Abnormal volumetric brain morphometry and cerebral blood flow in adolescents with depression.

BACKGROUND: Prior research has demonstrated that the brains of adolescents with depression exhibit distinct structural alterations. However, preliminary studies have documented the pathophysiological changes in certain brain regions, such as the cerebellum, highlighting a need for further research to support the current understanding of this disease. AIM: To study brain changes in depressed adolescents. METHODS: This study enrolled 34 adolescents with depression and 34 age-, sex-, and education-level-matched healthy control (HC) individuals. Structural and functional alterations were identified when comparing the brains of these two participant groups through voxel-based morphometry and cerebral blood flow (CBF) analysis, respectively. Associations between identified brain alterations and the severity of depressive symptoms were explored through Pearson correlation analyses. RESULTS: The cerebellum, superior frontal gyrus, cingulate gyrus, pallidum, middle frontal gyrus, angular gyrus, thalamus, precentral gyrus, inferior temporal gyrus, superior temporal gyrus, inferior frontal gyrus, and supplementary motor areas of adolescents with depression showed an increase in brain volume compared to HC individuals. These patients with depression further presented with a pronounced drop in CBF in the left pallidum (group = 98, and peak t = - 4.4324), together with increased CBF in the right percental gyrus (PerCG) (group = 90, and peak t = 4.5382). In addition, 17-item Hamilton Depression Rating Scale scores were significantly correlated with the increased volume in the opercular portion of the left inferior frontal gyrus (r = - 0.5231, P < 0.01). CONCLUSION: The right PerCG showed structural and CBF changes, indicating that research on this part of the brain could offer insight into the pathophysiological causes of impaired cognition.

Abnormal brain spontaneous activity in major depressive disorder adolescents with non-suicidal self injury and its changes after sertraline therapy.

Background: Non-suicidal self-injury (NSSI) commonly occurs among adolescents with major depressive disorder (MDD), causing adverse effects on the physical and mental health of the patients. However, the underlying neurobiological mechanism of NSSI in adolescents with MDD (nsMDDs) remains unclear, and there are still challenges in the treatment. Studies have suggested that sertraline administration could be an effective way for treatment. Methods: To verify the effectiveness and to explore the neurobiological processes, we treated a group of adolescents with nsMDDs with sertraline in this study. The brain spontaneous activity alteration was then investigated in fifteen unmedicated first-episode adolescent nsMDDs versus twenty-two healthy controls through the resting-state functional magnetic resonance imaging. Besides the baseline scanning for all participants, the nsMDDs group was scanned again after eight weeks of sertraline therapy to examine the changes after treatment. Results: At pre-treatment, whole brain analysis of mean amplitude of low-frequency fluctuation (mALFF) was performed to examine the neuronal spontaneous activity alteration, and increased mALFF was found in the superior occipital extending to lingual gyrus in adolescent nsMDDs compared with controls. Meanwhile, decreased mALFF was found in the medial superior frontal in adolescent nsMDDs compared with controls. Compared with the pre-treatment, the nsMDDs group was found to have a trend of, respectively, decreased and increased functional neuronal activity at the two brain areas after treatment through the region of interest analysis. Further, whole brain comparison of mALFF at pre-treatment and post-treatment showed significantly decreased spontaneous activity in the orbital middle frontal and lingual gyrus in adolescent nsMDDs after treatment. Also, depression severity was significantly decreased after treatment. Conclusion: The abnormal functional neuronal activity found at frontal and occipital cortex implied cognitive and affective disturbances in adolescent nsMDDs. The trend of upregulation of frontal neuronal activity and downregulation of occipital neuronal activity after sertraline treatment indicated that the therapy could be effective in regulating the abnormality. Notably, the significantly decreased neuronal activity in the decision related orbital middle frontal and anxiety-depression related lingual gyrus could be suggestive of reduced NSSI in adolescent MDD after therapy.

Predicting Responses to Electroconvulsive Therapy in Adolescents with Treatment-Refractory Depression Based on Resting-State fMRI.

