Sex differences in aberrant functional connectivity of three core networks and subcortical networks in medication-free adolescent-onset major depressive disorder.

Major depressive disorder demonstrated sex differences in prevalence and symptoms, which were more pronounced during adolescence. Yet, research on sex-specific brain network characteristics in adolescent-onset major depressive disorder remains limited. This study investigated sex-specific and nonspecific alterations in resting-state functional connectivity of three core networks (frontoparietal network, salience network, and default mode network) and subcortical networks in adolescent-onset major depressive disorder, using seed-based resting-state functional connectivity in 50 medication-free patients with adolescent-onset major depressive disorder and 56 healthy controls. Irrespective of sex, compared with healthy controls, adolescent-onset major depressive disorder patients showed hypoconnectivity between bilateral hippocampus and right superior temporal gyrus (default mode network). More importantly, we further found that females with adolescent-onset major depressive disorder exhibited hypoconnectivity within the default mode network (medial prefrontal cortex), and between the subcortical regions (i.e. amygdala, striatum, and thalamus) with the default mode network (angular gyrus and posterior cingulate cortex) and the frontoparietal network (dorsal prefrontal cortex), while the opposite patterns of resting-state functional connectivity alterations were observed in males with adolescent-onset major depressive disorder, relative to their sex-matched healthy controls. Moreover, several sex-specific resting-state functional connectivity changes were correlated with age of onset, sleep disturbance, and anxiety in adolescent-onset major depressive disorder with different sex. These findings suggested that these sex-specific resting-state functional connectivity alterations may reflect the differences in brain development or processes related to early illness onset, underscoring the necessity for sex-tailored diagnostic and therapeutic approaches in adolescent-onset major depressive disorder.

The Natural History and Risk Factors for the Development of Food Allergies in Children and Adults.

PURPOSE OF REVIEW: This narrative review explores food allergy prevalence and natural history stratified by life stages, especially in context of evolving knowledge over the last few decades. RECENT FINDINGS: The prevalence of food allergy remains highest in early childhood with common food triggers being cow's milk, soy, hen's egg, wheat, peanut, tree nuts, sesame, fish, and shellfish. This correlates with certain risk factors especially pertinent in the postnatal period which appear to predispose an individual to developing a food allergy. Some allergies (such as milk and egg) were previously thought to be easily outgrown in early life; however, recent studies suggest increasing rates of persistence of these allergies into young adulthood; the reason behind this is unknown. Despite this, there is also evidence demonstrating that food allergies can be outgrown in adolescents and adults. An understanding of the paradigm shifts in the natural history of food allergy allows clinicians to provide updated, age-appropriate, and tailored advice for patients on the management and prognosis of food allergy.

Links of platelet glutamate and glutathione metabolism with attenuated positive and negative symptoms in depressed patients at clinical high risk for psychosis.

Aim of the study is to reveal clinical and biological correlations in patients with adolescent depression and attenuated psychotic symptoms. Activity of platelet enzymes involved in glutamate-, glutathione- and energy metabolism was evaluated in control group and in the patients, because these systems are suspected as related to pathogenesis of psychosis. Adolescents (78 men, 16-25 years old) hospitalized with the first acute depressive state composed two groups: with prevalence of attenuated psychotic positive or negative symptoms (Gr1 and Gr2, 48 and 30 patients, respectively). Control group comprised 20 mentally healthy men of 19-25 years old. Gr1 differed significantly from Gr2 in scores by the Scale of Prodromal Symptoms (SOPS) for positive symptoms, p < 0.001, for disorganization symptoms, p < 0.003, and for total SOPS score, p < 0.001, before the treatment started. When patients from either Gr1 or Gr2 were compared with the control group, significantly decreased baseline activities of platelet glutamate dehydrogenase (GDH), glutathione reductase (GR) and glutathione S-transferase (GST) were found (p < 0.0001). Different correlations were found between baseline enzymatic activities in Gr1 and Gr2: GDH activity correlated with GR activity in Gr1 (R = 0.37), and with GST activity in Gr2 (R = 0.70). Significant correlations were found only in Gr2 between the delta of scores by SOPS negative symptoms (SOPS-N) under treatment and baseline GDH, GST, and GR activities (R = - 0.36, R = - 0.60, and R = 0.38, respectively). The found correlations of the baseline enzymatic activity levels with the value of the decrease (delta) in SOPS-N scores under the treatment represent interest for the prediction of the pharmacotherapy efficiency.

