The impact of childhood trauma on cognitive function in individuals with clinical high risk of psychosis / 中华行为医学与脑科学杂志

Objective:To explore the impact of cognitive function and childhood trauma in individuals with clinical high risk of psychosis (CHR).Methods:From June 2017 to September 2022, a total of 62 individuals with CHR(CHR group) were screened by structured interviews with psychiatric risk syndrome (SIPS) at Beijing Anding Hospital, and 61 healthy controls(healthy control group) matched in gender, age, and educational years were recruited. All participants were evaluated by the childhood trauma questionnaire (CTQ) and the Chinese version of the MATRICS consensus cognitive test battery (MCCB). Differences in cognitive function and childhood trauma between the two groups were compared by R4.1.1 software, and the correlation between cognitive function and childhood trauma in the CHR group was analyzed.Results:The scores of MCCB composite score (41.46±6.97), information processing speed (40.20±8.40), attention vigilance (40.92±11.00), working memory (41.09±9.97), verbal learning, and visual learning of CHR group were significantly lower than those of healthy controls(MCCB composite score(46.26±7.64), information processing speed(45.83±8.36), attention vigilance(46.30±9.57), working memory(46.18±8.49)), and with statistically significant differences ( t=-3.73--2.03, P<0.05). The total CTQ score, emotional abuse, physical abuse, and physical neglect factor scores of the CHR group (40.0 (36.0, 50.8), 7.5 (6.0, 10.0), 5.0 (5.0, 7.0), 9.0 (7.0, 11.0)) were significantly higher than those of the healthy control group (34.0 (31.0, 40.0), 6.0 (5.0, 8.0), 5.0 (5.0, 6.0), 9.0 (6.0, 10.0) ) ( Z=-4.07--2.06, P<0.05). In the CHR group, the total score of childhood trauma and the score of physical abuse factors were negatively correlated with working memory ( r=-0.29, -0.28, P<0.05), and the total score of cognitive function, attention vigilance, and word learning were negatively correlated with physical neglect ( r=-0.28, -0.26, -0.31, P<0.05). After partial correlation analysis using gender, age, years of education, and total SIPS score as covariates, the aforementioned correlation remained significant. Conclusion:CHR individuals have multiple cognitive deficits, and childhood trauma is more serious. Childhood trauma, especially physical trauma, may affect the cognitive function of CHR individuals.

Brain imaging characteristics and its clinical applications in the clinical high-risk population of psychosis / 中华行为医学与脑科学杂志

Clinical high risk (CHR) is the prodrome stage of schizophrenia and the population with CHR show subtle clinical symptoms and abnormal brain structure and function. Specifically, the pathological changes in the brain were mainly manifested as reduced gray matter volume in the anterior cingulate gyrus and hippocampus, damaged white matter fibers in the corpus callosum, uncinate tract and arcuate tract, cerebellar atrophy, and abnormal resting-state brain network connection.This paper reviews the brain imaging features, their relationship with clinical symptoms, and their role in predicting clinical outcomes in individuals with CHR. In the future, we can combine artificial intelligence and neuroimaging techniques to find specific markers of brain structure and function in the CHR population to guide early clinical detection and intervention.

A dopamine receptor D2 genetic polymorphism associated with transition to mental disorders in a cohort of individuals with at-risk mental state for psychosis

Objectives: To test the association of 45 single nucleotide polymorphisms (SNPs) with transition to psychiatric disorders in a cohort of individuals at ultrahigh risk (UHR) mental state for psychosis. Methods: Through general population screening, 88 non-help-seeking UHR subjects and 130 healthy control individuals were genotyped for 45 SNPs related to psychosis. They were followed for a mean of 2.5 years, and conversion to psychotic and to general psychiatric disorders was assessed. Genotype frequencies between controls, converters, and non-converters were analyzed. Results: There were no differences in sociodemographics between controls and UHR. Also, UHR converters and non-converters had no differences in their baseline symptoms scores. The dopamine receptor D2 gene (DRD2) SNP rs6277 was significantly more common among UHR who transitioned to psychosis (p < 0.001) and to UHR who transitioned to any psychiatric disorders (p = 0.001) when compared to UHR who did not transition. The rs6277 T allele was related to psychiatric morbidity in a dose-response fashion, being significantly more frequent in UHR converters than UHR non-converters and control subjects (p = 0.003). Conclusion: Our findings suggest that rs6277 could potentially constitute a genetic marker of transition to psychiatric disorders in subjects with at-risk mental states, warranting further investigation in larger samples.

