Cognitive enhancing effect of rTMS combined with tDCS in patients with major depressive disorder: a double-blind, randomized, sham-controlled study.

BACKGROUND: Cognitive dysfunction is one of the common symptoms in patients with major depressive disorder (MDD). Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have been studied separately in the treatment of cognitive dysfunction in MDD patients. We aimed to investigate the effectiveness and safety of rTMS combined with tDCS as a new therapy to improve neurocognitive impairment in MDD patients. METHODS: In this brief 2-week, double-blind, randomized, and sham-controlled trial, a total of 550 patients were screened, and 240 MDD inpatients were randomized into four groups (active rTMS + active tDCS, active rTMS + sham tDCS, sham rTMS + active tDCS, sham rTMS + sham tDCS). Finally, 203 patients completed the study and received 10 treatment sessions over a 2-week period. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess patients' cognitive function at baseline and week 2. Also, we applied the 24-item Hamilton Depression Rating Scale (HDRS-24) to assess patients' depressive symptoms at baseline and week 2. RESULTS: After 10 sessions of treatment, the rTMS combined with the tDCS group showed more significant improvements in the RBANS total score, immediate memory, and visuospatial/constructional index score (all p < 0.05). Moreover, post hoc tests revealed a significant increase in the RBANS total score and Visuospatial/Constructional in the combined treatment group compared to the other three groups but in the immediate memory, the combined treatment group only showed a better improvement than the sham group. The results also showed the RBANS total score increased significantly higher in the active rTMS group compared with the sham group. However, rTMS or tDCS alone was not superior to the sham group in terms of other cognitive performance. In addition, the rTMS combined with the tDCS group showed a greater reduction in HDRS-24 total score and a better depression response rate than the other three groups. CONCLUSIONS: rTMS combined with tDCS treatment is more effective than any single intervention in treating cognitive dysfunction and depressive symptoms in MDD patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100052122).

The phonological congruency modulated long-term form priming of Chinese characters.

Elucidating the interaction between lexical processing and word learning is essential for a complete understanding of the underlying mechanisms of each of them. Long-term priming for words reflects an interplay between lexical processing and word learning. Although robust long-term priming effects have been found between two occurrences of the same word and between semantically similar words, it remains unclear whether long-term priming between orthographically similar words (i.e., long-term form priming) is a reliable effect. Following the theoretical analysis based on the connectionist framework, we articulated the possibility that long-term form priming might be modulated by the phonological congruency between the prime and target words, and that if this modulator was under control, reliable effects of long-term form priming would emerge. However, this hypothesis has not been adequately tested empirically. The present study tested this hypothesis by using Chinese phonograms and the phonetic radicals embedded in them as the prime and target items. In three experiments that varied in the types of stimuli and testing tasks, we consistently found that when the prime and target had the same phonology, naming the prime facilitated later processing of the target, while when they had different phonologies, the priming effect was inhibitory. These observations were consistent with the connectionist account of long-term priming for words. Our findings help confirm the reliability, generalizability, and robustness of long-term form priming and elucidate its underlying mechanisms, and suggesting promising future directions on the interactions between lexical processing and word learning.

Sex differences in prevalence and clinical correlates of insomnia in Chinese patients with chronic schizophrenia.

OBJECTIVE: It is generally recognized that there are sex differences in many aspects of schizophrenia. The main purpose of this study was to investigate the sex differences in the prevalence and clinical correlates of insomnia in patients with chronic schizophrenia. METHODS: A total of 957 patients who met the DSM-IV diagnostic criteria for schizophrenia were recruited in this cross-sectional study (male/female = 630/327). Demographic, clinical, and insomnia data were collected using self-reported questionnaires. Fasting blood samples were collected to evaluate the status of blood lipids. Psychopathological symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). RESULTS: The prevalence rate of insomnia in female patients with schizophrenia was significantly higher than that in male patients (17.3% for males and 26.3% for females; χ2 = 10.74, p = 0.001). Regression analysis showed that in male patients, insomnia was independently associated with severe PANSS positive symptoms, severe PANSS depressive factor, and high levels of low-density lipoprotein levels, while in female patients, insomnia was associated with low education level, high PANSS depressive factor, and high levels of apolipoprotein B levels. CONCLUSION: This study illustrates that insomnia is more frequent in female than male schizophrenia patients, and that there are differences in the clinical correlates of insomnia by sex, suggesting that sex differences should be considered in prevention and treatment strategies for coexisting insomnia in schizophrenia patients.

