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Introduction: Risk of suicidal ideation and suicidal behaviors greatly increases during adolescence, and rates have risen dramatically over the past two decades. However, few risk factors or biomarkers predictive of suicidal ideation or attempted suicide have been identified in adolescents. Neuroimaging correlates hold potential for early identification of adolescents at increased risk of suicidality and risk stratification for those at high risk of suicide attempt., Methods: In this systematic review, we evaluated neural regions and networks associated with suicidal ideation and suicide attempt in adolescents derived from magnetic resonance imaging (MRI) studies. A total of 28 articles were included in this review., Results: After descriptively synthesizing the literature, we propose the Emotional paiN and social Disconnect (END) model of adolescent suicidality and present two key neural circuits: (1) the emotional/mental pain circuit and (2) the social disconnect/distortion circuit. In the END model, the emotional pain circuit-consisting of the cerebellum, amygdala, and hippocampus-shows similar aberrations in adolescents with suicidal ideation as in those with a history of a suicide attempt (but to a smaller degree). The social disconnect circuit is unique to adolescent suicide attempters and includes the lateral orbitofrontal cortex (OFC), the temporal gyri, and the connections between them., Conclusion: Our proposed END brain model of suicidal behavior in youth, if confirmed by future prospective studies, can have implications for clinical goals of early detection, risk stratification, and intervention development. Treatments that target emotional pain and social disconnect may be ideal interventions for reducing suicidality in adolescents., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Olga Tymofiyeva et al.)

Objective: Anorexia nervosa is a psychiatric disorder of unknown etiology. Understanding associations between behavior and neurobiology is important in treatment development. Using a novel monetary reward task during functional magnetic resonance brain imaging, the authors tested how brain reward learning in adolescent anorexia nervosa changes with weight restoration., Method: Female adolescents with anorexia nervosa (N=21; mean age, 16.4 years [SD=1.9]) underwent functional MRI (fMRI) before and after treatment; similarly, healthy female control adolescents (N=21; mean age, 15.2 years [SD=2.4]) underwent fMRI on two occasions. Brain function was tested using the reward prediction error construct, a computational model for reward receipt and omission related to motivation and neural dopamine responsiveness., Results: Compared with the control group, the anorexia nervosa group exhibited greater brain response 1) for prediction error regression within the caudate, ventral caudate/nucleus accumbens, and anterior and posterior insula, 2) to unexpected reward receipt in the anterior and posterior insula, and 3) to unexpected reward omission in the caudate body. Prediction error and unexpected reward omission response tended to normalize with treatment, while unexpected reward receipt response remained significantly elevated. Greater caudate prediction error response when underweight was associated with lower weight gain during treatment. Punishment sensitivity correlated positively with ventral caudate prediction error response., Conclusions: Reward system responsiveness is elevated in adolescent anorexia nervosa when underweight and after weight restoration. Heightened prediction error activity in brain reward regions may represent a phenotype of adolescent anorexia nervosa that does not respond well to treatment. Prediction error response could be a neurobiological marker of illness severity that can indicate individual treatment needs.

Several studies have reported that adults with major depressive disorder have shorter telomere length and reduced hippocampal volumes. Moreover, studies of adult populations without major depressive disorder suggest a relationship between peripheral telomere length and hippocampal volume. However, the relationship of these findings in adolescents with major depressive disorder has yet to be explored. We examined whether adolescent major depressive disorder is associated with altered peripheral telomere length and hippocampal volume, and whether these measures relate to one another. In 54 unmedicated adolescents (13-18 years) with major depressive disorder and 63 well-matched healthy controls, telomere length was assessed from saliva using quantitative polymerase chain reaction methods, and bilateral hippocampal volumes were measured with magnetic resonance imaging. After adjusting for age and sex (and total brain volume in the hippocampal analysis), adolescents with major depressive disorder exhibited significantly shorter telomere length and significantly smaller right, but not left hippocampal volume. When corrected for age, sex, diagnostic group and total brain volume, telomere length was not significantly associated with left or right hippocampal volume, suggesting that these cellular and neural processes may be mechanistically distinct during adolescence. Our findings suggest that shortening of telomere length and reduction of hippocampal volume are already present in early-onset major depressive disorder and thus unlikely to be only a result of accumulated years of exposure to major depressive disorder.

The current work reports a type of "smart" lanthanide-based theranostic nanoprobe, NaDyF4:Yb(3+)/NaGdF4:Yb(3+),Er(3+), which is able to circumvent the up-converting poisoning effect of Dy(3+) ions to give efficient near infrared (980 nm) triggered up-conversion fluorescence, and offers not only excellent dark T2-weighted MR contrast but also tunable bright and T1-weighted MR contrast properties. Due to the efficient up-converted energy transfer from the nanocrystals to chlorin e6 (Ce6) photosensitizers loaded onto the nanocrystals, cytotoxic singlet oxygen was generated and photodynamic therapy was demonstrated. Therefore, the current multifunctional nanocrystals could be potentially useful in various image-guided diagnoses where bright or dark MRI contrast could be selectively tuned to optimize image quality, but also as an efficient and more penetrative near-infrared activated photodynamic therapy agent.

