Longitudinal Changes in Brain Gyrification in Schizophrenia Spectrum Disorders

Previous magnetic resonance imaging (MRI) studies reported increased brain gyrification in schizophrenia and schizotypal disorder, a prototypic disorder within the schizophrenia spectrum. This may reflect deviations in early neurodevelopment; however, it currently remains unclear whether the gyrification pattern longitudinally changes over the course of the schizophrenia spectrum. The present MRI study using FreeSurfer compared longitudinal changes (mean inter-scan interval of 2.7 years) in the local gyrification index (LGI) in the entire cortex among 23 patients with first-episode schizophrenia, 14 with schizotypal disorder, and 39 healthy controls. Significant differences were observed in longitudinal LGI changes between these groups; the schizophrenia group exhibited a progressive decline in LGI, predominantly in the fronto-temporal regions, whereas LGI increased over time in several brain regions in the schizotypal and control groups. In the schizophrenia group, a greater reduction in LGI over time in the right precentral and post central regions correlated with smaller improvements in negative symptoms during the follow-up period. The cumulative medication dosage during follow-up negatively correlated with a longitudinal LGI increase in the right superior parietal area in the schizotypal group, but did not affect longitudinal LGI changes in the schizophrenia group. Collectively, these results suggest that gyrification patterns in the schizophrenia spectrum reflect both early neurodevelopmental abnormalities as a vulnerability factor and active brain pathology in the early stages of schizophrenia.

Association of Cognitive Impairment With Anhedonia in Patients With Schizophrenia

Anhedonia is considered as one of the five dimensions of negative symptoms and mainly refers to the reduction of the capacity of feeling pleasure. Increasing evidence suggests that anhedonia in schizophrenia may be partly explained by cognitive impairment. However, the associations between specific cognitive impairment and anhedonia are not fully investigated. The purpose of this study was to examine anticipatory anhedonia, consummatory anhedonia, and their cognitive associations in schizophrenia. A total number of 100 patients with schizophrenia and 67 healthy volunteers were recruited. The clinical symptoms of schizophrenia were assessed. Anticipatory pleasure, consummatory pleasure, and cognitive functions of each participant were measured. Multiple linear regression analysis was performed to investigate the influencing factors of anhedonia in schizophrenia. The results showed no significant differences in sex, age, education year, body mass index (BMI), and marital status between the schizophrenia group and healthy control group (all P > 0.05). Both anticipatory and consummatory pleasure in the schizophrenia group were significantly lower than those in the healthy control group (all P < 0.05). Immediate memory, visual spanning, language, attention, and delayed memory were significantly poorer in the schizophrenia group (all P < 0.05). The results showed that language deficit is an independent risk factor for anticipatory anhedonia (B' = 0.265, P = 0.008, 95% CI: 0.038-0.244), while delayed memory deficit is an independent risk factor for consummatory anhedonia (B' = 0.391, P < 0.001, 95% CI:0.085-0.237). To the best of our knowledge, this is the first study that reported the specific cognitive associations of anhedonia in schizophrenia. The findings have added new evidence on the influencing factors of anhedonia and provided clues for the associations between clinical manifestations of schizophrenia.

Elevated activity of superoxide dismutase in male late-life schizophrenia and its correlation with clinical symptoms and cognitive deficits

Background Despite inconsistent findings, accumulative evidence has shown abnormalities of the key antioxidant enzyme, superoxide dismutase (SOD), in patients with schizophrenia. However, few studies explored SOD in late-life schizophrenia (LLS). Our work aimed to investigate changes in SOD activity and the relationship between SOD activity and psychotic symptoms or cognitive deficits in LLS. Methods 32 geriatric male patients with schizophrenia (age ≥ 60) and 28 age-matched male normal controls were recruited in the study. We assessed cognitive functions with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), evaluated the severity of clinical symptoms with the Positive and Negative Syndrome Scale (PANSS), and measured the plasma levels of SOD. Results Patients with LLS presented with higher total levels of SOD compared to the controls (81.70 vs. 65.26 U/ml, p < .001). Except for the visuospatial index, the cognitive performance was significantly worse on RBANS total and other domain scores in the schizophrenia group than the control group. In the schizophrenia group, SOD levels were positively correlated with subscores of general psychopathology and negative symptoms and total scores of the PANSS (all p < .05), and inversely associated with performance in immediate memory, language, and RBANS total scores (all p < .05). Conclusions Our findings suggest that patients with LLS display disturbances in the antioxidant system, which may underlie the pathological process of cognitive impairments and negative symptoms in the late stage of schizophrenia. Supplementing with antioxidants could be a potential treatment.

