First-episode Drug-naive Schizophrenia Research Articles

Smoking, Symptoms Improvement, and Total Antioxidant Capacity in Patients with Drug-naive First-episode Schizophrenia: A Prospective Cohort Study.

It has been hypothesized that smoking is associated with the severity of negative symptoms. Until now, no studies have investigated whether the impact of smoking on negative symptoms is dependent on antioxidants. This study was designed to evaluate the effect of smoking on therapeutic response and total antioxidants capacity (TAOC) in antipsychotic-naïve first-episode (ANFE) patients. The severity of the patient's symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). A total of 237 ANFE patients were recruited and treated with risperidone (oral tablets, 4-6 mg/day twice a day) for 12 weeks. PANSS was assessed at baseline and a 12-week follow-up. Plasma TAOC levels were also assayed at baseline and week 12. Relative to nonsmokers with ANFE SZ, smokers had higher PANSS negative subscores. There was no significant difference in TAOC changes after 12 weeks of treatment with risperidone between smokers and non-smokers. However, we found greater improvement in negative symptoms in smokers compared to non-smokers. Further analysis in smokers with SZ demonstrated that improvements in negative symptoms were not associated with changes in TAOC. Our study suggested that smoking affected the severity of baseline negative symptoms and further contributed to their reduction after risperidone treatment. However, improvement in negative symptoms was not dependent on the changes in TAOC.

The altered volume of striatum: A neuroimaging marker of treatment in first-episode and drug-naïve schizophrenia

Although schizophrenia patients exhibit structural abnormalities in the striatum, it remains largely unknown for the role of the striatum subregions in the treatment response of antipsychotic drugs. The purpose of this study was to investigate the associations between the striatal subregions and improved clinical symptoms in first-episode drug-naïve (FEDN) schizophrenia. Forty-two FEDN schizophrenia patients and 29 healthy controls (HCs) were recruited. At baseline, the Positive and Negative Syndrome Scale (PANSS) was used to assess the clinical symptoms of patients, MRI scanner was used to obtain anatomical images of patients and HCs. After 12-week stable doses of risperidone treatment, clinical symptoms were obtained in 38 patients and anatomical images in 26 patients. After 12 weeks of treatment, the left nucleus accumbens volume decreased, whereas the left pallidum volume increased in schizophrenia patients. The decreased left nucleus accumbens volume was positively correlated with cognitive factor improvement measured by PANSS. Intriguingly, greater left nucleus accumbens volume at baseline predicted greater cognitive improvements. Furthermore, the responders who had >50 % improvement in cognitive symptoms exhibited significantly greater baseline left nucleus accumbens volume compared to non-responders. The left striatum volume at baseline and after treatment predicted the cognitive improvements in FEDN schizophrenia, which could be a potential biomarker for the development of precision medicine approaches targeting cognitive function.

Association between increased BMI and cognitive function in first-episode drug-naïve male schizophrenia.

Although the adverse effects of obesity in schizophrenia are documented, there is limited research exists on the implications for untreated initial schizophrenia. Our investigation aimed to explore the connections between BMI and cognitive function in first-episode drug-naïve (FEDN)schizophrenia. We enrolled 143 FEDN schizophrenia patients, and collected data on their body mass index, fasting blood glucose and lipid levels. Cognitive function was measured with the MATRICS Consensus Cognitive Battery (MCCB). Using correlation and regression analysis to assess the relationship between BMI and cognitive performance. The prevalence rate of overweight plus obesity in FEDN schizophrenia patients was 33.57%. Patients with FEDN schizophrenia exhibited extensive cognitive impairment, and those who were overweight/obesity demonstrated more severe impairments in working memory and visual learning when compared to normal/under weight counterparts. Correlation analysis indicated a negative association between working memory and BMI and TG, as well as a link between visual learning and BMI and LDL-C. Multiple linear regression analysis revealed that a higher BMI predicted a decrease in working memory in FEDN schizophrenia patients. Our results indicate that the rate of overweight plus obesity is high in FEDN schizophrenia patients, and there is an association between BMI and cognitive function in schizophrenia, particularly in relation to working memory.

