Early-onset Schizophrenia Patients Research Articles

Shared atypical spontaneous brain activity pattern in early onset schizophrenia and autism spectrum disorders: evidence from cortical surface-based analysis.

Schizophrenia and autism spectrum disorders (ASD) were considered as two neurodevelopmental disorders and had shared clinical features. we hypothesized that they have some common atypical brain functions and the purpose of this study was to explored the shared brain spontaneous activity strength alterations in early onset schizophrenia (EOS) and ASD in the children and adolescents with a multi-center large-sample study. A total of 171 EOS patients (aged 14.25 ± 1.87), 188 ASD patients (aged 9.52 ± 5.13), and 107 healthy controls (aged 11.52 ± 2.82) had scanned with Resting-fMRI and analyzed surface-based amplitude of low-frequency fluctuations (ALFF). Results showed that both EOS and ASD had hypoactivity in the primary sensorimotor regions (bilateral primary and early visual cortex, left ventral visual stream, left primary auditory cortex) and hyperactivity in the high-order transmodal regions (bilateral SFL, bilateral DLPFC, right frontal eye fields), and bilateral thalamus. EOS had more severe abnormality than ASD. This study revealed shared functional abnormalities in the primary sensorimotor regions and the high-order transmodal regions in EOS and ASD, which provided neuroimaging evidence of common changes in EOS and ASD, and may help with better early recognition and precise treatment for EOS and ASD.

Transcriptional patterns of the cortical Morphometric Inverse Divergence in first-episode, treatment-naïve early-onset schizophrenia

Early-onset Schizophrenia (EOS) is a profoundly progressive psychiatric disorder characterized by both positive and negative symptoms, whose pathogenesis is influenced by genes, environment and brain structure development. In this study, the MIND (Morphometric Inverse Divergence) network was employed to explore the relationship between morphological similarity and specific transcriptional expression patterns in EOS patients. This study involved a cohort of 187 participants aged between 7 and 17 years, consisting of 97 EOS patients and 90 healthy controls (HC). Multiple morphological features were used to construct the MIND network for all participants. Furthermore, we explored the associations between MIND network and brain-wide gene expression in EOS patients through partial least squares (PLS) regression, shared genetic predispositions with other psychiatric disorders, functional enrichment of PLS weighted genes, as well as transcriptional signature assessment of cell types, cortical layers, and developmental stages. The MIND showed similarity differences in the orbitofrontal cortex, pericalcarine cortex, lingual gyrus, and multiple networks in EOS patients compared to HC. Moreover, our exploration revealed a significant overlap of PLS2 weighted genes linking to EOS-related MIND differences and the dysregulated genes reported in other psychiatric diseases. Interestingly, genes correlated with MIND changes (PLS2-) exhibited a significant enrichment not only in metabolism-related pathways, but also in specific astrocytes, cortical layers (specifically layer I and III), and posterior developmental stages (late infancy to young adulthood stages). However, PLS2+ genes were primarily enriched in synapses signaling-related pathways and early developmental stages (from early-mid fetal to neonatal early infancy) but not in special cell types or layers. These findings provide a novel perspective on the intricate relationship between macroscopic morphometric structural abnormalities and microscopic transcriptional patterns during the onset and progression of EOS.

Cortical structural changes of morphometric similarity network in early-onset schizophrenia correlate with specific transcriptional expression patterns

