Table 1.
Summary of the brain connectivity studies that provide insights into development of psychiatric disorders in adolescents published the last 5-years.
| References | # of subjects | Subject age in Years (±std. dev) | Disorder/Trait | MRI method(s) | Diagnosis/Future risk/Predicting treatment response/Treatment effects | Group difference vs. Single subject | Main MRI findings |
|---|---|---|---|---|---|---|---|
| Adluru et al. (2017) | 100 | 13–18 | Anxiety | DTI | Diagnosis | Group difference | Within monozygotic twin pairs, the more anxious twin exhibited decreased significantly decreased FA and axial diffusivity in the left uncinate fasciculus, compared to the less anxious twin |
| Alarcón et al. (2018) | 40 | 15–18 | Non-clinical: rumination (relating to depression) | Task-based fMRI (conflict between self-referential processing and cognitive control) |
Future risk | Group difference | Girls displayed stronger fc of frontoparietal network (FPN) and DMN during self-referential processing (SRP) relative to boys. Co-rumination, which was the only self-reported measure that differentiated boys and girls, mediated cognitive control performance during SRP Incongruent conditions |
| Balevich et al. (2015) | 99 | 15.9 ± 1.7 (adol-S) 17.1 ± 2.1 (adol-C) 43.7 ± 10.2 (adult-S) 42.2 ± 11.5 (adult-C) |
Schizophrenia | DTI | Diagnosis | Group difference | Compared to healthy controls, both adult and adolescent patients with schizophrenia showed reduced anisotropy of the corpus callosum; however, adolescent patients showed reductions primarily in anterior regions, whereas adult patients showed more prominent reductions in posterior regions |
| Bebko et al. (2015) | 60 | 8–17 | Bipolar disorder ADHD Anxiety |
Resting state fMRI | Diagnosis | Group difference | This study examined relationships among symptom dimensions, diagnostic categories, and rsFC in behaviorally and emotionally dysregulated youth. Two dimensional measures showed significant inverse relationships with rsFC regardless of diagnosis: 1) PGBI-10M (mania, depression, and anxiety severity) with amygdala-left posterior insula/bilateral putamen, and 2) depressive symptoms with amygdala-right posterior insula connectivity. Diagnostic categories showed no significant relationships with rsFC. rsFC between the amygdala and posterior insula decreased with increasing severity of behavioral and emotional dysregulation and depression |
| Bédard et al. (2014) | 45 | 9–15 | ADHD | Task-based fMRI (N-back test of working memory for spatial position) |
Diagnosis | Group difference | Compared to healthy controls, youth with ADHD showed greater functional connectivity between the left dorsolateral PFC and left intraparietal sulcus and reduced left dorsolateral PFC connectivity with left mid-cingulate cortex and PCC for the high load contrast. Reanalysis with a more conservative statistical approach showed group differences in dorsolateral PFC-mid-cingulate connectivity |
| Boets et al. (2018) | 34 | 11–18 | Autism | DTI Global probabilistic tractography |
Diagnosis | Group difference | Compared to the control group, the ASD group showed reduced FA in the right and left inferior longitudinal fasciculus (ILF) and increased radial diffusivity in the right ILF Lower FA in the right ILF showed a slight association with the presence of more self-reported ASD characteristics |
| Chang et al. (2017) | 79 | 9–18 | Non-clinical: high risk for bipolar disorder | Task-based fMRI (implicit emotion perception task) |
Future risk | Group difference | High-risk youth showed greater fc between the right amygdala and ventrolateral PFC, and the visual cortical regions, compared to healthy controls |
| Chattopadhyay et al. (2017) | 116 (cross-sectional) 47 (longitudinal) |
11–17 | Depression | Resting state fMRI | Diagnosis Treatment effects |
Group difference | Compared to controls, depressed adolescents showed significantly greater rsFC to the left amygdala and bilateral supragenual ACC, but no difference in connectivity to the PFC. Treatment effects were observed in the right insula connected to the left supragenual ACC, with baseline case-control differences reduced and no concomitant differences in areas of cognitive control neural systems. rsFC changes were significantly correlated with changes in depression severity |
| Chen et al. (2017) | 109 | 15.6 ± 1.8 (S) 15.4 ± 1.6 (S-C) 13.1 ± 3.1 (A) 12.9 ± 2.9 (A-C) |
Schizophrenia Autism |
Resting state fMRI | Diagnosis | Single subject Group difference |
Classification between individuals with disorders and healthy controls was achieved with high accuracy. Shared atypical brain connections contributing to classification were mostly present in the DMN and SN. These functional connections were significantly associated with severity of social deficits in ASD. Distinct atypical connections were also more related to the DMN and SN, but showed different atypical connectivity patterns between the two disorders |
| Chuang et al. (2017) | 140 | 11–18 | Depression | Task-based fMRI (affective go/no-go task) | Diagnosis | Group difference | Compared to healthy male adolescents, depressed male adolescents showed decreased activation in the cerebellum with significant group-by-age interaction in connectivity |
| Cisler et al. (2018) | 88 | 11–17 | Non-clinical: early life trauma exposure (relating to PTSD) | Task-based fMRI (facial emotion processing task) | Future risk | Group difference | In healthy adolescent females, self-reported early life trauma was significantly associated with greater modularity, greater assortativity, and lesser global efficiency during facial emotion processing—even when controlling for PTSD symptom severity. Beyond the effect of early life trauma, PTSD diagnoses were associated with greater modularity. Individual differences in large-scale network modularity were predictive of both the degree of bilateral amygdala functional activation during the task, as well as degree of functional connectivity between the amygdala and medial PFC |
| Cisler et al. (2016) | 20 | 11–16 | PTSD | Task-based fMRI (facial emotion processing task) |
Predicting treatment response Treatment effects |
Group difference | Pre-treatment (trauma-focused CBT) individual differences in modularity, assortativity, and global efficiency during covert fear vs. neutral task blocks predicted PTSD symptom reduction. PTSD patients with greater treatment response showed greater network modularity and assortativity but lesser efficiency. At the group level, greater symptom reduction was associated with greater pre-to-post-treatment increases in network assortativity and modularity, and this was more pronounced among participants with less symptom improvement |
