Two distinct enriched housings differentially ameliorate object and place recognition deficits in a rat model of schizophrenia.

Schizophrenia is a psychiatric disorder characterized by cognitive dysfunctions. These dysfunctions significantly impact the daily lives of schizophrenic patients, yet effective interventions remain scarce. In this study, we explored the effects of two enriched housing types-cognitive and physical-on cognitive dysfunctions in a rat model of schizophrenia. Male neonatal Wistar-Imamichi rats were administered MK-801, a noncompetitive NMDAR antagonist, twice daily from postnatal day (PND) 7 to PND 20. Physical enrichment ameliorated memory deficits in both object and place recognition tests, while cognitive enrichment primarily improved object recognition performance. Our findings suggest that exercise therapy could be a potential approach to address cognitive dysfunctions in schizophrenia patients.

Acute and chronic response of supervised band-elastic resistance exercise in systemic cytokines levels of bipolar disorders and schizophrenia individuals: A pilot study.

Despite earlier research demonstrating the immunomodulatory effects of acute and chronic exercise in many medical illnesses, there is a lack of literature evaluating the acute and chronic effects of exercise on the cytokine levels in individuals with bipolar disorder (BD) or schizophrenia (SCH). This study aims to examine the acute effects of resistance exercise on cytokines and the chronic effects of resistance exercise by 10 weeks on cytokine levels, symptoms of disease, and muscular strength in individuals with BD and SCH. The included individuals (N=10) performed a single session of band-elastic resistance exercises (six exercises, 3 sets of 12-15 repetitions, 60 seconds of interval between sets). A sub-sample (N=6) of individuals performed a supervised band-elastic resistance exercise program (2 times a week, for 10 weeks, 6 exercises, 3 sets of 12-15 repetitions, 60 seconds of interval). We verified for acute effects: IL-2 (P=0.0085) and IL-4 (P=0.0253) levels increased, while IL-6 decreased (P=0.0435), and for chronic effects: increased IL-2 and IL-4 levels (significant effect size - Pre vs Post), a decrease in disease symptoms, and an increase in muscular strength. This study adds to what is already known about how resistance exercises affect people with BD and SCH in both short-term (systemic cytokines levels) and long-term (symptoms of disease, muscular strength, and systemic cytokines levels).

Dopamine D1 receptors activation rescues hippocampal synaptic plasticity and cognitive impairments in the MK-801 neonatal schizophrenia model.

Schizophrenia is a disorder with a higher cognitive decline in early adulthood, causing impaired retention of episodic memories. However, the physiological and behavioral functions that underlie cognitive deficits with a potential mechanism to ameliorate and improve cognitive performance are unknown. In this study, we used the MK-801 neurodevelopmental schizophrenia-like model. Rats were divided into two groups: one received MK-801, and the other received saline for five consecutive days (7-11 postnatal days, PND). We evaluated synaptic plasticity late-LTP and spatial memory consolidation in early adolescence and young adulthood using extracellular field recordings in acute hippocampal slices and the Barnes maze task. Next, we examined D1 receptor (D1R) activation as a mechanism to ameliorate cognitive impairments. Our results suggest that MK-801 neonatal treatment induces impairment in late-LTP expression and deficits in spatial memory retrieval in early adolescence that is maintained until young adulthood. Furthermore, we found that activation of dopamine D1R ameliorates the impairments and promotes a robust expression of late-LTP and an improved performance in the Barnes maze task, suggesting a novel and potential therapeutic role in treating cognitive impairments in schizophrenia.

Dynamic brain entropy predicts risky decision-making across transdiagnostic dimensions of psychopathology.

