First-episode Schizophrenia Patients Research Articles

Delphi Panel on the Dimensions and Assessment of Functional Recovery in First-Episode and Early-Phase Schizophrenia Patients

AbstractFunctional recovery is a treatment goal that goes beyond symptomatic remission and encompasses multiple aspects of schizophrenia patients’ lives, including quality of life, physical, and mental functioning. There is evidence that long-acting injectable (LAI) treatments promote adherence and reduce rehospitalisation and functional decline, which could facilitate patients’ ability to reach functional recovery. Despite this, LAIs are underused in the first-episode (FEP) and early-phase (EP) patient population, due to physician hesitancy and concerns around stigma. A Delphi panel was held to gain expert consensus on an approach to the domains and assessment of functional recovery elements in FEP and EP schizophrenia patients.A literature review and input from a steering committee of 5 experts in psychiatry informed statements development for a three-round modified Delphi process. Round one was conducted via one-to-one video conference interviews, and the successive rounds were conducted via electronic surveys, which enabled international collaboration. Statements on the different domains and assessment for functional recovery were presented to 17 psychiatrists, practicing in 7 countries (France, Italy, US, Germany, Spain, Denmark, and UK), experienced in the treatment of schizophrenia with LAIs. Several analysis rules determined whether a statement could progress to the next round and specified the level of agreement required to achieve consensus. Measures of central tendency (mode, mean) and variability (interquartile range) were reported back to help panelists look at their previous responses in the context of the overall group.A consensus was reached (defined a priori as ≥80% agreement) on all 27 statements covering the dimensions, assessment, and level of achieved functional recovery for FEP and EP patients. The following domains are important to consider when assessing functional recovery: depression, aggressive behaviour, social interaction, family functioning, education/employment, sexual functioning, and leisure activities. Additionally, panellists reached consensus that dimensions should be minimally impairing, if present (excluding sexual functioning) and asked about at every encounter with the patient (excluding sexual functioning and leisure activities). In summary, this Delphi panel yielded agreement that functional recovery is multidimensional and should be assessed regularly as part of usual care on an individual patient level in FEP and EP schizophrenia patients.FundingLundbeck Otsuka Alliance

Delphi Panel on the Relationship Between Long-Acting Injectable Antipsychotics and Longer-Term Functional Recovery in First-Episode and Early-Phase Schizophrenia Patients

AbstractSchizophrenia is among the top ten causes of years lost due to disability. Goals of treatment are evolving beyond remission of psychotic symptoms to include physical and mental functioning, quality of life, and long-term functional recovery. Evidence has shown long-acting injectables (LAIs) are beneficial for schizophrenia patients by increasing treatment adherence and decreasing relapse and rehospitalisation. This potentially reduces disease progression and facilitates functional recovery. However, LAIs are underused and often seen as a last resort for first-episode (FEP) and early-phase (EP) patients, due to physicians’ lack of familiarity and stigma.A three-round modified Delphi panel was held to gain expert consensus on an approach to functional recovery in FEP and EP patients with LAIs. A literature review and input from a steering committee of 5 experts in psychiatry informed the development of statements. Round one was carried out via one-to-one video conference interviews, and the subsequent rounds were conducted via electronic surveys, which enabled international collaboration. Delphi panellists were 17 psychiatrists with schizophrenia treatment experience, practicing in 7 countries (France, Italy, US, Germany, Spain, Denmark, and UK). Several analysis rules determined whether a statement could progress to the next round and specified the level of agreement required to achieve consensus. Measures of central tendencies (mode, mean) and variability (interquartile range) of aggregated responses from the previous round were reported to panelists to understand their response in relation to the group.There was consensus (defined a priori as ≥80% agreement) on the 8 statements relating to long-term treatment goals and LAI links to functional recovery. LAI treatment in FEP and EP patients increases adherence and reduces treatment burden and functional decline compared to the same and other oral medication. Additionally, there was consensus that LAIs lead to better treatment outcome and functional recovery. Other important factors to achieving functional recovery include patient attitude towards treatment and psychoeducation. Furthermore, consensus was reached that functional recovery and quality of life are linked. In summary, this Delphi panel yielded agreement that functional recovery is a reachable goal for FEP and EP patients and can be enhanced using LAIs.FundingLundbeck Otsuka Alliance