Insomnia in Chinese patients with chronic schizophrenia: prevalence, clinical correlates and relationship with cognitive impairment.

PURPOSE: Insomnia is a major public health concern that often occurs in patients with schizophrenia, complicating the treatment and prognosis of patients. This study aimed to investigate the prevalence of insomnia and its relationship with cognitive function in Chinese patients with chronic schizophrenia. METHODS: We recruited patients with schizophrenia and collected their clinical and demographic data. Insomnia data were collected through a self-reported questionnaire consisting of three questions. The positive and negative syndrome scale (PANSS) was used to measure psychopathological symptoms, while the repeatable battery for the assessment of neuropsychological status (RBANS) was used to measure cognitive performance. RESULTS: Of 957 Chinese patients with chronic schizophrenia 20.2% reported having insomnia (193/957). Male patients (107/630, 17.0%) had a lower rate of insomnia than female patients (86/327, 26.3%) (x2 = 11.60, p = 0.001). Patients with insomnia exhibited significantly higher PANSS total score and positive symptom, negative symptom, and general psychopathology scores, but significantly lower RBANS total score, language, attention and delayed memory scores compared to patients without insomnia (all p < 0.05). Logistic regression analysis showed that female sex, high PANSS total score and the use of diazepam were independently associated with insomnia (all p < 0.05). CONCLUSIONS: Insomnia is relatively common in Chinese patients with chronic schizophrenia. Some demographic data and clinical symptoms are associated with insomnia. Patients with schizophrenia and insomnia perform poorly on cognition tests suggesting that insomnia and cognitive function are closely related in patients with schizophrenia.

Demographics, clinical characteristics and cognitive symptoms of heavy smokers and non-heavy smokers in Chinese male patients with chronic schizophrenia.

Many studies have shown a high smoking rate and cognitive impairment in patients with schizophrenia. The effects of smoking and nicotine intake on cognitive function in schizophrenia are still controversial. In this study, we divided patients into heavy smoking and non-heavy smoking groups and compared the clinical characteristics and cognitive symptoms between the two groups in Chinese male patients with schizophrenia. A total of 154 heavy smoking patients and 372 non-heavy smoking patients were recruited. They completed a detailed questionnaire including general and socio-demographic data. Positive and Negative Syndrome Scale (PANSS) was rated for psychopathology. The Fagerstrom Test for Nicotine Dependence (FTND) was used to assess the degree of nicotine dependence. Heavy smokers were younger, started smoking earlier and had a higher FTND total score than non-heavy smoking patients. Moreover, we found that heavy smokers had significantly lower negative symptom scores and cognitive factor scores than non-heavy smokers. Logistic regression analysis showed that cognitive factor score and age of initial smoking were significantly associated with heavy smoking. Linear regression analysis showed that cognitive factor score, age of initial smoking and dose of antipsychotics were significant predictors of the amount of smoking. Our findings suggest that there are significant differences in some demographic and clinical variables between heavy and non-heavy smokers in Chinese male patients with chronic schizophrenia. Moreover, heavy smokers have less cognitive symptoms, suggesting that heavy smoking may be beneficial for cognition of patients with schizophrenia.

Association of negative symptoms with cognitive impairment in Chinese Han patients with chronic schizophrenia.

