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Transcranial magnetic stimulation potentiates glutamatergic neurotransmission in depressed adolescents.

ABSTRACT: Abnormalities in glutamate neurotransmission may have a role in the pathophysiology of adolescent depression. The present pilot study examined changes in cortical glutamine/glutamate ratios in depressed adolescents receiving high-frequency repetitive transcranial magnetic stimulation. Ten adolescents with treatment-refractory major depressive disorder received up to 30 sessions of 10-Hz repetitive transcranial magnetic stimulation at 120% motor threshold with 3000 pulses per session applied to the left dorsolateral prefrontal cortex. Baseline, posttreatment, and 6-month follow-up proton magnetic resonance spectroscopy scans of the anterior cingulate cortex and left dorsolateral prefrontal cortex were collected at 3T with 8-cm(3) voxels. Glutamate metabolites were quantified with 2 distinct proton magnetic resonance spectroscopy sequences in each brain region. After repetitive transcranial magnetic stimulation and at 6 months of follow-up, glutamine/glutamate ratios increased in the anterior cingulate cortex and left dorsolateral prefrontal cortex with both measurements. The increase in the glutamine/glutamate ratio reached statistical significance with the TE-optimized PRESS sequence in the anterior cingulate cortex. Glutamine/glutamate ratios increased in conjunction with depressive symptom improvement. This reached statistical significance with the TE-optimized PRESS sequence in the left dorsolateral prefrontal cortex. High-frequency repetitive transcranial magnetic stimulation applied to the left dorsolateral prefrontal cortex may modulate glutamate neurochemistry in depressed adolescents.

SUBMITTER: Croarkin PE

PROVIDER: S-EPMC4716879 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Transcranial magnetic stimulation potentiates glutamatergic neurotransmission in depressed adolescents.

Croarkin Paul E PE Nakonezny Paul A PA Wall Christopher A CA Murphy Lauren L LL Sampson Shirlene M SM Frye Mark A MA Port John D JD

Psychiatry research. Neuroimaging 20151127

Abnormalities in glutamate neurotransmission may have a role in the pathophysiology of adolescent depression. The present pilot study examined changes in cortical glutamine/glutamate ratios in depressed adolescents receiving high-frequency repetitive transcranial magnetic stimulation. Ten adolescents with treatment-refractory major depressive disorder received up to 30 sessions of 10-Hz repetitive transcranial magnetic stimulation at 120% motor threshold with 3000 pulses per session applied to t ...[more]

PMID: 26651598

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Project description:ObjectivesIt is estimated that 30-40% of adolescents with major depressive disorder (MDD) do not receive full benefit from current antidepressant therapies. Repetitive transcranial magnetic stimulation (rTMS) is a novel therapy approved by the US Food and Drug Administration to treat adults with MDD. Research suggests rTMS is not associated with adverse neurocognitive effects in adult populations; however, there is no documentation of its neurocognitive effects in adolescents. This is a secondary post hoc analysis of neurocognitive outcome in adolescents who were treated with open-label rTMS in two separate studies.MethodsEighteen patients (mean age, 16.2 ± 1.1 years; 11 females, 7 males) with MDD who failed to adequately respond to at least one antidepressant agent were enrolled in the study. Fourteen patients completed all 30 rTMS treatments (5 days/week, 120% of motor threshold, 10 Hz, 3,000 stimulations per session) applied to the left dorsolateral prefrontal cortex. Depression was rated using the Children's Depression Rating Scale-Revised. Neurocognitive evaluation was performed at baseline and after completion of 30 rTMS treatments with the Children's Auditory Verbal Learning Test (CAVLT) and Delis-Kaplan Executive Function System Trail Making Test.ResultsOver the course of 30 rTMS treatments, adolescents showed a substantial decrease in depression severity. Commensurate with improvement in depressive symptoms was a statistically significant improvement in memory and delayed verbal recall. Other learning and memory indices and executive function remained intact. Neither participants nor their family members reported clinically meaningful changes in neurocognitive function.ConclusionThese preliminary findings suggest rTMS does not adversely impact neurocognitive functioning in adolescents and may provide subtle enhancement of verbal memory as measured by the CAVLT. Further controlled investigations with larger sample sizes and rigorous trial designs are warranted to confirm and extend these findings.

Project description:Introduction: Transcranial magnetic stimulation (TMS) research has suggested dysfunction in cortical glutamatergic systems in adolescent depression, while proton magnetic resonance spectroscopy (1H-MRS) studies have demonstrated deficits in concentrations of glutamatergic metabolites in depressed individuals in several cortical regions, including the anterior cingulate cortex (ACC). However, few studies have combined TMS and MRS methods to examine relationships between glutamatergic neurochemistry and excitatory and inhibitory neural functions, and none have utilized TMS-MRS methodology in clinical populations or in youth. This exploratory study aimed to examine relationships between TMS measures of cortical excitability and inhibition and concentrations of glutamatergic metabolites as measured by 1H-MRS in depressed adolescents. Methods: Twenty-four adolescents (aged 11-18 years) with depressive symptoms underwent TMS testing, which included measures of the resting motor threshold (RMT), cortical silent period (CSP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF). Fourteen participants from the same sample also completed 1H-MRS in a 3 T MRI scanner after TMS testing. Glutamate + glutamine (Glx) concentrations were measured in medial ACC and left primary motor cortex voxels with a TE-optimized PRESS sequence. Metabolite concentrations were corrected for cerebrospinal fluid (CSF) after tissue segmentation. Pearson product-moment and Spearman rank-order correlations were calculated to assess relationships between TMS measures and [Glx]. Results: In the left primary motor cortex voxel, [Glx] had a significant positive correlation with the RMT. In the medial ACC voxel, [Glx] had significant positive correlations with ICF at the 10-ms and 20-ms interstimulus intervals (ISIs). Conclusion: These preliminary data implicate glutamate in cortical excitatory processes measured by TMS. Limitations included small sample size, lack of healthy control comparators, possible age- and sex-related effects, and observational nature of the study. Further research aimed at examining the relationship between glutamatergic metabolite concentrations measured through MRS and the excitatory and inhibitory physiology measured through TMS is warranted. Combined TMS-MRS methods show promise for future investigations of the pathophysiology of depression in adults as well as in children and adolescents.

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Transcranial magnetic stimulation potentiates glutamatergic neurotransmission in depressed adolescents.

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Transcranial magnetic stimulation potentiates glutamatergic neurotransmission in depressed adolescents.

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