Obesity, antioxidants and negative symptom improvement in first-episode schizophrenia patients treated with risperidone

Negative symptoms remain a main therapeutic challenge in patients with schizophrenia (SZ). Obesity is associated with more severe negative symptoms after the first episode of psychosis. Oxidative stress caused by an impaired antioxidant defense system is involved in the pathophysiology of SZ. Yet, it is unclear regarding the role of obesity and antioxidants in negative symptom improvements in SZ. Therefore, this longitudinal study was designed to assess the impact of obesity on antioxidant defenses and negative symptom improvements in first-episode SZ patients. A total of 241 medication-naive and first-episode patients with SZ were treated with risperidone for 3 months. Outcome measures including symptoms, body weight, and total antioxidant status (TAS) levels were measured at baseline and the end of the third month. We found that after 12 weeks of treatment with risperidone, the body weight increased and clinical symptoms significantly improved. Baseline body mass index (BMI) was negatively correlated with negative symptom improvement after treatment and an increase in TAS was negatively associated with an increase in BMI only in the high BMI group. More importantly, the TAS × BMI interaction at baseline was an independent predictor of negative symptom improvement. Our longitudinal study indicates that the improvement in negative symptoms by risperidone was associated with baseline BMI and TAS levels in patients with SZ. Baseline BMI and TAS may be a predictor for negative improvement in SZ patients after risperidone treatment.

Establishment of an assistive diagnostic model for schizophrenia with oxidative stress biomarkers.

Objective: In this study, alterations in oxidative stress-related indicators were evaluated in drug-naïve, first-episode schizophrenia (SCZ) patients, and the effectiveness of blood serum glucose, superoxide dismutase (SOD), bilirubin in the objective assistive diagnosis of schizophrenia was explored. Materials and methods: We recruited 148 drug-naïve, first-episode SCZ patients and 97 healthy controls (HCs). Blood biochemical indexes including blood glucose, SOD, bilirubin and homocysteine (HCY) in participants were measured, the indexes were compared between patients with SCZ and HCs. The assistive diagnostic model for SCZ was established on the basis of the differential indexes. Results: In SCZ patients, the blood serum levels of glucose, total (TBIL), indirect bilirubin (IBIL) and homocysteine (HCY) were significantly higher than those in HCs (p < 0.05), and the serum levels of SOD were significantly lower than those in HCs (p < 0.05). There was a negative correlation between SOD with the general symptom scores and total scores of PANSS. After risperidone treatment, the levels of uric acid (UA) and SOD tended to increase in patients with SCZ (p = 0.02, 0.19), and the serum levels of TBIL and HCY tended to decrease in patients with SCZ (p = 0.78, 0.16). The diagnostic model based on blood glucose, IBIL and SOD was internally cross-validated, and the accuracy was 77%, with an area under the curve (AUC) of 0.83. Conclusion: Our study demonstrated an oxidative state imbalance in drug-naïve, first-episode SCZ patients, which might be associated with the pathogenesis of the disease. Our study proved that glucose, IBIL and SOD may be potential biological markers of schizophrenia, and the model based on these markers can assist the early objective and accurate diagnosis of schizophrenia.

Striatum-related spontaneous coactivation patterns predict treatment response on positive symptoms of drug-naive first-episode schizophrenia with risperidone monotherapy.