The effect of continuous theta burst stimulation on antipsychotic-induced weight gain in first-episode drug-naive individuals with schizophrenia: a double-blind, randomized, sham-controlled feasibility trial

Antipsychotic intake may induce weight gain in drug-naive individuals with schizophrenia, leading to poor compliance in clinical management. However, there is still a lack of effective approaches to treat or prevent this side-effect. Therefore, we conducted this pilot study to investigate the effect of continuous theta burst stimulation (cTBS), a non-invasive magnetic stimulation technique, on preventing olanzapine-induced weight gain. Thirty-nine first-episode drug-naive individuals with schizophrenia were randomly assigned to receive either the active or sham cTBS intervention for 25 sessions (5 times per day for 5 consecutive days). The primary outcomes were changes in body weight and body mass index (BMI). Secondary outcomes included psychiatric symptoms, eating behavior scales, behavior tasks, and metabolic measures. For the result, the body weight and BMI increased significantly in the sham group but not in the active group, with a significant group effect. The active group exhibited a selective increase in the cognitive restraint domain in the Three-Factor Eating Questionnaire (TFEQ-CR) and a decrease in stop-signal reaction time compared to the sham group. The effect of cTBS on body weight was mediated by TFEQ-CR. Our findings demonstrated the feasibility that cTBS intervention could be a potential method for preventing olanzapine-induced weight gain in drug-naive first-episode schizophrenia patients through enhancing cognitive restraint to food. Trial registration: clinical trial registered with clinicaltrials.gov (NCT05086133).

Evaluation of the Correlation Between Peripheral Inflammatory Markers and Suicide Risk in Drug-Naive First-Episode Schizophrenia

Evaluation of the Correlation Between Peripheral Inflammatory Markers and Suicide Risk in Drug-Naive First-Episode Schizophrenia

The contribution of the cingulate cortex: treating depressive symptoms in first-episode drug naïve schizophrenia.

Our previous study has shown the cingulate cortex abnormalities in first-episode drug naïve (FEDN) schizophrenia patients with comorbid depressive symptoms. However, it remains largely unknown whether antipsychotics may induce morphometric change in cingulate cortex and its relationship with depressive symptoms. The purpose of this study was to further clarify the important role of cingulate cortex in the treatment on depressive symptoms in FEDN schizophrenia patients. In this study, 42 FEDN schizophrenia patients were assigned into depressed patients group (DP, n=24) and non-depressed patients group (NDP, n=18) measured by the 24-item Hamilton Depression Rating Scale (HAMD). Clinical assessments and anatomical images were obtained from all patients before and after 12-week treatment with risperidone. Although risperidone alleviated psychotic symptoms in all patients, depressive symptoms were decreased only in DP. Significant group by time interaction effects were found in the right rostral anterior cingulate cortex (rACC) and other subcortical regions in the left hemisphere. After risperidone treatment, the right rACC were increased in DP. Further, the increasing volume of right rACC was negatively associated with improvement in depressive symptoms. These findings suggested that the abnormality of the rACC is the typical characteristics in schizophrenia with depressive symptoms. It's likely key region contributing to the neural mechanisms underlying the effects of risperidone treatment on depressive symptoms in schizophrenia.

Association of dopamine-based genetic risk score with dynamic low-frequency fluctuations in first-episode drug-naïve schizophrenia.

Alterations in dynamic intrinsic brain activity and signaling of neurotransmitters, such as dopamine, have been independently detected in schizophrenia patients. Yet, it remains unclear whether the dopamine genetic risk variants have association with brain intrinsic activity. We aimed to investigate the schizophrenia-specific dynamic amplitude of low frequency fluctuation (dALFF) altered pattern, and its association with dopamine genetic risk score in first-episode drug-naïve schizophrenia (FES). Fifty-two FES and 51 healthy controls were included. A sliding-window method based on the dALFF was adopted to estimate the dynamic alterations in intrinsic brain activity. Subjects were genotyped, and a genetic risk score (GRS), which combined the additive effects of ten risk genotypes from five dopamine-related genes, was calculated. We used the voxel-wise correlation analysis to explore the association of dopamine-GRS with dALFF. FES showed significantly increased dALFF left medial prefrontal cortex and significantly decreased dALFF in the right posterior cingulate cortex compared with healthy controls. Greater dopamine GRS in FES was associated with higher dALFF in the left middle frontal gyrus and left inferior parietal gyrus. Our findings indicate that cumulative dopamine genetic risk is associated with a known imaging phenotype for schizophrenia.