Clinical profile and incidence of microvascular complications of childhood and adolescent onset type 1 and type 2 diabetes seen at a tertiary diabetes center in India.

AIM: To study the clinical characteristics and incidence of microvascular complications among childhood and adolescent onset type 1 (T1DM) and type 2 diabetes (T2DM) seen at a tertiary care diabetes center in India. METHODS: From our electronic medical records, we retrieved clinical and biochemical details of 4555 individuals with childhood and adolescent onset diabetes (diagnosed below the age of 20 years) seen between 1992 and 2017. T1DM was diagnosed if there was history of ketoacidosis or fasting C-peptide <0.3 PMol/mL and stimulated C-peptide <0.6 PMol/mL or if insulin treatment was required from the time of diagnosis. T2DM was diagnosed based on absence of ketosis, or fasting C-peptide ≥0.6 PMol/mL and stimulated >1.0 PMoL/mL, or response to oral hypoglycemic agents for more than 2 years. We calculated the incidence rates of retinopathy (presence of at least one definite microaneurysm by retinal photography), nephropathy (urinary albumin excretion ≥30 µg/mg of creatinine) and neuropathy (vibration perception threshold ≥20 V) per 1000 person-years of follow up. RESULTS: Among the 4555 individuals with childhood and adolescent-onset diabetes, 71.4% had T1DM, 19.5% T2DM and 9.1% other forms of diabetes. Age at first visit and duration of diabetes were significantly higher in T2DM when compared to T1DM. The age adjusted incidence of retinopathy was 52.9/1000 person years (Confidence Intervals [CI]: 42.9-62.8) in T1DM and 49.8/1000 person years (CI 30.8-68.8) in T2DM; nephropathy, 6.2 (CI 3.3-9.0) and 13.8 (CI 5.6-22.0); and neuropathy, 8.8(CI 3.6-14.0) and 24.0 (CI 9.8-38.2) in T1DM and T2DM, respectively. CONCLUSION: The incidence of microvascular complications is high among childhood and adolescent-onset T1DM and T2DM and these calls for more aggressive control of diabetes.

Decision making under ambiguity and risk in adolescent-onset schizophrenia.

OBJECTIVE: Numerous studies have identified impaired decision making (DM) under both ambiguity and risk in adult patients with schizophrenia. However, the assessment of DM in patients with adolescent-onset schizophrenia (AOS) has been challenging as a result of the instability and heterogeneity of manifestations. The Iowa Gambling Task (IGT) and Game of Dice Task (GDT), which are frequently used to evaluate DM respectively under ambiguity and risk, are sensitive to adolescents and neuropsychiatric patients. Our research intended to examine the performance of DM in a relatively large sample of patients with AOS using the above-mentioned two tasks. We also aimed to take a closer look at the relationship between DM and symptom severity of schizophrenia. METHODS: We compared the performance of DM in 71 patients with AOS and 53 well-matched healthy controls using IGT for DM under ambiguity and GDT for DM under risk through net scores, total scores and feedback ration. Neuropsychological tests were conducted in all participants. Clinical symptoms were evaluated by using Positive and Negative Syndrome Scale (PANSS) in 71 patients with AOS. Pearson's correlation revealed the relationship among total score of DM and clinical and neuropsychological data. RESULTS: Compared to healthy controls, patients with AOS failed to show learning effect and had a significant difference on the 5th block in IGT and conducted more disadvantageous choices as well as exhibited worse negative feedback rate in GDT. Apart from DM impairment under risk, diminished DM abilities under ambiguity were found related to poor executive function in AOS in the present study. CONCLUSIONS: Our findings unveiled the abnormal pattern of DM in AOS, mainly reflected under the risky condition, extending the knowledge on the performance of DM under ambiguity and risk in AOS. Inefficient DM under risk may account for the lagging impulse control and the combined effects of developmental disease. In addition, our study demonstrated that the performance on IGT was related to executive function in AOS.

Altered coupling of spontaneous brain activities and brain temperature in patients with adolescent-onset, first-episode, drug-naïve schizophrenia.