| Cisler et al. (2013) | 30 | 12–16 | PTSD Non-clinical: assaultive violence exposure |
Task-based fMRI (presentation of fearful vs. neutral facial expression images) |
Diagnosis Future risk |
Group difference | Within the frontocingulate network, PTSD severity was associated with weakened functional connectivity between the left amygdala and the perigenual anterior cingulate. Within the frontoparietal network, assaulted girls demonstrated weakened connectivity of the premotor cortex with the right middle frontal gyrus. Within the DMN, assault exposure and PTSD severity were associated with strengthened functional connectivity of the parahippocampus with the medial and lateral prefrontal cortex, respectively. Individual differences in functional connections within the frontocingulate network and frontoparietal network among the assaulted group were strongly associated with caregiver-rated family disengagement |
| Clasen et al. (2014) | 24 | 13–15 | Non-clinical: familial risk for depression | Resting state fMRI | Future risk | Group difference | High-risk adolescents with a parental history of depression showed lower levels of functional connectivity between a right inferior prefrontal region and other critical nodes of the attention control network, including the right middle frontal gyrus and right supramarginal gyrus. Among high-risk adolescents, increased severity of parents' worst episode of depression was associated with altered cognitive control network connectivity in adolescents |
| Cullen et al. (2016) | 13 | 12–19 | Depression | Resting state fMRI | Treatment effects | Group difference | Analysis of change in amygdala rsFC showed that treatment response was associated with increased amygdala rsFC with right frontal cortex, but decreased amygdala rsFC with right precuneus and right PCC |
| Das et al. (2013) | 58 | 15.1 ± 0.34 | Non-clinical: sub-clinical emotional syndromes | Task-based fMRI (image-based emotion processing task) | Future risk | Group difference | Between groups, the hippocampus showed a pattern of reverse coupling with the amygdala and insula that significantly correlated with trait anxiety |
| Davey et al. (2015) | 56 | 16.5 ± 0.5 (baseline) 18.8 ± 0.5 (follow-up) |
Depression | Resting state fMRI | Future risk | Group difference | Adolescents with no history of mental illness received an fMRI scan at baseline and a follow-up scan 2-years later. Magnitude of amygdala connectivity with sgACC showed significant positive correlation with negative affectivity at both time points. Change in amygdala-sgACC connectivity between assessments was correlated with change in negative affectivity. Of the 56 participants in the study, eight developed a first episode of depression between the baseline and follow-up assessments; they showed increased amygdala-subgenual connectivity at follow-up |
| Diwadkar et al. (2014) | 46 | 14.1 ± 3.1 (R) 15.4 ± 2.7 (C) |
Non-clinical: familial risk for schizophrenia or bipolar disorder | Task-based fMRI (attention and visual control tasks) |
Future risk | Group difference | Compared to healthy controls, higher-risk adolescents were characterized by significant reductions in coupling across both frontal-striatal and frontal-parietal pathways |
| Dorfman et al. (2016) | 71 | 13.2 ± 2.7 (A) 13.0 ± 2.7 (C) |
Anxiety | Resting state fMRI | Diagnosis | Group difference | Compared to healthy controls, anxious adolescents showed abnormally low intrinsic functional connectivity within the striatum (between the nucleus accumbens and caudate nucleus) and between the striatum and prefrontal regions (including the sgACC, posterior insula, and supplementary motor area) |
| Ellis et al. (2017) | 243 | 17–19 | Non-clinical: depressive symptoms | DTI and tractography | Future risk | Group difference | Adolescents that experienced increasing depression symptoms in early adolescence showed differences in several frontal and temporal brain regions, compared to adolescents with stable low levels of depression. Affected tracts corresponded to areas of white matter that are still maturing during adolescent, particularly frontolimbic regions |
| Fitzgerald et al. (2014) | 63 | 8–19 | OCD | DTI | Diagnosis | Group difference | Compared to healthy controls, patients with OCD showed more pronounced age-related increases in FA in the anterior corpus callosum, anterior cingulum bundle, and anterior limb of the internal capsule, as well as several other white matter tracts. Among OCD patients, greater FA in the anterior cingulum bundle correlated with more severe symptoms after controlling for age |
| Fowler et al. (2017) | 41 | 15.42 ± 0.33 | Non-clinical: stress-reactive rumination (relating to depression) | Task-based fMRI (emotion regulation task and social stress task) |
Future risk | Group difference | Positive functional connectivity between the amygdala and ventrolateral PFC during the emotion regulation task mediated the association between stress-reactive rumination and depressive symptoms |
| Friedman et al. (2017) | 54 | 9–21 (O) 12–21 (C) |
OCD | Task-based fMRI (uni-manual motor task) |
Diagnosis | Group difference | OCD subjects were characterized by hyper-modulation by the dorsal ACC. Dynamically-driven task demands during simple uni-manual motor control induced compensatory network interactions in cortical-thalamic regions in OCD |
| Fryer et al. (2019) | 125 | 11–29 | Schizophrenia Psychosis |
Task-based fMRI (go/no-go task) |
Diagnosis Future risk |
Group difference | Compared to the healthy control group, the early schizophrenia and clinical high risk (CHR) groups showed significantly less coupling during NoGo trials relative to Go trials between the ACC and the bilateral medial PFC, PCC, and precuneus |
| Gao et al. (2014) | 35 | 10–18 | Bipolar disorder | Resting state fMRI | Diagnosis | Group difference | Compared to healthy controls, depressed adolescents with bipolar disorder showed decreased regional homogeneity in the medial frontal gyrus, bilateral middle frontal gyrus and middle temporal gyrus, and right putamen. Depressed adolescents with bipolar disorder had significant negative correlations of mood and feelings questionnaire scores with mean regional homogeneity values in the medial frontal gyrus and right middle frontal gyrus |
| Geng et al. (2016) | 57 | 13–17 | Depression | Resting state fMRI DTI |
Diagnosis | Group difference | Compared to healthy controls, adolescents with depression showed significantly lower FA values in the fornix and decreased functional connectivity in four PFC regions. Among healthy controls, significant negative correlations were observed between fornix FA values and hippocampus-PFC functional connectivity. Among adolescents with depression, no significant correlation was found between the fornix FA and the strength of functional connectivity |
