Onset Of Schizophrenia Research Articles

The Hypothalamic-Pituitary-Gonadal Axis in Men with Schizophrenia.

Schizophrenia is a severe mental disorder with a chronic, progressive course. The etiology of this condition is linked to the interactions of multiple genes and environmental factors. The earlier age of onset of schizophrenia, the higher frequency of negative symptoms in the clinical presentation, and the poorer response to antipsychotic treatment in men compared to women suggests the involvement of sex hormones in these processes. This article aims to draw attention to the possible relationship between testosterone and some clinical features in male schizophrenic patients and discuss the complex nature of these phenomena based on data from the literature. PubMed, Web of Science, and Google Scholar databases were searched to select the papers without limiting the time of the publications. Hormone levels in the body are regulated by many organs and systems, and take place through the neuroendocrine, hormonal, neural, and metabolic pathways. Sex hormones play an important role in the development and function of the organism. Besides their impact on secondary sex characteristics, they influence brain development and function, mood, and cognition. In men with schizophrenia, altered testosterone levels were noted. In many cases, evidence from available single studies gave contradictory results. However, it seems that the testosterone level in men affected by schizophrenia may differ depending on the phase of the disease, types of clinical symptoms, and administered therapy. The etiology of testosterone level disturbances may be very complex. Besides the impact of the illness (schizophrenia), stress, and antipsychotic drug-induced hyperprolactinemia, testosterone levels may be influenced by, i.a., obesity, substances of abuse (e.g., ethanol), or liver damage.

Changes in neurofilament light chain protein (NEFL) in children and adolescents with Schizophrenia and Bipolar Disorder: Early period neurodegeneration

AimNeurofilament light chain protein (NEFL), is defined as a structural protein which exists particularly in axones of neurons and is released to the cerum in consequence of neuroaxonal damage. The aim of this study is to investigate the peripheral cerumNEFLlevels of children and adolescents with early onset schizophrenia and bipolar disorder. MethodIn this study, we evaluated serum levels of NEFL in children and adolescents (13–17 years) with schizophrenia, bipolar disorder and healthy control group. The study is conducted with 35 schizophrenia, 38 bipolar disorder manic episode patients and 40 healthy controls. ResultsThe median age of the patient and control groups was 16 (IQR- Interquartile Range: 2). There was no statistical difference in median age (p = 0.52) and gender distribution(p = 0.53) between groups. NEFL levels of the patients with schizophrenia were significantly higher than the controls. NEFL levels of the patients with bipolar disorder were significantly higher than the controls. Serum levels of NEFL of the schizophrenia were higher than the bipolar disorder; however, the difference was not statistically significant. ConclusionIn conclusion, serum NEFL level, as a confidential marker of neural damage, is increased in the children and adolescents with bipolar disorder and schizophrenia. This result may indicatea degenerative period in neurons of children and adolescents with schizophrenia or bipolar disorder and may play a role in the pathophisiology of these disorders. This result shows that there is neuronal damage in both diseases, but neuronal damage may be more in schizophrenia.

Practitioner Review: Psychosis in children and adolescents.

Psychotic symptoms, including hallucinations, delusions, and disorganized thinking and behaviors, are the hallmarks of schizophrenia; but may also present in the context of other psychiatric and medical conditions. Many children and adolescents describe psychotic-like experiences, which can be associated with other types of psychopathology and past experiences (e.g., trauma, substance use, and suicidality). However, most youth reporting such experiences do not have, nor will ever develop, schizophrenia or another psychotic disorder. Accurate assessment is critical because these different presentations have different diagnostic and treatment implications. For this review, we focus primarily on the diagnosis and treatment of early onset schizophrenia. In addition, we review the development of community-based first-episode psychosis programming, and the importance of early intervention and coordinated care.

A Sex-Dependent Association Between Doxycycline Use and Development of Schizophrenia.