BackgroundThis study aimed to investigate the neuroanatomical subtypes among early-onset schizophrenia (EOS) patients by exploring the association between structural alterations and molecular mechanisms using a combined analysis of morphometric similarity network (MSN) changes and specific transcriptional expression patterns.MethodsWe recruited 206 subjects aged 7 to 17 years, including 100 EOS patients and 106 healthy controls (HC). Heterogeneity through discriminant analysis (HYDRA) was used to identify the EOS subtypes within the MSN strength. The differences in morphometric similarity between each EOS subtype and HC were compared. Furthermore, we examined the link between morphometric changes and brain-wide gene expression in different EOS subtypes using partial least squares regression (PLS) weight mapping, evaluated genetic commonalities with psychiatric disorders, identified functional enrichments of PLS-weighted genes, and assessed cellular transcriptional signatures.ResultsTwo distinct MSN-based EOS subtypes were identified, each exhibiting different abnormal MSN strength and cognitive functions compared to HC. The PLS1 score mapping demonstrated anterior–posterior gradients of gene expression in EOS1, whereas inverse distributions were observed in EOS2 cohorts. Genetic commonalities were identified in autistic disorder and adult schizophrenia with EOS1 and inflammatory bowel diseases with EOS2 cohorts. The EOS1 PLS1- genes (Z < -5) were significantly enriched in synaptic signaling-related functions, whereas EOS2 demonstrated enrichments in virtual infection-related pathways. Furthermore, the majority of observed associations with EOS1-specific MSN strength differences contributed to specific transcriptional changes in astrocytes and neurons.ConclusionsThe findings of this study provide a comprehensive analysis of neuroanatomical subtypes in EOS, shedding light on the intricate relationships between macrostructural and molecular aspects of the EOS disease.

Early-onset schizophrenia: studying the links between cognitive and clinical dimensions

ABSTRACT Background Early-onset schizophrenia (EOS), a rare and severe chronic psychiatric condition, is defined by an onset of schizophrenia symptoms before the age of 18. Core symptoms also include cognitive impairments. However, little is known about links between psychiatric symptoms of EOS and cognitive abilities. Objective To explore the clinical and neurocognitive profiles of EOS patients and their links. Method EOS patients have been phenotyped using standardised psychiatric assessments for DSM-5 diagnoses (K-SADS-PL) and for symptoms (PANSS and SANS), together with neurocognitive evaluations. Results The EOS sample (n = 27, 12.4 +/−3.2 years) presented hallucinations (83%), negative symptoms (70%) and delusion (59%). 81% of patients presented comorbidities such as anxiety disorders (33%), autism spectrum disorder (26%) and attention-deficit hyperactivity disorder (26%). Patients presented borderline intellectual deficiency (total IQ = 72.5 +/−4.7), with low performances in working memory subtest. We highlight a positive correlation between the IQ and intensity of positive symptoms (PANSS) and between the IQ and a first treatment being administered at an older age. We also highlight a negative correlation between the IQ and attention items of SANS. Conclusion Cognitive skills are correlated with symptom intensity in EOS patients. An older age of onset seems to be a protective factor for cognitive development.

Macroscale Thalamic Functional Organization Disturbances and Underlying Core Cytoarchitecture in Early-Onset Schizophrenia.

Schizophrenia is a polygenetic mental disorder with heterogeneous positive and negative symptom constellations, and is associated with abnormal cortical connectivity. The thalamus has a coordinative role in cortical function and is key to the development of the cerebral cortex. Conversely, altered functional organization of the thalamus might relate to overarching cortical disruptions in schizophrenia, anchored in development. Here, we contrasted resting-state fMRI in 86 antipsychotic-naive first-episode early-onset schizophrenia (EOS) patients and 91 typically developing controls to study whether macroscale thalamic organization is altered in EOS. Employing dimensional reduction techniques on thalamocortical functional connectome (FC), we derived lateral-medial and anterior-posterior thalamic functional axes. We observed increased segregation of macroscale thalamic functional organization in EOS patients, which was related to altered thalamocortical interactions both in unimodal and transmodal networks. Using an ex vivo approximation of core-matrix cell distribution, we found that core cells particularly underlie the macroscale abnormalities in EOS patients. Moreover, the disruptions were associated with schizophrenia-related gene expression maps. Behavioral and disorder decoding analyses indicated that the macroscale hierarchy disturbances might perturb both perceptual and abstract cognitive functions and contribute to negative syndromes in patients. These findings provide mechanistic evidence for disrupted thalamocortical system in schizophrenia, suggesting a unitary pathophysiological framework.

Altered Functional Connectivity Strength in Distinct Brain Networks of Children With Early-Onset Schizophrenia.

