statistical analysis.
Time frame: baseline, after 12 weeks
Population: Sample sizes varied due to imaging results/scan viability. Excessive noise resulted in poor metabolite readings which in-turn were not used in the final analysis. Baseline: control group MACC n=7, LDLPC n=8, Bipolar group MACC n=18, LDLPC n=27. Bipolar group 12 weeks MACC n=12, LDLPC n=16. The control group did not do the procedure at 12 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bipolar Group | Glutamate+Glutamine (GLX) Measured in Mid Anterior Cingulate Cortex (MACC) & Left Dorsal Lateral Prefrontal Cortex (LDLPC) Using Long TE PRESS MRS Technique at Baseline for Both Groups; After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | 12 Weeks GLX measured in MACC | 12.69 Institutional Units (IU) | Standard Deviation 4.05 |
| Bipolar Group | Glutamate+Glutamine (GLX) Measured in Mid Anterior Cingulate Cortex (MACC) & Left Dorsal Lateral Prefrontal Cortex (LDLPC) Using Long TE PRESS MRS Technique at Baseline for Both Groups; After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | Baseline GLX measured in LDLPC | 14.0 Institutional Units (IU) | Standard Deviation 2.7 |
| Bipolar Group | Glutamate+Glutamine (GLX) Measured in Mid Anterior Cingulate Cortex (MACC) & Left Dorsal Lateral Prefrontal Cortex (LDLPC) Using Long TE PRESS MRS Technique at Baseline for Both Groups; After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | 12 Weeks GLX measured in LDLPC | 14.1 Institutional Units (IU) | Standard Deviation 2.7 |
| Bipolar Group | Glutamate+Glutamine (GLX) Measured in Mid Anterior Cingulate Cortex (MACC) & Left Dorsal Lateral Prefrontal Cortex (LDLPC) Using Long TE PRESS MRS Technique at Baseline for Both Groups; After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | Baseline GLX measured in MACC | 15.08 Institutional Units (IU) | Standard Deviation 3.88 |
| Control Group | Glutamate+Glutamine (GLX) Measured in Mid Anterior Cingulate Cortex (MACC) & Left Dorsal Lateral Prefrontal Cortex (LDLPC) Using Long TE PRESS MRS Technique at Baseline for Both Groups; After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | Baseline GLX measured in MACC | 11.98 Institutional Units (IU) | Standard Deviation 2.06 |
| Control Group | Glutamate+Glutamine (GLX) Measured in Mid Anterior Cingulate Cortex (MACC) & Left Dorsal Lateral Prefrontal Cortex (LDLPC) Using Long TE PRESS MRS Technique at Baseline for Both Groups; After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | 12 Weeks GLX measured in MACC | NA Institutional Units (IU) | — |
| Control Group | Glutamate+Glutamine (GLX) Measured in Mid Anterior Cingulate Cortex (MACC) & Left Dorsal Lateral Prefrontal Cortex (LDLPC) Using Long TE PRESS MRS Technique at Baseline for Both Groups; After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | 12 Weeks GLX measured in LDLPC | NA Institutional Units (IU) | — |
| Control Group | Glutamate+Glutamine (GLX) Measured in Mid Anterior Cingulate Cortex (MACC) & Left Dorsal Lateral Prefrontal Cortex (LDLPC) Using Long TE PRESS MRS Technique at Baseline for Both Groups; After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | Baseline GLX measured in LDLPC | 12.9 Institutional Units (IU) | Standard Deviation 1.4 |
Secondary
Glutamine/Glutamate Ratio Measured in the LDLPC at Baseline Using the ProFit Magnetic Resonance Spectroscopy (MRS) Technique
Two different MRS sequences were used to measure the brain chemicals in a single 2 x 2 x 2 cm cube located in the center of anterior cingulate cortex: an intermediate echo-time PRESS sequence and a 2D J-resolved averaged PRESS sequence. (Note: The 2D J-resolved averaged PRESS sequence was used for this outcome measure.) Spectroscopic data were inspected for quality; subjects whose data were contaminated by artifact were excluded from the study. Spectra were then processed using LCModel to quantify brain chemical levels. Regular brain MRI images were segmented, yielding a map of the amount of CSF in the head. The MRS voxel was overlaid onto the CSF map and the fraction of CSF within the voxel measured. This CSF-corrected measurement was then used for statistical analysis.