Doxycycline and minocycline are brain-penetrant tetracycline antibiotics, which recently gained interest because of their immunomodulatory and neuroprotective properties. Observational studies have suggested that exposure to these drugs may decrease the risk to develop schizophrenia, but results are inconsistent. The aim of this study was to investigate the potential association between doxycycline use and later onset of schizophrenia. We used data from 1 647 298 individuals born between 1980 and 2006 available through Danish population registers. 79 078 of those individuals were exposed to doxycycline, defined as redemption of at least 1 prescription. Survival analysis models stratified for sex with time-varying covariates were constructed to assess incidence rate ratios (IRRs) for schizophrenia (ICD-10 code F20.xx), with adjustment for age, calendar year, parental psychiatric status, and educational level. In the non-stratified analysis, there was no association between doxycycline exposure and schizophrenia risk. However, men who redeemed doxycycline had a significantly lower incidence rate for schizophrenia onset compared to men that did not (IRR 0.70; 95% CI 0.57-0.86). By contrast, women had a significantly higher incidence rate for schizophrenia onset, compared to women that did not redeem doxycycline prescriptions (IRR 1.23; 95% CI 1.08, 1.40). The effects were not found for other tetracycline antibiotics (IRR 1.00; 95% CI 0.91, 1.09). Doxycycline exposure is associated with a sex-dependent effect on schizophrenia risk. The next steps are replication of the results in independent well-characterized population cohorts, as well as preclinical studies to investigate sex-specific effects of doxycycline on biological mechanisms implicated in schizophrenia.

UNTIL IT BURSTS OR ALL OF US BURST. A SCHIZOTYPICAL CASE.

IntroductionSchizotypal disorder is conceptualized as a stable personality pathology (Cluster A) and as a latent manifestation of schizophrenia. It can be understood as an attenuated form of psychosis or high-risk mental state, which may precede the onset of schizophrenia or represent a more stable form of psychopathology that doesn’t necessarily progress to psychosis.ObjectivesTo exemplify the continuum of psychosisMethodsReview of scientific literature based on a relevant clinical case.Results39-year-old male living with his parents. He started studying philosophy. He is a regular cannabis user and has an aunt with schizophrenia. He’s admitted to psychiatry for behavioral disturbance in public. He refers to having been hearing a beeping noise in his street for months, what he interprets as a possible way of being watched due to his past ideology. Without specifying who and why, he sometimes shouts “until it bursts” to stop the noise and he thinks that his neighbours alerted the police about his behavior. During the interview he alludes to Milgram’s experiment, saying that throughout history there have been crimes against humanity and those who pointed them out were labeled “crazy”. His father refers that he has always been “strange” and with certain extravagant revolutionary ideas and thoughts. He doesn’t maintain social relationships and dedicates himself to reading and writing.ConclusionsIt’s important to understand psychosis as a continuum to advance the understanding of etiology, pathophysiology and resilience of psychotic disorders and to develop strategies for prevention and early interventionDisclosure of InterestNone Declared

