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.

[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.

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.

Atypical frontotemporal cortical activity in first-episode adolescent-onset schizophrenia during verbal fluency task: A functional near-infrared spectroscopy study.

Background: Frontotemporal cortex dysfunction has been found to be associated with cognitive impairment in patients with schizophrenia (SCZ). In patients with adolescent-onset SCZ, a more serious type of SCZ with poorer functional outcome, cognitive impairment appeared to occur at an early stage of the disease. However, the characteristics of frontotemporal cortex involvement in adolescent patients with cognitive impairment are still unclear. In the present study, we aimed to illustrate the frontotemporal hemodynamic response during a cognitive task in adolescents with first-episode SCZ. Methods: Adolescents with first-episode SCZ who were aged 12-17 and demographically matched healthy controls (HCs) were recruited. We used a 48-channel functional near-infrared spectroscopy (fNIRS) system to record the concentration of oxygenated hemoglobin (oxy-Hb) in the participants' frontotemporal area during a verbal fluency task (VFT) and analyzed its correlation with clinical characteristics. Results: Data from 36 adolescents with SCZ and 38 HCs were included in the analyses. Significant differences were found between patients with SCZ and HCs in 24 channels, mainly covering the dorsolateral prefrontal cortex, superior and middle temporal gyrus and frontopolar area. Adolescents with SCZ showed no increase of oxy-Hb concentration in most channels, while the VFT performance was comparable between the two groups. In SCZ, the intensity of activation was not associated with the severity of symptoms. Finally, receiver operating characteristic analysis indicated that the changes in oxy-Hb concentration could help distinguish the two groups. Conclusion: Adolescents with first-episode SCZ showed atypical cortical activity in the frontotemporal area during the VFT, and fNIRS features might be more sensitive indicators in cognitive assessment, indicating that the characteristic hemodynamic response pattern might be potential imaging biomarkers for this population.

Energy in functional brain states correlates with cognition in adolescent schizophrenia and healthy persons.

Adolescent-onset schizophrenia (AOS) is a relatively rare and under-studied form of schizophrenia with more severe cognitive impairments and poorer outcome compared to adult-onset schizophrenia. Several neuroimaging studies have reported alterations in regional activations that account for activity in individual regions (first-order model) and functional connectivity that reveals pairwise co-activations (second-order model) in AOS compared to controls. The pairwise maximum entropy model, also called the Ising model, can integrate both first-order and second-order terms to elucidate a comprehensive picture of neural dynamics and captures both individual and pairwise activity measures into a single quantity known as energy, which is inversely related to the probability of state occurrence. We applied the MEM framework to task functional MRI data collected on 23 AOS individuals in comparison with 53 healthy control subjects while performing the Penn Conditional Exclusion Test (PCET), which measures executive function that has been repeatedly shown to be more impaired in AOS compared to adult-onset schizophrenia. Accuracy of PCET performance was significantly reduced among AOS compared to controls as expected. Average cumulative energy achieved for a participant over the course of the fMRI negatively correlated with task performance, and the association was stronger than any first-order associations. The AOS subjects spent more time in higher energy states that represent lower probability of occurrence and were associated with impaired executive function suggesting that the neural dynamics may be less efficient compared to controls who spent more time in lower energy states occurring with higher probability and hence are more stable and efficient. The energy landscapes in both conditions featured attractors that corresponded to two distinct subnetworks, namely fronto-temporal and parieto-motor. Attractor basins were larger in the controls than in AOS; moreover, fronto-temporal basin size was significantly correlated with cognitive performance in controls but not among the AOS. The single trial trajectories for the AOS group also showed higher variability in concordance with shallow attractor basins among AOS. These findings suggest that the neural dynamics of AOS features more frequent occurrence of less probable states with narrower attractors, which lack the relation to executive function associated with attractors in control subjects suggesting a diminished capacity of AOS to generate task-effective brain states.

Large-scale networks underlie cognitive insight differs between untreated adolescents ongoing their first schizophrenic episode and their reference non-schizophrenic mates.