Schizophrenia is regarded as a brain network or connectome disorder that is associated with neurodevelopment. Children with early-onset schizophrenia (EOS) provide an opportunity to evaluate the neuropathology of schizophrenia at a very early stage without potential confounding factors. But dysfunction in brain networks of schizophrenia is inconsistent. To identify abnormal functional connectivity (FC) in EOS patients and relationships with clinical symptoms, we aimed to reveal neuroimaging phenotypes of EOS. Prospective, cross-sectional. Twenty-six female/22 male patients (age:14.3 ± 3.45 years) with first-episode EOS, 27 female/22 male age- and gender-matched healthy controls (HC) (age:14.1 ± 4.32). 3-T, resting-state (rs) gradient-echo echo-planar imaging and three-dimensional magnetization-prepared rapid gradient-echo imaging. Intelligence quotient (IQ) was measured by the Wechsler Intelligence Scale-Fourth edition for Children (WISC-IV). The clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). FC strength (FCS) from rs functional MRI (rsfMRI) was used to investigate functional integrity of global brain regions. In addition, associations between regionally altered FCS and clinical symptoms in EOS patients were examined. Two-sample t-test controlling for sample size, diagnostic method, brain volume algorithm, and age of the subjects, Bonferroni correction, Pearson's correlation analysis. A P-value <0.05 with a minimum cluster size of 50 voxels was considered statistically significant. Compared with HC, EOS patients had significantly lower total IQ scores (IQ:91.5 ± 16.1), increased FCS in the bilateral precuneus, left dorsolateral prefrontal cortex, left thalamus, and left parahippocampus (paraHIP), and decreased FCS in the right cerebellum posterior lobe and right superior temporal gyrus. The PANSS total score of EOS patients (PANSS total score:74.30 ± 7.23) was found to be positively correlated to FCS in the left paraHIP (r=0.45). Our study revealed that disrupted FC of brain hubs illustrate multiple abnormalities in brain networks in EOS patients. 1 TECHNICAL EFFICACY STAGE: 2.

Association of NKAPL rs1635 With Cognitive Function in Early-Onset Schizophrenia

BACKGROUND: Schizophrenia is a severe mental disorder with high heritability, and cognitive dysfunction is one of the core features. Growing evidence suggests the genetic risk of schizophrenia may contribute to cognitive impairments. The variant rs1635 (nucleotide sequence: c.455C>A; amino acid sequence: T152N) located on the (NFKB activating protein like) NKAPL gene confers risk for schizophrenia and might play a role in the neurodevelopmental process, which is particularly relevant to cognitive function. However, the relationship between rs1635 and cognitive function remains unclear. METHODS: A total of 130 patients with early-onset schizophrenia (EOS) and 300 patients with adult-onset schizophrenia (AOS) of Han Chinese were recruited and underwent neurocognitive tests by using the MATRICS Consensus Cognitive Battery (MCCB). The NKAPL rs1635 was genotyped by using DNA sequencing. The peripheral blood NKAPL mRNA expression level was examined in 152T or 152N carriers (n = 20) in EOS patients, by using the qRT-PCR. The phosphorylation level of NAKPL T152N polymorphism was detected by cell experiments. In utero electroporation of mouse embryos was examined to explore the effect of Nkapl on neuronal migration. RESULTS: Compared with rs1635 AA and AC carriers, CC (the CC genotype encodes the protein NKAPL-152T) carriers of EOS patients performed better in cognitive domain of speed of processing (t = 2.644, p = 0.009), trail making test (t = 2.221, p = 0.028) and category fluency (t = 2.578, p = 0.011). However, patients with AOS exhibited no significant differences in seven domains among the three genotype groups. There were no significant differences in cognitive performance between EOS and AOS. In EOS patients, NKAPL mRNA level in NKAPL-152N carriers is significantly lower than that of NKAPL-152T carriers. The phosphorylation level of NKAPL-152N is significantly decreased compared to NKAPL-152T. In utero electroporation showed that Nkapl deletion impairs the embryonic radial migration process. CONCLUSION: The present study found that NKAPL rs1635 was associated with cognitive impairments and peripheral blood mRNA expression level in EOS patients. The NKAPL full-length protein is required for embryonic cortical neuronal migration. The phosphorylation level of NKAPL-152N is significantly decreased. The NKAPL T152N may affect the NAKPL mRNA expression level and embryonic cortical neuronal migration by regulating the NAKPL protein phosphorylation. These data suggest that NKAPL rs1635 affects cognitive function by regulating early brain development in early-onset schizophrenia.