Evidence from functional magnetic resonance imaging (fMRI) studies of schizophrenia suggests that interindividual variation in the stationary striatal functional circuit may be correlated with antipsychotic treatment response. However, little is known about the role of the dynamic striatum-related network in predicting patients' clinical improvement. The spontaneous coactivation pattern (CAP) technique has recently been found to be important for elucidating the non-stationary nature of functional brain networks. Forty-two drug-naive first-episode schizophrenia patients underwent fMRI and T1W imaging before and after 8 weeks of risperidone monotherapy. The striatum was divided into 3 subregions, including the putamen, pallidum, and caudate. Spontaneous CAPs and CAP states were utilized to measure the dynamic characteristics of brain networks. We used DPARSF and Dynamic Brain Connectome software to analyze each subregion-related CAP and CAP state for each group and then compared the between-group differences in the neural network biomarkers. We used Pearson's correlation analysis to determine the associations between the neuroimaging measurements with between-group differences and the improvement in patients' psychopathological symptoms. In the putamen-related CAPs, patients showed significantly increased intensity in the bilateral thalamus, bilateral supplementary motor areas, bilateral medial, and paracingulate gyrus, left paracentral lobule, left medial superior frontal gyrus, and left anterior cingulate gyrus compared with healthy controls. After treatment, thalamic signals in the putamen-related CAP 1 showed a significant increase, while the signals of the medial and paracingulate gyrus in the putamen-related CAP 3 revealed a significant decrease. The increase in thalamic signal intensity in the putamen-related CAP 1 was significantly and positively correlated with the percentage reduction in PANSS_P. This study is the first to combine striatal CAPs and fMRI to explore treatment response-related biomarkers in the early phase of schizophrenia. Our findings suggest that dynamic changes in CAP states in the putamen-thalamus circuit may be potential biomarkers for predicting patients' variation in the short-term treatment response of positive symptoms.

Longitudinal multi-omics alterations response to 8-week risperidone monotherapy: Evidence linking cortical thickness, transcriptomics and epigenetics

Antipsychotic treatment-related alterations of cortical thickness (CT) and clinical symptoms have been previously corroborated, but less is known about whether the changes are driven by gene expression and epigenetic modifications. Utilizing a prospective design, we recruited 42 treatment-naive first-episode schizophrenia patients (FESP) and 38 healthy controls. Patients were scanned by TI weighted imaging before and after 8-week risperidone monotherapy. CT estimation was automatically performed with the FreeSurfer software package. Participants' peripheral blood genomic DNA methylation (DNAm) status, quantified by using Infinium® Human Methylation 450K BeadChip, was examined in parallel with T1 scanning. In total, CT measures from 118 subjects and genomic DNAm status from 114 subjects were finally collected. Partial least squares (PLS) regression was used to detect the spatial associations between longitudinal CT variations after treatment and cortical transcriptomic data acquired from the Allen Human Brain Atlas. Canonical correlation analysis (CCA) was then performed to identify multivariate associations between DNAm of PLS1 genes and patients' clinical improvement. We detected the significant PLS1 component (2,098 genes) related to longitudinal alterations of CT, and the PLS1 genes were significantly enriched in neurobiological processes, and dopaminergic- and cancer-related pathways. Combining Laplacian score and CCA analysis, we further linked DNAm of 33 representative genes from the 2,098 PLS1 genes with patients' reduction rate of clinical symptoms. This study firstly revealed that changes of CT and clinical behaviors after treatment may be transcriptionally and epigenetically underlied. We define a "three-step" roadmap which represents a vital step toward the exploration of treatment- and treatment response-related biomarkers on the basis of multiple omics rather than a single omics type as a strategy for advancing precise care.

Emotion-behaviour decoupling and experiential pleasure deficits predict negative symptoms and functional outcome in first-episode schizophrenia patients.

Emotion-behaviour decoupling refers to the failure to translate emotion into motivated behaviour, and is a putative marker for schizophrenia. The heterogeneity of experiential pleasure and emotion expressivity deficits has been reported in schizophrenia patients. These three constructs are believed to contribute to negative symptoms, but very few studies have examined their predictive ability for clinical and functional outcome of schizophrenia. This study aimed to clarify whether these three constructs influence clinical and functional outcome of schizophrenia. At baseline, 127 first-episode schizophrenia patients completed a behavioural paradigm for emotion-behaviour decoupling, and self-report scales for experiential pleasure and emotion expressivity deficits. Cluster-analysis was applied to characterize schizophrenia subgroups based on these three constructs. At end-point (mean follow-up = 5.37 years, SD = 1.03 years), 85 schizophrenia patients were reassessed using the Clinical Assessment Interview for Negative Symptoms (CAINS) and a clinician-rated social functioning scale. Cluster 1 (n=74) did not show emotion-behaviour decoupling, and had intact experiential pleasure and emotion expressivity. Cluster 2 (n=29) showed emotion-behaviour decoupling and experiential pleasure deficits. Cluster 3 (n=24) showed emotion expressivity deficits. At endpoint, the three clusters differed significantly in CAINS MAP factor (p=0.016) and social functioning (p=0.019), but not CAINS EXP factor. Specifically, Cluster 2 (n=18) showed more severe negative symptoms of CAINS MAP factor (p=0.046) and poorer social functioning (p=0.022) than Cluster 1 (n=49). Cluster 3 (n=18) did not differ from Cluster 1 and Cluster 2 in negative symptoms and social functioning. Emotion-behaviour decoupling and experiential pleasure deficits predicted clinical and functional outcome of schizophrenia.

