Symptoms In Schizophrenia Patients Research Articles

Obsessive-compulsive symptoms in schizophrenia patients and their first-degree relatives and the association with subclinical psychotic symptoms

Objective This study aimed to investigate the presence of obsessive-compulsive symptoms (OCS) in patients being followed for schizophrenia and their first-degree relatives (mother, father, siblings, and children) and the relationship between OCS and clinical/subclinical psychotic symptoms. Materials and methods The study included 110 schizophrenia patients followed up in a community mental health center and their first-degree relatives. Patients and relatives were evaluated using the SCID-I (Structured Clinical Interview Form for DSM-IV Axis-I Disorders) to ascertain their diagnosis and exclude other axis-I diagnoses. The Yale-Brown Obsessive Compulsive Scale was used to measure OCS severity. Psychotic symptom severity was evaluated in patients using the Positive and Negative Syndrome Scale (PANSS) and subthreshold psychotic symptoms and psychosis proneness were assessed in relatives using the Schizotypal Personality Questionnaire. Results The prevalence of clinically significant OCS was 41.8% in schizophrenia patients and 28.2% in their relatives. PANSS positive and general psychopathology subscale scores were higher in patients with OCS. Suspiciousness and interpersonal schizotypy scores were significantly higher in relatives with OCS compared to those without. The first-degree relatives of patients with OCS did not exhibit a higher prevalence of OCS or psychotic symptoms compared to the relatives of patients without OCS. Conclusion Our study demonstrates that obsessive-compulsive phenomena are common in schizophrenia patients and their relatives. Although there seems to be a positive association between OCS and psychotic symptoms in patients and their first-degree relatives, the intergenerational transmission of these two symptom groups may occur independently.

Association between the improvement in depressive symptoms and serum BDNF levels in drug-naive first episode patients with schizophrenia: A longitudinal follow-up

Depressive symptoms are frequent clinical manifestations in patients with schizophrenia. Decreased brain-derived neurotrophic factor (BDNF) has been shown to be involved in the development of depressive symptoms. However, the detailed molecular mechanism of BDNF in the depressive symptoms of schizophrenia patients remains to be fully elucidated. This study aimed to investigate the role of BDNF in the depressive symptoms in drug-naïve first-episode (DNFE) patients with schizophrenia and whether BDNF levels were associated with the improvement of depressive symptoms after olanzapine treatment. 50 DNFE schizophrenia patients and 55 healthy controls were recruited, and their serum BDNF levels were compared. All patients were treated with olanzapine monotherapy for 12 weeks, and 45 patients completed the trial. The serum BDNF levels and depressive symptoms were measured again at follow-up. We found that DNFE patients had lower BDNF levels, compared to controls. Last observation carried forward (LOCF) analysis was used for patients who dropped out after the second month, and 50 patients were included in the statistical analysis with LOCF. After 12 weeks of treatment with olanzapine, BDNF levels were significantly increased and depressive symptoms were significantly decreased. Correlation analysis showed that the change of BDNF levels after treatment was correlated with the change of HAMD total score from baseline. Further regression analysis showed that the change in BDNF levels was an independent predictor for the improvement in depressive symptoms, after controlling age, BMI change and the decrease of PANSS total score. However, the baseline BDNF levels were not associated with an improvement in depressive symptoms in patients. Our findings reveal that olanzapine treatment can increase BDNF levels and improve depressive symptoms in schizophrenia patients. Moreover, the changes in serum BDNF levels were related to the improvement in depressive symptoms.

The Associations between COMT and MAO-B Genetic Variants with Negative Symptoms in Patients with Schizophrenia.

Negative symptoms of schizophrenia, including anhedonia, represent a heavy burden on patients and their relatives. These symptoms are associated with cortical hypodopamynergia and impaired striatal dopamine release in response to reward stimuli. Catechol-O-methyltransferase (COMT) and monoamine oxidase type B (MAO-B) degrade dopamine and affect its neurotransmission. The study determined the association between COMT rs4680 and rs4818, MAO-B rs1799836 and rs6651806 polymorphisms, the severity of negative symptoms, and physical and social anhedonia in schizophrenia. Sex-dependent associations were detected in a research sample of 302 patients with schizophrenia. In female patients with schizophrenia, the presence of the G allele or GG genotype of COMT rs4680 and rs4818, as well as GG haplotype rs4818-rs4680, which were all related to higher COMT activity, was associated with an increase in several dimensions of negative symptoms and anhedonia. In male patients with schizophrenia, carriers of the MAO-B rs1799836 A allele, presumably associated with higher MAO-B activity, had a higher severity of alogia, while carriers of the A allele of the MAO-B rs6651806 had a higher severity of negative symptoms. These findings suggest that higher dopamine degradation, associated with COMT and MAO-B genetic variants, is associated with a sex-specific increase in the severity of negative symptoms in schizophrenia patients.