Thalamic Shape Abnormalities Differentially Relate to Cognitive Performance in Early-Onset and Adult-Onset Schizophrenia

Early-onset schizophrenia (EOS) shares many biological and clinical features with adult-onset schizophrenia (AOS), but may represent a unique subgroup with greater susceptibility for disease onset and worsened symptomatology and progression, which could potentially derive from exaggerated neurodevelopmental abnormalities. Neurobiological explanations of schizophrenia have emphasized the involvement of deep-brain structures, particularly alterations of the thalamus, which have been linked to core features of the disorder. The aim of this study was to compare thalamic shape abnormalities between EOS and AOS subjects and determine whether unique behavioral profiles related to these differences. It was hypothesized abnormal thalamic shape would be observed in anterior, mediodorsal and pulvinar regions in both schizophrenia groups relative to control subjects, but exacerbated in EOS. Magnetic resonance T1-weighted images were collected from adult individuals with EOS (n = 28), AOS (n = 33), and healthy control subjects (n = 60), as well as collection of clinical and cognitive measures. Large deformation high-dimensional brain mapping was used to obtain three-dimensional surfaces of the thalamus. General linear models were used to compare groups on surface shape features, and Pearson correlations were used to examine relationships between thalamic shape and behavioral measures. Results revealed both EOS and AOS groups demonstrated significant abnormal shape of anterior, lateral and pulvinar thalamic regions relative to CON (all p < 0.007). Relative to AOS, EOS exhibited exacerbated abnormalities in posterior lateral, mediodorsal and lateral geniculate thalamic regions (p = 0.003). Thalamic abnormalities related to worse episodic memory in EOS (p = 0.03) and worse working memory (p = 0.047) and executive functioning (p = 0003) in AOS. Overall, findings suggest thalamic abnormalities are a prominent feature in both early- and late-onset schizophrenia, but exaggerated in EOS and have different brain-behavior profiles for each. The persistence of these abnormalities in adult EOS patients suggests they may represent markers of disrupted neurodevelopment that uniquely relate to the clinical and cognitive aspects of the illness.

Systematically mapping gray matter abnormal patterns in drug-naïve first-episode schizophrenia from childhood to adolescence.

Schizophrenia originates early in neurodevelopment, underscoring the need to elaborate on anomalies in the still maturing brain of early-onset schizophrenia (EOS). Gray matter (GM) volumes were evaluated in 94 antipsychotic-naïve first-episode EOS patients and 100 typically developing (TD) controls. The anatomical profiles of changing GM deficits in EOS were detected using 2-way analyses of variance with diagnosis and age as factors, and its timing was further charted using stage-specific group comparisons. Interregional relationships of GM alterations were established using structural covariance network analyses. Antagonistic interaction results suggested dynamic GM abnormalities of the left fusiform gyrus, inferior occipital gyrus, and lingual gyrus in EOS. These regions comprise a dominating part of the ventral stream, a ventral occipitotemporal (vOT) network engaged in early social information processing. GM abnormalities were mainly located in the vOT regions in childhood-onset patients, whereas in the rostral prefrontal cortex (rPFC) in adolescent-onset patients. Moreover, compared with TD controls, patients' GM synchronization with the ventral stream was disrupted in widespread high-order social perception regions including the rPFC and salience network. The current findings reveal age-related anatomical abnormalities of the social perception system in pediatric patients with schizophrenia.

Abnormal functional connectivity of the striatum in first-episode drug-naive early-onset Schizophrenia.