Sleep disorders in patients with a first psychotic episode: a case-control study

Introduction Patients with chronic schizophrenia experience significant disturbances in the quality and quantity of their sleep and it had been mainly attributed to severity of symptoms and antipsychotic use. Recent studies suggested that antipsychotic-naïve early course patients with schizophrenia and their non-psychotic first-degree relatives also show altered sleep quality. Objectives In this study we aimed to compare sleep parameters in antipsychotic-naive first-episode schizophrenia patients to their healthy siblings and age- and sex-matched healthy controls. Methods We conducted a cross-sectional, descriptive case-control study in the Psychiatry « G » department at Razi Hospital, for a period of six months. Our sample consisted of three groups: a group of schizophrenic patients, a group of their healthy siblings and a group of healthy controls. The three groups were matched by age and sex. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of symptoms in patients with schizophrenia. The Morningness-Eveningness Questionnaire (MEQr), Epworth Sleepiness Scale (ESS), and Pittsburgh Sleep Quality Index (PSQI) were used in the three groups to assess Circadian preference, daytime sleepiness and sleep quality. Results There was no significant difference between the groups regarding the chronotype. Patients had significantly higher daytime sleepiness compared to siblings (p=0.001) and controls (p&lt;0.001). Patients also had poorer quality sleep (PSQI total score) than siblings (p&lt;0.001) and controls (p&lt;0.001), longer sleep latency than siblings (p=0.003) and controls (p&lt;0.001); lower habitual sleep efficiency than siblings (p=0.003) and controls (p&lt;0.001). Siblings had poorer sleep quality (p=0.001), longer sleep latency (p=0.006) and shorter sleep duration (p=0.033) compared to control subjects. Conclusions Our results joined those of the literature concerning the significant prevalence of sleep disorders in early psychosis. In addition, the alteration of sleep quality in unaffected siblings compared to healthy controls supports the hypotheses suggested in the literature that sleep disorders may be markers of genetic susceptibility to schizophrenia and serve as a potential endophenotype of the disease. Disclosure of Interest None Declared

Study on the Correlation between Psychological Defense Mechanism and Clinical Features in First-Episode Schizophrenia

Objective: To analyze the correlation between psychological defense mechanism and clinical features in patients with first-episode schizophrenia. Methods: During the period from June 2022 to 2023, a total of 120 patients with first-episode schizophrenia admitted to our hospital were selected as the observation group, and 120 healthy patients were selected as the control group. The correlation between psychological defense mechanism and clinical characteristics of first-episode schizophrenia patients was compared.Result:Compared with the healthy group, the use of immature defense mechanisms and intermediate defense mechanisms is significantly different in the first schizophrenia patients. The scores of various defense mechanisms in female patients are higher than those in male patients. The differences between fantasy, somatization and withdrawal in immature defense mechanisms and sublimation in mature defense mechanisms are obvious.After treatment, the negative scale score of male patients was higher than that of female patients (P &lt; 0.05). Conclusion: The immature psychological defense mechanism of first-episode schizophrenia is significant, and has a certain correlation with clinical characteristics, and there is a mutual influence relationship.

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.