Heart Rate Variability in Schizophrenia and Autism

Suppressed heart rate variability (HRV) has been found in a number of psychiatric conditions, including schizophrenia and autism. HRV is a potential biomarker of altered autonomic functioning that can predict future physiological and cognitive health. Understanding the HRV profiles that are unique to each condition will assist in generating predictive models of health. In the current study, we directly compared 12 adults with schizophrenia, 25 adults with autism, and 27 neurotypical controls on their HRV profiles. HRV was measured using an electrocardiogram (ECG) channel as part of a larger electroencephalography (EEG) study. All participants also completed the UCLA Loneliness Questionnaire as a measure of social stress. We found that the adults with schizophrenia exhibited reduced variability in R-R peaks and lower low frequency power in the ECG trace compared to controls. The HRV in adults with autism was slightly suppressed compared to controls but not significantly so. Interestingly, the autism group reported feeling lonelier than the schizophrenia group, and HRV did not correlate with feelings of loneliness for any of the three groups. However, suppressed HRV was related to worse performance on neuropsychological tests of cognition in the schizophrenia group. Together, this suggests that autonomic functioning is more abnormal in schizophrenia than in autism and could be reflecting health factors that are unique to schizophrenia.

The Relationship Between Abnormal Resting-State Functional Connectivity of the Left Superior Frontal Gyrus and Cognitive Impairments in Youth-Onset Drug-Naïve Schizophrenia

Objective: Age of onset is one of the heterogeneous factors in schizophrenia, and an earlier onset of the disease indicated a worse prognosis. The left superior frontal gyrus (SFG) is involved in numerous cognitive and motor control tasks. Hence, we explored the relationship between abnormal changes in SFG resting-state functional connectivity (rsFC) and cognitive function in the peak age of incidence to understand better the pathophysiological mechanism in youth-onset drug-naïve schizophrenia to search for reliable biomarkers.Methods: About 66 youth-onset drug-naïve schizophrenia patients and 59 healthy controls (HCs) were included in this study. Abnormal connectivity changes in the left SFG and whole brain were measured using the region of interest (ROI) rsFC analysis method. The cognitive function was assessed using the MATRICS Consensus Cognitive Battery (MCCB), and the severity of the clinical symptoms was evaluated by positive and negative syndrome scale (PANSS). Furthermore, we analyzed the relationships among abnormal FC values, cognition scores, and clinical symptoms.Results: We found decreased FC between left SFG and bilateral precuneus (PCUN), right hippocampus, right parahippocampal gyrus, left thalamus, left caudate, insula, and right superior parietal lobule (SPL), whereas increased FC was seen between the left SFG and right middle frontal gyrus (MFG) in the youth-onset drug-naïve schizophrenia group, compared with HCs. Meanwhile, the T-scores were lower in each cognitive domain than HCs. Moreover, in the youth-onset drug-naive schizophrenia group, the insula was negatively correlated with processing speed. No significant correlations were found between the FC-value and PANSS score.Conclusions: Our findings suggest widespread FC network abnormalities in the left SFG and widespread cognitive impairments in the early stages of schizophrenia. The dysfunctional connectivity of the left SFG may be a potential pathophysiological mechanism in youth-onset drug-naïve schizophrenia.

