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Background Growing evidence suggests an endophenotype for suicidality, including brain morphometric features, could provide an improved platform for suicide risk assessment. Reduced right superior temporal gyrus (rSTG) volumes have been implicated in suicidality across psychiatric disorders. Treatment-resistant depression (TRD) has unique neurobiology and adolescents with TRD are at increased suicide risk. Here, we investigated whether reduced rSTG volume was present in adolescents with TRD and history of suicide attempt. Methods 45 adolescents - 14 with history of suicide attempt and TRD, 14 without a suicide attempt history and TRD, and 17 healthy controls - underwent magnetic resonance imaging and reconstructed rSTG volumes were compared. Depressive and anxious symptoms were assessed with Hamilton depression and anxiety rating scales, and differences between attempters and non-attempters were explored. Results Adolescents with TRD and history of suicide attempt showed reduced rSTG volume compared to healthy controls. Exploratory analyses revealed greater diurnal variation in depressive symptoms in the suicide attempt group compared to non-attempters. Limitations Sample size and temporal separation between suicide attempt date and data collection limits interpretation of findings. Conclusions Reduced rSTG volume may serve as a marker of suicide attempt in adolescence and specific symptom features may have a role in suicide risk assessment. Presently, risk assessment is limited by patient self-report and clinical judgement. A biological model of suicidality will be key to improve risk assessment and could lead to novel treatment approaches. Our findings extend previous results and contribute to our neurobiological understanding of suicidality.

Background Smaller hippocampal volumes, as assessed by magnetic resonance imaging (MRI), and proton magnetic resonance spectroscopy ( 1 H-MRS) indexed alterations in brain metabolites have been identified in adults with major depressive disorder (MDD). Our group has found similar effects in MDD youth. However, this has not been studied in youth with treatment resistant MDD (TRD), nor has the interaction between regional N-acetyl-aspartate and volume deficits. N-acetyl-aspartate is an amino acid in the synthesis pathway of glutamate, and serves a marker of neuronal viability/number. Methods Fifteen typically developing youth (16–22 years of age; 7 males, 8 females) and eighteen youth with TRD (14–22 years of age; 8 males, 10 females) underwent 1 H-MRS and MRI on a 3 T scanner. A short echo PRESS protocol was used with voxels in the right and left hippocampi (6 mL each). Hippocampal volume was evaluated using FreeSurfer. Results Compared with the typically developing group, youth with TRD had lower concentrations of N-acetyl-aspartate in the left hippocampus (p=0.004), and a trend for smaller left hippocampal volume (p=0.067). In TRD subjects, hippocampal N-acetyl-aspartate was inversely correlated with left (r=−0.68, p=0.003) but not right hippocampal volume. Right hippocampal glutamate+glutamine was greater in TRD youth compared to typically developing controls (p=0.007). Conclusions These results suggest a neurochemical and structural deficit in the hippocampi of youth with TRD. These findings fit with the role of N-acetyl-aspartate in glutamate neurotransmission and the effect of glutamate on brain morphology.

Aim Structural, functional, and metabolic changes in the dorsolateral prefrontal cortex (DLPFC) are implicated in the pathogenesis of major depressive disorder (MDD). We used proton magnetic resonance spectroscopy ((1) H-MRS) to examine the metabolite choline (glycerophosphocholine plus phosphocholine), which is used as an index of membrane integrity in the left DLPFC, in adolescents and young adults with MDD who were treatment-resistant and had a positive family history compared to healthy controls. Differences in the choline resonance indicate an imbalance between synthesis and degradation activity of neuronal and glia membrane phospholipids. Methods Seventeen adolescents with MDD and 11 healthy controls underwent (1) H-MRS. A short echo point-resolved spectroscopy (echo time = 30 ms, repetition time = 2000 ms) protocol was used with a voxel (4.5cm(3) , 128 averages) placed within the left DLPFC. Results There were significantly increased choline (P = 0.04) and creatine concentrations (P = 0.005) in the left DLPFC of the MDD group compared to controls. In MDD participants, choline concentration correlated with scores on the Beck Depression Inventory (r = 0.41, P = 0.03). Conclusion Increased left DLPFC choline and creatine levels in depressed adolescents may be biomarkers for the disorder. The increased choline levels may indicate abnormalities in neuronal membrane integrity, and the increased creatine could be reflective of altered energy demands and metabolism.

Structural, functional, and metabolic changes in the dorsolateral prefrontal cortex (DLPFC) are implicated in the pathogenesis of major depressive disorder (MDD). We used proton magnetic resonance spectroscopy ((1) H-MRS) to examine the metabolite choline (glycerophosphocholine plus phosphocholine), which is used as an index of membrane integrity in the left DLPFC, in adolescents and young adults with MDD who were treatment-resistant and had a positive family history compared to healthy controls. Differences in the choline resonance indicate an imbalance between synthesis and degradation activity of neuronal and glia membrane phospholipids.Seventeen adolescents with MDD and 11 healthy controls underwent (1) H-MRS. A short echo point-resolved spectroscopy (echo time = 30 ms, repetition time = 2000 ms) protocol was used with a voxel (4.5cm(3) , 128 averages) placed within the left DLPFC.There were significantly increased choline (P = 0.04) and creatine concentrations (P = 0.005) in the left DLPFC of the MDD group compared to controls. In MDD participants, choline concentration correlated with scores on the Beck Depression Inventory (r = 0.41, P = 0.03).Increased left DLPFC choline and creatine levels in depressed adolescents may be biomarkers for the disorder. The increased choline levels may indicate abnormalities in neuronal membrane integrity, and the increased creatine could be reflective of altered energy demands and metabolism.