| Gold et al. (2016) | 82 | Youth: 14.76 ± 2.82 (A) 14.42 ± 2.62 (C) Adults: 32.90 ± 6.97 (A) 29.1 ± 7.50 (C) |
Anxiety | Task-based fMRI (extinction recall task) |
Diagnosis | Group difference | Whole-brain analyses showed significant interactions of anxiety, age, and attention task (threat appraisal, explicit threat memory, physical discrimination) on left amygdala functional connectivity with the ventral medial PFC and ventral ACC. During threat appraisal and explicit threat memory, anxious youth showed more negative amygdala-PFC coupling, whereas anxious adults showed more positive coupling |
| Green et al. (2017) | 38 | 9–17 | Autism | Exposure-based fMRI (mildly aversive auditory and tactile stimuli) | Diagnosis | Group difference | Compared to healthy controls, ASD subjects showed aberrant modulation of fc between pulvinar and cortex (including sensory-motor and prefrontal regions) during sensory stimulation. Among ASD subjects, pulvinar-amygdala connectivity was correlated with severity of sensory over-responsivity symptoms |
| Green et al. (2016) | 61 | 8–17 | Autism | Resting state fMRI Exposure-based fMRI (mildly aversive tactile and auditory stimuli) |
Diagnosis | Group difference | Sensory over-responsivity in youth with ASD was related to increased rsFC between SN nodes and brain regions implicated in primary sensory processing and attention. The strength of this connectivity at rest was related to the extent of brain activity in response to auditory and tactile stimuli |
| Gruner et al. (2014) | 46 | 9–17 | OCD | Resting state fMRI | Diagnosis | Single subject | Independent component analysis identified three components that maximally separated healthy controls from OCD adolescents: a middle frontal/dorsal anterior cingulate network, an anterior/posterior cingulate network, and a visual network—yielding an overall group classification of 76.1%. Compared to healthy controls, OCD patients showed significantly higher independent component expression scores in the middle frontal/dorsal anterior cingulate and anterior/posterior cingulate networks, but lower within the visual network. Among OCD patients, higher scores in the anterior/posterior cingulate network correlated with greater severity of compulsions among patients |
| Guo et al. (2016) | 65 | 12–18 | Autism | Resting state fMRI | Diagnosis | Group difference | Compared to healthy controls, adolescents with ASD showed decreased fc between the amygdala and subcortical regions, including the bilateral thalamus and right putamen |
| Hafeman et al. (2017) | 78 | 8–16 | Bipolar disorder ADHD |
Task-based fMRI (implicit emotion processing task) |
Diagnosis | Group difference | Fc between amygdala and left ventrolateral PFC in response to emotions vs. shapes significantly differed by group. Bipolar subjects showed positive functional connectivity (emotions > shapes), healthy controls showed inverse functional connectivity (emotions < shapes), and ADHD subjects showed intermediate functional connectivity. A significant group × emotion interaction was found in amygdala-subgenual cingulate fc, explained by differences in fc in response to negative emotions. Amygdala-subgenual fc was also positively associated with depressive symptoms and stimulant medication |
| Hamm et al. (2014) | 56 | 13.9 ± 3.1 (A) 14.6 ± 3.9 (C) |
Anxiety | Resting state fMRI | Diagnosis | Group difference | Compared to healthy controls, youth with anxiety disorders showed hyperconnectivity between the right amygdala and insula, and hypoconnectivity between the left amygdala and the ventromedial PFC and PCC. Among youth with anxiety disorders, connectivity was not correlated with anxiety severity |
| Harlalka et al. (2018) | 9–12 (children) 13–16 (adolescents) |
Autism | Resting state fMRI | Diagnosis | Group difference | Compared to healthy controls, children and adolescents with ASD showed increased functional integration at the expense of decreased functional segregation. Adolescents with ASD showed significant decrease in modularity and increase in participation coefficient, and significant hypoconnectivity in the DMN. In contrast, children with ASD showed both hyper- and hypoconnectivity | |
| Henje Blom et al. (2015) | 67 | 13–18 | Depression | Task-based fMRI (facial emotion processing task) |
Diagnosis | Group difference | Compared to healthy controls, adolescents with depression showed greater fc between the anterior/middle insular cortex and the right fusiform gyrus, left middle frontal gyrus, and right amygdala/parahippocampal gyrus |
| Ho et al. (2017) | 95 | 13–18 | Depression | Resting state fMRI Task-based fMRI (response inhibition task) |
Diagnosis | Group difference | Compared to controls, adolescents with depression showed inflexibility in local efficiency of the right dorsal ACC/medial frontal gyrus (MFG). Individual differences in flexibility (limited task-evoked vs. resting-state connectivity) of local right dorsal ACC/MFG significantly predicted inhibition performance, and reduced local efficiency of the dorsal ACC/MFG during a response inhibition task was significantly associated with an earlier age of depression onset |
| Ho et al. (2014) | 38 | 15.8 ± 1.4 (D) 16.1 ± 1.2 (C) |
Depression | Task-based fMRI (implicit fear facial affect recognition task) |
Diagnosis | Group difference | Compared to healthy controls, adolescents with depression showed significantly increased sgACC-amygdala functional connectivity and decreased sgACC-fusiform gyrus, sgACC-precuneus, sgACC-insula, and sgACC-middle frontal gyrus functional connectivity. Among depressed adolescents, sgACC-precuneus fc was significantly negatively correlated with depression severity. Compared to healthy controls, depressed adolescents showed poorer perceptual sensitivity in the task, and individual differences in perceptual sensitivity significantly correlated with sgACC fc and depression scores |
| Hong et al. (2017) | 184 | Children: 8.60 ± 0.75 (ADHD) 8.68 ± 0.65 (C) Teens: 13.17 ± 1.94 (ADHD) 12.21 ± 2.12 (C) Adults: 26.77 ± 2.54 (ADHD) 24.94 ± 1.41 (C) |
ADHD | Resting state fMRI | Diagnosis | Group difference | The degree centrality of the left middle temporal gyrus showed significant interaction effects between disease status (ADHD or healthy control) and age (child, adolescent, or adult). Other regions with significant interaction effects included the left superior frontal gyrus, left inferior frontal gyrus, right inferior frontal gyrus, right precentral gyrus, left superior temporal gyrus, left middle temporal gyrus, right postcentral gyrus, left insular gyrus, left medioventral occipital cortex, right medioventral occipital cortex, left amygdala, and left basal ganglia |