Shortened PANSS Developed for Children and Adolescents

Back to table of contents Previous article Next article Clinical & ResearchFull AccessShortened PANSS Developed for Children and AdolescentsNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:24 Feb 2023https://doi.org/10.1176/appi.pn.2023.03.3.15AbstractThe 10-item pediatric Positive and Negative Syndrome Scale (PANSS) is almost as accurate as the 30-item PANSS and can be administered in a fraction of the time.A 10-item version of the Positive and Negative Syndrome Scale (PANSS) can reliably assess psychosis symptoms in children and teens, according to a report in the Journal of the American Academy of Child and Adolescent Psychiatry.With the traditional PANSS, which was developed for adults, an interviewer evaluates the patient for 30 symptoms, rating each symptom on a scale of 1 (absent) to 7 (extreme). These symptoms fall under five domains:Positive symptoms (for example, hallucinations and delusions)Negative symptoms (for example, social withdrawal) Excited symptoms (for example, hostility) Cognitive symptoms (for example, poor attention) Affective symptoms (for example, depression and anxiety)An adult evaluation using the PANSS can take about an hour to administer, which places a burden on both the patient and interviewer, noted Robert L. Findling, M.D., M.B.A., professor and chair of psychiatry at Virginia Commonwealth University School of Medicine. When using the scale to evaluate children and adolescents, the interviewer has discussions with both the youth and their parents, which can add more time.Robert L. Findling, M.D., M.B.A., notes that the inclusion of hallucinations—considered one of the hallmark symptoms of schizophrenia—in the pediatric PANSS did not appear to improve the accuracy of the evaluation.Other researchers have tested shorter versions of PANSS that attempt to maintain the precision of the 30-item scale while reducing the time it takes to administer the evaluation. These include a 19-item scale and two brief 6-item versions. However, as with the 30-item PANSS, these shortened versions of the scale were developed using adult patient data, Findling explained. “It’s important that we develop and test a pediatric-specific scale, because while the diagnostic criteria for psychotic disorders are the same for youth and adults, the symptom presentations do differ,” he said.To create a pediatric PANSS, Findling and colleagues used baseline data from an eight-week clinical trial that compared the safety and efficacy of the antipsychotics olanzapine and risperidone with the older antipsychotic molindone in youth. For that study, which was published in The American Journal of Psychiatry, 116 participants aged 8 to 19 years with early onset schizophrenia or schizoaffective disorder were assessed with the 30-item PANSS along with other behavioral assessments every week for eight weeks.Findling and colleagues evaluated different combinations of symptoms using this patient data set to find a combination that maximized both fidelity to the full-length PANSS (for both mild or severe symptom profiles) and time savings. The researchers sought to include symptoms from the five domains of the 30-item PANSS when creating the pediatric PANSS but did not pick any specific items ahead of time. “We wanted to let the data speak for itself,” he said.The pediatric PANSS included 10 symptoms evenly spread across the five domains. They were as follows:Delusions and unusual thoughtsEmotional withdrawal and apathyHostility and poor impulse control Inattention and disorganized thinking Anxiety and feelings of guiltThe 10-item PANSS took significantly less time to administer and matched the 30-item PANSS in the AJP data set 88% of the time. It was also accurate for both mild and severe symptom scores and could reliably identify symptom changes over time.“Overall, I think this shortened version performs pretty well, as it preserves the PANSS’s broad coverage of symptoms in a format that is briefer and easier to interpret,” Findling said. “We need to validate this scale in more diverse populations.”This study was supported by funding from Signant Health. The trial that provided the data was supported by the National Institute of Mental Health. ■Resources“An Optimized Version of the Positive and Negative Symptoms Scale (PANSS) for Pediatric Trials” ISSUES NewArchived

Association of rs11644461 GRIN2A with clinical phenotype of schizophrenia

IntroductionThe glutamatergic system plays an important role in the neurobiology of schizophrenia. A lot of number of variants in the GRIN genes have been found in patients with various neuropsychiatric disorders (Myers et al. F1000Res 2019; 8(F1000 Faculty Rev) 1940). GluN2A, encoded by the GRIN2A gene, is the most abundant of the GluN2 NMDA receptor subunits in the mammalian CNS. Clinical symptoms of schizophrenia vary among individuals. The GRIN2A gene has previously been shown to be associated with early onset schizophrenia (Poltavskaya et al. Life (Basel) 2021; 11(10) 997).ObjectivesThe aim of the study was to identify associations of the GRIN2A gene rs11644461 polymorphism with features of the course of schizophrenia.MethodsThis study was carried out in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki 1975). 805 patients with schizophrenia (ICD-10: F20) were included. Clinical examination and diagnostic evaluation were performed using the Positive and Negative Syndrome Scale (PANSS). From the general group of patients, 2 subgroups were distinguished according to the PANSS survey: 391 patients with leading negative symptoms and 414 patients with leading positive symptoms. Also 2 subgroups were distinguished from the general group of patients: 398 patients with a continuous course of schizophrenia and 257 patients with episodic schizophrenia. Genotyping was performed by real-time PCR.ResultsAn association of the C rs11644461 GRIN2A allele with the continuous course of schizophrenia was revealed (p<0,047). The rs11644461 polymorphism was not associated with the leading symptoms of the disease (positive or negative). At the same time, the values of the total score on the PANSS scale differed statistically significantly in carriers of different genotypes for this polymorphism. The sum of PANSS scores (Me [Q25 – Q75]) in carriers of the TC rs11644461 genotype was statistically significantly higher (106 [92–113]) than in carriers of the CC genotype (101 [87–108]) (p=0.006).ConclusionsAccording to the results obtained, carriers of the TC rs11644461 GRIN2A genotype have a higher severity of schizophrenia symptoms according to the PANSS scale than carriers of the CC genotype. Also in the present study, it was shown that the C allele rs11644461 GRIN2A is associated with the continuous course of schizophrenia, which indicates the contribution of this locus to the formation of the course of the disease.Disclosure of InterestE. Poltavskaya Grant / Research support from: Russian Science Foundation # 21-15-00212, O. Fedorenko Grant / Research support from: Russian Science Foundation # 21-15-00212, E. Kornetova Grant / Research support from: Russian Science Foundation # 21-15-00212, I. Pozhidaev Grant / Research support from: Russian Science Foundation # 21-15-00212, D. Paderina Grant / Research support from: Russian Science Foundation # 21-15-00212