Background: A positive family history (FHP) of alcohol use disorders (AUD) is linked to increased risk for personal AUD, but the mechanisms behind this risk are unclear. Previous research suggests that a subtle neurodevelopmental lag in FHP adolescents may contribute to risk for future AUD., Methods: Functional magnetic resonance imaging (fMRI) response to a spatial working memory (SWM) task was examined for markers of neuromaturational delay in 85 youth with and without FHP. It was hypothesized that FHP adolescents (n = 24, ages 12-14 years), as compared to matched FHN youth (n = 26, ages 12-14 years), would show less similarity to brain connectivity observed in older adolescents (n = 35, ages 16-20 years) and that statistical comparison of SWM functional connectivity models would differentiate FHN and FHP youth. Structural equation modeling tested the fit of brain response connectivity between FH groups and against the older-adolescent model., Results: Patterns of connectivity were more similar between older adolescent and FHN than FHP adolescents; FHP youth demonstrated higher association between right posterior and left frontal brain regions than FHN and older adolescent youth. Comparison of FH groups indicated a significant difference on the pathway from the right superior parietal lobule to the left middle frontal gyrus., Conclusions: These findings provide additional support for the notion of a neuromaturational lag in FHP youth. Protracted neuromaturation may be a mechanism by which FH increases risk for alcohol dependence, and this less mature neural connectivity pattern may provide a novel endophenotype for identifying youth at risk for drinking problems.

Objective: The neurobiological underpinnings of anorexia nervosa (AN) are poorly understood. In this study, we tested whether brain gray matter (GM) and white matter (WM) in adolescents with AN would show alterations comparable to those in adults., Method: We used magnetic resonance imaging to study GM and WM volume, and diffusion tensor imaging to assess fractional anisotropy for WM integrity in 19 adolescents with AN and 22 controls., Results: Individuals with AN showed greater left orbitofrontal, right insular, and bilateral temporal cortex GM, as well as temporal lobe WM volumes compared to controls. WM integrity in adolescents with AN was lower (lower fractional anisotropy) in fornix, posterior frontal, and parietal areas, but higher in anterior frontal, orbitofrontal, and temporal lobes. In individuals with AN, orbitofrontal GM volume correlated negatively with sweet taste pleasantness. An additional comparison of this study cohort with adult individuals with AN and healthy controls supported greater orbitofrontal cortex and insula volumes in AN across age groups., Conclusions: This study indicates larger orbitofrontal and insular GM volumes, as well as lower fornix WM integrity in adolescents with AN, similar to adults. The pattern of larger anteroventral GM and WM volume as well as WM integrity, but lower WM integrity in posterior frontal and parietal regions may indicate that developmental factors such as GM pruning and WM growth could contribute to brain alterations in AN. The negative correlation between taste pleasantness and orbitofrontal cortex volume in individuals with AN could contribute to food avoidance in this disorder., (Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Recent studies suggest that altered function of higher-order appetitive neural circuitry may contribute to restricted eating in anorexia nervosa and overeating in bulimia nervosa. This study used sweet tastes to interrogate gustatory neurocircuitry involving the anterior insula and related regions that modulate sensory-interoceptive-reward signals in response to palatable foods., Method: Participants who had recovered from anorexia nervosa and bulimia nervosa were studied to avoid confounding effects of altered nutritional state. Functional MRI measured brain response to repeated tastes of sucrose and sucralose to disentangle neural processing of caloric and noncaloric sweet tastes. Whole-brain functional analysis was constrained to anatomical regions of interest., Results: Relative to matched comparison women (N=14), women recovered from anorexia nervosa (N=14) had significantly diminished and women recovered from bulimia nervosa (N=14) had significantly elevated hemodynamic response to tastes of sucrose in the right anterior insula. Anterior insula response to sucrose compared with sucralose was exaggerated in the recovered group (lower in women recovered from anorexia nervosa and higher in women recovered from bulimia nervosa)., Conclusions: The anterior insula integrates sensory reward aspects of taste in the service of nutritional homeostasis. One possibility is that restricted eating and weight loss occur in anorexia nervosa because of a failure to accurately recognize hunger signals, whereas overeating in bulimia nervosa could represent an exaggerated perception of hunger signals. This response may reflect the altered calibration of signals related to sweet taste and the caloric content of food and may offer a pathway to novel and more effective treatments.