Neuronal dysfunction in individuals at early stage of schizophrenia, A resting-state fMRI study

Schizophrenia has been associated with abnormal intrinsic brain activity, involving various cognitive impairments. Qualitatively similar abnormalities are seen in individuals at ultra-high risk (UHR) for psychosis. In this study, resting-state fMRI (rs-fMRI) data were collected from 44 drug-naïve first-episode schizophrenia (Dn-FES) patients, 48 UHR individuals, and 40 healthy controls (HCs). The fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and functional connectivity (FC), were performed to evaluate resting brain function. A support vector machine (SVM) was applied for classification analysis. Compared to HCs, both clinical groups showed increased fALFF in the central executive network (CEN), decreased ReHo in the ventral visual pathway (VVP) and decreased FC in temporal-sensorimotor regions. Excellent performance was achieved by using fALFF value in distinguishing both FES (sensitivity=83.21%, specificity=80.58%, accuracy=81.37%, p=0.009) and UHR (sensitivity=75.88%, specificity=85.72%, accuracy=80.72%, p<0.001) from HC group. Moreover, the study highlighted the importance of frontal and temporal alteration in the pathogenesis of schizophrenia. However, no fMRI features were observed that could well distinguish Dn-FES from UHR group. To conclude, fALFF in the CEN may provide potential power for identifying individuals at the early stage of schizophrenia and the alteration in the frontal and temporal lobe may be important to these individuals.

Comparative Analysis of the Pre- and Post-Medication Effects of Antipsychotic Agents on the Blood-Based Oxidative Stress Biomarkers in Patients with Schizophrenia: A Meta-Analysis.

Studies have shown that oxidative stress (OS) is related to the pathophysiology of schizophrenia (SCZ), but whether antipsychotics can induce OS has not been investigated well. Moreover, antipsychotics have differential effects on the OS level modulation, i.e., different types of antipsychotics have different effects on the cellular antioxidants or pro-oxidants. We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and investigated the OS indicators including both enzymatic and nonenzymatic markers, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), malondialdehyde (MDA), glutathione (GSH), vitamin C, etc., of SCZ patients at baseline and follow-up of mono-medication. Twenty studies met the inclusion criteria, with a total of 1162 patients enrolled at baseline, and 1105 patients completed the follow-up. OS markers were changed after a period of antipsychotic treatment in SCZ patients. The GPx activity and MDA level decreased in the whole blood (P<0.05), also the serum MDA level decreased (P<0.05). For the first-episode SCZ patients, the activity of GPx and the level of MDA decreased, while the level of vitamin C increased (all P<0.05). The levels of MDA in patients receiving atypical antipsychotics decreased (P<0.05), while the level of GSH in patients with typical antipsychotics decreased (P=0.05). Antipsychotic medication may cause changes in the levels of OS markers in different blood samples of SCZ patients. However, the available studies might not be sufficient to reveal the underlying facts accurately due to the poor quality of experimental designs in the published literature.

Virtual histology of morphometric similarity network after risperidone monotherapy and imaging-epigenetic biomarkers for treatment response in first-episode schizophrenia.

Antipsychotic treatment has been conceived to alter brain connectivity, but it is unclear how the changes of network phenotypes relate to the underlying transcriptomics. Given DNA methylation (DNAm) may alter transcriptional levels, we further integrated an imaging-transcriptomic-epigenetic analysis to explore multi-omics treatment response biomarkers. Forty-two treatment-naive first-episode schizophrenia patients were scanned by TI weighted (T1W) imaging and DTI before and after 8-week risperidone monotherapy, and their peripheral blood genomic DNAm values were examined in parallel with MRI scanning. Morphometric similarity network (MSN) quantified with DTI and T1W data were used as a marker of treatment-related alterations in interareal cortical connectivity. We utilized partial least squares (PLS) to examine spatial associations between treatment-related MSN variations and cortical transcriptomic data obtained from the Allen Human Brain Atlas. Longitudinal MSN alterations were related to treatment response on cognitive function and general psychopathology symptoms, while DNAm values of 59 PLS1 genes were on negative and positive symptoms. Virtual-histology transcriptomic analysis linked the MSN alterations with the neurobiological, cellular and metabolic pathways or processes, and assigned MSN-related genes to multiple cell types, specifying neurons and glial cells as contributing most to the transcriptomic associations of longitudinal changes in MSN. We firstly reveal how brain-wide transcriptional levels and cell classes capture molecularly validated cortical connectivity alterations after antipsychotic treatment. Our findings represent a vital step towards the exploration of treatment response biomarkers on the basis of multiple omics rather than a single omics type as a strategy for advancing precise care.