OBJECTIVE: Cognitive impairment is an essential feature of schizophrenia; however, the relationship between clinical psychiatric symptoms with cognitive impairment is still unclear. Therefore, we aimed to assess cognitive deficits and the relationship between clinical symptoms and cognitive function in patients with chronic schizophrenia, which provide a reference guide for psychiatrists. METHODS: We compared the cognitive function in 312 schizophrenia inpatients and 397 healthy controls by using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The positive and negative symptom scale (PANSS) was used to assess the clinical symptoms of the patients. RESULTS: Analysis of covariance showed that the RBANS total and four index scores (all p < 0.001) were significantly lower in patients than healthy controls. After Bonferroni correction, Pearson correlation analysis showed that there was a significant negative association between PANSS negative symptom subscale and RBANS total score and all 5 domain scores (all p < 0.01). Further regression analysis showed that negative symptoms, age, age of onset, and antipsychotic dose were important independent predictors of cognitive deficits. CONCLUSIONS: Our findings suggest that patients with chronic schizophrenia exhibit cognitive deficits compared with healthy people. Negative symptoms and some clinical variables are associated with cognitive impairment in patients with schizophrenia.KEYPOINTSThis study indicates that patients with chronic schizophrenia have extensive cognitive impairment shown on RBANS except for the visuospatial/constructional domain.Cognitive impairment in patients is associated with age, negative symptoms, age of onset, and antipsychotic dose.There is a significant negative association between cognitive deficits and negative symptoms in patients with chronic schizophrenia.The results of this study need to be confirmed in future studies with longitudinal designs with a large and sex-balanced sample in first-episode drug naïve patients with schizophrenia.

Relationship between cognitive function and brain activation in major depressive disorder patients with and without insomnia: A functional near-infrared spectroscopy (fNIRS) study.

BACKGROUND: Patients with major depressive disorder (MDD) frequently present with sleep disturbances and cognitive impairment. The purpose of this study was to investigate whether cognitive impairment is more severe in MDD patients with insomnia, and the underlying neural mechanisms. METHODS: A total of 41 MDD patients with insomnia and 43 MDD patients without insomnia were recruited. We used functional near-infrared spectroscopy (fNIRS) to assess changes in oxyhemoglobin (Oxy-Hb) concentrations in the brain of patients while performing a verbal fluency task (VFT). Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI), cognitive function by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and severity of depression by the Hamilton Depression Scale (HAMD). RESULTS: Compared to MDD patients without insomnia, those with insomnia had lower scores on the RBANS total and immediate memory, visuospatial/constructional, and delayed memory subscales, as well as lower oxy-Hb concentrations in the bilateral dorsolateral prefrontal cortex (DLPFC) and bilateral medial prefrontal cortex (mPFC).Further correlation analysis showed that there was a significant correlation between the RBANS total score in all brain regions except left mPFC in MDD patients with insomnia(all p < 0.05). Further multiple linear regression showed that Oxy-Hb concentrations of left DLPFC were independently associated with RBANS total score. CONCLUSION: Our study suggests that MDD patients with insomnia have more cognitive impairment, which is associated with impaired frontal brain activity. Our findings may provide new insights to understand the underlying neural mechanisms of both disorders MDD patients and provide potential clinical value for developing treatment strategies for insomnia in MDD patients.

Sex differences in the prevalence and clinical correlates of diabetes in Chinese patients with chronic schizophrenia.

Sex differences have been noted in schizophrenia (SCZ) and diabetes mellitus (DM); however, the effect of sex on SCZ patients with DM remains unknown. We aimed to investigate sex differences in the prevalence, demographic and clinical correlates of DM in Chinese patients with chronic SCZ. A total of 988 Han Chinese SCZ patients (male/female: 638/350) were recruited from two psychiatric hospitals in China. We used the Positive and Negative Syndrome Scale (PANSS) to evaluate the psychopathological symptoms of the patients. In addition, serum glucose and lipid levels were assayed. The prevalence of DM in female patients (57/350, 16.29%) was higher than that in male patients (79/638, 12.38%). Binary logistic regression analyses confirmed that the prevalence of DM in female patients was higher than that in male patients (P < 0.001, OR = 4.62, 95% CI = 2.11-10.11). Moreover, female patients had significantly higher positive symptoms than male patients (P = 0.003, OR = 1.08, 95% CI = 1.03-1.14). Further, higher body mass index (BMI) and higher triglyceride (TG) were significantly associated with DM in men (both P < 0.05). Decreased high density lipoprotein (HDL) was significantly associated with DM in both male and female patients (both P < 0.01). Comorbid DM is more common in female SCZ patients, and there are sex-specific correlates of DM in SCZ.