Triple network hypothesis-related disrupted connections in schizophrenia: A spectral dynamic causal modeling analysis with functional magnetic resonance imaging

ObjectiveThe symptom-related neurobiology characteristic of schizophrenia in the brain from a network perspective is still poorly understood, leading to a lack of potential biologically-based markers and difficulty identifying therapeutic targets. We aim to test the dysregulated cross-network interactions among the Salience Network (SN), Central Executive Network (CEN) and Default Mode Network (DMN) and how they contributed to different symptoms in schizophrenia patients. MethodsWe examined network interactions among the SN, CEN and DMN in 76 patients with schizophrenia vs. 80 well-matched controls using dynamic causal modeling (DCM). We further analyzed the relation between network dynamics and Positive and Negative Syndrome Scale (PANSS). ResultsWe observed that the DMN, CEN and SN across healthy controls and schizophrenia patients showed several similarities within or between-network pattern in the resting state. Comparing schizophrenia to controls, SN-centered cross-network interactions were most significantly reduced. Crucially, the strength of connections from CEN subnetwork 1 to DMN subnetwork 1 was positively correlated with the Positive Score of PANSS. The connection from the DMN subnetwork 2 to CEN subnetwork 2 was negatively correlated with the Negative Score of PANSS. ConclusionsOur study provides strong evidence for the dysregulation among SN, CEN and DMN in a triple-network perspective in schizophrenia. The connection between DMN and CEN could be clinically-relevant neurobiological signature of schizophrenia symptoms. Our study indicated that the description of brain triple network hypothesis could be a novel and possible bio-marker for schizophrenia.

Amisulpride: What’s Old Can Be New in the United States

Amisulpride: What’s Old Can Be New in the United States

Latent structure of self-report negative symptoms in patients with schizophrenia: A preliminary study.

Negative symptoms are associated with poor outcomes and functioning. Latent structure of negative symptoms is important for identifying potential intervention targets for novel treatments. Self-report instruments have been developed to measure negative symptoms. Previous findings on latent structure of negative symptoms are inconsistently and mainly rely on clinician-rated instruments. We aimed to explore the latent structure of the Self-Evaluation of Negative Symptoms Scale (SNS) in 204 clinically-stable outpatients with schizophrenia. Confirmatory factor analysis (CFA) was used to compare the competing models (i.e., one-factor, two-factor and five-factor models), and estimated goodness-of-fit indexes. Other clinician-rated scales for psychopathology and medication side-effects were also collected. The CFA found the five-factor model performing best, with a comparative fit index (CFI) of > 0.95, a Tucker Lewis Index (TLI) of > 0.95, and a root mean square error of approximation (RMSEA) of < 0.06. The robust chi-square difference test for the weighted least squares with mean and variance adjusted estimation (WLSMV) also indicated a significant better fit for the five-factor model. Our preliminary findings support a five-factor latent structure of self-report negative symptoms in schizophrenia patients. Further research in this area should utilize multiple clinician-rated and self-report measures, and recruit large and homogeneous samples with schizophrenia.

Negative symptoms of schizophrenia in patients with acute and transient psychotic disorders