Objectives: Cognitive insight (CI), the ability to perceive erroneous beliefs and correcting them based on safe experiences, is a common cognitive manifestation among schizophrenic individuals. Even though the functional morphology of the default mode network (DMN), the central executive network (CEN) and the salience network (SN) differs between non-schizophrenic and schizophrenic individuals, it is unclear whether such differences are already in place by the first schizophrenic episode. Methods: Forty-two adolescents, including twenty-one AOS subjects was recruited, and performed independent component analysis (ICA) on resting-state fMRI data to explore alterations in the three networks in schizophrenia and the association of network changes with Beck Cognitive Insight Scale (BCIS) scores. Results: Compared to the non-schizophrenic group, the AOS group showed hyper-connectivity in the left middle temporal gyrus (MTG) and hypo-connectivity in the right parahippocampal gyrus within the DMN; hypo-connectivity in the dorsal anterior cingulate (dACC) and supplementary motor area (SMA) within the SN were also detected in AOS individuals. CI subscores were positively correlated with functional connectivity (FC) in the right parahippocampal gyrus. Conclusions: The correlations reported here suggest that increased DMN connectivity in the right parahippocampal gyrus might be an early neural correlate of reduced cognitive insight in a number, but not all, adolescent untreated individuals ongoing their first schizophrenic episode.

Increased resting-state interhemispheric functional connectivity of striatum in first-episode drug-naive adolescent-onset schizophrenia.

BACKGROUND: Compared to adult-onset schizophrenia, relatively few neuroimaging studies have examined functional connectivity (FC) abnormalities in adolescent-onset schizophrenia (AOS). The present study was designed to investigate resting-state interhemispheric connectivity patterns among drug-naive first-episode AOS patients and potential changes following short-term antipsychotic drug treatment. METHODS: This study included 107 drug-naïve, first-episode AOS patients (age: 15.33 ± 1.62, 45 males) and 67 matched healthy controls (age: 15.43 ± 1.86, 30 males). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans, and 34 AOS patients (age: 15.12 ± 1.68, 12 males) also underwent a follow-up scan after 8 weeks of antipsychotic drug treatment. Interhemispheric functional connectivity was measured by voxel-mirrored homotopic connectivity (VMHC). RESULTS: Compared to healthy controls, AOS patients showed increased VMHC values in putamen and caudate. No significant differences were observed between the patients at baseline and after 8 weeks of treatment. CONCLUSIONS: First-episode, drug-naive AOS patients demonstrate abnormalities in interhemispheric FC, and these are not mitigated by short-term antipsychotic treatment.

Alterations in functional network centrality in first-episode drug-naïve adolescent-onset schizophrenia.

Schizophrenia is a disorder resulting from aberrant brain networks and circuits. In the current study, we aimed to investigate specific network alterations in adolescent-onset schizophrenia (AOS) and to help identify the neurophysiological mechanisms of this adolescent disorder. We recruited forty-one subjects, including 20 AOS patients and 21 matched healthy controls (HCs), and we acquired brain images to examine the specific changes in functional network patterns using degree centrality (DC), which quantifies the strength of the local functional connectivity hubs. Whole-brain correlation analysis was applied to assess the relationships between clinical characteristics and DC measurements. The AOS group exhibited increased DC in the right inferior frontal lobe, right fusiform gyrus and right thalamus (p < 0.05, AlphaSim correction). Whole-brain correlation analysis found that the DC value in the right parahippocampus was positively correlated with PANSS-positive symptom scores (r = 0.80); DC in the right superior parietal lobe (SPL) was positively correlated with PANSS-negative symptom scores (r = 0.79); DC in the left precuneus was positively correlated with self-certainty (SC) scores (r = 0.70); and DC in the left medial frontal gyrus (MFG) was negatively correlated with self-reflectiveness (SR) scores (r = 0.69). We conclude that frontoparietal network and cortico-thalamo-cortical pathway disruptions could play key roles in the neurophysiological mechanisms underlying AOS. In AOS patients, the right parahippocampus and SPL are important structures associated with positive and negative symptoms, respectively, and the left precuneus and MFG contribute to deficits in cognitive insights.

Abnormal global-brain functional connectivity and its relationship with cognitive deficits in drug-naive first-episode adolescent-onset schizophrenia.