| Hulvershorn et al. (2014) | 63 | 6–13 | ADHD | Resting state fMRI | Diagnosis | Group difference | Among youth with ADHD, higher emotional lability ratings were associated with greater positive intrinsic fc between the amygdala and rostral ACC, and negatively associated with intrinsic fc between bilateral amygdala and posterior insula/superior temporal gyrus. Patterns of amygdala-cortical intrinsic fc in ADHD youth with low emotional lability did not differ from the comparison group, and the effect sizes for these comparisons were smaller than those for the trend-level differences observed between the high emotional lability group and the healthy control group |
| Hwang et al. (2015) | 61 | 14.53 ± 2.00 (A) 13.91 ± 2.13 (C) |
ADHD | Task-based fMRI (affective Stroop paradigm) |
Diagnosis | Group difference | Compared to healthy controls, ADHD patients showed reduced fc between the dorsomedial frontal cortex and lateral frontal cortex during congruent and incongruent task trials relative to view trials. Among ADHD patients, decreased connectivity between the amygdala and lentiform nucleus was found in the presence of emotional stimuli |
| Iadipaolo et al. (2018) | 55 | 6–17 | Non-clinical: resilience (relating to depression) |
Resting state fMRI | Future risk | Group difference | Children and adolescents with higher trait resilience spent a significantly lower fraction of total time in a dynamic rsFC state characterized by increased rsFC between the anterior DMN and right CEN. Within this state, resilience was significantly associated with reduced SN rsFC with the anterior DMN and right CEN. More resilient youth reported lower depressive symptoms, but the effects of resilience on rsFC were independent of depressive symptoms and adversity exposure |
| Jack and Morris (2014) | 30 | 14.20 ± 1.61 (A) 13.80 ± 1.70 (C) |
Autism | fMRI imitation paradigm | Diagnosis | Group difference | Among adolescents with ASD, stronger psychophysiological interactions between Crus I of neocerebellum and right posterior superior temporal sulcus were associated with greater mentalizing abilities |
| Jacobs et al. (2016) | 22 | 15.41 ± 1.97 (RFCBT) 15.69 ± 1.89 (control) |
Depression | Resting state fMRI | Treatment effects | Group difference | This study was a pilot randomized control trial investigating the effects of rumination-focused cognitive behavior therapy (RFCBT) on reducing rumination and residual depressive symptoms in adolescents with a history of depression and risk of relapse. Over the course of 8 weeks, adolescents who received RFCBT showed significantly reduced rumination and self-reported depression, as well as significant decreases in connectivity between the left PCC and right inferior frontal gyrus and bilateral inferior temporal gyri. Degree of change in connectivity was correlated with changes in self-reported depression and rumination |
| Jacobs et al. (2014) | 53 | 18–23 | Depression | Task-based fMRI (go/no-go task) |
Diagnosis | Group difference | Compared to healthy controls, unmedicated adolescents with remitted depression showed hyperconnectivities from both PCC and sgACC seeds with lateral, parietal, and frontal regions of the CEN, extending to the dorsal medial wall. A factor analysis reduced extracted data and a PCC factor was inversely correlated with rumination among depressed adolescents. Two factors from the sgACC hyperconnectivity clusters were related to performance in cognitive control on a Go/No-Go task, one positively and one inversely |
| Jacobson McEwen et al. (2014) | 25 | 11–13 | Psychosis | Resting state fMRI | Diagnosis | Group difference | Compared to healthy controls, adolescents with psychotic symptoms showed reduced intrinsic fc between the right inferior frontal gyrus and the cingulate, between the right inferior frontal gyrus and the striatum, between the anterior cingulate and claustrum, and between the precuneus and supramarginal gyrus. Compared to healthy controls, adolescents with psychotic symptoms showed stronger intrinsic fc between the superior frontal gyrus and claustrum, and between the inferior frontal gyrus and the lingual gyrus |
| James et al. (2016) | 61 | 13–18 | Schizophrenia | DTI and tractography | Diagnosis | Group difference | Compared to healthy controls, patients with adolescent-onset schizophrenia showed generalized cognitive impairment with specific deficits in verbal learning and memory, and in processing speed. These measures correlated positively with dorsolateral PFC connectivity with the striatum, and with IQ. DTI voxel-wise comparisons showed lower connectivity between striatum and the motor and lateral orbitofrontal cortices bilaterally, the left amygdala-hippocampal complex, right ACC, left medial orbitofrontal cortex, and right dorsolateral PFC in adolescent-onset schizophrenia patients relative to healthy controls |
| Jann et al. (2015) | 39 | 13.8 ± 2.0 (A) 12.8 ± 3.6 (C) |
Autism | Resting state fMRI | Diagnosis | Group difference | Increased local fc in the anterior module of the DMN was accompanied by decreased cerebral blood flow in the same area. Both alterations were associated with greater social impairments. While fc was correlated with cerebral blood flow in healthy controls, this association was disrupted in ASD youth. Reduced long-range fc between the anterior and posterior modules of the DMN was also found in ASD youth |
| Jarcho et al. (2015) | 90 | 8–17 (adolescents) 18–49 (adults) |
Non-clinical: social anxiety | Task-based fMRI (prediction and social feedback task) |
Future risk | Group difference | For socially anxious adolescents, but not anxious adults or healthy controls of either age groups, social evaluation prediction errors elicited heightened negative fronto-striatal fc |
| Jin et al. (2017) | 229 | 15 ± 0.583 | Non-clinical: sensitivity to loss (relating to depression) | Task-based fMRI (monetary gambling task with win and loss feedback) |
Future risk | Group difference | Increased OFC-posterior insula connectivity during loss was marginally associated with higher concurrent depressive symptoms and significantly associated future depressive symptoms, but this relationship was not moderated by parental history of depression. In contrast, OFC connectivity changes in response to win did not predict concurrent or future depression symptoms |
| Johnston et al. (2017) | 68 | 14–25 | Bipolar disorder (suicide attempts) |
DTI Task-based fMRI (emotion processing task) |