A Comparative Study on the Burden of Disease of Schizophrenia, Bipolar Disorder Type I, and Autism Spectrum Disorder on the Family Caregivers in Iran

Objective: Patients with severe psychiatric diseases, due to the debilitating and chronic nature of these diseases, requires prolonged care by family and other rated people. In addition to the patient, these diseases affect the caregiver and create high psychological, social, and individual pressure to take care of themselves. This study aims to compare the burden of schizophrenia, Bipolar Disorder (BD) type 1, and Autism Spectrum Disorder (ASD) on the family caregivers in Iran. Materials & Methods: In this descriptive-analytical study, using the non-probability sampling method, 450 family caregivers of patients with schizophrenia, BD type 1, and ASD were selected based on the inclusion criteria. Data collection tools comprised a demographic checklist, short-form Zarit Burden Interview (ZBI-12), and the Depression, Anxiety, and Stress Scale (DASS). The questionnaires were distributed to the patients selected from the Psychiatric Institute of Tehran, Iran Psychiatric Hospital, and Ali Asghar Hospital. The collected data were analyzed using descriptive statistics, ANOVA for evaluating the relationship of demographic factors with the amount and severity of disease burden, and interclass correlation coefficient in SPSS v. 22. Results: The disease burden was higher on caregivers of ASD patients, followed by that of BD type 1 and schizophrenia patients. The highest and lowest hours of care were related to the ASD and schizophrenia groups, respectively. Women made up the majority of family caregivers. The educational level of family caregivers was higher in the BD type 1 group and was lower in the schizophrenia group. Most caregivers in the BD type 1 group were employed, while most of them in the schizophrenia group were housewives. The lowest and highest income levels were related to the family caregivers of ASD and schizophrenia groups, respectively. The highest and lowest hospitalization frequencies were seen in the BD type 1 and ASD groups, respectively. Conclusion: The burden of three diseases on the family caregivers is high. It is recommended that state-run consulting and screening centers be more active in this field. Because of the low-income level of some family caregivers, it is better to plan for more employment of family caregivers with the assistance of governmental and non-governmental organizations. It is better to hold strategic classes for the family caregivers to reduce their disease burden. Different methods to reduce the burden of diseases in caregivers, such as lowering care hours and using respite care and respite recess and dividing tasks between caregivers, using social or daycare services, can reduce their symptoms of depression and anxiety. Their depression and anxiety should be monitored, and pharmacological and non-pharmacological measures should be used for their treatment.

Main characteristics of dermatoglypics associated with schizophrenia and its clinical subtypes

Dermatoglypic patterns are extensively investigated to apply in disease-related risk assessment due to an obvious association between morphological and genetic characteristics. In the current study, we aimed to determine whether the fingerprint and palmar patterns vary between case population with schizophrenia and general population. A cross sectional study was conducted in people diagnosed with schizophrenia (cases) and a control population between 2016 and 2019. In this study, 252 people were participated. Ink and paper method was used to evaluate the difference of fingerprints palm prints between patients with schizophrenia and participants in control group.93 participants were analyzed in schizophrenic group and 142 participants were investigated in the control group. The percentage of arches on the right ring finger was significantly different between the schizophrenic patient group and control group (p = 0.011). The whorl pattern type (U-W-U-W-W-W-W-U-W-U) was dominantly observed in both of the schizophrenic patient group and control group. A-B ridge count in schizophrenic patient group and control group produced a markedly significant difference (p<0.05). Interestingly, a strong significant difference was produced in comparing of A-B ridge count in catatonic schizophrenia group with residual schizophrenia group (p<0.005). In comparison, index of pattern intensity in control group was slightly higher than that in schizophrenic patient group. Taking together, these results showed that the dermatoglypic characteristics might be a valuable tool to describe the nature of schizophrenia and its clinical subtypes and further studies are needed in clinical application.

Impairment in acquisition of conditioned fear in schizophrenia: a pooled analysis of four studies

Background: Individuals with schizophrenia show impairments in associative learning. One well-studied, quantifiable form of associative learning is Pavlovian fear conditioning. However, to date, studies of fear conditioning in schizophrenia have been inconclusive, possibly because they lacked sufficient power. Methods: To address this issue, data were pooled from 4 independent fear conditioning studies that included a total of 77 individuals with schizophrenia and 74 control subjects. Skin conductance responses (SCRs) during fear conditioning to stimuli that were paired (the CS+) and not paired (CS-) with an aversive, unconditioned stimulus were measured, and the success of acquisition of differential conditioning (the magnitude of CS+ vs CS- SCRs) and responses to CS+ and CS- separately were assessed. Results: Acquisition of differential conditioned fear responses was significantly lower in individuals with schizophreania than in healthy controls (Cohen's d = 0.53). This effect was primarily related to a significantly higher response to the CS- stimulus in the schizophrenia compared to the control group. The magnitude of this response to the CS- in the schizophrenia group was correlated with the severity of delusional ideation. Other symptoms or antipsychotic dose were not associated with fear conditioning measures. Conclusions: Individuals with schizophrenia who endorse delusional beliefs are over-responsive to neutral stimuli during fear conditioning. This finding is consistent with prior models of aberrant learning in psychosis.