OBJECTIVES: Maladaptive risky decision-making is a common pathological behavior among patients with various psychiatric disorders. Brain entropy, which measures the complexity of brain time series signals, provides a novel approach to assessing brain health. Despite its potential, the dynamics of brain entropy have seldom been explored. This study aimed to construct a dynamic model of brain entropy and examine its predictive value for risky decision-making in patients with mental disorders, utilizing resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: This study analyzed the rs-fMRI data from a total of 198 subjects, including 48 patients with bipolar disorder (BD), 47 patients with schizophrenia (SZ), 40 patients with adult attention deficit hyperactivity disorder (ADHD), as well as 63 healthy controls (HC). Time series signals were extracted from 264 brain regions based on rs-fMRI. The traditional static entropy and dynamic entropy (coefficient of variation, CV; rate of change, Rate) were constructed, respectively. Support vector regression was employed to predict risky decision-making utilizing leave-one-out cross-validation within each group. RESULTS: Our findings showed that CV achieved the best performances in HC and BD groups (r = -0.58, MAE = 6.43, R2 = 0.32; r = -0.78, MAE = 12.10, R2 = 0.61), while the Rate achieved the best in SZ and ADHD groups (r = -0.69, MAE = 10.20, R2 = 0.47; r = -0.78, MAE = 7.63, R2 = 0.60). For the dynamic entropy, the feature selection threshold rather than the time window length and overlapping ratio influenced predictive performance. CONCLUSIONS: These results suggest that dynamic brain entropy could be a more effective predictor of risky decision-making than traditional static brain entropy. Our findings offer a novel perspective on exploring brain signal complexity and can serve as a reference for interventions targeting risky decision-making behaviors, particularly in individuals with psychiatric diagnoses.

Abnormal hippocampal neurogenesis and impaired social recognition memory in two neurodevelopmental models of schizophrenia.

Schizophrenia is a mental disorder characterized by cognitive impairments, specifically deficits in social recognition memory (SRM). Abnormal hippocampal neurogenesis has been implicated in these deficits. Due to the pathogenetic heterogeneity of schizophrenia, studying the hippocampal neurogenesis and SRM in two models with prenatal and postnatal defects could enhance our understanding of the developmental aspects of the biological susceptibility to schizophrenia. Here, we examined SRM and hippocampal neurogenesis in two developmental models of schizophrenia: gestational exposure to methylazoxymethanol acetate (MAM) and postweaning social isolation (SI). Our findings revealed that gestational MAM exposure induced a decay of social memory while postweaning SI led to impaired social memory formation and decay. In both models, we observed a correlation between impaired SRM and reduced number, and abnormal differentiation and less complex morphology of hippocampal neurons. These results indicate that aberrant hippocampal neurogenesis may contribute to the deficits of SRM in both models, and these abnormalities may be a shared underlying pathogenic factor in developmental models of schizophrenia, regardless of prenatal and postnatal pathogenesis.

The Relationship Between Attention and Suicidal Ideation Among Patients With Adult-Onset Chronic Schizophrenia.

BACKGROUND: Patients with chronic schizophrenia (SZ) have a high risk of suicide, and their cognition function is impaired. We aimed to explore the relationship between attention and suicidal ideation among patients with adult-onset chronic SZ. METHODS: A total of 416 patients with adult-onset chronic SZ were enrolled in this study. We divided patients into suicidal ideation group and non-suicidal ideation group according to the evaluation results of the Beck Scale for Suicide Ideation. Psychotic symptoms were measured by Positive and Negative Syndrome Scale (PANSS), and cognitive function was measured by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Insomnia symptoms were measured by Insomnia Severity Index (ISI). RESULTS: Age was significantly different (44.28 ± 10.58 vs. 48.46 ± 12.23, t = 10.64, p = 0.001) between the two groups, and the patients with suicidal ideation were younger than patients without suicidal ideation. The positive symptom scores of the PANSS, the scores of ISI, and attention scores of RBANS were higher in patients with suicidal ideation than patients without suicidal ideation (17.30 ± 5.67 vs. 15.58 ± 4.90, t = 9.633, p = 0.002; 3.00 [1.00-6.00] vs. 2.00 [1.00-3.50], Z = -2.048, p = 0.041; 81.80 ± 14.99 vs. 76.91 ± 13.88, t = 10.101, p = 0.002). In the logistic regression analysis, age (odds ratio [OR], 0.973; 95% confidence interval [95%CI], [0.955-0.992]; p = 0.005), positive symptom scores of PANSS (OR, 1.063; 95%CI, [1.019-1.109]; p = 0.005), ISI scores (OR, 1.098; 95%CI, [1.037-1.163]; p = 0.001), and attention scores of RBANS (OR, 1.029; 95%CI, [1.013-1.047]; p = 0.001) were independently associated with the occurrence of suicidal ideation among patients with adult-onset chronic SZ. CONCLUSIONS: High attention scores of RBANS were a risk factor for suicidal ideation among patients with adult-onset chronic SZ.