Effectiveness of Switching to Long-acting Injectable Aripiprazole in Patients with Recent-onset and Chronic Schizophrenia.

This study investigated the effectiveness of switching to once-monthly long-acting injectable (LAI) aripiprazole from other second-generation antipsychotics including LAI paliperidone palmitate in both recent-onset and chronic schizophrenia patients. This was a 24-week prospective, open-label, flexible dose-switching study in patients with schizophrenia. Scores on the Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance (PSP) scale, Clinical Global Impression (CGI), Subjective Well-being Under Neuroleptics-Short Form (SWN-K), and a computerized emotional recognition test (ERT) were evaluated. Subjects were divided into two groups (recent onset and chronic) based on 5 years' duration of the illness. Among the 82 patients participating, 67 (81.7%) completed the 24-week study. The discontinuation rate after switching to LAI aripiprazole did not differ according to clinical characteristics including type of previous antipsychotics. Scores on the PANSS, PSP, SWN-K, CGI, and ERT were significantly improved after a switch to LAI aripiprazole without exacerbation of metabolic parameters and bodyweight. The improvements in the PANSS, PSP, and CGI scores were significantly greater in patients with recent-onset than in those with chronic schizophrenia; the improvement in metabolic parameters was significantly greater in the latter group. High rates of successful switching to LAI aripiprazole from other antipsychotics suggest its good tolerability and effectiveness. Improvements in psychopathology and social functioning were more evident in patients with recent- onset schizophrenia, and improvements in metabolic abnormalities were more prominent in patients with chronic schizophrenia.

Association between Arachidonic Acid and the Risk of Schizophrenia: A Cross-National Study and Mendelian Randomization Analysis.

Polyunsaturated fatty acids (PUFAs), especially long-chain PUFAs (LCPUFAs), are crucial for both the structural and functional integrity of cells. PUFAs have been reported to be insufficient in schizophrenia, and the resulting cell membrane impairments have been hypothesized as an etiological mechanism. However, the impact of PUFA deficiencies on the onset of schizophrenia remain uncertain. We investigated the associations between PUFAs consumption and schizophrenia incidence rates through correlational analyses and conducted Mendelian randomization analyses to reveal the causal effects. Using dietary PUFA consumption and national schizophrenia incidence rates in 24 countries, we found that incidence rates of schizophrenia were inversely correlated with arachidonic acid (AA) and ω-6 LCPUFA consumption (rAA = -0.577, p < 0.01; rω-6 LCPUFA = -0.626, p < 0.001). Moreover, Mendelian randomization analyses revealed that genetically predicted AA and gamma-linolenic acid (GLA) were protective factors against schizophrenia (ORAA = 0.986, ORGLA = 0.148). In addition, no significant relationships were observed between schizophrenia and docosahexaenoic acid (DHA) or other ω-3 PUFAs. These findings show that the deficiencies of ω-6 LCPUFAs, especially AA, are associated with schizophrenia risk, which sheds novel insight into the etiology of schizophrenia and a promising diet supplementation for the prevention and treatment of schizophrenia.

Genetic variations in DOCK4 contribute to schizophrenia susceptibility in a Chinese cohort: A genetic neuroimaging study