Changes of microstructure of white matter and clinical high risk for psychosis / 中华行为医学与脑科学杂志

The research on clinical high-risk for psychosis is a hotspot in recent years, which is helpful to the early identification and early intervention of psychosis. White matter fibers are the important structural basis of complex information transmission function among brain regions. The existing literatures show that there are abnormal white matter microstructures in individuals at clinical high-risk for psychosis, which is related to their clinical symptoms and social function. Diffusion tensor imaging is the only non-invasive technique to study the microstructure of brain white matter. This paper reviews the existing evidences of microstructural abnormalities of white matter at clinical high-risk for psychosis by diffusion tensor imaging, in order to comprehensively analyze the potential neurobiomarkers in the early stage of the disease and the pathological evolution characteristics in the development of the disease.

Prediction of functional connectivity of fronto-limbic network in the outcome of subjects with clinical high-risk for psychosis / 上海交通大学学报（医学版）

Objective: To explore the role of functional connectivity (FC) within the fronto-limbic network in predicting the onset of psychosis in the subjects with clinical high-risk for psychosis (CHR). Methods: A total of 164 CHR subjects and 89 healthy controls (HC) who underwent resting-state functional MRI were recruited. FCs between frontal [medial prefrontal cortex and bilateral or-bitofrontal cortex (OFC)] and limbic (bilateral hippocampus and bilateral amygdala) brain regions at baseline were calculated. CHR subjects were further divided into 3 subgroups, i.e., CHR converters (CHR-C) group, symptomatic CHR (CHR-S) group and remitted CHR (CHR-R) group according to clinical outcome after one-year follow-up. The FCs of fronto-limbic network were compared between the groups and among the subgroups, and their interaction with brain regions, as well as their correlations with positive and negative symptoms were analyzed. Results: There was no significant main effect of group (P=0.110), but a significant interaction of subgroups and brain regions (P=0.049). CHR-C group had lower FC between bilateral OFC and bilateral amygdala than HC group and CHR-R group (all P<0.05). The FCs between left OFC and left hippocampus in the three CHR subgroups were all lower than that in HC group (all P<0.05). In addition, the FC between left OFC and right amygdala was positively correlated with the severity of negative symptoms in CHR-C group, while the FCs between left OFC and bilateral hippocampus and between right OFC and left hippocampus were negatively correlated with the severity of positive symptoms in CHR-C group. Conclusion: The decrease of OFC-hippocampus connectivity may be common in the subjects with CHR, while the decrease of OFC-amygdala connectivity may predict CHR subjects will convert to schizophrenia in the later stage.

Abnormality of θ oscillation in auditory event-related potential P300 in patients with clinical high risk of psychosis or first-episode schizophrenia / 上海交通大学学报（医学版）

Objective • To explore the relationship between θ oscillation of auditory event-related potential P300 and clinical symptoms in the patients with clinical high risk (CHR) of psychosis or first episode schizophrenia (FES). Methods • A total of 18 patients with CHR of psychosis (CHR group), 18 patients with FES (FES group) and 19 healthy controls (control group) were recruited to complete the standard auditory Oddball paradigm as well as electroencephalogram (EEG) recording with 64-channel EEG cap. Fz, Cz and Pz electrodes were selected to compare the amplitudes and peak latent periods among the three groups, and time-frequency analysis of the θ oscillation in P300 was performed. Results • There was significant difference in the amplitudes of P300 among the three groups (P=0.004). The amplitudes of P300 in FES group (P=0.001) and CHR group (P=0.026) were both significantly lower than that of control group. There was no difference between CHR group and FES group in P300 amplitude (P>0.05). θ Oscillation induced power was significantly different among the three groups (P=0.022). The induced power value of FES group was significantly lower than that of control group (P=0.008); and it was marginally lower in CHR group as compared to that of control group (P=0.054). There was no difference between CHR group and FES group (P>0.05). There was trending difference in θ oscillation evoked power among the three groups (P=0.054). The correlation analysis showed that the total and subscale scores of Positive and Negative Syndrome Scale in FES group were significantly correlated with the amplitudes of P300 at Cz and Pz electrodes (P<0.05). Conclusion • There are significant abnormalities in the amplitude of auditory P300 and θ oscillation of P300 in both CHR and FES patients; however, the change in CHR patients is less severe than that of FES patients. The impaired θ oscillation of P300 in CHR patients is limited to induced power, but evoked power is not impaired.