Assessing the Trajectory of Schizophrenia Effectively in Order to Treat Effectively.

INTRODUCTION: Schizophrenia is a complex psychiatric disorder characterized by heterogeneous symptom trajectories that significantly impact patient outcomes. We believe that the study of the trajectories of Schizophrenia is useful in assessing treatment options and outcomes. While the Positive and Negative Syndrome scale is usually used on one occasion to measure symptoms at a single time, if measured repeatedly , the PANSS is also useful in measuring trajectories. In order to illustrate and promote this serial use, we have reviewed papers which describe the delineation of Trajectories of Symptoms in Schizophrenia based on PANSS scores. This review integrates findings from longitudinal studies focusing on the trajectories of positive symptoms, negative symptoms, the relation between positive and negative symptoms and cognition, soft neurological signs, and treatment response in schizophrenia. METHODS: Studies were identified from the PUBMED database .Studies included in this review employed diverse methodologies such as trajectory analyses, longitudinal assessments, and clinical trials. Data were extracted from a range of patient cohorts, including those with first-episode psychosis and chronic schizophrenia. RESULTS: Longitudinal studies consistently demonstrate variability in the trajectories of positive symptoms, with most patients experiencing early stable remission, though a subgroup exhibits persistent or fluctuating symptomatology. Negative symptoms, on the other hand, often show poor improvement over time, correlating with impaired social and neurocognitive functioning. Cognitive deficits also vary, with some domains showing improvement while others, such as logical memory, deteriorate in certain patient subgroups. The relationship between positive and negative symptom trajectories highlights their complex relationship, influencing overall functioning and treatment outcomes. Antipsychotic medications demonstrate varied responses across patient cohorts, with distinct trajectory patterns observed based on medication type and patient-specific factors such as co-morbid substance abuse and duration of untreated psychosis. CONCLUSION: Understanding the longitudinal trajectories of symptoms in schizophrenia is crucial for optimizing therapeutic strategies and improving patient outcomes. Personalised interventions tailored to individual symptom profiles and early clinical responses are recommended to enhance treatment efficacy and promote recovery. The PANSS scale can be used to delineate Trajectories of various symptom Groups in Schizophrenia.

Small world properties of schizophrenia and OCD patients derived from fNIRS based functional brain network connectivity metrics.

Individuals suffering from obsessive compulsive disorder (OCD) and schizophrenia (SCZ) frequently exhibit symptoms of cognitive disassociations, which are linked to poor functional integration among brain regions. The loss of functional integration can be assessed using graph metrics computed from functional connectivity matrices (FCMs) derived from neuroimaging data. A healthy brain at rest is known to exhibit small-world features with high clustering coefficients and shorter path lengths in contrast to random networks. The aim of this study was to compare the small-world properties of prefrontal cortical functional networks of healthy subjects with OCD and SCZ patient groups by use of hemodynamic data obtained with functional near infrared spectroscopy (fNIRS). 13 healthy subjects and 47 patients who were clinically diagnosed with either OCD (N = 21) or SCZ (N = 26) completed a Stroop test while their prefrontal cortex (PFC) hemodynamics were monitored with fNIRS. The Stroop test had a block design consisting of neutral, congruent and incongruent stimuli. For each subject and stimuli type, FCMs were derived separately which were then used to compute small world features that included (i) global efficiency (GE), (ii) clustering coefficient (CC), (iii) modularity (Q), and (iv) small-world parameter ( σ ). Small-world features of patients exhibited random networks which were indicated by higher GE and lower CC values when compared to healthy controls, implying a higher neuronal operational cost.

Mechanisms of glutamate receptors hypofunction dependent synaptic transmission impairment in the hippocampus of schizophrenia susceptibility gene Opcml-deficient mouse model.