BackgroundEmerging evidence suggests that the DOCK4 gene increases susceptibility to schizophrenia. However, no study has hitherto repeated this association in Chinese, and further investigated the relationship between DOCK4 and clinical symptoms in schizophrenic patients using clinical scales and functional magnetic resonance imaging (fMRI). MethodsIn this study, we genotyped three single nucleotide polymorphisms (SNPs) (rs2074127, rs2217262, and rs2074130) within the DOCK4 gene using a case-control design (including 1289 healthy controls and 1351 patients with schizophrenia). 55 first-episode schizophrenia (FES) patients and 59 healthy participants were divided by the genotypes of rs2074130 into CC and CT+TT groups. We further investigated the association with clinical symptoms and neural characteristics (brain activation/connectivity and nodal network metrics). ResultsOur results showed significant associations between all selected SNPs and schizophrenia (all P < 0.05). In patients, letter fluency and motor speed scores of T allele carriers were significantly higher than the CC group (all P < 0.05). Interestingly, greater brain activity, functional connectivity, and betweenness centrality (BC) in language processing and motor coordination were also observed in the corresponding brain zones in patients with the T allele based on a two-way ANCOVA model. Moreover, a potential positive correlation was found between brain activity/connectivity of these brain regions and verbal fluency and motor speed. ConclusionOur findings suggest that the DOCK4 gene may contribute to the onset of schizophrenia and lead to language processing and motor coordination dysfunction in this patient population from China.

Bounce of caregivers expressed emotions on schizophrenia

Schizophrenia is a severe type of mental illness that is both persistent and burdensome. Because they are under a lot of stress coping with caring for schizophrenia patients, family members of these patients often have a negative attitude and a wide spectrum of expressed emotion towards them. The quality of interaction patterns and the type of family ties among family caregivers and individuals with schizophrenia and other psychiatric conditions are classified as an unfavorable family environment. [1] Large volumes of emotion directed directly at a person or within a family environment are referred to as “high expressed emotion.”One or more parents’ critical or emotionally over-involved attitudes and behaviors toward their schizophrenia offspring are referred to as expressed emotion. [2]. Any aberrant processes inside a family, such as conflict, communication problems, cold parenting, criticism, control, and excessive amounts of expressed emotions, are referred to as family dysfunction.. These could be risk factors for schizophrenia onset and maintenance. Schizophrenics who returned home to such a family were more prone to relapse than those who returned home to a family that expressed little or no emotion. While not on medication, returning to a high expressed emotion family resulted in a large rate of recurrence. [20] Family members of schizophrenia patients require psychosocial nursing care to assist them cope with their stress. [21]

Associations between theory of mind and clinical symptoms in recent onset schizophrenia spectrum disorders.

People with schizophrenia often present with Theory of mind (ToM) deficits, and the link between these deficits and clinical symptoms remains to be refined, for instance through the use of more recent assessment methods. The objective of this study was to examine the associations between a psychometrically sound ToM task and the clinical symptoms of schizophrenia as measured with the five dimensions of the Positive and Negative Syndrome Scale (PANSS) namely positive, negative, cognitive/disorganization, depression/anxiety and excitability/hostility, while controlling for non-social cognitive abilities. Seventy participants with recent-onset schizophrenia spectrum disorders (SSD) were assessed for ToM using the Combined stories task (COST) and for clinical symptoms using the PANSS. The results revealed significant correlations between ToM and the positive (r = -0.292, p = 0.015) and cognitive/disorganization (r = -0.480, p < 0.001) dimensions when controlling for non-social cognitive abilities. In contrast, the negative symptoms dimension was only significantly correlated with ToM when non-social cognitive abilities were not controlled for (r = -0.278, p = 0.020). Very few prior studies used the five-dimensions of the PANSS to examine the link with ToM and this study is the first to rely on the COST, which includes a non-social control condition. This study highlights the importance of taking non-social cognitive abilities into account when considering the relationship between ToM and symptoms.

Sunshine duration and risks of schizophrenia hospitalizations in main urban area: Do built environments modify the association?