Orbitofrontal cortex-hippocampus potentiation mediates relief for depression: A randomized double-blind trial and TMS-EEG study.

It has been 15 years since repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex (DLPFC) was approved by the FDA for clinical depression treatment. Yet, the underlying mechanisms for rTMS-induced depression relief are not fully elucidated. This study analyzes TMS-electroencephalogram (EEG) data from 64 healthy control (HC) subjects and 53 patients with major depressive disorder (MDD) before and after rTMS treatment. Prior to treatment, patients with MDD have lower activity in the DLPFC, the hippocampus (HPC), the orbitofrontal cortex (OFC), and DLPFC-OFC connectivity compared with HCs. Following active rTMS treatment, patients with MDD show a significant increase in the DLPFC, HPC, and OFC. Notably, the increase in HPC activity is specifically associated with amelioration of depressive symptoms but not anxiety or sleep quality. The orbitofrontal-hippocampal pathway plays a crucial role in mediating depression relief following rTMS treatment. These findings suggest potential alternative targets for brain stimulation therapy against depression (chictr.org.cn: ChiCTR2100052007).

Association of empathy with clinical symptoms and cognitive function in Chinese chronic schizophrenia patients with and without deficit syndrome.

BACKGROUND: Patients with deficit syndrome (DS) are known to experience cognitive impairment. However, there is no consistent conclusion on the impairment of neurocognitive features in DS patients, and no studies have examined their empathy. The purpose of this study was to compare neurocognition and empathy in patients with DS and non-DS schizophrenia. METHODS: Totally, 665 patients with chronic schizophrenia were enrolled. DS patients were identified by the Proxy Scale for Deficit Syndrome (PDS). Neurocognition and social cognition were assessed by Repeatable Battery for the measurement of Neuropsychological Status (RBANS) and the Interpersonal Reactivity Index (IRI), respectively. In addition, psychopathological symptom severity was assessed by the Positive and Negative Syndrome Scale (PANSS). RESULTS: Participants included 150 patients with DS and 140 patients with non-DS. DS patients performed significantly worse on the all RBANS domain (except for visuospatial) and total scores as well as IRI scores. Regression analysis showed that PANSS general psychopathology and education were associated with RBANS total score in the DS group (adjusted R2 = 0.29), while education and PANSS negative symptoms were correlated with RBANS total score in non-DS patients (adjusted R2 = 0.33). In the non-DS group, suicide attempts and PANSS negative symptom score were independently associated with IRI total score (adjusted R2 = 0.06), whereas in the DS group, no variable was associated with IRI total score. CONCLUSIONS: Our findings suggest that patients with DS may have poor neurocognitive and empathy performance. In chronic schizophrenia patients, negative symptoms may play a different role in cognition between DS and non-DS groups.

Alcohol use history increases the likelihood of suicide behavior among male chronic patients with schizophrenia in a Chinese population.

AIMS: This study was designed to detect the association between the history of alcohol drinking and suicidality in schizophrenia (SCZ) inpatients in a Chinese population. METHODS: We recruited 616 male SCZ inpatients and collected demographic and clinical data. Five-factor model of the Positive and Negative Syndrome Scale (PANSS) was used to assess their psychopathological symptoms. RESULTS: Our results showed that 31.33% of SCZ patients had a history of alcohol drinking. They had higher rates of lifetime suicide attempt and suicidal ideation than those without a history of alcohol drinking. Moreover, patients with a history of drinking were more likely to attempt suicide (14.51% vs. 7.09%; χ2  = 7.70, df = 1, p = 0.006), with an odds ratio (OR) of 2.22 and have suicidal ideation (29.02% vs. 17.49%; χ2  = 9.89, df = 1, p = 0.002), with an OR of 1.93. In addition, patients who used to drink alcohol were more likely to be smokers and had more severe positive and depressive symptoms (all p < 0.05). CONCLUSIONS: Our study indicates that history of alcohol drinking may increase the prevalence of lifetime suicide attempt and suicidal ideation in male patients with chronic SCZ. Moreover, the history of alcohol drinking may be associated with some demographic data and clinical symptoms.