Abnormal brain network connectivity is strongly implicated in the pathogenesis of schizophrenia. The striatum, consisting of the caudate and putamen, is the major treatment target for antipsychotics, the primary treatments for schizophrenia; however, there are few studies on the functional connectivity (FC) of striatum in drug‐naive early‐onset schizophrenia (EOS) patients. We examined the FC values of the caudate nucleus and putamen with whole brain by resting‐state functional magnetic resonance imaging (RS‐fMRI) and the associations with indices of clinical severity. Patients demonstrated abnormal FC between subregions of the putamen and both the visual network (left middle occipital gyrus) and default mode network (bilateral anterior cingulate, left superior frontal, and right middle frontal gyri). Furthermore, FC between dorsorostral putamen and left superior frontal gyrus correlated with both positive symptom subscore and total score on the Positive and Negative Syndrome Scale (PANSS). These findings demonstrate abnormal FC between the striatum and other brain areas even in the early stages of schizophrenia, supporting neurodevelopmental disruption in disease etiology and expression.

Altered topographical organization of grey matter structural network in early-onset schizophrenia

Schizophrenia is characterized by both disrupted neurodevelopmental processes and abnormal brain connectivity. However, few studies have examined the atypical features of brain network topography associated with schizophrenia during childhood and adolescence. We used graph theory to compare the grey matter structural networks of individuals (aged 10-15 years) with early-onset schizophrenia (EOS) (n = 25) and a typically-developing (TD) comparison group (n = 31). Compared with the TD group, EOS patients showed significantly increased clustering and local efficiency across a range of network densities (0.3 – 0.4). The network of EOS patients also had more modules (6 modules in EOS vs. 3 modules in controls), indicating a more segregated network at the cost of functional integration. Although our results were preliminary and failed to survive corrections for multiple comparisons, EOS patients might be characterized by altered nodal centrality in several higher-order associative regions including the prefrontal cortex, the hippocampus and the cerebellum. The EOS structural network also lacked the typical left-hemispheric-dominant hub distribution compared with the TD group. These findings suggest that brain structural network was not only globally but also regionally altered in EOS patients.

Neurodevelopment regulators miR-137 and miR-34 family as biomarkers for early and adult onset schizophrenia

Early-onset schizophrenia (EOS) may have stronger familial aggregation and a more severe outcome than adult-onset schizophrenia (AOS). MicroRNA (miRNA) takes on dual roles as a genetic and epigenetic modulator, which may mediate the influence of genetic risk. Neurological soft signs (NSS) are neurological abnormalities that may be intermediate phenotypes or endophenotypes for schizophrenia. Our previous study found poorer performance on NSS tests from patients with EOS and their unaffected first-degree relatives. Thus, we aimed to identify a set of aberrant neurodevelopmental-related miRNAs that could serve as potential biomarkers for EOS or schizophrenia with NSS. This study included 215 schizophrenia patients (104 EOS and 111 AOS), 72 unaffected first-degree relatives, 31 patients with bipolar disorder, and 100 healthy controls. Differential expression analysis revealed that miR-137, miR-34b, and miR-34c were significantly up-regulated in patients with schizophrenia and their unaffected first-degree relatives compared to healthy controls. Receiver operating characteristic (ROC) analysis showed that the miR-137 expression signature could be used to discriminate between patients with EOS and healthy controls (AUC = 0.911). Additionally, miR-34b had the highest ability to discriminate between EOS and AOS (AUC = 0.810), which may indicate different aetiological pathways to disease onset. Moreover, miR-137 dysregulation was correlated with almost all NSS subscales (i.e., sensory integration, motor sequencing, etc.) and, when EOS patients with NSS, miR-137 expression discriminated these patients from healthy controls to a greater extent (AUC = 0.957). These findings support the potential for neurodevelopmental-related miRNAs to be used as indicators of vulnerability to EOS.