BackgroundAlthough studies have explored the relationship between sunshine duration and schizophrenia, the evidence was ambiguous. Different built environments may alter the effect of sunlight on schizophrenia, thus the purpose of this study was to investigate the effects of built environments on the sunshine duration-schizophrenia association. Materials and methodsDaily schizophrenia hospitalizations data during 2017–2020 in Hefei's main urban area, China, and corresponding meteorological factors as well as ambient pollutants were collected. The impact of sunshine duration on schizophrenia admissions in urban areas was investigated using a generalized additive model combined with a distributed lagged nonlinear model. Additionally, the various modifying effects of different Building Density, Building Height, Normalized Vegetation Index, and Nighttime Light were also explored between sunshine duration and schizophrenia. ResultsWe observed that inadequate sunshine duration (<5.3 h) was associated with an increase in schizophrenia hospital admissions, with a maximum relative risk of 1.382 (95 % confidence interval (CI): 1.069–1.786) at 2.9 h. In turn, adequate sunshine duration reduced the risk of schizophrenia hospitalizations. Subgroup analyses indicated females and old patients were particularly vulnerable. In the case of insufficient sunshine duration, significant positive effects were noticed on schizophrenia risk at High-Building Density and High-Nighttime Light. Higher NDVI as well as Building Height were found to be associated with lower risks of schizophrenia. ConclusionsGiven that sunshine duration in various built environments might lead to distinct effects on schizophrenia hospitalizations. Our findings assist in identifying vulnerable populations that reside in particular areas, thus suggesting policymakers provide advice to mitigate the onset of schizophrenia by allocating healthcare resources rationally and avoiding adverse exposures to vulnerable populations timely.

Sensory gating deficits and childhood trauma in the onset of first-episode schizophrenia

Studies have shown sensory gating deficits and severe childhood trauma in patients with schizophrenia; however, their relationship with this condition remains unclear. Here, we hypothesized that sensory gating deficits mediate the effects of childhood trauma on schizophrenia onset. We recruited 79 patients with first-episode schizophrenia (PFES) and 76 health controls (HC). The auditory conditioning (S1) and testing (S2) stimulus paradigm was used to detect P50 sensory gating. The Childhood Trauma Questionnaire (CTQ) was used to assess childhood trauma experiences. Compared with HC, the PFES group had more severe childhood trauma experiences together with sensory gating deficits. In a partial correlation analysis, sexual abuse was negatively correlated with the P50 S2 latency, physical neglect was negatively correlated with the S1 latency, while emotional neglect was positively correlated with the S2/S1 ratio and negatively correlated with the S1-S2 difference in the PFES group. However, there was no correlation between the CTQ total and each sub-scores and P50 indicators in the HC. The S1-S2 difference was the mediator between emotional neglect and the onset of schizophrenia. Childhood trauma might be associated with schizophrenia by influencing sensory gating deficits. Early intervention targeting childhood trauma might reduce the incidence of sensory gating deficits and thus schizophrenia.

Personality traits and transition to psychosis one year after the first assessment.

Several studies have identified ultra-high-risk criteria that may characterize an at-risk mental state and predict the transition of psychotic evolution. Personality traits may play a crucial role in this process. The current study aims to: (a) explore the evolution of an initial diagnosis over 12 months; (b) assess differences in social and occupational functioning; (c) identify common (trans-diagnostic) personality traits of psychotic risk. The sample includes 97 (44 males and 53 females) young adults. They completed an assessment that consists of socio-demographic data, the Social and Occupational Functioning Scale, the Early Recognition Inventory-retrospective assessment onset of schizophrenia, and the Personality Inventory for DSM-5 (PID-5). According to the tests' assessment, the sample was divided into three different groups: Ultra-High Risk (UHR), At-Risk, and Not at risk. One year after the first evaluation, psychiatrists administered the QuickSCID-5 to verify the diagnostic trajectories of the sample. Overall, the most prevalent category diagnoses were anxiety/depression, personality disorders, and psychosis. Specifically, the most common diagnosis in the UHR group was psychosis. Moreover, in the UHR group, the social and occupational functioning score was the lowest. In terms of differences in PID-5 personality traits, the At-risk and UHR groups scored highest in detachment and disinhibition. No statistically significant differences were found between the groups for negative affectivity, antagonism, and psychoticism traits. Results obtained by the current study should be considered an attempt to better understand the diagnostic trajectories and trans-diagnostic personality traits in a group of young help-seekers, specifically in UHR. Findings highlight both the importance of diagnosis and personality traits evaluation to customize a specific intervention based on the level of psychotic risk. Clinical suggestions are reported.

Short-term Medication Effects on Brain Functional Activity and Network Architecture in First-Episode psychosis: a longitudinal fMRI study.