The month of walking alone and BDNF level differ between drug-naive first-episode schizophrenia patients and healthy controls.

Schizophrenia is a neurodevelopmental disorder, characterized by impairment in reasoning, affectivity, and social relationships. Previous studies have shown delayed motor development and Brain-Derived Neurotrophic Factor (BDNF) level change in individuals with schizophrenia. We researched the month of walking alone (MWA) and BDNF level between drug-naive first-episode schizophrenia patients (FEP) and healthy control (HC), as well as how they behave in neurocognitive function and severity of symptoms. Predictors of schizophrenia were further explored too. We researched the MWA and BDNF levels between FEP and HCs in the Second Xiangya Hospital of Central South University from August 2017 to January 2020, as well as how they behave in neurocognitive function and the severity of symptoms. A binary logistic regression analysis was used to examine the risk factors affecting the onset and treatment outcome of schizophrenia. We find that FEP showed a walking delay and lower BDNF levels compared to HCs, which were associated with cognitive impairment and severity of symptoms. According to the difference and correlation analysis results, and combined with the appropriate application conditions for binary logistic regression, Wechsler Intelligence Scale Picture completion, Hopkins Verbal Learning Test-Revised, and Trail Making Test: part A were added to the binary logistic regression analysis to distinguish FEP and HCs. Our study has shown delayed motor development and changes in BDNF levels in schizophrenia, extending insight into the early identification of patients with schizophrenia versus healthy populations.

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.

Hippocampal Development Deviation and Its Relationship With Cognition in Major Psychiatric Disorders

To investigate hippocampal development deviation and its association with cognition in patients with major psychiatric disorders (MPDs), including schizophrenia, bipolar disorder and major depressive disorder. The T1-weighted MRI data of 174 first-episode drug-naïve schizophrenia (FES) atients, 169 bipolar disorder (BD) patients, 184 major depressive disorder (MDD) patients, and 321 healthy controls were collected and their hippocampal volume was extracted after preprocessing with Freesurfer 5.3. A normative neurodevelopment model was applied to calculate the hippocampal deviation scores. Data on cognitive functions, including visual memory, attention, spatial working memory, were collected. Comparison by different sexes was made to identify difference between the hippocampal development deviation scores of the control group and those of the disease groups. We also investigated the moderating effect of age on the deviation score and explored the association between the deviation score and cognitive function. The hippocampal development deviation scores of patients with MPDs were significantly lower than those of the healthy controls (false discovery rate [FDR]-P<0.05). Analysis of the moderating effect of age revealed lower deviation scores in young patients (<[25.83-28.56] yr.) and higher deviation scores in old patients (>[35.87-54.35] yr.) in comparison with those of the healthy controls. The right hippocampal deviation scores in male FES patients were positively correlated with the number of errors for tasks concerning spatial working memory ( r=0.32, FDR-P=0.04). Our findings suggest abnormal hippocampal development in MPDs patients and its different distribution in MPDs patients of different age groups. The hippocampal development deviation score may provide a new perspective for further understanding of etiology in MPDs.

P50 inhibition defects, psychopathology and gray matter volume in patients with first-episode drug-naive schizophrenia.

Sensory gating deficits and gray matter volume (GMV) abnormalities have been found to be associated with the pathogenesis and psychopathology of patients with schizophrenia (SCZ). However, no studies have investigated their interrelationship in first-episode treatment-naive (FETN) SCZ patients. We recruited 52 FETN SCZ patients and 57 healthy controls. The Positive and Negative Syndrome Scale (PANSS) was used to measure the psychopathology of the patients. We collected magnetic resonance imaging and P50 inhibition data from all participants. Compared to healthy controls, patients had shorter S1 and S2 latencies but larger S2 amplitudes and P50 ratio (Bonferroni adjusted all p<0.01). In patients, S2 latency was independently associated with PANSS total score, negative symptoms and general psychopathology (t=2.26-2.58, both P<0.05), whereas S1 (t=2.44, P<0.05) and S2 latencies (t=2.13, P<0.05) were associated with PANSS cognitive factor. Moreover, GMV in the left inferior temporal gyrus, left lingual gyrus and right superior occipital gyrus, and bilateral dorsolateral superior frontal gyrus were each associated with the P50 components (all p<0.05). In addition, GMV associated with S2 latency was negatively correlated with PANSS general psychopathology (t=-2.46, p<0.05) and total score (t=-2.34, p<0.05). Our findings indicate that FETN SCZ patients exhibit deficits in P50 inhibition and GMV of brain regions associated with these deficits may be associated with their psychopathological symptoms, suggesting that brain structures associated with P50 components may be important biomarkers of SCZ psychopathology. Future studies could use a prospective longitudinal design to investigate the potential causal relationship of brain structures associated with P50 components in the psychopathological symptoms of SCZ patients.