Differences in patterns of metabolic abnormality and metabolic syndrome between early-onset and adult-onset first-episode drug-naive schizophrenia patients

Although metabolic abnormalities and metabolic syndrome (MetS) often occur in schizophrenia, few studies have investigated them in early-onset schizophrenia (EOS) patients. To our knowledge, this was the first to compare clinical correlates of metabolic abnormalities between first-episode drug-naïve (FEDN) EOS and adult-onset schizophrenia (AOS) patients. A total of 489 Chinese FEDN schizophrenia patients (116 EOS and 373 AOS) and 451 healthy controls were recruited in this cross-sectional study. Blood pressure, waist circumference (WC), Body mass index (BMI), total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), glucose, hemoglobin A1c (HbA1c), insulin and insulin resistance were measured. The Positive and Negative Syndrome Scale (PANSS) was applied to evaluate the clinical symptoms of schizophrenia patients, and higher scores on PANSS indicate increased severity. EOS patients had lower rates of: MetS, elevated WC, hypertriglyceridemia, hypercholesterolemia, and hyper-LDLC than EOS patients (all p < 0.05). In EOS patients, WC was positively associated with PANSS general psychopathology score (p = 0.04). In AOS patients, WC (p = 0.01; p = 0.02) and glucose (p < 0.001; p < 0.001) were positively associated with PANSS general psychopathology and total score. HOMA-IR was positively associated with PANSS total score (p = 0.04). Systolic BP, triglycerides and HDLC were main contributors to MetS in AOS (all p < 0.05), but not in EOS. BMI was a risk factor of MetS in EOS, while BMI and HOMA-IR were risk factors of MetS in AOS (all p < 0.05). Our results indicate differences in metabolic abnormalities patterns, risk factors and their association with clinical characteristics between Chinese EOS and AOS patients. Data Availability StatementThe datasets that support the findings of this study are not publically available due to ongoing analyses for further publications, but are available from the corresponding author X.Z. upon reasonable request.

Performance on verbal fluency in late-onset schizophrenia is more preserved than in early-onset schizophrenia

IntroductionAccording to the literature, cognition may be more preserved in late-onset schizophrenia (LOS) compared to early-onset schizophrenia (EOS), but data are limited.ObjectivesTo compare performance on cognitive tests in LOS and EOS.MethodsLOS patients (n=14, mean age 58.1±8.2, 13 females, illness duration 1.07±1.5 years) and age-comparable controls (n=17, mean age 55.3±7.8, 12 females), EOS patients (n=25, mean age 20.7±3.9, 25 males, illness duration 0.75±0.62 years) and age-comparable controls (n=15, mean age 22.9±2.3, 15 males) underwent the Brief Assessment of Cognition in Schizophrenia (BACS) comprised of six subtests: Verbal Memory, Digit Sequencing, Verbal Fluency, Token Motor Task, Symbol Coding, and Tower of London. The Mann-Whitney U test with Bonferroni correction for multiple comparisons was applied (p &lt;.05/8, i.e. p &lt;.006).ResultsCompared to LOS, EOS patients had lower score on Verbal Fluency (VF): U=78, p=.004; mean T-scores are 43.5±9.5 and 33.6±12.6 for LOS and EOS, respectively. Additionally, we compared VF performance in each clinical group with age-comparable controls and revealed significantly lower performance in both LOS (U=37.5, p=.001) and EOS (U=56.5, p=.000).ConclusionsPerformance on VF is deteriorated in clinical groups, but may be more intact in LOS compared to EOS. This result is of particular interest because low performance on VF is considered as a cognitive endophenotype of schizophrenia. Performance on VF requires preserved executive functions, language, and processing speed. Our results are in line with the idea that LOS and EOS may be different subtypes of schizophrenia. Limitation of this study is that the clinical groups are not sex-matched.

CNVs and Chromosomal Aneuploidy in Patients With Early-Onset Schizophrenia and Bipolar Disorder: Genotype-Phenotype Associations.