Objective: Although substantial literature has reported regional cerebral blood flow (rCBF) abnormalities in adults with depression, these studies commonly necessitated the injection of radioisotopes into subjects. The recent development of arterial spin labeling (ASL), however, allows noninvasive measurements of rCBF. Currently, no published ASL studies have examined cerebral perfusion in adolescents with depression. Thus, the aim of the present study was to examine baseline cerebral perfusion in adolescent depression using a newly developed ASL technique: pseudocontinuous arterial spin labeling (PCASL)., Method: A total of 25 medication-naive adolescents (13-17 years of age) diagnosed with major depressive disorder (MDD) and 26 well-matched control subjects underwent functional magnetic resonance imaging. Baseline rCBF was measured via a novel PCASL method that optimizes tagging efficiency., Results: Voxel-based whole brain analyses revealed significant frontal, limbic, paralimbic, and cingulate hypoperfusion in the group with depression (p < .05, corrected). Hyperperfusion was also observed within the subcallosal cingulate, putamen, and fusiform gyrus (p < .05, corrected). Similarly, region-of-interest analyses revealed amygdalar and insular hypoperfusion in the group with depression, as well as hyperperfusion in the putamen and superior insula (p < .05, corrected)., Conclusions: Adolescents with depression and healthy adolescents appear to differ on rCBF in executive, affective, and motor networks. Dysfunction in these regions may contribute to the cognitive, emotional, and psychomotor symptoms commonly present in adolescent depression. These findings point to possible biomarkers for adolescent depression that could inform early interventions and treatments, and establishes a methodology for using PCASL to noninvasively measure rCBF in clinical and healthy adolescent populations., (Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: To study magnetic resonance imaging (MRI) correlates of novel (new-onset) psychiatric disorders (NPD) after traumatic brain injury (TBI) and orthopedic injury (OI)., Method: Participants were 7 to 17 years of age at the time of hospitalization for either TBI or OI. The study used a prospective, longitudinal, controlled design with standardized psychiatric assessments conducted at baseline (reflecting pre-injury function) and 3 months post-injury. MRI assessments including diffusion tensor imaging (DTI)-derived fractional anisotropy (FA), volumetric measures of gray and white matter regions, volumetric measures of lesions, and cortical thickness were conducted. Injury severity was assessed by standard clinical scales. The outcome measure was the presence of an NPD identified during the first 3 months after injury., Results: There were 88 participants (TBI, 44; OI, 44). NPD occurred more frequently in the TBI (21/44; 48%) versus the OI (6/44; 14%) group (Fisher's exact test, p = .001). NPD in TBI participants was not related to injury severity. Multivariate analysis of covariance of the relationship between FA in hypothesized regions of interest (bilateral frontal and temporal lobes, bilateral centrum semiovale, bilateral uncinate fasciculi) and NPD and group (TBI versus OI) was significant, and both variables (NPD, p < .05; group, p < .001) were jointly significantly related to FA. NPD was not significantly related to volumetric measures of white or gray matter structures, volumetric measures of lesions, or cortical thickness measures., Conclusions: Lowered white matter integrity may be more important in the pathophysiology of NPD than indices of gray matter or white matter atrophic changes, macroscopic lesions, and injury severity., (Copyright © 2012 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Fluorescent optical probes have been intensively used in the area of bio-imaging. In this review article, we describe the recent advancements in the synthesis and application of bimodal magnetic-fluorescent probes for bioimaging. The bimodal probes consist of fluorescent [semiconducting quantum dots (e.g., CdSe/ZnS) or rare-earth doped (e.g., NaYF(4) :Yb,Er)] nanoparticles (NPs) and magnetic (iron oxide or gadolinium based) NPs for optical and magnetic resonance (MR) imaging., (Copyright © 2010 Wiley-Liss, Inc.)

We demonstrate a simple synthetic strategy for the fabrication of single-phase rare earth (RE) doped gadolinium oxide (Gd(2)O(3):RE where RE = terbium (Tb), ytterbium (Yb), and erbium (Er)) nanorods (NRs) as multimodal imaging probes. The NRs are ultranarrow and exhibit both emission and magnetic characteristics. The Tb-doped and Yb/Er-codoped Gd(2)O(3) NRs exhibit down- and up-conversion fluorescence respectively, and also exhibit paramagnetism. Importantly, these codoped NRs possess excellent magnetic characteristics, as shown in their longitudinal relaxation time (T1) -weighted image contrast, which is closer to that of commercial Gadovist for magnetic resonance imaging (MRI) applications. This property opens up new avenues in the development of contrast agents.