PURPOSE: A recent study has reported that schizophrenia patients show an uncoupled association between intraventricular brain temperature (BT) and cerebral blood flow (CBF). CBF has been found to be closely coupled with spontaneous brain activities (SBAs) derived from resting-state BOLD fMRI metrics. Yet, it is unclear so far whether the relationship between the intraventricular BT and the SBAs may change in patients with adolescent-onset schizophrenia (AOS) compared with that in healthy controls (HCs). METHODS: The present study recruited 28 first-episode, drug-naïve AOS patients and 22 matched HCs. We measured the temperature of the lateral ventricles (LV) using diffusion-weighted imaging thermometry and measured SBAs using both regional homogeneity and amplitude of low-frequency fluctuation methods. A nonparametric Wilcoxon rank sum test was used to detect the difference in intraventricular BT between AOS patients and HCs with LV volume, age, and sex as covariates. We also evaluated the relationship between the intraventricular BT and the SBAs using partial correlation analysis controlling for LV volume, age, and sex. RESULTS: We found that HCs showed a significant negative correlation between the intraventricular BT and the local SBAs in the bilateral putamina and left superior temporal gyrus, while such a correlation was absent in AOS patients. Additionally, no significant difference between the two groups was found in the intraventricular BT. CONCLUSION: These findings suggest that AOS patients may experience an uncoupling between intraventricular BT and SBAs in several schizophrenia-related brain areas, which may be associated with the altered relationships among intraventricular BT, CBF, and metabolism.

Decreased Resting-State Interhemispheric Functional Connectivity Correlated with Neurocognitive Deficits in Drug-Naive First-Episode Adolescent-Onset Schizophrenia.

Background: Given that adolescence is a critical epoch in the onset of schizophrenia, studying aberrant brain changes in adolescent-onset schizophrenia, particularly in patients with drug-naive first-episode schizophrenia, is important to understand the biological mechanism of this disorder. Previous resting-state functional magnetic resonance imaging studies have shown abnormal functional connectivity in separate hemispheres in patients with adult-onset schizophrenia. Our aim to study adolescent-onset schizophrenia can provide clues for the early aetiology of schizophrenia. Method: A total of 48 drug-naïve, first-episode, adolescent-onset schizophrenia outpatients and 31 healthy controls underwent resting-state functional magnetic resonance imaging scans. Data were subjected to voxel-mirrored homotopic connectivity and support vector machine analyses. Results: Compared with the healthy controls, the adolescent-onset schizophrenia group showed significantly lower voxel-mirrored homotopic connectivity values in different brain regions, including the fusiform gyrus, superior temporal gyrus/insula, precentral gyrus, and precuneus. Decreased voxel-mirrored homotopic connectivity values in the superior temporal gyrus/insula were significantly correlated with Trail-Making Test: Part A performance (r = -0.437, P = .002). A combination of the voxel-mirrored homotopic connectivity values in the precentral gyrus and precuneus may be used to discriminate patients with adolescent-onset schizophrenia from controls with satisfactory classification results, which showed sensitivity of 100%, specificity of 87.09%, and accuracy of 94.93%. Conclusion: Our findings highlight resting-state interhemispheric FC abnormalities within the sensorimotor network of patients with adolescent-onset schizophrenia and confirm the relationship between adolescent-onset schizophrenia and adult-onset schizophrenia. These findings suggest that reduced interhemispheric connectivity within the sensorimotor network has a pivotal role in the pathogenesis of schizophrenia.

Effect of Posterior Fossa Decompression for Chiari Malformation-I on Scoliosis.

BACKGROUND/AIMS: Scoliosis is common in patients with Chiari malformation-I (CM-I). This study examined the change in scoliosis severity after posterior fossa decompression (PFD) for CM-I. METHODS: We conducted a retrospective review at a single tertiary center for children undergoing PFD with untreated scoliosis, and identified 17 patients with complete follow-up data and imaging. RESULTS: Overall, scoliosis improved in 7 (41.2%) patients, worsened in 9 (52.9%), and remained unchanged in 1 (5.9%) after PFD (mean follow-up of 7.8 ± 4.1 months). We found that 3 of the 8 (38%) children with early-onset scoliosis eventually needed scoliosis corrective surgery, which was needed in 7 of the 9 (78%) patients with adolescent-onset scoliosis. In addition, only 1 patient (17%) with a preoperative scoliosis curve <35 degrees and 9 patients (82%) with a curve ≥35 degrees required surgery for scoliosis correction despite PFD (p = 0.018). CONCLUSION: In certain patients, PFD for CM-I may lead to improvement or stabilization of scoliosis.