Schizophrenia is a severe psychiatric disorder with high heritability, characterized by positive and negative symptoms as well as cognitive abnormalities. Dysfunction in glutamate synapse is strongly implicated in the pathophysiology of schizophrenia. However, the precise role of the perturbed glutamatergic system in contributing to the cognitive abnormalities of schizophrenia at the synaptic level remains largely unknown. Although our previous work found that Opcml promotes spine maturation and Opcml-deficient mice exhibit schizophrenia-related cognitive impairments, the synaptic mechanism remains unclear. By using whole-cell patch clamp recording, we found that decreased neuronal excitability and alterations in intrinsic membrane properties of CA1 PNs in Opcml-deficient mice. Furthermore, Opcml deficiency leads to impaired glutamatergic transmission in hippocampus, which is closely related to postsynaptic AMPA/NMDA receptors dysfunction, resulting in the disturbances of E/I balance. Additionally, we found that the aripiprazole which we used to ameliorate abnormal cognitive behaviors also rescued the impaired glutamatergic transmission in Opcml-deficient mice. These findings will help to understand the synaptic mechanism in schizophrenia pathogenesis, providing insights into schizophrenia therapeutics with glutamatergic disruption.

Long-Term Changes in Cognition Among Patients With Schizophrenia Spectrum Disorders and Different Durations of Illness: A Meta-Analysis.

Objective: In this meta-analysis, we evaluated changes in cognition for patients with schizophrenia spectrum disorders (SSD) with different durations of illness (DOIs).Data Sources: Records were identified through searches in PubMed, PsycINFO, CINAHL, and Cochrane until December 2021. We used terms related to SSDs, chronicity, course, and recovery.Study Selection and Data Extraction: We included 57 longitudinal studies, with a follow-up length of at least 1 year, investigating changes in 10 domains of cognition of patients who are all diagnosed with SSD. Changes in cognition were analyzed through effect sizes of change between baseline and follow-up assessments within each study. These changes were evaluated in different subgroups of studies including patients with a DOI <5 years, 5-10 years, or >10 years. We also investigated the influence of 19 potential moderators on these changes in cognition.Results: We found marginal improvements in overall cognition (d =0.13), small improvements in verbal memory (d = 0.21), processing speed (d = 0.32), marginal improvements in visual memory (d = 0.17), executive functioning (d = 0.19), and language skills (d = 0.13), and no significant improvements in the other cognitive domains. The largest improvements were achieved for patients with a DOI <10 years. Changes are more favorable for patients with a younger age, no schizophrenia diagnosis, female gender, higher education level, and low negative symptom severity.Conclusions: We observed only modest cognitive improvement in SSD almost exclusively in patients with early psychosis. Future research should focus on optimizing interventions targeting cognition in specific subgroups and the interrelationships with other life domains.

Impaired motor-to-sensory transformation mediates auditory hallucinations.

Distinguishing reality from hallucinations requires efficient monitoring of agency. It has been hypothesized that a copy of motor signals, termed efference copy (EC) or corollary discharge (CD), suppresses sensory responses to yield a sense of agency; impairment of the inhibitory function leads to hallucinations. However, how can the sole absence of inhibition yield positive symptoms of hallucinations? We hypothesize that selective impairments in functionally distinct signals of CD and EC during motor-to-sensory transformation cause the positive symptoms of hallucinations. In an electroencephalography (EEG) experiment with a delayed articulation paradigm in schizophrenic patients with (AVHs) and without auditory verbal hallucinations (non-AVHs), we found that preparing to speak without knowing the contents (general preparation) did not suppress auditory responses in both patient groups, suggesting the absent of inhibitory function of CD. Whereas, preparing to speak a syllable (specific preparation) enhanced the auditory responses to the prepared syllable in non-AVHs, whereas AVHs showed enhancement in responses to unprepared syllables, opposite to the observations in the normal population, suggesting that the enhancement function of EC is not precise in AVHs. A computational model with a virtual lesion of an inhibitory inter-neuron and disproportional sensitization of auditory cortices fitted the empirical data and further quantified the distinct impairments in motor-to-sensory transformation in AVHs. These results suggest that "broken" CD plus "noisy" EC causes erroneous monitoring of the imprecise generation of internal auditory representation and yields auditory hallucinations. Specific impairments in functional granularity of motor-to-sensory transformation mediate positivity symptoms of agency abnormality in mental disorders.

Multilayer network analysis reveals instability of brain dynamics in untreated first-episode schizophrenia.