Time frame: baseline
Population: Sample sizes varied between both scanning locations LDLPC and MACC and between metabolites due to imaging results/scan viability. Some subject scans yielded more viable information/ less noise during the scan process. Excessive noise resulted in poor metabolite readings which in-turn were not used in the final analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bipolar Group | Glutamine/Glutamate Ratio Measured in the LDLPC at Baseline Using the ProFit Magnetic Resonance Spectroscopy (MRS) Technique | 1.27 ratio | Standard Deviation 0.62 |
Secondary
Mean Glutamate (GLU) Measured in the MACC and LDLPC Using the ProFit MRS Technique at Baseline for Both Groups, After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group
Two different MRS sequences were used to measure the brain chemicals in a single 2 x 2 x 2 cm cube located in the center of anterior cingulate cortex: an intermediate echo-time PRESS sequence and a 2D J-resolved averaged PRESS sequence. (Note: The 2D J-resolved averaged PRESS sequence was used for this outcome measure.) Spectroscopic data were inspected for quality; subjects whose data were contaminated by artifact were excluded from the study. Spectra were then processed using LCModel to quantify brain chemical levels. Regular brain MRI images were segmented, yielding a map of the amount of CSF in the head. The MRS voxel was overlaid onto the CSF map and the fraction of CSF within the voxel measured. This CSF-corrected measurement was then used for statistical analysis.
Time frame: baseline, 12 weeks
Population: Sample sizes varied due to imaging results/scan viability. Excessive noise resulted in poor metabolite readings which in-turn were not used in the final analysis. Baseline: control group MACC n=8, LDLPC n=8, Bipolar group MACC n=13, LDLPC n=13. Bipolar group 12 weeks MACC n=8, LDLPC n=17. The control group did not do the procedure at 12 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bipolar Group | Mean Glutamate (GLU) Measured in the MACC and LDLPC Using the ProFit MRS Technique at Baseline for Both Groups, After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | Baseline MACC | 147.55 Institutional Units (IU) | Standard Deviation 32.57 |
| Bipolar Group | Mean Glutamate (GLU) Measured in the MACC and LDLPC Using the ProFit MRS Technique at Baseline for Both Groups, After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | 12 Weeks MACC | 134 Institutional Units (IU) | Standard Deviation 13.5 |
| Bipolar Group | Mean Glutamate (GLU) Measured in the MACC and LDLPC Using the ProFit MRS Technique at Baseline for Both Groups, After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | Baseline LDLPC | 65.4 Institutional Units (IU) | Standard Deviation 15.5 |
| Bipolar Group | Mean Glutamate (GLU) Measured in the MACC and LDLPC Using the ProFit MRS Technique at Baseline for Both Groups, After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | 12 Weeks LDLPC | 63.5 Institutional Units (IU) | Standard Deviation 11.6 |
| Control Group | Mean Glutamate (GLU) Measured in the MACC and LDLPC Using the ProFit MRS Technique at Baseline for Both Groups, After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | Baseline LDLPC | 64.1 Institutional Units (IU) | Standard Deviation 12.6 |
| Control Group | Mean Glutamate (GLU) Measured in the MACC and LDLPC Using the ProFit MRS Technique at Baseline for Both Groups, After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | Baseline MACC | 157.51 Institutional Units (IU) | Standard Deviation 36.17 |
| Control Group | Mean Glutamate (GLU) Measured in the MACC and LDLPC Using the ProFit MRS Technique at Baseline for Both Groups, After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | 12 Weeks LDLPC | NA Institutional Units (IU) | — |
| Control Group | Mean Glutamate (GLU) Measured in the MACC and LDLPC Using the ProFit MRS Technique at Baseline for Both Groups, After 12 Weeks of Lamotrigine Monotherapy for the Bipolar Group | 12 Weeks MACC | NA Institutional Units (IU) | — |
Secondary
N-acetylaspartic Acid (NAA) Measured in the MACC and LDLPC Using the Long TE (TE80) PRESS MRS Technique at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar (BP) Group and BP Responders and Non-responders
Two different MRS sequences were used to measure the brain chemicals in a single 2 x 2 x 2 cm cube located in the center of anterior cingulate cortex: an intermediate echo-time PRESS sequence and a 2D J-resolved averaged PRESS sequence. (Note: The intermediate echo-time PRESS sequence was used for this outcome measure.) Spectroscopic data were inspected for quality; subjects whose data were contaminated by artifact were excluded from the study. Spectra were then processed using LCModel to quantify brain chemical levels. Regular brain MRI images were segmented, yielding a map of the amount of CSF in the head. The MRS voxel was overlaid onto the CSF map and the fraction of CSF within the voxel measured. This CSF-corrected measurement was used for statistical analysis.