Future risk | Group difference | Compared to bipolar adolescents and young adults without a history of suicide attempts, patients with prior suicide attempts showed significant reductions in: white matter integrity in the uncinate fasciculus, ventral frontal, and right cerebellum regions; and amygdala fc to the left ventral and right rostral PFC. Among attempters, significant negative associations were found between right rostral prefrontal connectivity and suicidal ideation, and between left ventral prefrontal connectivity and attempt lethality |
| Joshi et al. (2017) | 31 | 15–29 | Autism | Resting state fMRI | Diagnosis | Group difference | Compared to healthy controls, the ASD group showed a weaker pattern of positive intra-DMN and negative extra-DMN rsFC correlations. The strength of intra-DMN coupling was significantly reduced with the medial PFC and the bilateral angular gyrus regions, and the polarity of the extra-DMN correlation with the right hemispheric task-positive regions of fusiform gyrus and supramarginal gyrus was reversed from typically negative to positive |
| Kaczkurkin et al. (2018) | 120 | 11–23 | Psychosis (overall psychopathology) |
Resting state fMRI | Future risk | Group difference | Overall psychopathology was associated with decreased fc between the dorsal ACC and bilateral caudate |
| Keding and Herringa (2016) | 53 | 8–18 | PTSD | Task-based fMRI (facial emotion processing task) |
Diagnosis | Group difference | Connectivity analyses revealed paradoxical coupling in prefrontal–amygdala circuits, including dACC–dorsomedial (dm)PFC, amygdala–dmPFC, and amygdala–ventrolateral (vl)PFC. PTSD youth showed reduced connectivity in response to angry faces, but increased connectivity in response to happy faces, the reverse of healthy youth |
| Kim et al. (2016) | 42 | 13–18 | Depression | Resting state fMRI | Diagnosis | Group difference | Compared to healthy controls, depressed adolescents with disruptive behaviors showed lower rsFC from the amygdala to the orbitofrontal cortex and parahippocampal gyrus, as well as higher PCC rsFC in a cluster that included the left precentral gyrus, left insula, and left parietal lobe. Among depressed adolescents with disruptive behaviors, depression scores were negatively correlated with rsFC from the amygdala to the right orbitofrontal cortex, while disruptive behavior scores were positively correlated with rsFC from the PCC to the left insular cortex |
| Klimes-Dougan et al. (2018) | 11 | 12–19 | Depression | Resting state fMRI | Predicting treatment response | Group difference | This study assessed improvement in depression symptoms after 8 weeks of SSRI treatment. Higher levels of pre-treatment amygdala rsFC with the right central parietal opercular cortex and Heschl's gyrus predicted better treatment response. Higher levels of pre-treatment amygdala rsFC with the right precentral gyrus and with left SMA predicted a worse treatment response |
| Kujawa et al. (2016) | 118 | 7–25 | Anxiety | Task-based fMRI (facial emotion processing task) |
Diagnosis | Group difference | Anxiety interacted with age to predict amygdala-ACC connectivity across emotional faces. Age was negatively correlated with connectivity among healthy controls, but was positively correlated among anxious subjects. Group effects were observed on amygdala connectivity with mid-cingulate and middle frontal gyri. Effects of anxiety and age on amygdala activation were not significant |
| LeWinn et al. (2018) | 75 | 13–17 | Depression | Task-based fMRI (cognitive reappraisal task) |
Diagnosis | Group difference | Among adolescents with depression, reduced connectivity was found between the left dorsomedial PFC and the anterior insula/inferior frontal gyri bilaterally, and between the left dorsolateral PFC and left anterior insula/inferior frontal gyri |
| LeWinn et al. (2014) | 94 | 13–17 | Depression | DTI | Diagnosis | Group difference | Compared to healthy controls, adolescents with depression showed significantly lower FA and higher radial diffusivity in the bilateral uncinate fasciculus. No significant differences were observed in the cingulum. Tract-based spatial statistics showed lower FA values in the white matter associated with the limbic-cortical-striatal-thalamic circuit, corpus callosum, and anterior and superior corona radiata |
| Li et al. (2019) | 65 | 12–18 | Schizophrenia | Functional MRI | Diagnosis | Group difference | Compared to healthy controls, adolescent-onset schizophrenia (AOS) patients showed significantly decreased global efficiency of the brain functional network and reduced nodal efficiency and strength in the bilateral posterior parahippocampus, bilateral precuneus, and left hippocampus. In the left hippocampus of healthy controls, there were significant negative associations between nodal efficiency and age as well as between nodal strength and age, both of which were reversed in AOS patients. Reduced efficiency identified in the right posterior parahippocampus showed a negative correlation with illness duration within AOS patients |
| Manelis et al. (2015) | 81 | 7–17 | Non-clinical: familial risk for bipolar disorder | Task-based fMRI (facial emotion processing task) |
Future risk | Group difference | Offspring of bipolar parents showed significantly more negative right amygdala-ACC fc in response to emotional faces vs. shapes, but significantly more positive right amygdala-left ventrolateral PFC fc in response to happy faces, in comparison to healthy controls and to offspring of parents with other psychopathology |
| Marusak et al. (2018) | 42 | 6–17 | Non-clinical: mindfulness (relating to anxiety) | Resting state fMRI | Future risk | Group difference | Trait mindfulness in adolescents relates to dynamic but not static rsFC. More mindful youth transitioned more between brain states over the course of the scan, spent overall less time in a certain connectivity state, and showed a state-specific reduction in connectivity between the SN and CEN. The number of state transitions mediated the link between higher mindfulness and lower anxiety |
| Marusak et al. (2017) | 86 | 7–17 | Non-clinical: early exposure to violence and/or abuse | Resting state fMRI | Future risk | Group difference | Trauma-exposed youth showed lower functional connectivity between the ventral tegmental area (VTA) and the hippocampus, compared to unexposed youth. No group differences in substantia nigra connectivity were observed. Increased anxiety symptoms were associated with reduced substantia nigra-nucleus accumbens connectivity |
| Morgan et al. (2016) | 166 | 20 | Depression | Task-based fMRI (monetary reward paradigm) |