[Cerebral grey matter changes of pre- and post-treatment in first-episode drug-naive adolescents schizophrenia].

Objective: To investigate the gray matter(GM) volume and the change of GM volume after antipsychotic treatment for 8 weeks in first-episode drug-naive adolescents with schizophrenia. Methods: T1-weighted brain MRIs were obtained on a 3T scanner in 35 controls and 35 subjects with adolescents schizophrenia who were admitted to the Second Affiliated Hospital of Xinxiang Medical College from April 2015 to June 2016 and not given antipsychotic medication, the schizophrenia patients received second scan after 8 weeks of antipsychotic treatment. Positive and negative syndrome scale (PANSS) assessments were performed in patients pre- and post-treatment; voxel-based morphometry (VBM) was used to analyze changes of GM volume and the correlation between the baseline GM volume and the PANSS scores was further analyzed. Results: GM volumes in the left frontal gyrus (MIN(x, y, z): -13.5, 36, 46.5), left superior parietal lobule (MIN(x, y, z): -52.5, -42, 52.5), left inferior parietal lobule (MIN(x, y, z): -31.5, -45, 69) and left central anterior (MIN(x, y, z): 9, 21, 61.5) were significantly smaller than those in the normal control group (t=-4.384 0, -4.556 2, -6.430 9, -4.313 9 respectively, P<0.001); after treatment for 8 weeks PANSS scores were significantly lower than those of baseline (P<0.001), however, there was no significant difference in regional GM volume between the pre-and post-treatment (P>0.05) and no significant correlation was found between GM volume and PANSS scores. Conclusion: There are local GM volume reductions in subjects with adolescents schizophrenia and these regions may be independent to mental symptoms of patients.

Diagnostic clusters associated with an early onset schizophrenia diagnosis among children and adolescents.

OBJECTIVE: Given the greater severity and chronicity of psychiatric disorders that first declare in individuals under the age of 18, early onset schizophrenia (EOS) and its association with co-occurring psychiatric conditions deserve further investigation. METHODS: Cluster and discriminant analyses were used to examine the heterogeneity of children and adolescents diagnosed with schizophrenia in 1 statewide system of care. A retrospective cohort design was employed, using South Carolina's (USA) Medicaid claims dataset covering outpatient and inpatient medical services between January, 1999 and December, 2013 to identify patients ≤17 years of age. RESULTS: Among the 613 EOS patients selected, 3 main clusters of ICD-9 psychiatric diagnoses were identified: (1) older children with schizophrenia coaggregated with a spectrum of mood/emotional dysregulation conditions; (2) younger children with coaggregated schizophrenia, mental retardation/intellectual disability or autism spectrum disorders; and (3) older children with schizophrenia and significantly fewer diagnosed co-occurring conditions. Externalizing/disruptive behavior disorders (i.e., attention deficit hyperactivity disorder, conduct disorder, and oppositional defiant disorder) were significantly associated with Clusters 1 and 2. CONCLUSION: Symptom patterns plus age of first diagnosis are important differentiators of EOS subgroups in this cohort. Earlier recognition of psychiatric symptom/syndrome patterns that frequently co-occur may enable clinicians to stratify/tailor treatment interventions.

Canadian Guidelines for the Pharmacological Treatment of Schizophrenia Spectrum and Other Psychotic Disorders in Children and Youth.

OBJECTIVE: Schizophrenia spectrum and other psychotic disorders often have their onset in adolescence. The sequelae of these illnesses can negatively alter the trajectory of emotional, cognitive, and social development in children and youth if left untreated. Early and appropriate interventions can improve outcomes. This article aims to identify best practices in the pharmacotherapy management of children and youth with schizophrenia spectrum disorders. METHODS: A systematic search was conducted for published guidelines for schizophrenia and schizophrenia spectrum disorders in children and youth (under age 18 years). Recommendations were drawn from the National Institute for Health and Care Excellence guidelines on psychosis and schizophrenia in children and youth (2013 and 2015 updates). Current guidelines were adopted using the ADAPTE process, which includes consensus ratings by a panel of experts. RESULTS: Recommendations identified covered a range of issues in the pharmacotherapy management of children and youth with schizophrenia spectrum disorders. Further work in this area is warranted as we continue to further understand their presentation in the developing brain. CONCLUSIONS: Canadian guidelines for the pharmacotherapy management of children and youth with schizophrenia spectrum disorders are essential to assist clinicians in treating this vulnerable population. Ongoing work in this area is recommended.