Although aberrant static functional brain network activity has been reported in schizophrenia, little is known about how the dynamics of neural function are altered in first-episode schizophrenia and are modulated by antipsychotic treatment. The baseline resting-state functional magnetic resonance imaging data were acquired from 122 first-episode drug-naïve schizophrenia patients and 128 healthy controls (HCs), and 44 patients were rescanned after 1-year of antipsychotic treatment. Multilayer network analysis was applied to calculate the network switching rates between brain states. Compared to HCs, schizophrenia patients at baseline showed significantly increased network switching rates. This effect was observed mainly in the sensorimotor (SMN) and dorsal attention networks (DAN), and in temporal and parietal regions at the nodal level. Switching rates were reduced after 1-year of antipsychotic treatment at the global level and in DAN. Switching rates at baseline at the global level and in the inferior parietal lobule were correlated with the treatment-related reduction of negative symptoms. These findings suggest that instability of functional network activity plays an important role in the pathophysiology of acute psychosis in early-stage schizophrenia. The normalization of network stability after antipsychotic medication suggests that this effect may represent a systems-level mechanism for their therapeutic efficacy.

Schizophrenia and cognitive dysfunction.

Schizophrenia is a psychiatric disorder with cognitive dysfunction as a core symptom along with positive and negative symptoms. Cognitive dysfunction in schizophrenia can be broadly classified into neurocognitive and social cognitive deficits, with these deficits significantly influencing social functioning. Therapeutic interventions aiming to enhance neurocognition and social cognition have been developed. In this review, we describe the characteristics of cognitive dysfunction in patients with schizophrenia, its relationship to social function, and intervention strategies. J. Med. Invest. 71 : 205-209, August, 2024.

Diagnosis of Schizophrenia Using EEG Sensor Data: A Novel Approach with Automated Log Energy-Based Empirical Wavelet Reconstruction and Cepstral Features.

Schizophrenia (SZ) is a severe mental disorder characterised by disruptions in cognition, behaviour, and perception, significantly impacting an individual's life. Traditional SZ diagnosis methods are labour-intensive and prone to errors. This study presents an innovative automated approach for detecting SZ acquired through electroencephalogram (EEG) sensor signals, aiming to improve diagnostic efficiency and accuracy. We utilised Fast Independent Component Analysis to remove artefacts from raw EEG sensor data. A novel Automated Log Energy-based Empirical Wavelet Reconstruction (ALEEWR) technique was introduced to reconstruct decomposed modes based on their variability, ensuring effective extraction of meaningful EEG signatures. Cepstral-based features-cepstral activity, cepstral mobility, and cepstral complexity-were used to capture the power, rate of change, and irregularity of the cepstrum of preprocessed EEG signals. ANOVA-based feature selection was applied to refine these features before classification using the K-Nearest Neighbour (KNN) algorithm. Our approach achieved an exceptional accuracy of 99.4%, significantly surpassing previous methods. The proposed ALEEWR and cepstral analysis demonstrated high precision, sensitivity, and specificity in the automated diagnosis of schizophrenia. This study introduces a highly accurate and efficient method for SZ detection using EEG technology. The proposed techniques offer significant improvements in diagnostic accuracy, with potential implications for enhancing SZ diagnosis and patient care through automated systems.

Neural Circuitry and Therapeutic Targeting of Depressive Symptoms in Schizophrenia Spectrum Disorders.

OBJECTIVE: Conceptual similarities between depressive and negative symptoms complicate biomarker and intervention development. This study employed a data-driven approach to delineate the neural circuitry underlying depressive and negative symptoms in schizophrenia spectrum disorders (SSDs). METHODS: Data from three studies were analyzed (157 participants with SSDs) to assess brain-behavior relationships: two neuroimaging studies and a randomized trial of repetitive transcranial magnetic stimulation (rTMS). Partial least squares correlation (PLSC) was used to investigate associations between resting-state functional connectivity and depressive and negative symptoms. Secondary analyses of rTMS trial data (active, N=37; sham, N=33) were used to assess relationships between PLSC-derived symptom profiles and treatment outcomes. RESULTS: PLSC identified three latent variables (LVs) relating functional brain circuitry with symptom profiles. LV1 related a general depressive symptom factor with positive associations between and within the default mode network (DMN), the frontoparietal network (FPN), and the cingulo-opercular network (CON). LV2 related negative symptoms (no depressive symptoms) via negative associations, especially between the FPN and the CON, but also between the DMN and the FPN and the CON. LV3 related a guilt and early wakening depression factor via negative rather than positive associations with the DMN, FPN, and CON. The secondary visual network had a positive association with general depressive symptoms and negative associations with guilt and negative symptoms. Active (but not sham) rTMS applied bilaterally to the dorsolateral prefrontal cortex (DLPFC) reduced general depressive but not guilt-related or negative symptoms. CONCLUSIONS: The results clearly differentiate the neural circuitry underlying depressive and negative symptoms, and segregated across the two-factor structure of depression in SSDs. These findings support divergent neurobiological pathways of depressive symptoms and negative symptoms in people with SSDs. As treatment options are currently limited, bilateral rTMS to the DLPFC is worth exploring further for general depressive symptoms in people with SSDs.