Diagnosis | Group difference | Compared to boys with no psychiatric history, boys with a history of depression showed heightened positive connectivity between the nucleus accumbens and the medial PFC when winning rewards relative to losing rewards. This altered fronto-striatal connectivity pattern was associated with a greater number of lifetime depressive episodes |
| O'Halloran et al. (2018) | 818 | 14.55 ± 0.45 (normative) 14 ± 0.38 (ADHD) 14 ± 0.41 (C) |
ADHD | Task-based fMRI (Stop Signal Task (SST)) |
Diagnosis | Group difference | In the normative dataset, good sustained attention was characterized by stronger negative fc between cerebellum and motor networks, while stronger positive fc within the motor network was a signature of poorer sustained attention. In separate samples, relative to controls, adolescents with ADHD symptoms had significantly higher intra-individual response variability (IRV) and stronger positive connectivity within low sustained attention networks associated with high IRV, as well as stronger positive connectivity within good sustained attention networks associated with low IRV. There were no differences between the groups for anti-correlated connections in networks associated with either high or low IRV |
| Ordaz et al. (2018) | 40 | 14–17 | Depression (suicidal ideation) |
Resting state fMRI | Future risk | Group difference | Coherence of the lateral CEN, anterior DMN, and SN were significantly associated with lifetime severity of suicidal ideation. Only lateral CEN coherence was a significant predictor of lifetime suicidal ideation severity, was associated with current suicidal ideation, and was associated with a previously initiated suicide attempt |
| Osuch et al. (2014) | 28 | 16–24 | Non-clinical: repetitive non-suicidal self-injury | Exposure-based fMRI (painfully cold and comparison cool stimuli) | Future risk | Group difference | Reduced fc between the right orbitofrontal cortex and ACC was found in non-suicidal self-injury (NSSI) adolescents |
| Pan et al. (2017) | 637 | 6–12 | Depression | Resting state fMRI | Future risk | Group difference | Increased left ventral striatum node strength predicted increased risk for future depressive disorder. Among 11 reward network nodes examined, only the left ventral striatum significantly predicted depression. Striatal node strength did not predict anxiety, ADHD, or substance use |
| Pannekoek et al. (2014) | 52 | 15.4 ± 1.5 (D) 14.7 ± 1.5 (C) |
Depression | Resting state fMRI | Diagnosis | Group difference | Compared to healthy controls, adolescents with depression showed increased rsFC of the left amygdala with right parietal cortical areas, and decreased right amygdala rsFC with left frontal cortical areas and with right occipito-parietal areas. In depressed adolescents, the bilateral dorsal ACC showed decreased rsFC with the right middle frontal gyrus, frontal pole, and inferior frontal gyrus. No abnormalities in DMN rsFC were found, and differences in rsFC did not correlate with clinical measures |
| Paquola et al. (2017) | 64 | 14–26 | Non-clinical: childhood abuse, adulthood stress | Resting state fMRI | Future risk | Group difference | Worse psychiatric symptoms were significantly associated with higher levels of lifetime stress. Subjects with mismatched childhood and recent stress levels had reduced ACC-ventrolateral PFC rsFC, and greater ACC-hippocampus rsFC, compared to subjects with matched childhood and recent stress levels |
| Park et al. (2016) | 52 | <10 (child) 10–19 (teen) |
ADHD | Resting state fMRI | Diagnosis | Group difference | In comparing brain connectivity patterns between child and adolescent ADHD patients, the DMN and frontoparietal networks showed significant group-wise connectivity pattern differences between child and adolescent ADHD patients |
| Patriat et al. (2016) | 59 | 14.6 ± 2.6 (P) 14.0 ± 2.3 (C) |
PTSD | Resting state fMRI | Diagnosis | Group difference | Compared to healthy controls, PTSD youth showed increased connectivity within the DMN (including increased PCC-inferior parietal gyrus connectivity) and age-related increases in PCC-ventromedial PFC connectivity. PTSD youth also showed greater anti-correlation between the PCC and multiple nodes within SN and attention control networks of the task-positive network. Among PTSD youth, DMN and task-positive network connectivity strength were positively and negatively associated, respectively, with re-experiencing symptoms of PTSD |
| Pitskel et al. (2014) | 31 | 9–17 | Autism | Task-based fMRI (cognitive reappraisal and emotional responses to disgusting images) |
Diagnosis | Group difference | Compared to ASD youth, controls showed increased fc between the amygdala and ventrolateral PFC, as well as decreased functional connectivity between the amygdala and OFC, when down-regulating disgust |
| Platt et al. (2015) | 30 | 15–17 | Depression | Task-based fMRI (reappraisal paradigm) |
Diagnosis | Group difference | During fMRI, subjects attended to and implemented reappraisal techniques in response to rejection. Reappraisal reduced negative mood and belief in negative thoughts in both depressed adolescents and healthy controls; however, during reappraisal trials depressed adolescents showed greater connectivity between the right frontal pole and numerous subcortical and cortical regions |
| Price et al. (2016) | 78 | 9–14 | Anxiety | Task-based fMRI (dot-probe task) |
Diagnosis | Group difference | Among clinically anxious adolescents completing a dot-probe ask to assess vigilance to threat, vigilance toward threat was positively associated with self-reported distraction and suppression. Fc between a right amygdala seed region and dorsomedial and right dorsolateral PFC regions was inversely related to self-reported suppression and distraction, and dorsolateral PFC-amygdalar connectivity mediated the relationship between attentional vigilance and real-world distraction |
| Price et al. (2014) | 121 | 9–13 | Anxiety | Task-based fMRI (dot-probe task) |
Diagnosis | Group difference | Among adolescents with anxiety, reduced fc between the rostrodorsal ACC and left parahippocampus/hippocampus was associated with greater anxiety |
| Quinlan et al. (2017) | 1288 | 13–15 | Non-clinical: symptoms of hyperactivity, inattention, and/or conduct problems (relating to ADHD) | Task-based fMRI (viewing of dynamic angry and neutral facial expressions) |
Diagnosis | Group difference | Amygdala-precuneus connectivity was associated with hyperactivity/inattention symptoms |