IntroductionThe ICD-10 acute and transient psychotic disorders (ATPD, F23) without symptoms of schizophrenia are considered predominantly reactive psychotic disorders or affective pathology. However, negative symptoms of schizophrenia may be revealed in some of these cases after the psychotic reduction.ObjectivesTo investigate the association between the developmental characteristics of psychosis and the negative symptoms detection after the psychotic reduction of ATPD without symptoms of schizophrenia.Methods68 adult inpatients with ATPD without symptoms of schizophrenia (F23.0) were examined. Negative symptoms were assessed with the PANSS negative symptom subscale (PANSS-NSS). The sample was divided into two groups: with PANSS-NSS score&gt;14 (n=12) and with PANSS-NSS score≤14 (n=56), respectively. Clinical-psychopathological, psychometric and statistical methods were applied.ResultsThe results of the study are presented in Table 1.Table 1. The ATPD developmental featuresFeaturesThe 1st group (n=12)The 2nd group (n=56)Pearson’s contingency coefficient (C)Males7 (58,3%)37 (66,1%)0.062Females5 (41,7%)19 (33,9%)0.062Mean age of psychotic onset, years (М±m)24,9±10,530,8±10,2-Family history of schizophrenia*4 (33,3%)1 (1,8%)0.418Poor premorbid social adaptation*5 (41,7%)00.520Prodromal functional decline*9 (75,0%)4 (7,1%)0.550Prodromal non-psychotic symptoms9 (75,0%)30 (53,6%)0.163Associated acute stress4 (33,3%)27 (48,2%)0.113*p&lt;0,001ConclusionsThe probability of negative symptoms detection in ATPD without symptoms of schizophrenia is relatively strongly associated with the family history of schizophrenia, poor premorbid social adaptation and functional decline prior to the psychotic onset.DisclosureNo significant relationships.

Odour identification impairment is a trait but not a disease-specific marker for bipolar disorders: Comparisons of bipolar disorder with different episodes, major depressive disorder and schizophrenia.

Olfactory deficits have been reported in bipolar disorder, but this finding is controversial. This study investigated whether olfactory deficit can serve as a specific marker for bipolar disorder by comparing olfactory function in different mood episodes of bipolar disorder. We also compared olfactory function in bipolar disorder and other mental disorders - namely, major depressive disorder and schizophrenia. The study consisted of two experiments. Experiment 1 enrolled 175 bipolar disorder patients (70 depressed subgroup, 70 manic subgroup and 35 euthymic subgroup) and 47 controls. Experiment 2 enrolled the participants from Experiment 1, along with 85 major depressive disorder and 90 schizophrenia patients. The Sniffin' Sticks test was used to evaluate odour identification ability and odour threshold (as a measure of odour sensitivity). The Hamilton Depression Rating Scale and Young Mania Rating Scale were used to assess depressive symptoms in all subjects and manic symptoms in bipolar disorder patients, respectively. We also used the Positive and Negative Syndrome Scale to assess clinical symptoms in schizophrenia patients. All three bipolar disorder patient subgroups (depressed, manic and euthymic subgroup) showed reduced odour identification ability compared to controls; however, only patients in the acute phase of a mood episode (depressed, and manic subgroup) showed impaired odour sensitivity. Clinical symptoms were negatively correlated with odour sensitivity but not odour identification ability. Bipolar disorder and major depressive disorder patients showed less odour identification and sensitivity impairment than schizophrenia patients. Odour sensitivity is a potential dopaminergic marker for distinguishing between bipolar disorder patients in acute phase vs remission, while odour identification is a trait but a nonspecific marker of bipolar disorder.

Association of СОМТ, DRD2/ANKK1, MTHFR, MIR 137, DNMT3B polymorphisms with the clinical features of schizophrenia patients in acute stage and remission

Updated view of genetic features of schizophrenia based on rare SNPs/CNVs with a huge influence on a disease and common SNPs with a small effect of each allele is presented. Altogether these genetic factors are acting to create neuropathophysiological disturbances observed in schizophrenia. Association of five polymorphisms MIR137 rs1625579, DRD2/ANKK1 rs1800497, MTHFR rs1801133, DNMT3B rs2424913, СОМТ rs4680 with the risk of schizophrenia in the Belarusian population, the level of symptoms of schizophrenia patients assessed by PANSS in the acute stage and remission, cognitive impairments, and treatment trajectory of schizophrenia patients during antipsychotic treatment were analyzed. The A/A-genotype of СОМТ rs4680 (р = 0.008) and the С/С-genotype of MTHFR rs1801133 (р = 0.02) are associated with the risk of schizophrenia among Belarusians. The T-allele of MTHFR rs1801133 is a risk factor of positive symptoms (р = 0.02). Combining the C/C-genotype (DNMT3B rs2424913) and the G-allele (COMT rs4680) is associated with a significant difference in negative symptoms level between men and women. The polymorphism of СОМТ rs4680 (р &lt; 0.05) and the combination of СОМТ rs4680 + DRD2/ANKK1 rs1800497 (р = 0.005) as well as MTHFR rs1801133 + DNMT3B rs2424913 (р = 0.006) are related to the cognitive parameters measured by the WCST and Stroop test respectively. Schizophrenia patients who are the G-allele carriers of MIR137 rs1625579 demonstrated a more favorable negative symptom trajectory in comparison to Т/Тhomozygotes (F = 2.2, p = 0.03). The trajectory of negative symptoms (F = 2.2, p = 0.03) and general psychopathological symptoms (F = 4.3, p = 0.0001) is different between men and women under antipsychotic treatment. These differences are associated with a minor amount of alleles of MIR137 rs1625579, DRD2/ANKK1 rs1800497, MTHFR rs1801133 polymorphic sites.