Analysis of niacin skin flush in clinical high risk population of psychosis / 上海交通大学学报（医学版）

Objective • To explore and analyze the characteristics of nicotinic acid skin sensitivity in clinical high risk (CHR) population of psychosis. Methods • One hundred and five patients with CHR of psychosis (CHR group) and fifty-one patients with first episode schizophrenia (FES) (FES group) in Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine from Jun. 2016 to Jun. 2018, and fifty-four healthy controls (HC group) were included. The patients of CHR group met the criteria of prodromal syndromes, and the patients of FES group met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). The patients of HC group were matched with CHR group in age and gender. The niacin skin flush of the three groups were detected. The niacin skin flush scores of the three groups were compared by single factor repeated measurement variance analysis (MANOVA). The niacin flush negative rates of the three groups were compared by Chi-square test. Results • Compared with HC group, the niacin skin flush of CHR group and FES group reduced at different concentrations and time points. MANOVA showed a significant main group effect of niacin skin flush (F=1.746, P=0.009). There were no significant group × concentration interaction (F=1.628, P=0.138) and group × time interaction (F=0.851, P=0.531). Compared with HC group, the niacin total flush scores of CHR group were lower (t=-2.697, P=0.008). The significant differences of the proportion of patients with negative niacin reaction among the three groups were found for the concentration of 0.1 mol/L at 5 min (χ2=16.709, P=0.000) and 0.001 mol/L at 20 min (χ2=6.380, P=0.041). Conclusion • The reduction of the niacin skin flush can occur not only in the patients with schizophrenia but also in the CHR of psychosis in the precursor phase. Niacin skin flush may be an early biological marker of schizophrenia.

Characteristics of smooth pursuit eye-movement in subjects at clinical high risk for psychosis / 中国神经精神疾病杂志

Objective To investigate the eye-movement features of smooth pursuit in subjects at clinical high risk for psychosis.Methods sixty subjects at clinical high risk for psychosis and sixty healthy controls were recruited.The smooth pursuit tasks were assessed in both horizontal (0.4 Hz) and Lissajous (0.2 or 0.4 Hz) condition.The Wechsler Memory Scale-third edition and spatial span subtest were used to assess working memory.The difference of the smooth pursuit performance between the two groups and the relationship between smooth pursuit and working memory were analyzed.Results Subjects at clinical high risk for psychosis showed significantly lower Horizontal components for pursuit gain [Lissajous 0.2 Hz task (0.82±0.12) vs.(0.89±0.09),Lissajous 0.4 Hz task (0.78±0.13) vs.(0.84±0.14)],lower vertical components for pursuit gain [Lissajous 0.2 Hz task (0.80±0.14) vs.(0.86±0.12),Lissajous 0.4 Hz task (0.71±0.15)vs.(0.77±0.16)] and higher mean positional error [Lissajous 0.2 Hz task (37.00±19.10) vs.(30.45± 16.18),Lissajous 0.4 Hz task (44.18±19.70) vs.(37.61±16.26)] compared to healthy controls (P＜0.05).There was a significant correlation between pursuit gain and performance on Spatial Span (Horizontal components:r=0.361,P=0.005;vertical components:r=0.327,P=0.01 1) in the Subjects at clinical high risk for psychosis.Conclusions Subjects at clinical high risk for psychosis showed deficits in smooth pursuit,and the deficits were related to the working memory.