The effect of antipsychotic medications is critical for the long-term outcome of symptoms and functions during first-episode psychosis (FEP). However, how brain functions respond to the antipsychotic treatment in the early stage of psychosis and its underlying neural mechanisms remain unclear. In this study, we explored the cross-sectional and longitudinal changes of regional homogeneity (ReHo), whole-brain functional connectivity, and network topological properties via resting-state functional magnetic resonance images. Thirty-two drug-naïve FEP patients and 30 matched healthy volunteers (HV) were included, where 23 patients were re-visited with effective responses after two months of antipsychotic treatment. Compared to HV, drug-naive patients demonstrated significantly different patterns of functional connectivity involving the right thalamus. These functional alterations mainly involved decreased ReHo, increased nodal efficiency in the right thalamus, and increased thalamic-sensorimotor-frontoparietal connectivity. In the follow-up analysis, patients after treatment showed reduced ReHo and nodal clustering in visual networks, as well as disturbances of visual-somatomotor and hippocampus-superior frontal gyrus connectivity. The longitudinal changes of ReHo in the visual cortex were associated with an improvement in general psychotic symptoms. This study provides new evidence regarding alterations in brain function linked to schizophrenia onset and affected by antipsychotic medications. Moreover, our results demonstrated that the functional alterations at baseline were not fully modulated by antipsychotic medications, suggesting that antipsychotic medications may reduce psychotic symptoms but limit the effects in regions involved in disease pathophysiology.

Schizophrenia among young people first admitted to psychiatric inpatient care during early and middle adolescence

ObjectiveThis study explored the incidence and stability of schizophrenia in a large national register data of all adolescents first admitted to psychiatric inpatient care at ages 13–17 in Finland 1980–2010. MethodsThe study population (N 17,112) comprised all Finnish citizens aged 13–17 receiving their first ever psychiatric inpatient treatment between 1980 and 2010 in Finland. To explore incidence and stability of schizophrenia, the diagnostic information on inpatient care or disability pension was obtained from the appropriate registers. ResultsThe incidence of schizophrenia disorders (F20 + F25) during adolescence was higher in the study population for those admitted to psychiatric inpatient care 1980–1989 than in other decades examined. Overall, psychiatric inpatient care during adolescence was a risk factor for subsequent schizophrenia, especially if a diagnosis of F20–29 was set although a considerable share of those with psychotic disorders other than schizophrenia diagnosis did not subsequently convert to schizophrenia. The stability of adolescent onset schizophrenia diagnosis was high. ConclusionAdolescents requiring psychiatric inpatient care have a higher later rate of schizophrenia diagnosis than prevalence at community level. Whereas adolescent onset schizophrenia diagnosis is a fairly stable diagnosis, there are other adolescent psychotic disorders which are more transient in nature.

The Poly I:C maternal immune stimulation model shows unique patterns of brain metabolism, morphometry, and plasticity in female rats.

Introduction: Prenatal infections are associated with an increased risk of the onset of schizophrenia. Rodent models of maternal immune stimulation (MIS) have been extensively used in preclinical studies. However, many of these studies only include males, omitting pathophysiological features unique to females. The aim of this study is to characterize the MIS model in female rats using positron emission tomography (PET), structural magnetic resonance imaging (MR), and neuroplasticiy studies. Methods: In gestational day 15, Poly I:C (or Saline) was injected into pregnant Wistar rats to induce the MIS model. Imaging studies: [18F]-fluoro-2-deoxy-D-glucose-PET scans of female-offspring were acquired at post-natal day (PND) 35 and PND100. Furthermore, T2-MR brain images were acquired in adulthood. Differences in FDG uptake and morphometry between groups were assessed with SPM12 and Regions of Interest (ROI) analyses. Ex vivo study: The density of parvalbumin expressing interneurons (PV), perineuronal nets (PNN), and parvalbumin expressing interneurons surrounded by perineuronal nets (PV-PNN) were evaluated in the prelimbic cortex and basolateral amygdala using confocal microscopy. ROIs and neuroplasticity data were analyzed by 2-sample T-test and 2-way-ANOVA analyses, respectively. Results: A significant increase in brain metabolism was found in all animals at adulthood compared to adolescence. MIS hardly modified brain glucose metabolism in females, highlighting a significant hypometabolism in the thalamus at adulthood. In addition, MIS induced gray matter (GM) enlargements in the pituitary, hippocampus, substantia nigra, and cingulate cortex, and GM shrinkages in some thalamic nuclei, cerebelar areas, and brainstem. Moreover, MIS induced white matter shrinkages in the cerebellum, brainstem and corpus callosum, along with cerebrospinal fluid enlargements in the lateral and 4th ventricles. Finally, MIS reduced the density of PV, PNN, and PV-PNN in the basolateral amygdala. Conclusion: Our work showed in vivo the differential pattern of functional and morphometric affectation in the MIS model in females, as well as the deficits caused at the synaptic level according to sex. The differences obtained highlight the relevance of including both sexes in psychiatric research in order to consider their pathophysiological particularities and successfully extend the benefits obtained to the entire patient population.