The effectiveness and safety of cariprazine in schizophrenia patients with negative symptoms and insufficient effectiveness of previous antipsychotic therapy: an observational study.

The aim of the study was to examine the effectiveness and safety of cariprazine in routine psychiatric settings on schizophrenia patients with negative symptoms who have been treated with antipsychotics previously but without sufficient success. This was an open-label, flexible-dose, 16-week, observational study in Latvia. The primary outcome measure was an array of anamnesis-based clinical questions on schizophrenia symptoms rated on a seven-point scale. Other outcome measurements were the clinical global impression improvement (CGI-I) and severity (CGI-S) scales. Safety parameters included spontaneous reports of adverse events and specific assessments of extrapyramidal side-effects. A mixed model for repeated measures was fit to the data to evaluate the mean change from baseline for all visits. A total of 116 patients enrolled in the study (completion: 83%). Change from baseline to termination in symptom control was statistically significant (-7.3; P < 0.001), with the most improvement in negative symptoms (-6.3; P < 0.001). Over 70% of patients improved minimally or much based on the CGI-I scores at the final visit, and the CGI-S scores indicated an overall improvement in severity from moderately to mildly ill. 40% of patients experienced treatment-emergent adverse events. Over 70% of doctors were satisfied with the effectiveness and tolerability of cariprazine. Cariprazine significantly improved negative symptoms in schizophrenia patients.

Neurological Soft Signs Are Associated With Altered Cerebellar-Cerebral Functional Connectivity in Schizophrenia.

Cerebellar dysfunction is associated with neurological soft signs (NSS), which is a promising endophenotype for schizophrenia spectrum disorders. However, the relationship between cerebellar-cerebral resting-state functional connectivity (rsFC) and NSS is largely unexplored. Moreover, both NSS and cerebellar-cerebral rsFC have been found to be correlated with negative symptoms of schizophrenia. Here, we investigated the correlations between NSS and cerebellar-cerebral rsFC, explored their relationship with negative symptoms in a main dataset, and validated the significant findings in a replication dataset. Both datasets comprised schizophrenia patients and healthy controls. In schizophrenia patients, we found positive correlations between NSS and rsFC of the cerebellum with the inferior frontal gyrus and the precuneus, and negative correlations between NSS and rsFC of the cerebellum with the inferior temporal gyrus. In healthy controls, NSS scores were positively correlated with rsFC of the cerebellum with the superior frontal gyrus and negatively correlated with rsFC between the cerebellum and the middle occipital gyrus. Cerebellar-prefrontal rsFC was also positively correlated with negative symptoms in schizophrenia patients. These findings were validated in the replication dataset. Our results suggest that the uncoupling of rsFC between the cerebellum and the cerebral cortex may underlie the expression of NSS in schizophrenia. NSS-related cerebellar-prefrontal rsFC may be a potential neural pathway for possible neural modulation to alleviate negative symptoms.

Neuroprotective effect of agomelatine in rat model of psychosis: Behavioural and histological evidence