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.

Altered controllability of white matter networks and related brain function changes in first-episode drug-naive schizophrenia.

Understanding how structural connectivity alterations affect aberrant dynamic function using network control theory will provide new mechanistic insights into the pathophysiology of schizophrenia. The study included 140 drug-naive schizophrenia patients and 119 healthy controls (HCs). The average controllability (AC) quantifying capacity of brain regions/networks to shift the system into easy-to-reach states was calculated based on white matter connectivity and was compared between patients and HCs as well as functional network topological and dynamic properties. The correlation analysis between AC and duration of untreated psychosis (DUP) were conducted to characterize the controllability progression pattern without treatment effects. Relative to HCs, patients exhibited reduced AC in multiple nodes, mainly distributed in default mode network (DMN), visual network (VN), and subcortical regions, and increased AC in somatomotor network. These networks also had impaired functional topology and increased temporal variability in dynamic functional connectivity analysis. Longer DUP was related to greater reductions of AC in VN and DMN. The current study highlighted potential structural substrates underlying altered functional dynamics in schizophrenia, providing a novel understanding of the relationship of anatomic and functional network alterations.

Smoke, GPx activity and symptoms improvement in patients with drug-naive first-episode schizophrenia: A large-scale 12-week follow-up study.

The relationship between tobacco smoke and schizophrenia (SZ) is well established. Smoking is hypothesized to alleviate symptoms and reduce the adverse effects of antipsychotic medications in patients with SZ. However, the underlying biological mechanisms by which smoke improves symptoms in SZ remain unclear. The aim of this study was to investigate the effect of smoking on clinical symptoms and antioxidant enzyme activity after risperidone treatment in a 12-week prospective cohort study of drug-naïve first-episode (DNFE) SZ patients. Two hundred and fifteen DNFE patients were recruited and received 12 weeks of risperidone monotherapy. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of patient's symptoms at baseline and post-treatment. Plasma GPx activity was also measured at baseline and at the end of 12 weeks. Smokers showed greater improvement in negative symptoms relative to nonsmokers with DNFE SZ. In addition, repeated ANCOVA analysis showed no significant interaction of time and group on GPx activity. Improvement in negative symptoms was not associated with changes in GPx activity. However, in nonsmokers, increased GPx activity was correlated with improvement in positive symptoms.

Risperidone-induced changes in DNA methylation in peripheral blood from first-episode schizophrenia patients parallel changes in neuroimaging and cognitive phenotypes

BackgroundSecond generation antipsychotics such as risperidone are first-line pharmacotherapy treatment choices for schizophrenia. However, our ability to reliably predict and monitor treatment reaction is impeded by the lack of relevant biomarkers. As a biomarker for the susceptibility of schizophrenia and clozapine treatment response, DNA methylation (DNAm) has been studied, but the impact of antipsychotics on DNAm has not been explored in drug-naïve patients. ObjectiveThe aim of the present study was to examine changes of DNAm after short-term antipsychotic therapy in first-episode drug-naïve schizophrenia (FES) to identify the beneficial and adverse effect of risperidone on DNAm and their relation to treatment outcome. MethodsThirty-eight never treated schizophrenia patients and 38 demographically matched individuals (healthy controls) were assessed at baseline and at 8-week follow-up with symptom ratings, and cognitive and functional imaging procedures, at which time a blood draw for DNAm studies was performed. During the 8-week period, patients received treatment with risperidone monotherapy. An independent data set was used as replication. ResultsWe identified brain related pathways enriched in 4,888 FES-associated CpG sites relative to controls. Risperidone administration in patients altered DNAm in 5,979 CpG sites relative to baseline. Significant group differences in DNAm at follow-up were seen in FES patients at 6,760 CpG sites versus healthy controls. Through comparison of effect size, we found 87.54% out of the risperidone-associated changes in DNAm showed possible beneficial effect, while only 12.46% showed potential adverse effect. There were 580 DNAm sites in which changes shifted methylation levels to be indistinguishable from controls after risperidone treatment. The DNAm changes of some sites that normalized after treatment were correlated with treatment-related changes in symptom severity, spontaneous neurophysiological activity, and cognition. We replicated our results in an independent data set. ConclusionThe normalizing effect of risperidone monotherapy on gene DNAm, and its correlation with clinically relevant phenotypes, indicates that risperidone therapy is associated with DNAm changes that are related to changes in brain physiology, cognition and symptom severity.