| Rosso et al. (2014) | 36 | 10–19 | OCD | DTI | Diagnosis | Group difference | Compared to healthy controls, patients with OCD had significantly lower FA in 7 white matter clusters, with over 80% of significant voxels in the bilateral frontal cortex and corpus callosum. No regions were found of significantly higher FA in patients relative to controls. OCD patients also had significantly higher radial diffusivity in the right frontal cortex and right body of the corpus callosum. Among patients, earlier age at onset of OCD correlated significantly with lower FA in the right thalamus and with higher radial diffusivity in the right corpus callosum. FA and radial diffusivity were not significantly associated with symptom severity |
| Rzepa and McCabe (2016) | 35 | 13–18 | Non-clinical: high risk for depression | Resting state fMRI | Future risk | Group difference | Compared to adolescents at low risk for depression, adolescents at high risk were found to have decreased rsFC between the amygdala and the pregenual ACC, hippocampus, and precuneus; between the pregenual ACC and the putamen; and between the dorsal medial PFC and the precuneus. High risk adolescents were also found to have increased rsFC between the pregenual ACC and the PFC, and between the amygdala and the temporal pole |
| Sacchet et al. (2016) | 111 | 13–18 | Depression | Resting state fMRI | Diagnosis | Group difference | Compared to healthy controls, depressed adolescents showed hypoconnectivity between large-scale brain networks. Depressed adolescents showed significantly reduced connectivity between a specific set of resting-state networks, including components of the attention network, CEN, SN, and DMN. Among depressed adolescents, longer duration of depression was significantly correlated with reduced connectivity in this set of network interactions, specifically with reduced connectivity between components of the dorsal attention network, and the dorsal attention network was also characterized by reduced intra-network connectivity |
| Sadeghi et al. (2017) | 60 | 14–42 (A) 10–39 (C) |
Autism | Resting state fMRI | Diagnosis | Single subject Group difference |
In this study, screening for ASD was developed based on characteristics of functional networks. Local and global parameters of the brain functional network were first calculated using graph theory, and network parameters of ASD subjects were statistically compared to those of healthy controls. Significantly altered parameters were used as input features of the screening system, and performance of the system was verified using multiple classification techniques. The support vector machine showed an accuracy of 92% |
| Scheuer et al. (2017) | 37 | 12–16 | Non-clinical: escalating depression symptom expression | Resting state fMRI | Future risk | Group difference | Compared to controls, adolescents with ≥ 10 point increase in depression scale t-scores (as assessed by the Childhood Depression Inventory) over time (range: 6–54 months) had decreased rsFC between the right amygdala and left inferior frontal supramarginal gyrus and right mid-cingulate cortex, and increased rsFC between the left amygdala and cerebellum |
| Singh et al. (2014) | 49 | 8–17 | Non-clinical: high risk for bipolar disorder | Resting state fMRI | Future risk | Group difference | Compared to low-risk youth (no personal or family psychopathology), high-risk youth (offspring of a parent with bipolar disorder) showed increased connectivity in the ventrolateral PFC subregion of the left CEN, which includes frontoparietal regions critical for emotion regulation. Compared to low-risk youth, high-risk youth also showed decreased connectivities between the left amygdala and pregenual cingulate, between the subgenual cingulate and supplementary motor cortex, and between the left ventrolateral PFC and left caudate. High-risk youth showed stronger connections in the ventrolateral PFC with age and higher functioning, and weaker connections between the left ventrolateral PFC and caudate with more family chaos |
| Stoddard et al. (2016) | 117 | 10–50 | Bipolar disorder | Resting state fMRI | Diagnosis | Group difference | Compared to healthy controls, bipolar adolescents and adults showed areas of dysconnectivity across the brain, comprising two networks—temporal and parietal areas involved in late stages of visual processing, and corticostrial areas involved in attention, cognitive control, and response generation. No significant age-group by diagnosis interactions were found |
| Straub et al. (2017) | 38 | 13–18 | Depression | Resting state fMRI | Diagnosis Treatment effects Predicting treatment response |
Group difference | In comparing healthy controls and adolescents with depression prior to group CBT, patients with depression showed stronger amygdala and sgACC connectivity with regions of the DMN, whereas healthy controls showed stronger seed-based connectivity with affective regions and regions processing cognition and salient stimuli. Relative to pre-CBT in depressed adolescents, post-CBT functional connectivity significantly increased between the amygdala and the left dorsolateral PFC, bilateral dorsal ACC, and the left anterior insula. Changes in connectivity correlated with significant pre-to-post CBT symptom improvement, and pre-treatment amygdala connectivity predicted treatment response in depressed adolescents |
| Traynor et al. (2018) | 62 | 10–21 | Autism | Resting state fMRI | Diagnosis | Group difference | Compared to controls, ASD adolescents showed negative connectivity of the PCC with the angular gyrus, positive connectivity of the PCC with the superior temporal gyrus, over-connectivity of the hippocampus with the associative visual cortex, over-connectivity of the thalamus with multiple sensory processing areas of the cortex, over-connectivity of basal ganglia structures (putamen and globus pallidus) with somatosensory and motor cortices and with the fusiform gyrus, and under-connectivity of the left hippocampus with the right peri-rhinal cortex. Within the ASD group, a significant positive association was found between total RBS-R (Repetitive Behavior Score—Revised) score and connectivity between the left primary visual cortex and right inferior frontal gyrus, pars orbitalis |
| Tymofiyeva et al. (2019) | 30 | 13.2–17.8 | Depression | DTI and tractography | Predicting treatment response | Single subject | Machine learning classification applied to DTI-based structural connectome resulted in an 83% accuracy of predicting depressive symptom reduction with CBT |