• Ketamine caused hyper-locomotion, increased stereotypy, ataxia, and decreased social withdrawal. • Agomelatine reversed the behavioural effects of ketamine. • Ketamine decreased neuronal count in the hippocampus and increased it in the amygdala. • The ketamine effects on neuronal count were reversed by agomelatine. • Agomelatine has the potential to alleviate negative symptoms of schizophrenia. Schizophrenia is a complex psychiatric disorder associated with positive (delusion, hallucination, and disorganised speech) and negative (affective flatering, avolition and social withdrawal) symptoms. Agomelatine (AGO) has been used as an anti-depressant to improve the negative symptoms in schizophrenia patients with co-morbid major depressive disorder. Therefore, the present study aimed to investigate the anti-psychotic effect of AGO in ketamine (KET)-induced psychosis rat model. Four groups ( n = 12/ group) of wistar rats were administered normal saline, KET (20 m/kg, i.p) and KET + AGO (20 and 40 mg/kg, i.p) for seven days. Behavioural tests were conducted on the seventh day after drug administration. Seven days administration of AGO at two different doses decreased the KET induced stereotypic and ataxic behaviour as compared with KET treated rats. In addition, AGO increased the social interaction time and decreased the horizontal and vertical locomotor behaviour in KET treated rats. Histologically, KET adminstration decreased hippocampal and increased basolateral amygdala (BLA) neuronal counts. AGO administration (at two different doses) significantly reversed the KET induced neuronal loss in the two brain areas. These findings suggest that AGO has a protective effect against KET-induced psychosis in this rat model. This study warrants further research to delineate the possible role of AGO in experimental model of psychosis particularly neurochemical and neuromolecular aspects.

Schizophrenia patients with a metabolically abnormal obese phenotype have milder negative symptoms

BackgroundSchizophrenia patients with a metabolically abnormal obese (MAO) phenotype have been shown poor cardiovascular outcomes, but the characteristics of their current psychiatric symptoms have not been characterized. This study mainly explored the psychiatric symptoms of schizophrenia patients with the MAO phenotype.MethodsA total of 329 patients with schizophrenia and 175 sex- and age-matched people without schizophrenia from Anhui Province in China were enrolled. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate the mental symptoms of the schizophrenia patients. The MAO phenotype was defined as meeting 1–4 metabolic syndrome criteria (excluding waist circumference) and having a body mass index (BMI) ≥ 28 kg/m2. And, metabolically healthy normal-weight (MHNW) phenotype was defined as meeting 0 criteria for metabolic syndrome and 18.5 ≤ BMI < 24 kg/m2.ResultsOverall, 15.8% of the schizophrenia patients and 9.1% of the control group were consistent with the MAO phenotype, and the prevalence of MAO in the schizophrenia group was higher than that in the control group. Among the patients with schizophrenia, the MAO group had lower negative factor, cognitive factor and total PANSS scores than the MHNW group. However, when confounding factors were controlled, only the negative factor remained lower significantly.ConclusionWe found that schizophrenia patients with the MAO phenotype had reduced negative symptoms, which may indicate an internal mechanism linking metabolic disorders and negative symptoms.Trial registrationThis study was registered in the China Clinical Trial Registration Center (No. chiCTR 1,800,017,044).

A Comprehensive Analysis of the Effect of SIRT1 Variation on the Risk of Schizophrenia and Depressive Symptoms.

Depressive symptoms could be considered a mutual manifestation of major depressive disorder and schizophrenia. Rs3758391 is a functional locus of Sirtuin (SIRT1) involving depression etiology. In this study, we hypothesized that the SIRT1 SNP rs3758391 might be a hazard for schizophrenia pathogenesis, especially related to the appearance of depressive symptoms. We recruited 723 healthy controls and 715 schizophrenia patients, the occurrence of psychotic and depressive symptoms was evaluated by Calgary Depression Scale (CDSS) and PANSS. Meanwhile, qt-PCR was used to detect the mRNA levels of SIRT1 in peripheral blood of 197 olanzapine monotherapy schizophrenia patients. 45.6% of schizophrenia patients had depressive symptoms. In the patient group, mRNA levels of patients with depressive symptoms were significantly lower than those without depressive symptoms (P < 0.01). CDSS scores of schizophrenia patients with different rs3758391 genotypes were significantly different (P < 0.01). Post hoc comparisons indicated that the CDSS scores of rs3758391 C/C and C/T carriers were higher than those of T/T carriers (Ps < 0.01). In the occipital cortex, our eQTL analysis showed that there was a clear correlation between rs3758391 and the SIRT1 mRNA levels. Our preliminary findings provide suggestive evidence that SIRT1 makes schizophrenia patients more prone to depressive symptoms. This SNP might be a biomarker of depression in schizophrenia.