OBJECTS: The efficacy of electroconvulsive therapy (ECT) in the treatment of adolescents with treatment-refractory depression is still unsatisfactory, and the individual differences are large. It is not clear which factors are related to the treatment effect. Resting-state fMRI may be a good tool to predict the clinical efficacy of this treatment, and it is helpful to identify the most suitable population for this treatment. METHODS: Forty treatment-refractory depression adolescents were treated by ECT and evaluated using HAMD and BSSI scores before and after treatment, and were then divided into a treatment response group and a non-treatment group according to the reduction rate of the HAMD scale. We extracted the ALFF, fALFF, ReHo, and functional connectivity of patients as predicted features after a two-sample t-test and LASSO to establish and evaluate a prediction model of ECT in adolescents with treatment-refractory depression. RESULTS: Twenty-seven patients achieved a clinical response; symptoms of depression and suicidal ideation were significantly improved after treatment with ECT, which was reflected in a significant decrease in the scores of HAMD and BSSI (p < 0.001). The efficacy was predicted by ALFF, fALFF, ReHo, and whole-brain-based functional connectivity. We found that models built on a subset of features of ALFF in the left insula, fALFF in the left superior parietal gyrus, right superior parietal gyrus, and right angular, and functional connectivity between the left superior frontal gyrus, dorsolateral-right paracentral lobule, right middle frontal gyrus, orbital part-left cuneus, right olfactory cortex-left hippocampus, left insula-left thalamus, and left anterior cingulate gyrus-right hippocampus to have the best predictive performance (AUC > 0.8). CONCLUSIONS: The local brain function in the insula, superior parietal gyrus, and angular gyrus as well as characteristic changes in the functional connectivity of cortical-limbic circuits may serve as potential markers for efficacy judgment of ECT and help to provide optimized individual treatment strategies for adolescents with depression and suicidal ideation in the early stages of treatment.

Severity related neuroanatomical and spontaneous functional activity alteration in adolescents with major depressive disorder.

Background: Major depressive disorder (MDD) is a disabling and severe psychiatric disorder with a high rate of prevalence, and adolescence is one of the most probable periods for the first onset. The neurobiological mechanism underlying the adolescent MDD remains unexplored. Methods: In this study, we examined the cortical and subcortical alterations of neuroanatomical structures and spontaneous functional activation in 50 unmedicated adolescents with MDD vs. 39 healthy controls through the combined structural and resting-state functional magnetic resonance imaging. Results: Significantly altered regional gray matter volume was found at broader frontal-temporal-parietal and subcortical brain areas involved with various forms of information processing in adolescent MDD. Specifically, the increased GM volume at the left paracentral lobule and right supplementary motor cortex was significantly correlated with depression severity in adolescent MDD. Furthermore, lower cortical thickness at brain areas responsible for visual and auditory processing as well as motor movements was found in adolescent MDD. The lower cortical thickness at the superior premotor subdivision was positively correlated with the course of the disease. Moreover, higher spontaneous neuronal activity was found at the anterior cingulum and medial prefrontal cortex, and this hyperactivity was also negatively correlated with the course of the disease. It potentially reflected the rumination, impaired concentration, and physiological arousal in adolescent MDD. Conclusion: The abnormal structural and functional findings at cortico-subcortical areas implied the dysfunctional cognitive control and emotional regulations in adolescent depression. The findings might help elaborate the underlying neural mechanisms of MDD in adolescents.

Electroconvulsive therapy-induced neuroimaging alterations measured by cerebral blood flow in adolescents with major depressive disorder.

BACKGROUND: Electroconvulsive therapy (ECT) is a novel treatment strategy for adolescents with major depressive disorder (MDD). However, its related neurobiological changes associated with ECT remain undetermined. OBJECTIVE: To elucidate the impact of ECT on the regional cerebral blood flow (CBF), and to identify alterations in the CBF associated with clinical outcomes in adolescents with MDD. METHODS: Fifty-two treatment-naive adolescents who had experienced their first episode of MDD and 36 healthy controls (HCs) were recruited. To assess baseline parameters, all subjects were scanned with arterial spin labeling resting-state functional magnetic resonance imaging (ASL-fMRI) at the beginning of the study. Subsequently, 27 MDD adolescents were re-scanned after 2 weeks after ECT. CBF imaging was used for the prediction of specific clinical outcomes. Lastly, the associations between alterations seen on brain imaging alterations after ECT and ECT clinical efficacy (ΔHAMD scores) were determined. RESULTS: Relative to HCs, adolescents with MDD exhibited reduced CBF in the left medial superior frontal gyrus (SFGmed) (cluster = 243, peak t = -3.9373, and P < 0.001) and augmented CBF in the right percental gyrus (PerCG) (cluster = 321, peak t = 4.3332, and P < 0.001) at baseline. Following ECT, MDD adolescents exhibited reduced CBF in the right fusiform gyrus (FFG) (cluster = 309, peak t = -4.346, and P < 0.001) and left hippocampus (HIP) (cluster = 290, peak t = -4.706, and P < 0.001), and enhanced CBF in the left orbital part of the inferior frontal gyrus (ORBinf) (cluster = 214, peak t = 4.073, and P < 0.001). Correlation analysis suggested an inverse association between ΔHAMD scores and CBF values in the left ORBinf (R2 = 0.196, P = 0.021). CONCLUSIONS: It was found that ECT resulted in alterations in CBF in specific brain areas, highlighting the significance of ORBinf in ECT pathophysiology in MDD adolescents.

Changes in gray matter volume following electroconvulsive therapy in adolescent depression with suicidal ideation: A longitudinal structural magnetic resonance imaging study.

