Daskalakis, Zafiris J.

Suicidality is increased in autism spectrum disorder (ASD), yet effective interventions are lacking. Developing biologically based approaches for preventing and treating suicidality in ASD hinges on the identification of biomarkers of suicidal ideation (SI). Here, we assessed magnetic resonance spectroscopy (MRS) markers of glutamatergic neurotransmission in ASD youth and young adults. Twenty-eight ASD participants (16–33 years) underwent 1H-MRS, and metabolites were quantified using LCModel. N-acetylaspartate (NAA), glutamate (Glu), and the NAA/Glu ratio from the left dorsolateral prefrontal cortex were compared between ASD SI+ (n = 13) and ASD SI− (n = 15) participants. We found that ASD SI+ participants had a higher NAA/Glu ratio compared ASD SI- participants. The NAA/Glu ratio also predicted SI and significantly discriminated between ASD SI+/SI− participants. All analyses including NAA and Glu alone were non-significant. Here, we provide preliminary evidence for the importance of NAA/Glu in ASD with SI, with implications for biomarker discovery. Further mechanistic research into risk and interventional approaches to address SI in ASD are needed.

Abstract Up to 50% of youth with depression do not respond to conventional first-line treatments. However, little research has been conducted on the pathophysiology of youth depression, hindering the identification of more effective treatments. Our goal was to identify neurophysiological markers that differentiate youth with depression from healthy youth and could serve as targets of novel treatments. We hypothesized that youth with depression would exhibit network-specific cortical reactivity and connectivity abnormalities compared with healthy youth. Transcranial magnetic stimulation combined with electroencephalography and magnetic resonance imaging was employed in combination with clinical and behavioral assessments to study cortical reactivity and connectivity in bilateral dorsolateral prefrontal cortex (DLPFC), motor cortex, and inferior parietal lobule, sites linked to the frontoparietal network, sensorimotor network, and default mode network, respectively. In youth depression, greater cortical reactivity was observed specific to the left and right DLPFC stimulation only, which correlated with anhedonia scores. Additionally, the connectivity of the right DLPFC was significantly higher in youth depression. Source reconstruction attributed the observed connectivity dysregulation to regions belonging to the default mode network. The neurophysiological signatures identified in this study have high potential to inform the development of more effective and targeted interventions for the youth depression population.

AbstractBackgroundThe goal of this study was to examine baseline transcranial magnetic stimulation measures of cortical inhibition and excitability in depressed patients and characterize their longitudinal posttreatment changes.MethodsFifteen adolescents (age 13–17 years) with moderate to severe major depressive disorder and 22 healthy controls (age 9–17) underwent single- and paired-pulse transcranial magnetic stimulation and clinical assessments. Transcranial magnetic stimulation measures included short-interval intracortical inhibition (2 and 4 milliseconds), long-interval intracortical inhibition (100, 150, and 200 milliseconds), cortical silent period, and intracortical facilitation (10, 15, and 20 milliseconds). Ten participants with major depressive disorder initiated antidepressant treatment or had dose adjustments. These participants were reassessed after treatment. Depression symptom severity was measured with the Children’s Depression Rating Scale, Revised. Robust regression modeling compared healthy and depressed adolescents at baseline. Relationships between changes in cortical inhibition and changes in depressive symptom severity were assessed in the depressed adolescents receiving antidepressant treatment.ResultsOur results revealed that at baseline, short-interval intracortical inhibition-2 was significantly reduced (Padj = .01) in depressed participants, suggesting impaired cortical inhibition compared with healthy controls. At follow-up, improvement in Children’s Depression Rating Scale, Revised scores correlated with improvement in short-interval intracortical inhibition-4 amplitude (greater inhibition) after antidepressant treatment (R2 = 0.63; P = .01).ConclusionsThese results suggest that cortical inhibition measures may have promise as biomarkers in adolescents treated for depression.