Abnormal functional connectivity (FC) has been reported in drug-naive first-episode adolescent-onset schizophrenia (AOS) with inconsistent results due to differently selected regions of interest. The voxel-wise global-brain functional connectivity (GFC) analysis can help explore abnormal FC in an unbiased way in AOS. A total of 48 drug-naive first-episode AOS as well as 31 sex-, age- and education-matched healthy controls were collected. Data were subjected to GFC, correlation analysis and support vector machine analyses. Compared with healthy controls, the AOS group exhibited increased GFC in the right middle frontal gyrus (MFG), and decreased GFC in the right inferior temporal gyrus, left superior temporal gyrus (STG)/precentral gyrus/postcentral gyrus, right posterior cingulate cortex /precuneus and bilateral cuneus. After the Benjamini-Hochberg correction, significantly negative correlations between GFC in the bilateral cuneus and Trail-Making Test: Part A (TMT-A) scores (r=-0.285, p=0.049), between GFC in the left STG/precentral gyrus/postcentral gyrus and TMT-A scores (r=-0.384, p=0.007), and between GFC in the right MFG and the fluency scores (r=-0.335, p=0.020) in the patients. GFC in the left STG/precentral gyrus/postcentral gyrus has a satisfactory accuracy (up to 86.08%) in classifying patients from controls. AOS shows abnormal GFC in the brain areas of multiple networks, which bears cognitive significance. These findings suggest potential abnormalities in processing self-monitoring and sensory prediction, which further elucidate the pathophysiology of AOS.

Treatment-resistant schizophrenia: Addressing white matter integrity, intracortical glutamate levels, clinical and cognitive profiles between early- and adult-onset patients.

BACKGROUND: Treatment-resistance in schizophrenia is 30-40%. Its neurobiology remains unclear; to explore it, we conducted a combined spectrometry/tractography/cognitive battery and psychopathological rating study on patients with treatment-resistant schizophrenia (TRS), dividing the sample into early-onset (N = 21) and adult-onset TRS (N = 20). Previous studies did not differentiate between early- (onset 13-18 years) and adult-onset (>18 years at formal diagnosis of schizophrenia) TRS. METHODS: We evaluated cross-sectionally 41 TRS patients (26 male and 15 female) and 20 matched healthy controls (HCs) with psychopathological and cognitive testing prior to participating in brain imaging scanning using magnetic resonance spectroscopy and diffusion tensor imaging to determine the relationship between their symptoms and their glutamate levels and white matter integrity. RESULTS: TRS patients scored lower than HCs on all cognitive domains; early-onset patients performed better than adult-onset patients only on the Symbol Coding domain. TRS correlated with symptom severity, especially negative symptoms. Glutamate levels and glutamate/creatine were increased in anterior cingulate cortex. Diffusion tensor imaging showed low fractional anisotropy in TRS patients in specific white matter tracts compared to HCs (bilateral anterior thalamic radiation, cortico-spinal tract, forceps minor, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, and right uncinate fasciculus). CONCLUSIONS: We identified specific magnetic resonance spectroscopy and diffusion tensor imaging alterations in TRS patients. Adult-onset TRS differed little from early-onset TRS on most measures; this points to alterations being present since the outset of schizophrenia and may constitute a biological signature of treatment-resistance.

Frequency-specific altered global signal topography in drug-naïve first-episode patients with adolescent-onset schizophrenia.

Adolescent-onset schizophrenia (AOS) is a severe neuropsychiatric disease associated with frequency-specific abnormalities across distributed neural systems in a slow rhythm. Recently, functional magnetic resonance imaging (fMRI) studies have determined that the global signal. (GS) is an important source of the local neuronal activity in 0.01-0.1 Hz frequency band. However, it remains unknown whether the effects follow a specific spatially preferential pattern in different frequency bands in schizophrenia. To address this issue, resting-state fMRI data from 39 drug-naïve AOS patients and 31 healthy controls (HCs) were used to assess the changes in GS topography patterns in the slow-4 (0.027-0.073 Hz) and slow-5 bands (0.01-0.027 Hz). Results revealed that GS mainly affects the default mode network (DMN) in slow-4 and sensory regions in the slow-5 band respectively, and GS has a stronger driving effect in the slow-5 band. Moreover, significant frequency-by-group interaction was observed in the frontoparietal network. Compared with HCs, patients with AOS exhibited altered GS topography mainly located in the DMN. Our findings demonstrated that the influence of the GS on brain networks altered in a frequency-specific way in schizophrenia.

Abnormal causal connectivity of left superior temporal gyrus in drug-naïve first- episode adolescent-onset schizophrenia: A resting-state fMRI study.