Altered static and dynamic functional connectivity of habenula in first-episode, drug-naïve schizophrenia patients, and their association with symptoms including hallucination and anxiety.

The pathogenesis of schizophrenia (SCH) is related to the dysfunction of monoamine neurotransmitters, and the habenula participates in regulating the synthesis and release of dopamine. We examined the static functional connectivity (sFC) and dynamic functional connectivity (dFC) of habenula in first-episode schizophrenia patients using resting state functional magnetic resonance imaging (rs-fMRI) in this study. A total of 198 first-Episode, drug-Naïve schizophrenia patients and 199 healthy controls (HC) underwent rs-fMRI examinations. The sFC and dFC analysis with habenula as seed was performed to produce a whole-brain diagram initially, which subsequently were compared between SCH and HC groups. Finally, the correlation analysis of sFC and dFC values with the Positive and Negative Symptom Scale (PANSS) were performed. Compared with the HC groups, the left habenula showed increased sFC with the bilateral middle temporal gyrus, bilateral superior temporal gyrus, and right temporal pole in the SCH group, and the right habenula exhibited increased sFC with the left middle temporal gyrus, left superior temporal gyrus, and left angular gyrus. Additionally, compared with the HC group, the left habenula showed decreased dFC with the bilateral cuneus gyrus and bilateral calcarine gyrus in the SCH group. The PANSS negative sub-scores were positively correlated with the sFC values of the bilateral habenula with the bilateral middle temporal gyrus, superior temporal gyrus and angular gyrus. The PANSS general sub-scores were positively correlated with the sFC values of the right habenula with the left middle temporal gyrus and left superior temporal gyrus. The hallucination scores of PANSS were negatively correlated with the sFC values of the left habenula with the bilateral cuneus gyrus and bilateral calcarine gyrus; The anxiety scores of PANSS were positively correlated with the dFC values of the left habenula with the right temporal pole. This study provides evidence that the habenula of the first-episode schizophrenia patients presented abnormal static functional connectivity with temporal lobe and angular gyrus, and additionally showed weakened stability of functional connectivity in occipital lobe. This abnormality is closely related to the symptoms of hallucination and anxiety in schizophrenia, which may indicate that the habenula involved in the pathophysiology of schizophrenia by affecting the dopamine pathway.

Epigenetic clock analysis of blood samples in drug-naive first-episode schizophrenia patients

BackgroundSchizophrenia (SCZ) is a severe and chronic psychiatric disorder with premature age-related physiological changes. However, numerous previous studies examined the epigenetic age acceleration in SCZ patients and yielded inconclusive results. In this study, we propose to explore the epigenetic age acceleration in drug-naive first-episode SCZ (FSCZ) patients and investigate whether epigenetic age acceleration is associated with antipsychotic treatment, psychotic symptoms, cognition, and subcortical volumes.MethodsWe assessed the epigenetic age in 38 drug-naive FSCZ patients and 38 healthy controls by using three independent clocks, including Horvath, Hannum and Levine algorithms. The epigenetic age measurements in SCZ patients were repeated after receiving 8 weeks risperidone monotherapy.ResultsOur findings showed significantly positive correlations between epigenetic ages assessed by three clocks and chronological age in both FSCZ patients and healthy controls. Compared with healthy controls, drug-naive FSCZ patients have a significant epigenetic age deceleration in Horvath clock (p = 0.01), but not in Hannum clock (p = 0.07) and Levine clock (p = 0.43). The epigenetic ages of Hannum clock (p = 0.002) and Levine clock (p = 0.01) were significantly accelerated in SCZ patients after 8-week risperidone treatment. However, no significant associations between epigenetic age acceleration and psychotic symptoms, cognitive function, as well as subcortical volumes were observed in FSCZ patients.ConclusionThese results demonstrate that distinct epigenetic clocks are sensitive to different aspects of aging process. Further investigations with comprehensive epigenetic clock analyses and large samples are required to confirm our findings.