Abnormal functional connectivity strength in patients with adolescent-onset schizophrenia: a resting-state fMRI study.

Structural and functional abnormalities were reported in the brain of patients with adolescent-onset schizophrenia (AOS). However, evidence of abnormal functional connectivity of the brain in AOS patients is limited. Thus, we analyzed the resting-state functional magnetic resonance scans of 48 drug-naive AOS patients and 31 healthy controls to determine their functional connectivity strength (FCS) and examined if FCS abnormalities were correlated with clinical characteristics. Compared with healthy controls, AOS patients showed significantly increased FCS in the left cerebellum VI and right inferior frontal gyrus/insula. A positive correlation was observed between FCS values in the right inferior frontal gyrus/insula and general psychopathology scores of positive and negative syndrome scale. Results suggest that functional connectivity pattern is disrupted in drug-naive AOS patients. The FCS values in this abnormal region have potential for evaluating the disease severity.

Treatment Outcome of Adolescent Inpatients With Early-Onset and Adolescent-Onset Disruptive Behavior.

OBJECTIVE: Unlike adolescents with adolescent-onset (AO) disruptive behavior, adolescents with early-onset (EO) disruptive behavior may not benefit from treatment. METHOD: Using Symptom Checklist (SCL-90-R) ratings at admission and discharge of adolescent inpatients with EO (n = 85) and AO (n = 60) disruptive behavior treatment outcome was determined by (a) a change in mean scores and (b) the Reliable Change Index. For a subgroup, ratings on the Satisfaction Questionnaire Residential Youth Care for Parents (n = 83) were used to verify the treatment outcome. RESULTS: Inpatients with EO disruptive behavior had a higher risk of dropout (44.4%) from treatment than the AO group (24.7%). Among the treatment completers, both onset groups reported improvements on the SCL-90-R, with 26.9% recovering and 31.7% improving. Inpatients who reported improvement were mostly rated as improved by their parents (r = .33). CONCLUSION: As EO inpatients are more likely to drop out, interventions should aim at motivating youngsters to continue treatment, particularly given the poor outcome in this group. Treatment may benefit both groups because those EO youths who stayed in treatment improved to the same extent as AO inpatients.

The potential predictive value and relationship of blood-based inflammatory markers with the clinical symptoms of Han Chinese patients with first-episode adolescent-onset schizophrenia.

Background: Inflammation is associated with the pathophysiology of schizophrenia. The blood markers for systemic inflammation include neutrophil-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), lymphocyte-monocyte ratio (LMR), system inflammation response index (SIRI), and platelet-lymphocyte ratio (PLR). However, these inflammation markers and their relationships with clinical phenotypes among Han Chinese patients with first-episode adolescent-onset schizophrenia (AOS) is unclear. This investigation aimed to elucidate the impact of inflammation on Han Chinese AOS patients as well as the association of blood-based inflammation markers with clinical symptoms. Methods: Altogether, 203 Han Chinese individuals participated in this study, 102 first-episode AOS patients and 101 healthy controls. The assessment of inflammatory indices was based on complete blood cell count. Furthermore, schizophrenia-related clinical symptoms were evaluated using the five-factor model of the Positive and Negative Syndrome Scale (PANSS). Results: In Han Chinese first-episode AOS patients, levels of SIRI, PLR, SII, and NLR were significantly increased (p < 0.001), while LMR decreased (p < 0.001) compared to healthy controls. Furthermore, multivariate logistic regression showed that LMR, NLR, SII, and SIRI (all p < 0.05) were independently associated with AOS. Moreover, Receiver operating characteristics assessment indicated that NLR, SIRI, LMR, and SII could effectively distinguish AOS patients from healthy controls. Their areas under the curves were 0.734, 0.701, 0.715, and 0.730 (all p < 0.001). In addition, Correlation analysis revealed that LMR was negatively correlated with the PANSS total, negative, and cognitive factor scores (all p < 0.05); NLR was positively correlated with the cognitive factor score (p < 0.01); SII was negatively correlated with the positive factor score and positively with the negative and cognitive factor scores (all p < 0.05); SIRI was positively correlated with the PANSS total and cognitive factor scores (all p < 0.01). Conclusions: This research established the involvement of peripheral blood inflammatory markers (LMR, NLR, SII, and SIRI) with the clinical manifestations and pathophysiology of schizophrenia, and these can serve as screening tools or potential indices of the inflammatory state and AOS symptoms severity.