Changes of Serum Insulin-like Growth Factor-2 Response to Negative Symptom Improvements in Schizophrenia Patients Treated with Atypical Antipsychotics

SummaryAccumulating evidence suggests that a disruption of early brain development, in which insulin-like growth factor-2 (IGF-2) has a crucial role, may underlie the pathophysiology of schizophrenia. Our previous study has shown that decreased serum IGF-2 was correlated with the severity of psychopathology in patients with schizophrenia. Here we conducted a prospective observation trial to investigate the effects of atypical antipsychotics on serum IGF-2 level and its relationship with clinical improvements in schizophrenia patients. Thirty-one schizophrenia patients with acute exacerbation and 30 healthy individuals were recruited in this study. Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and serum IGF-2 levels were determined using ELISA. We found that schizophrenia patients with acute exacerbation had lower serum IGF-2 levels than control individuals at baseline (P<0.05). After 2 months of atypical antipsychotic treatment, a significant improvement in each PANSS subscore and total score was observed in patients (all P<0.01), and the serum IGF-2 levels of patients were significantly increased compared with those at baseline (203.13±64.62 vs. 426.99±124.26 ng/mL; t =−5.044, P<0.001). Correlation analysis revealed that the changes of serum IGF-2 levels in patients were significantly correlated with the improvements of negative symptoms (r=−0.522, P=0.006). Collectively, our findings demonstrated changes of serum IGF-2 response to improvements of negative symptoms in schizophrenia patients treated with atypical antipsychotics, suggesting that serum IGF-2 might be a treatment biomarker for schizophrenia.

Homocysteine, but not MTHFR gene polymorphism, influences depressive symptoms in patients with schizophrenia

BackgroundMethylenetetrahydrofolate reductase (MTHFR) is the key enzyme of folate metabolism in the process of one-carbon cycle and its deficiency results in elevated homocysteine concentration. In this study, we hypothesized that MTHFR C677T polymorphism and homocysteine concentration may play important roles in the development of depressive symptoms in schizophrenia. MethodsWe recruited 715 patients with stable schizophrenia, and among them, 197 schizophrenia patients under olanzapine monotherapy were enrolled for homocysteine concentration analysis. The Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) were employed to evaluate psychiatric and depressive symptoms. ResultsWhen the 715 schizophrenia patients were evaluated by CDSS, 326 individuals (45.6%) had depressive symptoms. No significant differences were observed in C677T genotype and allele distributions between the schizophrenia with or without depression groups. Schizophrenia patients with depression have higher levels of homocysteine than those without depression (P = 0.019). There was a positive correlation between the homocysteine levels and CDSS score (r = 0.22, P = 0.002). ConclusionOur findings suggested that higher levels of homocysteine may be a risk factor for the development of depressive symptoms in schizophrenia patients.

The interaction of histone modification related H3F3B and NSD2 genes increases the susceptibility to schizophrenia in a Chinese population

The role of histone modifications in the pathogenesis of schizophrenia has been proposed previously. H3F3B is a member of the histone 3. NSD2 is a histone methyltransferase that mediates dimethylation of Histone 3 lysine 36 (H3K36me2). The aim of the current study was to explore the associations between SNPs within H3F3B gene (rs60700976, rs3214028) and NSD2 gene (rs13148597, rs75820801) and the susceptibility to schizophrenia in a Chinese population. A total of 810 patients and 490 healthy controls were recruited and genetic association analyses were performed. The H3F3B gene polymorphisms rs3214028 and rs60700976 were significantly associated with schizophrenia. Rs60700976 was also associated with psychotic symptoms in schizophrenia patients. Furthermore, we found the interaction between NSD2 gene and H3F3B gene was related to the susceptibility to schizophrenia. The corresponding best three-locus model was H3F3B (rs60700976) - NSD2 (rs75820801, rs13148597), and the high-risk genotype combination was rs13148597(CC)- rs60700976(GG)-rs75820801(TT) (OR = 1.388[1.091–1.766], P = .007). The low-risk genotype combination was rs13148597(CC)-rs60700976(GG)-rs75820801(CT) (OR = 0.57 [0.330–0.985], P = .042). Our findings provided the preliminary evidence that the histone modification related H3F3B and NSD2 genes may confer the susceptibility to schizophrenia in a Chinese population.

Dynamic Functional Connectivity Strength Within Different Frequency-Band in Schizophrenia.