Time frame: baseline, 12 weeks
Population: Samples varied due to imaging results/scan viability. Baseline: control group MACC (M) and LDLPC (L) n=8, BP whole M n=28 (3 didn't complete), L n=27, BP Responders M n=13, L n=11, BP nonresponders M and L n=12; BP whole 12 weeks M and L n=16. BP Responders M and L n=10, BP nonresponders M and L n=6. Controls didn't do the procedure at 12 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bipolar Group | N-acetylaspartic Acid (NAA) Measured in the MACC and LDLPC Using the Long TE (TE80) PRESS MRS Technique at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar (BP) Group and BP Responders and Non-responders | LDLPC Baseline NAA | 19.5 Institutional Units (IU) | Standard Deviation 1.9 |
| Bipolar Group | N-acetylaspartic Acid (NAA) Measured in the MACC and LDLPC Using the Long TE (TE80) PRESS MRS Technique at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar (BP) Group and BP Responders and Non-responders | MACC 12 weeks NAA | 14.3 Institutional Units (IU) | Standard Deviation 3.2 |
| Bipolar Group | N-acetylaspartic Acid (NAA) Measured in the MACC and LDLPC Using the Long TE (TE80) PRESS MRS Technique at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar (BP) Group and BP Responders and Non-responders | MACC Baseline NAA | 15.7 Institutional Units (IU) | Standard Deviation 2.9 |
| Bipolar Group | N-acetylaspartic Acid (NAA) Measured in the MACC and LDLPC Using the Long TE (TE80) PRESS MRS Technique at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar (BP) Group and BP Responders and Non-responders | LDLPC 12 weeks NAA | 20.3 Institutional Units (IU) | Standard Deviation 2.1 |
| Control Group | N-acetylaspartic Acid (NAA) Measured in the MACC and LDLPC Using the Long TE (TE80) PRESS MRS Technique at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar (BP) Group and BP Responders and Non-responders | MACC Baseline NAA | 17.51 Institutional Units (IU) | Standard Deviation 1.77 |
| Control Group | N-acetylaspartic Acid (NAA) Measured in the MACC and LDLPC Using the Long TE (TE80) PRESS MRS Technique at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar (BP) Group and BP Responders and Non-responders | MACC 12 weeks NAA | NA Institutional Units (IU) | — |
| Control Group | N-acetylaspartic Acid (NAA) Measured in the MACC and LDLPC Using the Long TE (TE80) PRESS MRS Technique at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar (BP) Group and BP Responders and Non-responders | LDLPC 12 weeks NAA | NA Institutional Units (IU) | — |
| Control Group | N-acetylaspartic Acid (NAA) Measured in the MACC and LDLPC Using the Long TE (TE80) PRESS MRS Technique at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar (BP) Group and BP Responders and Non-responders | LDLPC Baseline NAA | 20.1 Institutional Units (IU) | Standard Deviation 1.5 |
| Bipolar Lamotrigine Non-Responders Group | N-acetylaspartic Acid (NAA) Measured in the MACC and LDLPC Using the Long TE (TE80) PRESS MRS Technique at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar (BP) Group and BP Responders and Non-responders | MACC Baseline NAA | 15.2 Institutional Units (IU) | Standard Deviation 3.3 |
| Bipolar Lamotrigine Non-Responders Group | N-acetylaspartic Acid (NAA) Measured in the MACC and LDLPC Using the Long TE (TE80) PRESS MRS Technique at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar (BP) Group and BP Responders and Non-responders | LDLPC Baseline NAA | 21.0 Institutional Units (IU) | Standard Deviation 2.8 |
| Bipolar Lamotrigine Non-Responders Group | N-acetylaspartic Acid (NAA) Measured in the MACC and LDLPC Using the Long TE (TE80) PRESS MRS Technique at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar (BP) Group and BP Responders and Non-responders | LDLPC 12 weeks NAA | 20.8 Institutional Units (IU) | Standard Deviation 2.9 |
| Bipolar Lamotrigine Non-Responders Group | N-acetylaspartic Acid (NAA) Measured in the MACC and LDLPC Using the Long TE (TE80) PRESS MRS Technique at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar (BP) Group and BP Responders and Non-responders | MACC 12 weeks NAA | 14.9 Institutional Units (IU) | Standard Deviation 3.8 |
| Bipolar Lamotrigine Group as Whole | N-acetylaspartic Acid (NAA) Measured in the MACC and LDLPC Using the Long TE (TE80) PRESS MRS Technique at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar (BP) Group and BP Responders and Non-responders | MACC 12 weeks NAA | 14.5 Institutional Units (IU) | Standard Deviation 3.4 |
| Bipolar Lamotrigine Group as Whole | N-acetylaspartic Acid (NAA) Measured in the MACC and LDLPC Using the Long TE (TE80) PRESS MRS Technique at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar (BP) Group and BP Responders and Non-responders | MACC Baseline NAA | 15.4 Institutional Units (IU) | Standard Deviation 3 |
| Bipolar Lamotrigine Group as Whole | N-acetylaspartic Acid (NAA) Measured in the MACC and LDLPC Using the Long TE (TE80) PRESS MRS Technique at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar (BP) Group and BP Responders and Non-responders | LDLPC 12 weeks NAA | 20.5 Institutional Units (IU) | Standard Deviation 2.4 |
| Bipolar Lamotrigine Group as Whole | N-acetylaspartic Acid (NAA) Measured in the MACC and LDLPC Using the Long TE (TE80) PRESS MRS Technique at Baseline for Both Groups, and After 12 Weeks of Lamotrigine Monotherapy for the Bipolar (BP) Group and BP Responders and Non-responders | LDLPC Baseline NAA | 20.0 Institutional Units (IU) | Standard Deviation 2.5 |