Objective: We aimed to investigate changes in whole-brain gray matter volumes (GMVs) before and after electroconvulsive therapy (ECT) in adolescents with major depressive disorder (MDD) and suicidal ideation (SI). Methods: Thirty adolescents with MDD and SI were observed, and structural magnetic resonance imaging (sMRI) was performed at baseline and after ECT for each patient. But Twenty-five healthy controls (HCs) were scanned only at baseline. The voxel-based morphometry (VBM) techniques were used to examine GMVs. Results: Compared with HCs, MDDs at baseline showed decreased GMVs in the left middle temporal gyrus, right superior temporal gyrus, right middle temporal gyrus, left precuneus, right precuneus, and left superior frontal gyrus. After ECT, MDDs showed increased GMVs in the right superior frontal gyrus and right superior temporal gyrus. Pearson's correlation found that Beck Scale for Suicide Ideation (BSSI) scores at baseline were negatively correlated with GMVs in the left superior frontal gyrus and HAMD and BSSI scores after ECT were negatively correlated with GMVs in the right superior temporal gyrus. Conclusion: Frontal-temporal-precuneus structure changes may be a potential cause of depressive and suicidal symptoms in adolescents. ECT may improve depressive and suicidal symptoms in adolescents by regulating brain structures to compensate original defects.

Altered Regional Homogeneity and Amplitude of Low-Frequency Fluctuations Induced by Electroconvulsive Therapy for Adolescents with Depression and Suicidal Ideation.

Resting-state functional magnetic resonance imaging (rs-fMRI) was used to investigate the effects of electroconvulsive therapy (ECT) causing brain function changes in adolescents who suffered from depression and suicidal ideation (SI). A total of 30 patients (MDDs) and 25 healthy controls (HCs) matched by gender, age, and education level were enrolled. The amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were used to compare differences between HCs and MDDs at baseline, and differences in ALFF and ReHo pre/post ECT in MDDs. Pearson correlation analysis was used to evaluate the relationship between altered brain function and clinical symptoms. At baseline, MDDs showed decreased ALFF in the left inferior temporal gyrus and right amygdala, decreased ReHo in left inferior temporal gyrus, and increased ReHo in the right inferior frontal gyrus, opercular part and left middle occipital gyrus. After ECT, MDDs showed increased ALFF in the right middle occipital gyrus, decreased ALFF in left temporal pole, left inferior frontal gyrus, opercular part, and right frontal middle gyrus, increased ReHo in the right middle occipital gyrus, and left inferior temporal gyrus. Pearson correlation found HAMD scores at baseline were negatively correlated with ALFF in the left inferior temporal gyrus, and HAMD and BSSI scores after ECT were negatively correlated with ALFF in the right middle occipital gyrus. The abnormal activities of amygdala, inferior temporal gyrus and middle occipital gyrus might be related to depressive and suicidal symptoms in adolescents.

Cerebral blood flow in adolescents with drug-naive, first-episode major depressive disorder: An arterial spin labeling study based on voxel-level whole-brain analysis.

Purpose: The major depressive disorder (MDD) can be a threat to the health of people all over the world. Although governments have developed and implemented evidence-based interventions and prevention programs to prevent MDD and maintain mental health in adolescents, the number of adolescents with this condition has been on the rise for the past 10 years. Methods: A total of 60 adolescents were recruited, including 32 drug-naive adolescents with first-episode MDD and 28 healthy controls (HCs). Alterations in the intrinsic cerebral activity of the adolescents with MDD were explored using arterial spin labeling (ASL) while differences in the regional cerebral blood flow (rCBF) of the two groups were assessed based on voxel-based whole-brain analysis. Finally, correlations between the regional functional abnormalities and clinical variables were investigated for adolescents with MDD. Results: Compared with HCs, MDD patients had a lower rCBF in the left triangular part of the inferior frontal gyrus (IFGtriang) but a higher one in the right Precental gyrus (PreCG). Negative correlations were also noted between the CBF in the left IFGtriang and the Hamilton depression scale (HAMD) scores of MDD patients. Conclusion: Elucidating the neurobiological features of adolescent patients with MDD is important to adequately develop methods that can assist in early diagnosis, precaution and intervention.

Resting-state functional magnetic resonance imaging-based identification of altered brain the fractional amplitude of low frequency fluctuation in adolescent major depressive disorder patients undergoing electroconvulsive therapy.