Association between empathy and clinical symptoms in chronic schizophrenia: A large sample study based on Chinese Han population.

BACKGROUND: In patients with schizophrenia, clinical symptoms and cognitive impairment are its core features, both of which have a significant impact on the prognosis and functional outcome. Empathy, as an important social cognition, has been found to be associated with the clinical symptoms in schizophrenia, but the conclusions on this issue are inconsistent. Therefore, this study will continue to explore it through a large sample of inpatients with chronic schizophrenia in the Chinese Han population. METHODS: We obtained the sociodemographic characteristics of 987 inpatients, measured their clinical symptoms using the Positive and Negative Syndrome Scale (PANSS), and assessed their self-reported empathy using the Interpersonal Reactivity Index (IRI). The factor score for negative symptoms (FSNS) of PANSS was additionally calculated. RESULTS: Correlation and linear regression analysis showed that patients' PANSS scores were widely correlated with their IRI scores. In particular, the negative symptoms of patients were significantly correlated to IRI total score (r = -0.131, p < .001) and subscales such as Perspective Taking (PT) (r = -0.233, p < .001). FSNS had close relationships with empathy as well. There are also many significant associations between other dimensions, such as general psychopathology and Perspective Taking (PT) or Fantasy (FS) (all p < .05). CONCLUSIONS: Our results indicated that clinical symptoms, especially negative symptoms, were closely related to their current empathy in patients with schizophrenia, suggesting that the severity of clinical symptoms may be a powerful factor in predicting social cognition such as empathy of schizophrenia.

Prevalence, clinical correlates of suicide attempt and its relationship with empathy in patients with schizophrenia.

OBJECTIVES: Previous studies have shown that cognitive impairment plays a key role in suicide, an important factor leading to premature death in schizophrenia (SCZ) patients. Empathy has received extensive attention recently; however, the relationship of empathy with suicide in schizophrenia is still unknown. The main aim of this study was to investigate the prevalence of suicide attempts and its association with empathy and other characteristics in Chinese chronic SCZ patients. METHODS: The suicide attempt data, together with demographic characteristics and clinical variables were collected from 627 chronic inpatients with schizophrenia. We utilized the Positive and Negative Syndrome Scale (PANSS) for the psychopathological symptoms, and the Interpersonal Reactivity Index (IRI) for affective and cognitive empathy in this study. RESULTS: We found a suicide attempt rate of 11.3% in chronic SCZ patients. Compared to non-attempters, suicide attempters were more likely to be women, had younger age and higher education levels, as well as higher positive symptoms and depressive factor score, but lower negative symptoms of PANSS (all p < .05). Moreover, after controlling the confounding factors, suicide attempters scored higher in Personal Distress subscale of IRI (F1, 455 = 5.446, p = .020) than non-attempters. CONCLUSIONS: The prevalence of suicide attempt is high in chronic SCZ patients. Its risk factors include some demographic and clinical variables. Moreover, suicide attempters experienced stronger personal distress, suggesting that stronger empathy may be a risk factor of suicide.

Association of cigarette smoking with cognitive impairment in male patients with chronic schizophrenia.