Structure-function coupling changes in first-episode, treatment-naïve schizophrenia correlate with cell type-specific transcriptional signature.

BACKGROUND: First-episode schizophrenia (FES) is a complex and progressive psychiatric disorder. The etiology of FES involves genetic, environmental, and neurobiological factors. This study investigates the association between alterations in structural-functional (SC-FC) coupling and transcriptional expression in FES. METHODS: This study encompassed a cohort of 214 participants, comprising 111 FES patients and 103 healthy controls (HC). Furthermore, we examined the abnormalities within SC-FC coupling in FES and their correlations with meta-analytic cognitive terms, neurotransmitters, and transcriptional patterns through partial least squares regression (PLS), involving similarity with other psychiatric disorders or psychiatric-related diseases, functional enrichments, special cell types, peripheral inflammation, and cortical layers. RESULTS: FES patients exhibited lower SC-FC coupling in the visual, sensorimotor, and ventral attention networks compared to controls. Furthermore, case-control t-maps revealed a negative correlation with neurotransmitters such as serotonin and dopamine, while showing a positive correlation with opioids. Positive t-maps were associated with cognitive functions, including reasoning, judgment, and action, whereas negative t-maps correlated with cognitive functions such as learning, stress, and mood. Moreover, there was a significant overlap between genes linked to abnormalities in SC-FC coupling and those dysregulated in inflammatory bowel diseases. PLS2- genes linked to SC-FC coupling demonstrated significant enrichment in pathways related to immunity and inflammation, as well as in cortical layers I and V. Conversely, PLS2 + genes were primarily enriched in synaptic signaling processes, specific excitatory neurons, and layers II and IV. Additionally, changes in SC-FC coupling were negatively associated with gene expression related to antipsychotics and lymphocytes. CONCLUSIONS: These findings offer a new perspective on the complex interplay between SC-FC coupling abnormalities and transcriptional expression in the initial phases of schizophrenia.

Diagnosis of schizophrenia by integrated saccade scores and associations with psychiatric symptoms, and functioning.

Eye movement as a neurobiological biomarker of schizophrenia. We aim to estimate diagnostic accuracy of integrated pro/antisaccade eye movement measurements to discriminate between healthy individuals and schizophrenic patients. We compared the eye movement performance of 85 healthy individuals and 116 schizophrenia-stable patients during prosaccade and antisaccade tasks. The difference eye movement measurements were accumulated by stepwise discriminant analysis to produce an integrated score. Finally, the diagnostic value of the integrated score was calculated by the receiver operating characteristic (ROC) area under the curve (AUC), and the best sensitivity and specificity were calculated based on the given cutoff values. Using discriminant analysis, an integrated score included the residual gain and latency (step) during the prosaccade test, the error rate, and the corrected error rate during the antisaccade test. We found that the integrated score could well classify schizophrenia patients and healthy individuals with an accuracy of 80.6%. In the ROC, Youden's index was 0.634 (sensitivity = 81.0%, specificity = 82.4%) and AUC was 0.871. There were significant difference patterns of correlation between the severity of psychiatric symptoms and daily functioning and diagnostic eye movement measurements. Using only 2 saccade tasks to discriminate well between schizophrenia patients and healthy controls, suggesting that abnormalities in saccade behavior is a potential biomarker and efficient diagnostic tool for identifying schizophrenia. The underlying neuropathologic mechanisms associated with abnormal saccades may provide insights into the intervention and diagnosis of schizophrenia.