As a complex psychiatric disorder, schizophrenia is interpreted as a “dysconnection” syndrome, which is linked to abnormal integrations in between distal brain regions. Recently, neuroimaging has been widely adopted to investigate how schizophrenia affects brain networks. Furthermore, some studies reported frequency dependence of the abnormalities of functional network in schizophrenia, however, dynamic functional connectivity with frequency dependence is rarely used to explore changes in the whole brain of patients with schizophrenia (SZ). Therefore, in the current study, dynamic functional connectivity strength (dFCS) was performed on resting-state functional magnetic resonance data from 96 SZ patients and 121 healthy controls (HCs) at slow-5 (0.01–0.027 Hz), slow-4 (0.027–0.073 Hz), slow-3 (0.073–0.198 Hz), and slow-2 (0.198–0.25 Hz) frequency bands and further assessed whether the altered dFCS was correlated to clinical symptoms in SZ patients. Results revealed that decreased dFCS of schizophrenia were found in salience, auditory, sensorimotor, visual networks, while increased dFCS in cerebellum, basal ganglia, and prefrontal networks were observed across different frequency bands. Specifically, the thalamus subregion of schizophrenic patients exhibited enhanced dynamic FCS in slow-5 and slow-4, while reduced in slow-3. Moreover, in slow-5 and slow-4, significant interaction effects between frequency and group were observed in the left calcarine cortex, the bilateral inferior orbitofrontal gyrus, and anterior cingulum cortex (ACC). Furthermore, the altered dFCS of insula, thalamus (THA), calcarine cortex, orbitofrontal gyrus, and paracentral lobule were partial correlated with clinical symptoms of SZ patients in slow-5 and slow-4 bands. These results demonstrate the abnormalities of dFCS in schizophrenia patients is rely on different frequency bands and may provide potential implications for exploring the neuropathological mechanism of schizophrenia.

Parvalbumin Interneuron Activation-Dependent Adult Hippocampal Neurogenesis Is Required for Treadmill Running to Reverse Schizophrenia-Like Phenotypes.

Physical exercise can alleviate some of the schizophrenia symptoms in patients, the mechanisms, however, are still unclear. To investigate whether the GABAergic interneuron involved in the therapeutic effect of treadmill running on schizophrenia, the parvalbumin (PV)-positive GABAergic interneurons in the dentate gyrus (DG) was specifically activated or abolished and the effects were evaluated. In the MK801-induced schizophrenia-like animal model, we found:(1) Treadmill running rescued the schizophrenia-related behavioral phenotypes, promoted the adult hippocampal neurogenesis, and increased the dendrite number and complexity of newborn neurons. (2) Treadmill running increased the number of PV-positive interneurons in the DG; genetic ablation of these interneurons reduced adult neurogenesis and abolished the effect of treadmill running on the schizophrenia-related behaviors. Consistently, chemogenetic activation of these interneurons improved neurogenesis and alleviated the schizophrenia-related behaviors. These results suggest a pivotal role of PV-positive interneuron-mediated adult neurogenesis in exercise. (3) However, schizophrenia-related behavioral phenotypes and adult neurogenesis in the DG could still be reversed by exercise after specifically knocking out the schizophrenia-related gene ErbB4 in PV interneurons, as a means to reduce their GABA release. These results suggest that activation of PV interneurons in the DG is sufficient for treadmill running to reverse schizophrenia-like phenotypes.

Fluctuating asymmetry in patients with schizophrenia is related to hallucinations and thought disorganisation

Fluctuating asymmetry represents the degree to which the right and left side of the body are asymmetrical, and is a sign of developmental instability. Higher levels of fluctuating asymmetry have been observed in individuals within the schizophrenia spectrum. We aimed to explore the associations of fluctuating asymmetry with psychotic and affective symptoms in schizophrenia patients, as well as with propensity to these symptoms in non-clinical individuals. A measure of morphological fluctuating asymmetry was calculated for 39 patients with schizophrenia and 60 healthy individuals, and a range of clinical and subclinical psychiatric symptoms was assessed. Regression analyses of the fluctuating asymmetry measure were conducted within each group. In the patient cohort, fluctuating asymmetry was significantly associated with the hallucination and thought disorganisation scores. T-test comparisons revealed that the patients presenting either hallucinations or thought disorganisation were significantly more asymmetrical than were the healthy individuals, while the patients without these key symptoms were equivalent to the healthy individuals. A positive association with the anxiety score emerged in a subsample of 36 healthy participants who were rated on affective symptoms. These findings suggest that fluctuating asymmetry may be an indicator of clinical hallucinations and thought disorganisation rather than an indicator of schizophrenia disease.