| Tymofiyeva et al. (2017) | 98 | 13–17 | Depression | DTI and tractography | Diagnosis | Group difference | Compared to healthy controls, depressed subjects showed significantly lower FA-weighted node strength of the right caudate. FA-weighted node strength was correlated positively with age across both groups. Network-Based Statistic analysis showed a cluster of lower FA-based connectivity in depressed subjects centered on the right caudate, including connections to the frontal gyri, insula, and anterior cingulate. Within this cluster, the strongest difference between controls and depressed subjects was the connection between the right caudate and middle frontal gyrus, which showed a significant diagnosis by stress interaction and a negative correlation with total stress in depressed subjects |
| Velasquez et al. (2017) | 108 | 8–19 | Autism | Task-based fMRI (face processing task) | Diagnosis | Group difference | During face processing tasks, ASD youth with low-expressing 5-HTTLPR (serotonin transporter-linked polymorphic region) genotypes showed significantly greater amygdala-sgACC connectivity compared to healthy controls and to ASD youth with higher-expressing genotypes. ASD youth with higher-expressing genotypes also showed a negative relationship between amygdala-sgACC connectivity and social dysfunction |
| Wang et al. (2018) | 136 | 21.5 ± 4.2 (control) 21.7 ± 3.6 (ARMS-NT) 19.7 ± 3.1 (ARMS-T) |
Psychosis | Resting state fMRI | Future risk | Group difference | Subjects with At Risk Mental State (ARMS) that transitioned to psychosis (ARMS-T) during follow-up showed significant reductions in functional connectivity at baseline, primarily involving the limbic system, in comparison to healthy controls and to ARMS subjects that did not transition (ARMS-NT). ARMS-T subjects also exhibited reduced global efficiency at baseline in comparison to ARMS-NT subjects. In the salience network, the mean nodal efficiency computed over regions that were reduced in the ARMS-T group was associated with baseline positive and negative syndrome scale (PANSS) general scores. At the whole brain level, the ARMS-T group network community structure displayed a distinct pattern from that of the ARMS-NT group and of healthy controls |
| Wang et al. (2018a) | 79 | 13–18 | Schizophrenia | Resting state fMRI | Diagnosis | Group difference | Compared to healthy controls, patients with adolescent-onset schizophrenia had increased long-range and short-range positive fc in the right middle frontal gyrus and right superior medial PFC within the anterior DMN, decreased long-range and short-range positive fc in several regions of the posterior DMN, and decreased long-range positive functional connectivity within the SN. Decreased long-range positive fc in the left superior temporal gyrus was positively correlated with cognitive impairment |
| Wang et al. (2018b) | 79 | 13–18 | Schizophrenia | Resting state fMRI | Diagnosis | Single subject Group difference |
Patients with adolescent-onset schizophrenia showed significantly increased regional homogeneity (local fc) values in the bilateral superior medial PFC and significantly decreased values in the left superior temporal gyrus, right precentral lobule, right inferior parietal lobule (IPL), and left paracentral lobule when compared to controls. A combination of the regional homogeneity values in the bilateral superior medial PFC, left superior temporal gyrus, and right IPL was used to discriminate patients from healthy controls |
| Wang et al. (2017) | 79 | 13–18 | Schizophrenia | Resting state fMRI | Diagnosis | Group difference | Compared to healthy controls, patients with adolescent-onset schizophrenia showed significantly increased functional connectivity strength in the left cerebellum VI and right inferior frontal gyrus/insula. Functional connectivity strength values in the right inferior frontal gyrus/insula positively correlated with general psychopathology scores of positive and negative syndrome scale |
| Wolf and Herringa (2016) | 48 | 8–18 | PTSD | Task-based fMRI (facial emotion processing task) |
Diagnosis | Group difference | Among youth with PTSD, dorsomedial PFC activation and amygdala-medial PFC connectivity were inversely related to PTSD severity |
| Yao et al. (2017) | 52 | 16.85 ± 0.60 (A) 16.56 ± 0.96 (control) |
Anxiety | Resting state fMRI | Diagnosis | Single subject Group difference |
This study used temporal features derived from dynamic fc to identify generalized anxiety disorder in adolescents. Instantaneous synchronization of pairwise signals was estimated as dynamic fc, and the Hurst exponent (regularity of a time series) and variance (variable degree of a time series) were calculated as temporal features of dynamic fc. By leave-one-out cross-validation (LOOCV), an accuracy of 88.46% was achieved when Hurst exponent and variance of dynamic fc were combined as features. Disease-related regions were also identified, including regions belonging to the DMN and cerebellar network |
| You et al. (2020) | 31 | 9–13 | Autism | Resting state fMRI Task-based fMRI (sustained attention task) |
Diagnosis | Group difference | Distant fc of regions in the left frontal lobe, right parietal lobe, and left posterior middle temporal cortex showed a group by state interaction such that in the task state (relative to the resting state), fc was reduced (became focal) in healthy controls but increased (became diffuse) in children with ASD. In ASD children, higher state-related increase in distant connectivity of the left frontal and right angular gyrus predicted worse inattention, and global efficiency and modularity were also sensitive to group by state differences, with the magnitude of state-related change predicting inattention |
| Zhang et al. (2016) | 100 | 15–25 | Depression (suicidality) |
Resting state fMRI | Diagnosis Future risk |
Group difference | Compared to healthy controls, depressed patients showed increased fc in select DMN regions. Among depressed patients, suicidal patients showed increased connectivity in the left cerebellum and decreased connectivity in the right PCC, whereas non-suicidal patients showed increased connectivity in the left superior frontal gyrus, left lingual gyrus, and right precuneus, and decreased connectivity in the left cerebellum. No differences in the scores of any clinical scales were found between suicidal and non-suicidal depressed patients |
C, controls; ADHD, attention-deficit/hyperactivity disorder; ASD, autism spectrum disorder; OCD, obsessive-compulsive disorder; PTSD, post-traumatic stress disorder; CBT, cognitive-behavioral therapy; fMRI, functional MRI; fc, functional connectivity; rsFC, resting state functional connectivity; DTI, diffusion tensor imaging; FA, fractional anisotropy; ACC, anterior cingulate cortex; sgACC, subgenual anterior cingulate cortex; PFC, prefrontal cortex; OFC, orbitofrontal cortex; PCC, posterior cingulate cortex; DMN, default mode network; CEN, central executive network; SN, salience network.