The conversion of Clinical high risk for psychosis: Association with Theory of Mind / 中国神经精神疾病杂志

Objective To explore the clinical outcome of individuals with Clinical High Risk (CHR) for psychosis and its relationship with Theory of Mind (ToM) function.Methods The Structured Interview for Prodromal Symptoms/Scale of Prodromal Syndromes (SIPS/SOPS) was applied to assess prodromal psychosis.The Reading the mind in the Eyes and faux pas Task were conducted to assess the function of Theory of Mind among the individuals of clinical high risk of psychosis.All participants had completed the 2-year follow-up.Conversion was determined using the criteria of presence of psychotic symptoms (POPS).According to the outcome,CHR individuals were divided into conversion group (n=20) and no-conversion group (n=50).The baseline clinical symptom characteristics and Theory of Mind were compared between groups.Results There was no significant difference in clinical symptom characteristics among individuals with CHR (P＞0.05).In the faux pas text,there were significant differences in Faux Pas Detection (P=0.01),Faux Pas Understanding (P=0.01) and Faux Pas Total (P=0.02) but not in control stories and the Reading the Mind in the Eyes Test between convertors and non-convertors (P＞0.05).Conclusion The ToM disability in clinical high risk population increases risk for conversion to psychosis.

Reconsidering Clinical Staging Model: A Case of Genetic High Risk for Schizophrenia

The clinical staging model is considered a useful and practical method not only in dealing with the early stage of psychosis overcoming the debate about diagnostic boundaries but also in emerging mood disorder. However, its one limitation is that it cannot discriminate the heterogeneity of individuals at clinical high risk for psychosis, but lumps them all together. Even a healthy offspring of schizophrenia can eventually show clinical symptoms and progress to schizophrenia under the influence of genetic vulnerability and environmental stress even after the peak age of onset of schizophrenia. Therefore, individuals with genetic liability of schizophrenia may require a more intensive intervention than recommended by the staging model based on current clinical status.

A study of event-related potential P300 in subjects with clinical high risk of psychosis / 中国神经精神疾病杂志

Objective To investigate the characteristics of auditory P300 amplitude and latency and cognition in patients with clinical high-risk of psychosis (CHR). Method Thirty six CHR (study group) and thirty five healthy con?trols (control group) were included. Oddball paradigm and MATRICS Consensus Cognitive Battery (MCCB) were used to record auditory P300 and to evaluate the cognition, respectively. The structured interview for psychosis-risk syndromes (SIPS) was used to evaluate the clinic symptoms of patients. Result The cognition of CHR was significantly lower than healthy controls in information processing, attention/vigilance, working memory, verbal learning, visual learning, reason?ing and problem solving and social cognition (P<0.01). The study group showed decreased amplitude in Fz, Cz and Pz and delayed latency in Pz (P<0.05). P300 latency of CHR in Fz positively correlated with positive score of SOPS (r=0.544, P=0.001), while P300 amplitude positively correlated with verbal fluency (r=0.339,P=0.043). Conclusion Cogni?tion and P300 is abnormal in CHR. The correlation between P300 and clinical symptoms, cognitive dysfunction reminds that we should put more attention on the role of P300 in CHR subjects.

Characteristics of Subjects at Clinical High Risk for Schizophrenia: Natural Follow up Study in 'Seoul Youth Clinic'- Pilot Study / 신경정신의학

OBJECTIVES: The aims of this study were to identify the intake and following process for subjects at high risk of transition to schizophrenia and to examine the neurocognitive, social, and emotional functions of the subjects compared with healthy controls. METHODS: Symptomatic individuals judged at high risk for schizophrenia ('clinical high risk') within Youth Clinic were assessed and followed up. They performed a neurocognitive function test, a social function test and an affective function test. Twenty healthy controls were recruited in this study. RESULTS: Among eighty-two subjects contacted through the Youth clinic, sixteen subjects were judged as the clinical high risk group. Fourteen subjects among the clinical high risk group showed deficits in several domains of neurocognitive functions, such as visual recall memory, verbal short term memory and executive function. Social and affective functions are also impaired in the clinical high risk group compared with healthy controls. Two of 15 subjects (13%) developed a psychotic disorder within 6 months. CONCLUSION: This study illustrates the state of follow-up study for a clinical high risk group. Despite low numbers and short durations, some impairment of several functions in the clinical high risk group suggests possible predictors of psychosis.