Facet Joint Bridging in Adolescent-Onset Adult Idiopathic Scoliosis with Thoracolumbar/Lumbar Curves.

OBJECTIVE: This study aims to comprehend the natural history of adolescent idiopathic scoliosis (AIS) patients and determine risk factors for facet joint bridging in adolescent-onset adult idiopathic scoliosis with thoracolumbar/lumbar (TL/L) curves. METHODS: We included 50 patients with residual AIS with TL/L curves (3 males, 47 females; age 41.5 ± 17.3 years, TL/L Cobb angle 59.4 ± 11.8°). They were >20 years old and diagnosed with AIS during their adolescence. Radiographic parameters were measured, and facet joint bridging was defined from axial computed tomography images. RESULTS: The sagittal vertical axis (SVA) significantly increased with age (r = 0.71, P < 0.01). Coronal Cobb angle of the TL/L curve, L4 tilt, C7 translation, lumbar lordosis (LL), pelvic incidence-LL, pelvic tilt, and thoracolumbar kyphosis were also correlated to age (P < 0.05). There were significant differences in age, SVA, pelvic incidence-LL, vertebral bridging, facet tropism, and apical vertebral rotation (AVR) between the facet joint bridging group (n = 10) and the non-facet joint bridging group (n = 40). In the multivariate logistic regression analysis, SVA, vertebral bridging, and AVR emerged as notable risk determinants for facet joint bridging. The threshold for facet joint bridging based on SVA was 2.1 cm (area under the curve: 0.801; sensitivity = 90%; specificity = 65%). CONCLUSIONS: This research revealed that large SVA, the presence of vertebral bridging, and large AVR are associated with facet joint bridging in adolescent-onset adult idiopathic scoliosis patients with TL/L curves. The cutoff value for facet joint bridging based on SVA was 2.1 cm.

Abnormal regional homogeneity as a potential imaging indicator for identifying adolescent-onset schizophrenia: Insights from resting-state functional magnetic resonance imaging.

BACKGROUND: In patients with schizophrenia, there is abnormal regional functional synchrony. However, whether it also in patients with adolescent-onset schizophrenia (AOS) remains unclear. The goal of this study was to analyze the regional homogeneity (ReHo) of resting functional magnetic resonance imaging to explore the functional abnormalities of the brain in patients with AOS. METHODS: The study included 107 drug-naive first-episode AOS patients and 67 healthy, age, sex, and education-matched controls using resting-state functional magnetic resonance imaging scans. The ReHo method was used to analyze the imaging dataset. RESULTS: Compared with the control group, the ReHo values of the right inferior frontal gyrus orbital part, right middle frontal gyrus (MFG.R), left inferior parietal, but supramarginal and angular gyri, and left precentral gyrus (PreCG.L) were significantly increased and the ReHo value of the left posterior cingulate cortex/anterior cuneiform lobe was significantly decreased in schizophrenia patients. ROC analysis showed that the ReHo values of the MFG.R and PreCG.L might be regarded as potential markers in helping to identify patients. Furthermore, the PANSS scores in the patient group and the ReHo values showed a positive correlation between MFG.R ReHo values and general scores. CONCLUSIONS: Our results suggested that AOS patients had ReHo abnormalities. The ReHo values of these abnormal regions may serve as potential imaging biomarkers for the identification of AOS patients.

Structural covariance network activity in the medial prefrontal cortex is modulated by childhood abuse in adolescents with depression.