Longitudinal changes of cognitive function and its relationship with subdomains of negative symptoms in patients with adult-onset first-episode schizophrenia: A 4-year follow up study

BackgroundsThis study explores the longitudinal changes and trajectories of cognitive functions in patients with adult-onset first-episode schizophrenia (FES) over four years and their relationships with the baseline subdomains of negative symptoms. MethodsA total of 177 patients of age 25–55 with FES were recruited. Baseline demographics, clinical, social and cognitive functions were assessed. Diminished expression and diminished motivation of negative symptoms were assessed with Scale for the Assessment of Negative Symptoms (SANS). Patients had yearly follow-up of cognitive function assessments over four years. Latent class growth analysis (LCGA) and mixed linear regression model were used to explore the longitudinal changes of cognitive functions and the effect of baseline negative symptoms on the longitudinal cognitive function changes. Relationships of baseline negative symptoms subdomains and cognitive functions were also explored. ResultsTwo trajectories of cognitive functions were identified. Longitudinal improvements were found in most cognitive functions apart from the logical memory. One trajectory of patients had significant deterioration of logical memory while the other group had significant improvement. Baseline diminished expression was associated with baseline and longitudinal changes of processing speed and verbal fluency while diminished motivation was associated with baseline and longitudinal changes of processing speed. ConclusionsAdult-onset FES patients had a homogeneous longitudinal improvement in most cognitive functions but not for logical memory suggesting the unique nature of verbal memory. The distinct relationship between baseline subdomains of negative symptoms with baseline and longitudinal cognitive functions suggesting the presence of differential overlapping etiology between negative symptom subdomains and cognitive functions.

Neurological soft signs and structural network changes: a longitudinal analysis in first-episode schizophrenia

BackgroundNeurological soft signs (NSS) are often reported in patients with schizophrenia and may vary with psychopathological symptoms during the course of disease. Many cross-sectional neuroimaging studies have shown that NSS are associated with disturbed network connectivity in schizophrenia. However, it remains unclear how these associations change over time during the course of disorder.MethodsIn present study, 20 patients with first-episode schizophrenia and 20 controls underwent baseline structural magnetic resonance imaging (MRI) scan and at one-year follow-up. Structural network characteristics of patients and controls were analyzed using graph theoretical approach based on MRI data. NSS were assessed using the Heidelberg scale.ResultsAt baseline, patients demonstrated significant changes of the local network properties mainly involving regions of the cortical-subcortical-cerebellar circuits compared to healthy controls. For further analysis, the whole patient group was dichotomized into a NSS-persisting and NSS-decreasing subgroup. After one-year follow-up, the NSS-persisting subgroup showed decreased betweenness in right inferior opercular frontal cortex, left superior medial frontal cortex, left superior temporal cortex, right putamen and cerebellum vermis and increased betweenness in right lingual cortex. However, the NSS-decreasing subgroup exhibited only localized changes in right middle temporal cortex, right insula and right fusiform with decreased betweenness, and in left lingual cortex with increased betweenness.ConclusionsThese findings provide evidence for brain network reorganization subsequent to clinical disease manifestation in patients with first-episode schizophrenia, and support the hypothesis that persisting NSS refer to progressive brain network abnormalities in patients with schizophrenia. Therefore, NSS could help to establish a better prognosis in first-episode schizophrenia patients.

Hypercoagulable state in patients with schizophrenia: different effects of acute and chronic antipsychotic medications.