Long-term effects of a double hit murine model for schizophrenia on parvalbumin expressing cells and plasticity-related molecules in the thalamic reticular nucleus and the habenula.

The exposure to aversive experiences during early-life affects brain maturation and induces changes in behavior. Additionally, when these experiences coincide with subtle neurodevelopmental alterations, they may contribute to the emergence of psychiatric disorders, such as schizophrenia. Studies in patients and animal models have identified changes in parvalbumin (PV) expressing inhibitory neurons, highlighting their significance in the etiology of this disorder. Most studies have been focused on the cortex, but PV+ neurons also provide inhibitory input to diencephalic regions, particularly to the thalamus (through cells in the thalamic reticular nucleus, TRN) and the habenula. Remarkably, alterations in both nuclei have been described in schizophrenia. Some of these changes in PV+ cells may be mediated by perineuronal nets (PNN), specialized regions of the extracellular matrix that often surround them and regulate their synaptic input and activity. Interestingly, the physiological maturation and integration of PV+ neurons, which involves the assembly of PNN, occurs during early postnatal life. Plasticity molecules associated to inhibitory neurons, such as PSA-NCAM, or NMDA receptors (NMDAR) can also influence the structure and function of these cells. Growing evidence also indicates that glial cells regulate the physiology of PV+ neurons by influencing their maturation and modulating their synaptic connectivity. To explore the impact of early-life aversive experiences and concomitant subtle neurodevelopmental alterations on diencephalic PV+ cells, we analyzed adult male mice subjected to a double-hit model (DHM) of schizophrenia, combining a single injection of an NMDAR antagonist at P7 and post-weaning social isolation. We observed that exploratory behavior, PV+ neurons and their associated PNN, as well as PSA-NCAM and NMDAR expression and glial cells, in the TRN and the habenula were affected by the DHM or one of its factors. To our knowledge, this is the first report on such alterations in these diencephalic structures in an animal model combining neurodevelopmental alterations and early-life stress during adolescence. Our findings complement previous work on PV+ neurons in cortical regions and underscore the importance of studying diencephalic inhibitory networks and their intricate interactions with aversive experiences and neurodevelopmental alterations during early life in the context of schizophrenia.

Validity of handgrip strength for assessing cognition and psychotic symptoms in hospitalized patients with stable schizophrenia.

BACKGROUND AND OBJECTIVES: A correlation between low handgrip strength (HGS), HGS asymmetry, and low cognitive performance has been demonstrated. However, it remains unclear whether low HGS is associated with psychotic symptoms and whether HGS asymmetry is associated with cognitive and psychotic symptoms in hospitalized patients with schizophrenia. This study aimed to investigate the validity of HGS as a measure for assessing cognition and psychotic symptoms in hospitalized patients with stable schizophrenia. METHODS: A total of 235 inpatients with stable schizophrenia were recruited between August 1, 2023, and August 31, 2023. The highest HGS values from three tests on the dominant hand were used to determine low HGS (male < 28 kg, female < 18 kg), and HGS asymmetry was identified when the non-dominant HGS/dominant HGS ratio was outside 0.9-1.1. Cognition and psychotic symptoms were assessed using the Chinese Montreal Cognitive Assessment (MoCA-C) and Positive and Negative Syndrome Scale (PANSS). Generalized linear model analyses examined the relationship between HGS and scale scores. RESULTS: Covariate-adjusted generalized linear models confirmed a strong association between low HGS alone and the MoCA-C score (OR = 0.819, 95% CI = 0.710‒0.945, p = 0.006) and PANSS score (OR = 1.113, 95% CI = 1.036‒1.239, p = 0.006). Similarly, the combination of low and asymmetric HGS was strongly associated with both MoCA-C (OR = 0.748, 95% CI = 0.653‒0.857, p<0.001) and PANSS scores (OR = 1.118, 95% CI = 1.032‒1.211, p = 0.006). CONCLUSIONS: The results suggest that hospitalized patients with schizophrenia and low HGS, with or without asymmetry, are likely to have lower MoCA-C scores and higher PANSS scores. Screening stable schizophrenia patients with low HGS, with or without asymmetry, could be a valuable and straightforward approach to identifying those with lower cognition and severe psychotic symptoms.