BACKGROUND: Previous studies have shown that patients with schizophrenia have higher smoking rates and worse cognitive function than healthy controls. However, there is no consistent conclusion about the relationship between smoking and cognitive impairment. OBJECTIVES: The main purpose of this study was to explore the effects of smoking on cognitive function by using MATRICS Cognitive Consensus Battery (MCCB) in Chinese male patients with schizophrenia. METHODS: There were 164 patients with chronic schizophrenia and 82 healthy controls. All subjects were interviewed about smoking status. The cognitive function was assessed by MCCB and Stroop tests. The Positive and Negative Syndrome Scale (PANSS) was used to assess the clinical symptoms of the patients. RESULTS: Compared with healthy controls, patients had lower MCCB scores in all of its domain scores (all p < 0.05). In the patients, the scores of spatial span test (42.3 ± 11.6), digital sequence test (42.9 ± 10.6), and Hopkins Verbal Learning Test (42.2 ± 10.1) were lower in smokers than those in nonsmokers (all p < 0.05, effect size: 0.28-0.45). Logistic regression analysis showed that the smoking status of the patients was correlated with digital sequence score (p < 0.05, OR = 1.072, 95%CI: 1.013-1.134). Multivariate regression analysis showed that the spatial span total score (ß = - 0.26, t = - 2.74, p < 0.001) was associated with the duration of smoking in patients with schizophrenia. CONCLUSIONS: Our findings show that smoking patients with chronic schizophrenia exhibit more severe cognitive impairment than nonsmoking patients, especially in working memory and executive function.

Association of cognitive and P50 suppression deficits in chronic patients with schizophrenia.

OBJECTIVE: Cognitive deficits are core symptoms of schizophrenia; however, their pathophysiological mechanisms are still unclear. A sensory gating deficit, as reflected by P50 suppression, has been repeatedly shown in schizophrenia patients, which may be associated with cognitive deficits in this disorder. The present study was to examine the relationship between the P50 suppression and cognitive deficits in patients with schizophrenia, which is still under-investigated. METHOD: We recruited 38 chronic schizophrenia patients and 32 matched healthy controls, and assessed their cognition with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and P50 suppression with the electroencephalography system. RESULTS: The total and its 4 index scores (all p < 0.05) except for the visuospatial/ constructional index of RBANS were significantly lower in patients compared with healthy controls. However, only the language and attention passed Bonferroni corrections. Patients displayed a significantly higher P50 ratio, higher S2 amplitude, and lower S1 amplitude (all p < 0.05) than healthy controls. Interestingly, only in the patients, the S1 amplitude was associated with both language and attention, and the S2 amplitude with both visuospatial/ constructional and language (all p < 0.05), although all of these significances did not pass the Bonferroni corrections. The P50 ratio was not associated with any of the RBANS scores (all p > 0.05). CONCLUSIONS: Our results suggest the P50 suppression deficits in Chinese patients with schizophrenia, which may be associated with cognitive impairments of this illness. Moreover, the amplitude of S1 and the amplitude of S2 may be involved in the different cognitive domain deficits in schizophrenia patients. SIGNIFICANCE: This study suggests that the P50 components may possibly be effective biomarkers for cognitive deficits in patients with schizophrenia.

P50 inhibition deficit in patients with chronic schizophrenia: Relationship with cognitive impairment of MATRICS consensus cognitive battery.

OBJECTIVE: Cognitive impairment is a core symptom of schizophrenia (SCZ); however, its pathophysiological mechanisms remain unclear. The sensory gating (SG) deficits reflected by P50 inhibition are recurring in SCZ, and this inhibition may be related to the cognitive deficits seen in these individuals. This study aimed to investigate the relationship between P50 inhibition and cognitive dysfunction in SCZ, which has not been fully investigated up to this point. METHODS: A total of 270 individuals with chronic SCZ and 116 healthy controls were enrolled in the study. Psychopathology of SCZ was rated by the positive and negative syndrome scale (PANSS), while cognitive function and P50 inhibition of subjects were assessed by the MATRICS Consensus Cognitive Battery (MCCB) and the electroencephalography system. RESULTS: The MCCB total and its 10 index scores were significantly lower in patients than those in healthy controls (all p < 0.001). SCZ patients had a lower amplitude of S1, and higher P50 ratio than healthy controls (both p < 0.01). However, there were no significant correlations between the P50 ratio and any of the PANSS total and its subscale scores in SCZ patients (all p > 0.05). Moreover, no correlation was found between the P50 components and the MCCB scores (all p > 0.05). CONCLUSIONS: Our findings suggest that the P50 inhibition deficits occur in Chinese individuals with SCZ, which may not be associated with their clinical symptoms and cognitive impairment.