Previous studies reported higher incidences of venous thromboembolism and cardiovascular disease in schizophrenia patients and higher indicators of thrombosis, thrombocyte activation, and platelet dysfunction. To check if first-episode schizophrenia (FES) patients have a hypercoagulable state and determine whether acute and chronic antipsychotics have the same effect on blood coagulation or fibrinolysis-related biomarkers. Case-control study. A total of 81 participants were grouped in FES, chronic schizophrenia (CS), and healthy controls (HCs). In addition to demographic data and clinical characteristics, immunological analyses were performed to measure plasma levels of D-dimer, plasminogen activator inhibitor-1 (PAI-1), soluble P selectin (sP-sel), tissue plasminogen activator (tPA), thrombotic precursor protein (TpP), and von Willebrand's disease factor (vWF). Compared to HC group, FES patients showed higher PAI-1 (28.61 ng/ml versus 15.69 ng/ml), sP-sel (2.78 ng/ml versus 1.18 ng/ml), and TpP (15.61 µg/ml versus 5.59 µg/ml) along with a higher PAI-1/tPA (3.12 versus 2.00). Acute antipsychotic medication reduced higher PAI-1 (28.61 → 21.99), sP-sel (2.78 → 1.87), tPA (9.59 → 5.83), TpP (15.61 → 10.54), and vWF (383.18 → 291.08) in FES patients. However, plasma sP-sel and vWF in CS patients returned to the pre-treatment levels in FES patients, and PAI-1/tPA significantly decreased compared to FES patients. These results suggest a hypercoagulable state in FES patients and demonstrate contrast effects of acute and chronic antipsychotics on coagulation or fibrinolysis in schizophrenia patients.

Blood Viscosity and Inflammation in First-Episode and Acute Exacerbations of Schizophrenia: A Case-Control Study with Healthy Controls.

Elevated proinflammatory status and alterations in blood flow, both of which are associated with the pathophysiology of schizophrenia, may be linked with an increased risk of cardiovascular diseases. However, such a relationship at different acute stages of schizophrenia has not been evaluated. We aimed to examine whether blood viscosity and systemic inflammatory status varied between first-episode schizophrenia (FES) and acute exacerbations of schizophrenia. Fifty-two patients with FES, 69 schizophrenia patients with acute exacerbation (S-AE) and 56 healthy controls (HC) were included in the study. Whole blood viscosity (WBV) was calculated according to de Simone's formula at low and high shear rates (LSR and HSR). Systemic immune-inflammation index (SII) and systemic inflammatory response index (SIRI) were calculated from hemogram screening data at admission. When adjusted for age, WBV at both LSR and HSR were significantly decreased in both FES and S-AE groups compared to HCs. Systemic inflammatory response index was significantly higher in FES patients than in the S-AE and HC groups. Total cholesterol (TC) and WBV at HSR were correlated in patients. Total cholesterol predicted WBV at LSR in patients with FES whereas other independent variables including age and SIRI did not. Both first and subsequent episodes of schizophrenia are associated with reduced blood viscosity. Increased inflammatory status may not fully explain such a relationship. Extrapolation of hemorheological characteristics in schizophrenia may help to stratify cardiovascular risk and reflect the pathophysiological process in the early and later stages of schizophrenia.

Eye Movement Abnormalities Can Distinguish First-Episode Schizophrenia, Chronic Schizophrenia, and Prodromal Patients From Healthy Controls.

This study attempts to replicate in a Chinese population an earlier UK report that eye movement abnormalities can accurately distinguish schizophrenia (SCZ) cases from healthy controls (HCs). It also seeks to determine whether first-episode SCZ differ from chronic SCZ and whether these eye movement abnormalities are enriched in psychosis risk syndrome (PRS). The training set included 104 Chinese HC and 60 Chinese patients with SCZ, and the testing set included 20 SCZ patients and 20 HC from a UK cohort. An additional 16 individuals with PRS were also enrolled. Eye movements of all participants were recorded during free-viewing, smooth pursuit, and fixation stability tasks. Group differences in 55 performance measures were compared and a gradient-boosted decision tree model was built for predictive analyses. Extensive eye-movement abnormalities were observed in patients with SCZ on almost all eye-movement tests. On almost all individual variables, first-episode patients showed no statistically significant differences compared with chronic patients. The classification model was able to discriminate patients from controls with an area under the curve of 0.87; the model also classified 88% of PRS individuals as SCZ-like. Our findings replicate and extend the UK results. The overall accuracy of the Chinese study is virtually identical to the UK findings. We conclude that eye-movement abnormalities appear early in the natural history of the disorder and can be considered as potential trait markers for SCZ diathesis.