Introduction: Early-onset schizophrenia (EOS) and bipolar disorder (EOB) start before the age of 18 years and have a more severe clinical course, a worse prognosis, and a greater genetic loading compared to the late-onset forms. Copy number variations (CNVs) are an important genetic factor in the etiology of psychiatric disorders. Therefore, this study aimed to analyze CNVs in patients with EOS and EOB and to establish genotype-phenotype relationships for contiguous gene syndromes or genes affected by identified CNVs.Methods: Molecular karyotyping was performed in 45 patients, 38 with EOS and seven with EOB hospitalized between 2010 and 2017. The exclusion criteria were medical or neurological disorders or IQ under 70. Detected CNVs were analyzed according to the standards and guidelines of the American College of Medical Genetics.Result: Molecular karyotyping showed CNVs in four patients with EOS (encompassing the PAK2, ADAMTS3, and ADAMTSL1 genes, and the 16p11.2 microduplication syndrome) and in two patients with EOB (encompassing the ARHGAP11B and PRODH genes). In one patient with EOB, a chromosomal aneuploidy 47, XYY was found.Discussion: Our study is the first study of CNVs in EOS and EOB patients in Slovenia. Our findings support the association of the PAK2, ARHGAP11B, and PRODH genes with schizophrenia and/or bipolar disorder. To our knowledge, this is also the first report of a multiplication of the ADAMTSL1 gene and the smallest deletion of the PAK2 gene in a patient with EOS, and one of the few reports of the 47, XYY karyotype in a patient with EOB.

Dynamic Alterations of Amplitude of Low-Frequency Fluctuations in Patients With Drug-Naïve First-Episode Early Onset Schizophrenia.

Abnormalities in static neural activity have been widely reported in early onset schizophrenia (EOS). However, dynamic brain activity alterations over time in EOS are unclear. Here, we investigated whether temporal dynamic changes in spontaneous neural activity are influenced by EOS. A total of 78 drug-naïve first-episode patients with EOS and 90 healthy controls (HCs) were enrolled in this study. Dynamic amplitude of low-frequency fluctuations (dALFF) was performed to examine the abnormal time-varying local neural activity in EOS. Furthermore, we investigated the relationships between abnormalities in dALFF variability and clinical characteristics in EOS patients. Compared to HCs, EOS patients showed significantly decreased dALFF variability in the bilateral precuneus, right superior marginal gyrus, right post-central gyrus and increased dALFF in the right middle temporal gyrus (MTG). Moreover, increased dALFF variability in MTG was negatively associated with negative symptoms in EOS. Our findings reveal increased dynamic local neural activity in higher order networks of the cortex, suggesting that enhanced spontaneous brain activity may be a predominant neural marker for brain maturation. In addition, decreased dALFF variability in the default mode network (DMN) and limbic system may reflect unusually dynamic neural activity. This dysfunctional brain activity could distinguish between patients and HCs and deepen our understanding of the pathophysiological mechanisms of EOS.

Self-reported sensory responsiveness patterns in typically-developing and early-onset schizophrenia adolescents: Its relationship with schizotypal and autistic traits

Altered behavioural responses to sensory stimuli, including both hypo- and hyper-reactivity, have been found in individuals with schizophrenia. However, how specific sensory responsiveness patterns are associated with symptomatology of schizophrenia remains largely unknown. The present study aimed to examine sensory responsiveness in typically-developing (TD) adolescents (n = 98) and adolescents with early-onset schizophrenia (EOS) (n = 29) and investigate the relationship between schizotypal traits and sensory responsiveness patterns. All participants completed the Adult/Adolescent Sensory Profile (AASP), the Schizotypal Personality Questionnaire (SPQ) and the Autism Spectrum Quotient (AQ). Results showed that higher levels of hypersensitivity and hyposensitivity coexisted in EOS patients and were correlated with positive and negative symptoms of schizophrenia. Atypical sensory experiences except for sensory seeking were found to be positively correlated with higher levels of schizotypal traits regardless of diagnostic status. Moreover, the strength and pattern of such correlations were comparable in both EOS and TD groups. This study also provided evidence that higher levels of autistic traits would intensify the positive correlation between schizotypal traits and sensory responsiveness abnormalities, suggesting an additive effect of co-occurring schizotypal and autistic traits on atypical sensory experiences. These findings extend previous research by depicting sensory responsiveness patterns in younger populations with schizophrenia, and may have implications for future development of sensory-related interventions in clinical settings.

The Effects of Combined Social Cognition and Interaction Training and Paliperidone on Early-Onset Schizophrenia.