Genetic mechanisms underlying gray matter volume changes in patients with drug-naive first-episode schizophrenia.

Brain structural damage is a typical feature of schizophrenia. Investigating such disease phenotype in patients with drug-naive first-episode schizophrenia (DFSZ) may exclude the confounds of antipsychotics and illness chronicity. However, small sample sizes and marked clinical heterogeneity have precluded definitive identification of gray matter volume (GMV) changes in DFSZ as well as their underlying genetic mechanisms. Here, GMV changes in DFSZ were assessed using a neuroimaging meta-analysis of 19 original studies, including 605 patients and 637 controls. Gene expression data were derived from the Allen Human Brain Atlas and processed with a newly proposed standardized pipeline. Then, we used transcriptome-neuroimaging spatial correlations to identify genes associated with GMV changes in DFSZ, followed by a set of gene functional feature analyses. Meta-analysis revealed consistent GMV reduction in the right superior temporal gyrus, right insula and left inferior temporal gyrus in DFSZ. Moreover, we found that these GMV changes were spatially correlated with expression levels of 1,201 genes, which exhibited a wide range of functional features. Our findings may provide important insights into the genetic mechanisms underlying brain morphological abnormality in schizophrenia.

Altered Coupling of Cerebral Blood Flow and Functional Connectivity Strength in First-Episode Schizophrenia Patients With Auditory Verbal Hallucinations.

ObjectiveAuditory verbal hallucinations (AVHs) are a major symptom of schizophrenia and are connected with impairments in auditory and speech-related networks. In schizophrenia with AVHs, alterations in resting-state cerebral blood flow (CBF) and functional connectivity have been described. However, the neurovascular coupling alterations specific to first-episode drug-naïve schizophrenia (FES) patients with AVHs remain unknown.MethodsResting-state functional MRI and arterial spin labeling (ASL) was performed on 46 first-episode drug-naïve schizophrenia (FES) patients with AVHs (AVH), 39 FES drug-naïve schizophrenia patients without AVHs (NAVH), and 48 healthy controls (HC). Then we compared the correlation between the CBF and functional connection strength (FCS) of the entire gray matter between the three groups, as well as the CBF/FCS ratio of each voxel. Correlation analyses were performed on significant results between schizophrenia patients and clinical measures scale.ResultsThe CBF/FCS ratio was reduced in the cognitive and emotional brain regions in both the AVH and NAVH groups, primarily in the crus I/II, vermis VI/VII, and cerebellum VI. In the AVH group compared with the HC group, the CBF/FCS ratio was higher in auditory perception and language-processing areas, primarily the left superior and middle temporal gyrus (STG/MTG). The CBF/FCS ratio in the left STG and left MTG positively correlates with the score of the Auditory Hallucination Rating Scale in AVH patients.ConclusionThese findings point to the difference in neurovascular coupling failure between AVH and NAVH patients. The dysfunction of the forward model based on the predictive and computing role of the cerebellum may increase the excitability in the auditory cortex, which may help to understand the neuropathological mechanism of AVHs.