The Neural Correlates of Effortful Cognitive Processing Deficits in Schizophrenia: An ERP Study

Background: Individuals’ information processing includes automatic and effortful processes and the latter require sustained concentration or attention and larger amounts of cognitive “capacity.” Event-related potentials (ERPs) reflect all neural activities that are related to a certain stimulus. Investigating ERP characteristics of effortful cognitive processing in people with schizophrenia would be helpful in further understanding the neural mechanism of schizophrenia.Methods: Both schizophrenia patients (SCZ, n = 33) and health controls (HC, n = 33) completed ERP measurements during the performance of the basic facial emotion identification test (BFEIT) and the face-vignette task (FVT). Data of ERP components (N100, P200, and N250), BFEIT and FVT performances were analyzed.Results: Schizophrenia patients’ accuracies of face emotion detection in the BFEIT and vignette emotion detection in the FVT were both significantly worse than the performance of the HC group. Repeated-measures ANOVAs performed on mean amplitudes and latencies revealed that the interaction effect for group × experiment × site (prefrontal, frontal, central, parietal, and occipital site) was significant for N250 amplitude. In FVT experiment, N250 amplitudes at prefrontal and frontal sites in schizophrenia group were larger than those of HC group; the maximum N250 amplitude was present at the prefrontal site in both the groups. For N250 latency, the interaction effect for group × experiment was significant; N250 latencies in the schizophrenia group were longer than those of the HC group.Conclusion: Schizophrenia patients present effortful cognitive processing dysfunctions which reflect in abnormal ERP components, especially N250 at prefrontal cortex and frontal cortex sites. These findings have important implications for further clarifying the neural mechanism of effortful cognitive processing deficits in schizophrenia.

Associations between hemispheric asymmetry and schizophrenia-related risk genes in people with schizophrenia and people at a genetic high risk of schizophrenia

Background Schizophrenia is considered a polygenic disorder. People with schizophrenia and those with genetic high risk of schizophrenia (GHR) have presented with similar neurodevelopmental deficits in hemispheric asymmetry. The potential associations between neurodevelopmental abnormalities and schizophrenia-related risk genes in both schizophrenia and those with GHR remains unclear. Aims To investigate the shared and specific alternations to the structural network in people with schizophrenia and those with GHR. And to identify an association between vulnerable structural network alternation and schizophrenia-related risk genes. Method A total of 97 participants with schizophrenia, 79 participants with GHR and 192 healthy controls, underwent diffusion tensor imaging (DTI) scans at a single site. We used graph theory to characterise hemispheric and whole-brain structural network topological metrics. For 26 people in the schizophrenia group and 48 in the GHR group with DTI scans we also calculated their schizophrenia-related polygenic risk scores (SZ-PRSs). The correlations between alterations to the structural network and SZ-PRSs were calculated. Based on the identified genetic–neural association, bioinformatics enrichment was explored. Results There were significant hemispheric asymmetric deficits of nodal efficiency, global and local efficiency in the schizophrenia and GHR groups. Hemispheric asymmetric deficit of local efficiency was significantly positively correlated with SZ-PRSs in the schizophrenia and GHR groups. Bioinformatics enrichment analysis showed that these risk genes may be linked to signal transduction, neural development and neuron structure. The schizophrenia group showed a significant decrease in the whole-brain structural network. Conclusions The shared asymmetric deficits in people with schizophrenia and those with GHR, and the association between anomalous asymmetry and SZ-PRSs suggested a vulnerability imaging marker regulated by schizophrenia-related risk genes. Our findings provide new insights into asymmetry regulated by risk genes and provides a better understanding of the genetic–neural pathological underpinnings of schizophrenia.