This study aimed to investigate the alterations of causal connectivity between the brain regions in Adolescent-onset schizophrenia (AOS) patients. Thirty-two first-episode drug-naïve AOS patients and 27 healthy controls (HC) were recruited for resting-state functional MRI scanning. The brain region with the between-group difference in regional homogeneity (ReHo) values was chosen as a seed to perform the Granger causality analysis (GCA) and further detect the alterations of causal connectivity in AOS. AOS patients exhibited increased ReHo values in left superior temporal gyrus (STG) compared with HCs. Significantly decreased values of outgoing Granger causality from left STG to right superior frontal gyrus and right angular gyrus were observed in GC mapping for AOS. Significantly stronger causal outflow from left STG to right insula and stronger causal inflow from right middle occipital gyrus (MOG) to left STG were also observed in AOS patients. Based on assessments of the two strengthened causal connectivity of the left STG with insula and MOG, a discriminant model could identify all patients from controls with 94.9% accuracy. This study indicated that alterations of directional connections in left STG may play an important role in the pathogenesis of AOS and serve as potential biomarkers for the disease.

Abnormal white matter functional connectivity density in antipsychotic-naive adolescents with schizophrenia.

OBJECTIVES: This study aimed to assess the white matter (WM) functional hubs and abnormal functional connectivity pattern in adolescents with schizophrenia (AOS) and to explore the potential mechanisms. METHODS: Based on resting-state fMRI data, we measured the WM functional connectivity density (FCD) at local- and long- ranges in 39 AOS and 31 healthy controls (HCs). Group comparison was conducted between the two groups. Spearman rank correlation analysis between the altered WM FCD and clinical PANSS scores was performed. RESULTS: In the local scale, the functional hubs of the WM were mainly located in the corona radiata and cerebellum. Compared with HCs, AOS patients exhibited decreased FCD in the superior corona radiata. In the long-range, the functional hubs of the WM were mainly located in the external capsule and pons. AOS patients exhibited increased FCD in the cingulum but decreased FCD in the right dorsal raphe nuclei (DR). Furthermore, the aberrant long-range FCD in the right DR was inversely proportional to the clinical symptoms. CONCLUSION: These findings indicated that the pathophysiology of schizophrenia may also lie in WM functional dysconnectivity. SIGNIFICANCE: The current results provided initial evidence for the hypothesis of abnormal WM functional connectivity in schizophrenia.

Abnormal dynamic functional network connectivity of the mirror neuron system network and the mentalizing network in patients with adolescent-onset, first-episode, drug-naïve schizophrenia.

Previous studies based on an assumption of connectivity stationarity reported disconnections in mirror neuron system (MNS) and mentalizing networks of schizophrenic brains with social cognitive disruptions. However, recent studies demonstrated that functional brain connections are dynamic, and static connectivity metrics fail to capture time-varying properties of functional connections. The present study used a dynamic functional connectivity (dFC) method to test whether alterations of functional connectivity in the two networks are time-varying in adolescent-onset schizophrenia (AOS) patients. We collected resting-state fMRI data from 28 patients with AOS and 22 matched healthy controls. Static functional connectivity and dFC were used to explore the connectivity difference in the MNS and mentalizing networks between the two groups, respectively. Then a Pearson's correlation analysis between the connectivity showing intergroup differences and clinical scores was conducted in the AOS group. Compared with static functional connectivity analyses, dFC revealed state-specific connectivity decreases within the MNS network in the AOS group. Additionally, the dFC between the left middle temporal gyrus and left V5 was negatively correlated with the item2 of PANSS negative scores across all the AOS patients. Our findings suggest that social dysfunctions in AOS patients may be associated with the altered integrity and interaction of the MNS and mentalizing networks, and the functional impairments in the MNS are dynamic over time.

Abnormal default-mode network homogeneity and its correlations with neurocognitive deficits in drug-naive first-episode adolescent-onset schizophrenia.

The default mode network (DMN), is one of the most popularly employed resting-state networks applied in schizophrenia (SCZ) research. However, the homogeneity of this network in adolescent-onset SCZ (AOS) remains unknown. This study aims to use network homogeneity (NH) to explore the functional connectivity in the DMN of AOS patients. Resting-state functional magnetic resonance imaging scans were used to study 48 drug-naïve, first-episode AOS patients and 31 healthy age, gender, and education matched control. An automatic NH approach was employed to analyze the imaging dataset. Our results revealed that the patients had significantly higher NH values in the left medial prefrontal cortex (MPFC), and significantly lower values in the bilateral posterior cingulate cortex/precuneus (PCC/PCu) than those in healthy controls. We performed the receiver operating characteristic curve analysis to show that NH values of the left superior MPFC might be regarded as a potential marker in helping to identify patients. In addition, negative associations were found regarding abnormal values of NH in the left PCC/PCu as well as in the Maze and Stroop color-word tests in patients. The outcomes showed abnormal NH values in the DMN of drug-naïve, first-episode AOS suggesting specific functions of the DMN in the pathophysiology of SCZ.