Objective: Functional neuroimaging studies have led to a significantly deeper understanding of the underlying neural correlates and the development of several mature models of depression in adults. In contrast, our current understanding of the underlying neural substrates of adolescent depression is very limited. Although numerous studies have consistently demonstrated a hyperactive amygdala in depressed adults, the few published pediatric studies have reported opposite results in the amygdala. Thus, the main purpose of this study was to further our knowledge of the underlying neural substrates of adolescent depression by examining the bilateral amygdala specifically and the whole brain in depressed adolescents compared to healthy controls., Method: Twelve unmedicated adolescents diagnosed with current major depressive disorder without a comorbid psychiatric disorder and 12 well-matched controls ages 13 to 17 years performed a facial-emotion matching task during functional magnetic resonance imaging at 3 T., Results: Region-of-interest analyses demonstrated: (1) significant bilateral amygdala activation in depressed and healthy adolescents, and (2) significantly greater left amygdala activation in depressed adolescents compared to controls. Whole-brain analysis revealed areas of significantly different brain activity in depressed adolescents compared to controls., Conclusions: These results suggest that (1) depressed adolescents without a comorbid psychiatric disorder exhibit an abnormally hyperactive amygdala compared to healthy controls; (2) models of adult depression might be extended to include depressed adolescents; and (3) neuropsychiatric interventions that have been developed in depressed adults should be further examined in adolescents.

Background: Individuals with major depressive disorder (MDD) show abnormal functional coupling (FC) between several nodes of a widely distributed cortico-limbic network that includes the amygdala and anterior cingulate. The aim of this study was to examine the degree to which alterations in amygdala-cingulate FC relate to severity of current depressive symptoms in a group of depressed individuals without significant co-morbidities., Methods: Fifteen young, unmedicated subjects with current MDD and 16 healthy controls (HC) with no lifetime history of psychiatric illness performed a validated emotional face-matching task during functional magnetic resonance imaging. Amygdala activity and strength of amygdala-cingulate FC during emotional face processing were contrasted between the groups., Results: Although both groups activated the extended amygdala (EA) during emotion processing, the MDD relative to the HC group showed more task-related co-activation of the subgenual cingulate, which is involved in processing negative self-referential information; and less co-activation of the supragenual cingulate, which is involved in the cognitive control of emotion. Greater depressive symptom severity correlated positively with decreased FC between bilateral EA and supragenual cingulate in MDD subjects., Limitations: This study included a demographically homogeneous population of subjects, which may limit the generalizability of the findings., Conclusions: These results elaborate current neurobiological models of MDD by providing unique evidence that decreased FC between the EA and supragenual cingulate is related to increased severity of current depressive symptoms. We speculate that the clinical manifestations of MDD may result in part from a failed ability to co-activate a cognitive control network during emotion processing.

Background: Marijuana intoxication appears to impair response inhibition, but it is unclear if impaired inhibition and associated brain abnormalities persist after prolonged abstinence among adolescent users. We hypothesized that brain activation during a go/no-go task would show persistent abnormalities in adolescent marijuana users after 28 days of abstinence., Methods: Adolescents with (n = 16) and without (n = 17) histories of marijuana use were compared on blood oxygen level dependent (BOLD) response to a go/no-go task during functional magnetic resonance imaging (fMRI) after 28 days of monitored abstinence. Participants had no neurological problems or Axis I diagnoses other than cannabis abuse/dependence., Results: Marijuana users did not differ from non-users on task performance but showed more BOLD response than non-users during inhibition trials in right dorsolateral prefrontal, bilateral medial frontal, bilateral inferior and superior parietal lobules, and right occipital gyri, as well as during "go" trials in right prefrontal, insular, and parietal cortices (p < 0.05, clusters > 943 microl). Differences remained significant even after controlling for lifetime and recent alcohol use., Conclusions: Adolescent marijuana users relative to non-users showed increased brain processing effort during an inhibition task in the presence of similar task performance, even after 28 days of abstinence. Thus, increased brain processing effort to achieve inhibition may predate the onset of regular use or result from it. Future investigations will need to determine whether increased brain processing effort is associated with risk to use.

Objective: To study the possible role of the amygdala in the recognition of happy and sad facial expressions in adolescents aged 13 to 17 years., Method: Twelve healthy adolescents (6 females and 6 males) underwent noninvasive 3-Tesla functional magnetic resonance imaging while viewing pictures of happy, sad, and neutral facial expressions., Results: Happy faces produced significant bilateral amygdalar activation when compared with neutral faces (p <.05, corrected). Sad faces relative to neutral did not produce significant amygdalar activation., Conclusions: These results extend the role of the amygdala in adolescents to include the recognition of happy facial expressions. They demonstrate the feasibility of using happy facial expressions to noninvasively study amygdalar function in adolescents and establish a baseline against which the amygdalar response to emotional stimuli in several psychiatric conditions may be compared.