ERVWE1 Reduces Hippocampal Neuron Density and Impairs Dendritic Spine Morphology through Inhibiting Wnt/JNK Non-Canonical Pathway via miR-141-3p in Schizophrenia.

Human endogenous retroviruses (HERVs) are remnants of ancestral germline infections by exogenous retroviruses. Human endogenous retroviruses W family envelope gene (HERV-W env, also called ERVWE1), located on chromosome 7q21-22, encodes an envelope glycoprotein from the HERV-W family. Mounting evidence suggests that aberrant expression of ERVWE1 involves the etiology of schizophrenia. Moreover, the genetic and morphological studies indicate that dendritic spine deficits may contribute to the onset of schizophrenia. Here, we reported that ERVWE1 changed the density and morphology of the dendritic spine through inhibiting Wingless-type (Wnt)/c-Jun N-terminal kinases (JNK) non-canonical pathway via miR-141-3p in schizophrenia. In this paper, we found elevated levels of miR-141-3p and a significant positive correlation with ERVWE1 in schizophrenia. Moreover, serum Wnt5a and actin-related protein 2 (Arp2) levels decreased and demonstrated a significant negative correlation with ERVWE1 in schizophrenia. In vitro experiments disclosed that ERVWE1 up-regulated miR-141-3p expression by interacting with transcription factor (TF) Yin Yang 1 (YY1). YY1 modulated miR-141-3p expression by binding to its promoter. The luciferase assay revealed that YY1 enhanced the promoter activity of miR-141-3p. Using the miRNA target prediction databases and luciferase reporter assays, we demonstrated that miR-141-3p targeted Wnt5a at its 3' untranslated region (3' UTR). Furthermore, ERVWE1 suppressed the expression of Arp2 through non-canonical pathway, Wnt5a/JNK signaling pathway. In addition, ERVWE1 inhibited Wnt5a/JNK/Arp2 signal pathway through miR-141-3p. Finally, functional assays showed that ERVWE1 induced the abnormalities in hippocampal neuron morphology and spine density through inhibiting Wnt/JNK non-canonical pathway via miR-141-3p in schizophrenia. Our findings indicated that miR-141-3p, Wnt5a, and Arp2 might be potential clinical blood-based biomarkers or therapeutic targets for schizophrenia. Our work also provided new insight into the role of ERVWE1 in schizophrenia pathogenesis.

Lightweight 3D Convolutional Neural Network for Schizophrenia Diagnosis Using MRI Images and Ensemble Bagging Classifier

Structural alterations have been thoroughly investigated in the brain during the early onset of schizophrenia (SCZ) with the development of neuroimaging methods. The objective of the paper is an efficient classification of SCZ in 2 different classes: cognitive normal (CN) and SCZ using magnetic resonance imaging (MRI) images. This paper proposes a lightweight 3D convolutional neural network (CNN) based framework for SCZ diagnosis using MRI images. In the proposed model, lightweight 3D CNN is used to extract both spatial and spectral features simultaneously from 3D volume MRI scans, and classification is done using an ensemble bagging classifier. Ensemble bagging classifier contributes to preventing overfitting, reduces variance, and improves the model’s accuracy. The proposed algorithm is tested on datasets taken from three benchmark databases available as open-source: MCICShare, COBRE, and fBRINPhase-II. All MRI images have undergone preprocessing steps to register all the MRI images to the standard template and reduce the artifacts. The model achieves the highest accuracy 92.22%, sensitivity 94.44%, specificity 90%, precision 90.43%, recall 94.44%, F1-score 92.39%, and G-mean 92.19% as compared to the current state-of-the-art techniques. The performance metrics evidenced the use of this model to assist the clinicians in automatic accurate diagnosis of SCZ.