Aberrant cortical surface and cognition function in drug-naive first-episode schizophrenia

ObjectiveImpaired cognitive function is a central symptom of schizophrenia and is often correlated with inferior global functional outcomes. However, the role of some neurobiological factors such as cortical structure alterations in the underlying cognitive damages in schizophrenia remains unclear. The present study attempted to explore the neurobiomarkers of cognitive function in drug-naive, first-episode schizophrenia by using structural magnetic resonance imaging (MRI).MethodsThe present study was conducted in patients with drug-naive, first-episode schizophrenia (SZ) and healthy controls (HCs). MRI T1 images were pre-processed using CAT12. Surface-based morphometry (SBM) was utilised to evaluate structural parameters such as cortical thickness and sulcus depth. The positive and negative syndrome scale (PANSS) and Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) consensus cognitive battery (MCCB) were employed to estimate the psychotic symptoms and cognition, respectively.ResultsA total of 117 patients with drug-naive first-episode schizophrenia (SZ) and 98 healthy controls (HCs) were included. Both the cortical thickness and sulcus depth in the frontal lobe were lower in patients with SZ than in the HCs under family-wise error correction (p < 0.05). Attention and visual learning in MCCB were positively correlated with the right lateral orbitofrontal cortical thickness in the patients with SZ (p < 0.01).ConclusionsThe reduced surface value of multiple cortical structures, particularly the cortical thickness and sulcus depth in the frontal lobe, could be the potential biomarkers for cognitive impairment in SZ.

Lack of neural load modulation explains attention and working memory deficits in first-episode schizophrenia

ObjectiveAlthough working memory (WM) deficits are well-recognized core features of schizophrenia, the underlying pathophysiological substrates of impairment in early psychosis before medication remain unclear. One possibility is that deficits in selective attention contribute to WM impairment. MethodsEEG was acquired from 25 first-episode drug-naive schizophrenia patients and 26 matched controls while they performed a WM task. ResultsCompared with controls, schizophrenia patients showed a deficit in WM capacity in both behavioral and electrophysiological measures. Notably, the increased parieto-occipital pre-encoding stimulus alpha power in patients with schizophrenia predicted their subsequent reduced N2pc and symptom severity, whereas this relationship was absent in controls. Moreover, lacking load effect in neural activities predicted the serious impairment in behavior for schizophrenia. ConclusionsThis pilot study provides preliminary evidence that the lack of load effect in neural activities may serve as potential underlying mechanisms for the impaired selective attention and WM capacity in schizophrenia. Our results emphasize the importance of pre-encoding stimulus alpha power in first-episode drug-naive schizophrenia. SignificanceThese findings provide a neurophysiological correlate for the subjective reports of working memory deficits in schizophrenia and indicate the potential effective targets for clinical intervention.

Discriminative Analysis of Schizophrenia Patients Using Topological Properties of Structural and Functional Brain Networks: A Multimodal Magnetic Resonance Imaging Study.

Interest in the application of machine learning (ML) techniques to multimodal magnetic resonance imaging (MRI) data for the diagnosis of schizophrenia (SZ) at the individual level is growing. However, a few studies have applied the features of structural and functional brain networks derived from multimodal MRI data to the discriminative analysis of SZ patients at different clinical stages. In this study, 205 normal controls (NCs), 61 first-episode drug-naive SZ (FESZ) patients, and 79 chronic SZ (CSZ) patients were recruited. We acquired their structural MRI, diffusion tensor imaging, and resting-state functional MRI data and constructed brain networks for each participant, including the gray matter network (GMN), white matter network (WMN), and functional brain network (FBN). We then calculated 3 nodal properties for each brain network, including degree centrality, nodal efficiency, and betweenness centrality. Two classifications (SZ vs. NC and FESZ vs. CSZ) were performed using five ML algorithms. We found that the SVM classifier with the input features of the combination of nodal properties of both the GMN and FBN achieved the best performance to discriminate SZ patients from NCs [accuracy, 81.2%; area under the receiver operating characteristic curve (AUC), 85.2%; p < 0.05]. Moreover, the SVM classifier with the input features of the combination of the nodal properties of both the GMN and WMN achieved the best performance to discriminate FESZ from CSZ patients (accuracy, 86.2%; AUC, 92.3%; p < 0.05). Furthermore, the brain areas in the subcortical/cerebellum network and the frontoparietal network showed significant importance in both classifications. Together, our findings provide new insights to understand the neuropathology of SZ and further highlight the potential advantages of multimodal network properties for identifying SZ patients at different clinical stages.