Aberrant structural covariance (SC) in the medial prefrontal cortex (mPFC) is believed to play a crucial role in adolescent-onset major depressive disorder (AO-MDD). However, the effect of childhood abuse (CA) on SC in AO-MDD patients is still unknown. Here, we measured anomalous SC in the mPFC of AO-MDD patients and assessed the potential modulation of this feature by CA. We acquired T1-weighted structural images of AO-MDD patients (n = 93) and healthy controls (HCs, n = 81). Using voxel-based morphometry analysis, we calculated gray matter volumes for each subject. Subsequently, we classified abnormal SC in the mPFC into three subtypes according to overall CA. Compared with HCs, AO-MDD patients showed alterations in the structural covariance network of the mPFC, which is a central region in the default mode network (DMN). We also found an anterior-posterior dissociation in the structural covariance connectivity of the DMN. A history of CA modulated bilateral mPFC SC. These changes were primarily focused on the SC between the mPFC and the limbic system, indicating a gap in the rate of neural maturation between these regions. In summary, the DMN and frontal-limbic system, which are involved in emotional processing, appear to play a significant role in the development of AO-MDD. These findings highlight the crucial effects of CA on neurophysiological alterations in individuals with AO-MDD.

Altered Temporal Dynamics of Resting-State Functional Magnetic Resonance Imaging in Adolescent-Onset First-Episode Psychosis.

BACKGROUND: Dynamic functional connectivity (dFC) alterations have been reported in patients with adult-onset and chronic psychosis. We sought to examine whether such abnormalities were also observed in patients with first episode, adolescent-onset psychosis (AOP), in order to rule out potential effects of chronicity and protracted antipsychotic treatment exposure. AOP has been suggested to have less diagnostic specificity compared to psychosis with onset in adulthood and occurs during a period of neurodevelopmental changes in brain functional connections. STUDY DESIGN: Seventy-nine patients with first episode, AOP (36 patients with schizophrenia-spectrum disorder, SSD; and 43 with affective psychotic disorder, AF) and 54 healthy controls (HC), aged 10 to 17 years were included. Participants underwent clinical and cognitive assessments and resting-state functional magnetic resonance imaging. Graph-based measures were used to analyze temporal trajectories of dFC, which were compared between patients with SSD, AF, and HC. Within patients, we also tested associations between dFC parameters and clinical variables. STUDY RESULTS: Patients with SSD temporally visited the different connectivity states in a less efficient way (reduced global efficiency), visiting fewer nodes (larger temporal modularity, and increased immobility), with a reduction in the metabolic expenditure (cost and leap size), relative to AF and HC (effect sizes: Cohen's D, ranging 0.54 to.91). In youth with AF, these parameters did not differ compared to HC. Connectivity measures were not associated with clinical severity, intelligence, cannabis use, or dose of antipsychotic medication. CONCLUSIONS: dFC measures hold potential towards the development of brain-based biomarkers characterizing adolescent-onset SSD.

Prevalence and correlates of childhood-onset bipolar disorder among adolescents.

AIM: Early-onset bipolar disorder (BD) is associated with a more severe illness as well as a number of clinical factors among adults. Early-onset can be categorized as childhood- (age < 13) or adolescent- (age ≥ 13) onset, with the two displaying different clinical profiles. We set out to examine differences in clinical, and familial characteristics among adolescents with childhood- versus adolescent-onset BD. METHODS: The study included 195 adolescents with BD, ages 14-18 years. Age of onset was determined retrospectively by self-report. Participants completed the semi-structured K-SADS-PL diagnostic interviews along with self-reported dimensional scales. Analyses examined between-group differences for clinical and familial variables. Variables associated with age of onset at p < 0.1 in univariate analyses were evaluated in a logistic regression model. RESULTS: Approximately one-fifth of participants had childhood-onset BD (n = 35; 17.9%). A number of clinical and familial factors were significantly associated with childhood-onset BD. However, there were no significant differences in depressive and manic symptom severity. In multivariate analyses, the variables most strongly associated with childhood-onset were police contact, and family history of suicidal ideation. Smoking and psychiatric hospitalization were associated with adolescent-onset. CONCLUSIONS: In this large clinical sample of adolescents with BD, one-fifth reported childhood-onset BD. Correlates of childhood-onset generally aligned with those observed in the literature. Future research is warranted to better understand the genetic and environmental implications of high familial loading of psychopathology associated with childhood-onset, and to integrate age-related treatment and prevention strategies.