BackgroundThe limitations associated with antipsychotics in early-onset schizophrenia patients have stimulated more interest in psychological interventions in this population. Nevertheless, the isolated psychosocial interventions are unrealistic in a treatment success covering the complex array of symptoms, and the psychosocial interventions could be an adjunct treatment to the pharmacological treatment. It is necessary to find the benefits of psychological interventions with limited and targeted use of antipsychotics. Social cognition and interaction training (SCIT) was a program for social cognitive rehabilitation in adult schizophrenia. However, it is unclear how generalizable this is to early-onset patients.MethodsThe current study tested this hypothesis that combined SCIT and paliperidone was superior to paliperidone alone in treating early-onset schizophrenia patients on cognitive, functional, and symptom outcomes. Two hundred eight inpatients with schizophrenia aged 13 to 17 years old participated in a 24-week work intervention program. Patients completed a battery of measures administered at a pre-SCIT intervention baseline, 4, 8, 12, and 24 weeks post-SCIT, respectively.ResultsSCIT had significant added benefits above paliperidone for the speed of processing, attention/vigilance, and social cognition of the Chinese version of MATRICS consensus cognitive battery (MCCB) domains (p<0.05). The following logistic regression analysis on the exploration of the influential factors also confirmed the effects of SCIT. However, combined SCIT and paliperidone intervention had a null impact on social functioning and symptomatology.ConclusionsThe present study provides the first evidence that combined SCIT and paliperidone intervention has the potential to improve cognitive functions for the early-onset schizophrenia patients. The findings in the current study are suggestive of the extreme importance of SCIT as an adjunctive treatment in early-onset schizophrenia patients.

Variants and expression changes in PPAR-encoding genes display no significant association with schizophrenia.

A few studies suggested the contribution of PPARs to the etiology of schizophrenia (SCZ). However, it is still not clear whether variants in PPAR-encoding genes have a direct association with SCZ. The potential linkage between SCZ and the variants within PPAR encoding genes (PPARA, PPARD, and PPARG) was tested in a large cohort genome-wide association study (GWAS). Then, a mega-analysis was conducted using 14 gene expression profiling experiments in various human brain regions. Finally, the expression levels of the three PPAR-encoding genes were quantified in early-onset SCZ patients. Only one PPARG polymorphisms, rs62242085, presented a minor frequency deviation in the SCZ cohort (P-value = 0.035). None of the PPAR-encoding genes presented significant expression change within the brain regions profiled in 14 datasets acquired from different populations (P-value > 0.14) or in the whole blood of early-onset overall SCZ patients (P-value > 0.22). However, compared with healthy female controls, female early-onset SCZ patients presented a moderate but significant decrease in the expression level of PPARD (LFC = −0.55; P-value = 0.02) and a strong, but non-significant decrease in expression of PPARG (LFC = −1.30; P-value = 0.13). Our results do not support a significant association between variants in PPAR-encoding genes and SCZ, but suggest a necessity to explore the role of PPARD and PPARG in early SCZ phenotypes, specifically in females.

Independent living skills and cognition in early-onset and late-onset of schizophrenia patients: a pilot study

Aim. To evaluate cognitive functions and independent living skills in patients with late-onset schizophrenia (LOS) compared to patients with early-onset schizophrenia (EOS).&#x0D; Methods. The study included two clinical groups: 8 EOS patients (M=51.37.2; 7 males) and 8 LOS patients (M=67.89.9; 8 females), with comparable illness duration (22.69.1 and 19.911.9 respectively). Cognitive functions were assessed through the Brief Assessment of Cognition in Schizophrenia (BACS). The Autonomy Assessment Scale (AS) was used to measure independent living skills. The MannWhitney U-test was applied to determine differences between groups.&#x0D; Results. LOS group performed significantly better on Digit Sequencing Task, Verbal Fluency and Tower Test of the BACS. Composite score on AS was also significantly better in LOS group along with better scores on AS`s subscales assessing primarily social skills.&#x0D; Conclusion. LOS patients have milder cognitive dysfunction along with better independent living and social skills compared to AOS patients.