Purpose: While electroconvulsive therapy (ECT) has been repeatedly been shown to effectively and efficiently treat the major depressive disorder (MDD), the mechanistic basis for such therapeutic efficacy remains to be firmly established. As such, further research exploring the ECT-based treatment of MDD in an adolescent population is warranted. Methods: This study included 30 treatment-naïve first-episode MDD patients and 30 healthy control (HC) individuals (aged 12-17 years). All participants were scanned using rs-fMRI, and the 30 MDD patients were scanned again after 2 weeks of the ECT treatment period. Intrinsic local activity in each voxel was assessed based on the fractional amplitude of low frequency fluctuation (fALFF) parameter, with all fALFF analyses being completed using the REST application. Correlations between ECT-related changes in fALFF and clinical parameters were additionally examined. Results: Relative to HCs, MDD patients exhibited increased fALFF values in the right inferior frontal gyrus (ORBinf), inferior occipital gyrus (IOG), and the left middle frontal gyrus (MFG) at baseline. Following ECT, these patients exhibited significant increases in fALFF values in the right medial superior frontal gyrus (SFGmed), dorsolateral superior frontal gyrus (SFGdor), anterior cingulate, and paracingulate gyrus (ACG), median cingulate and paracingulate gyrus (DCG), and left MFG. MDD patient HAMD scores were negatively correlated with fALFF values when analyzing pre-ECT vs. post-HCT ΔHAMD and fALFF values in the right SFGmed, SFGdor, and the left MFG. Conclusion: These data suggest that ECT induced altered fALFF in some regions of the brain, suggesting that these alterations may serve as a neurobiological indicator of ECT effectiveness in MDD adolescents.

A Resting State Functional Magnetic Resonance Imaging Study of Unmedicated Adolescents With Non-suicidal Self-Injury Behaviors: Evidence From the Amplitude of Low-Frequency Fluctuation and Regional Homogeneity Indicator.

Background: Non-suicidal self-injury (NSSI) behaviors are common in adolescents with major depressive disorder (MDD). Brain studies specifically targeting adolescents with MDD and NSSI may provide new insights into suicide warnings in adolescents with MDD. Methods: This study examined the whole-brain neural activity in adolescents aged between 12-17 years, 50 unmedicated MDD patients with (nsMDDs) or without NSSI (nnsMDDs), and 25 healthy controls (HCs) participated in this study, and analyzed the correlation between the values of amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) in significantly different brain regions and the scores of the relevant clinical psychological scale. Results: Compared with nnsMDDs, nsMDDs had enhanced ALFF values in left middle occipital gyrus and left median cingulate and paracingulate gyri; the fALFF values of the right caudate nucleus was weakened in the nsMDDs; the ReHo values of right middle occipital gyrus and right middle temporal gyrus weakened and the ReHo values of right medial cingulate gyrus enhanced in nsMDDs. And all of differences were statistically significant. In nsMDDs, the value of ALFF in the left calcarine fissure and surrounding cortex was negatively correlated with the score of Children's depression Inventory (CDI); the value of fALFF in the right caudate nucleus was positively correlated with the score of Beck Scale for Suicidal Ideations (BSSI); the value of ReHo in the right middle temporal gyrus was positively correlated with the score of Multidimensional Anxiety Scale for Children (MASC); and the value of ReHo in the right median cingulate and paracingulate gyri was negatively correlated with the score of BSSI. Conclusions: We found that in ALFF, fALFF and ReHo, the significant differences between nsMDDs and nnsMDDs are mainly located in default mode network (DMN) and visual network (VN), and there may be brain regions related to NSSI in DMN and VN. The significant differences brain regions in ALFF, fALFF and ReHo between nsMDDs and nnsMDDs were related to the total score of the relevant clinical psychological scale, and may be related to NSSI.

Alteration of Whole Brain ALFF/fALFF and Degree Centrality in Adolescents With Depression and Suicidal Ideation After Electroconvulsive Therapy: A Resting-State fMRI Study.

Major depressive disorder (MDD) is one of the most widespread mental disorders and can result in suicide. Suicidal ideation (SI) is strongly predictive of death by suicide, and electroconvulsive therapy (ECT) is effective for MDD, especially in patients with SI. In the present study, we aimed to determine differences in resting-state functional magnetic resonance imaging (rs-fMRI) in 14 adolescents aged 12-17 with MDD and SI at baseline and after ECT. All participants were administered the Hamilton Depression Scale (HAMD) and Beck Scale for Suicide Ideation (BSSI) and received rs-fMRI scans at baseline and after ECT. Following ECT, the amplitude of low frequency fluctuation (ALFF) and fractional ALFF (fALFF) significantly decreased in the right precentral gyrus, and the degree centrality (DC) decreased in the left triangular part of the inferior frontal gyrus and increased in the left hippocampus. There were significant negative correlations between the change of HAMD (ΔHAMD) and ALFF in the right precentral gyrus at baseline, and between the change of BSSI and the change of fALFF in the right precentral gyrus. The ΔHAMD was positively correlated with the DC value of the left hippocampus at baseline. We suggest that these brain regions may be indicators of response to ECT in adolescents with MDD and SI.