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Previous studies suggested that serotonergic neurons and platelets share similarities in serotonin (5-HT) uptake by serotonin transporter (SERT), storage, metabolism and release mechanisms, indicating that platelets may be used as a reliable peripheral surrogate to measure central SERT activity in neuropsychiatric research. In this study, platelet 5-HT content and 5-HT uptake capacity of SERT in depression and anxiety patients were measured by ELISA and flow cytometry with IDT307 at baseline and after serotonin reuptake inhibitors (SSRIs) treatment for 4 weeks. Healthy persons matched with age and gender were used as reference. The clinical presentations of the patients were assessed with Hamilton Depression (HAMD) and Anxiety Rating Scales (HAMA) at the same time points. Compared to healthy subjects, anxiety and depression patients showed higher levels of platelet 5-HT and IDT307 fluorescence intensity, but the values were comparable between the patient groups. SSRIs administration for 4 weeks significantly decreased scores of HAMD (29 vs 14) and HAMA (22 vs 14) in depression and anxiety patients, respectively; while it decreased platelet 5-HT content, but did not change the IDT307 fluorescence intensity of platelets. After incubation with fluoxetine in vitro, the IDT307 fluorescence intensity of isolated platelets from both healthy subjects and patients decreased in a dose-dependent manner. These results provide further evidence supporting the employment of platelet 5-HT content and SERT as peripheral surrogates in depression and anxiety patients, and are of help in understanding the several weeks' delay from the initiation of antidepressant medication to their full therapeutic effects in the patients.

This study explored specificity and visual perspective of mental time travel in schizophrenia. Fifteen patients with schizophrenia and 18 controls were recruited. Participants were asked to recall or imagine specific events according to cue words. Results showed that schizophrenia patients generated fewer specific events than controls, the recalled events were more specific than imagined events. Schizophrenia adopted less field perspective and more observer perspective than controls. These results suggested that patients with schizophrenia were impaired in mental time travel both in specificity and visual perspective. Further studies are needed to identify the underlying mechanisms.

Research on the relationship between insight and social cognition, in particular Theory of Mind (ToM), in schizophrenia has yielded mixed findings to date. Very few studies, however, have assessed both clinical insight and cognitive insight when examining their relationships with ToM in schizophrenia. The current study thus investigated the relationship between clinical insight, cognitive insight, and ToM in a sample of 56 patients with schizophrenia and 30 healthy controls. Twenty-seven patients were classified as low in clinical insight according to their scores on the 'insight' item (G12) of the Positive and Negative Syndrome Scale (PANSS). Moreover, cognitive insight and ToM were assessed with the Beck Cognitive Insight Scale (BCIS) and the Yoni task, respectively. The results indicated that patients with poor clinical insight performed worse on taslcs of second-order cognitive and affective ToM, while the ToM performance of patients with high clinical insight was equivalent to that of healthy controls. Furthermore, while clinical insight was correlated with ToM and clinical symptoms, cognitive insight did not correlate with clinical insight, ToM, or clinical symptoms. Clinical insight thus appears to be an important factor related to ToM in schizophrenia. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Major depressive disorder (MDD), one of the most frequently encountered forms of mental illness and a leading cause of disability worldwide, poses a major challenge to genetic analysis. To date, no robustly replicated genetic loci have been identified, despite analysis of more than 9,000 cases. Here, using low-coverage whole-genome sequencing of 5,303 Chinese women with recurrent MDD selected to reduce phenotypic heterogeneity, and 5,337 controls screened to exclude MDD, we identified, and subsequently replicated in an independent sample, two loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene (P = 2.53 × 10(-10)), the other in an intron of the LHPP gene (P = 6.45 × 10(-12)). Analysis of 4,509 cases with a severe subtype of MDD, melancholia, yielded an increased genetic signal at the SIRT1 locus. We attribute our success to the recruitment of relatively homogeneous cases with severe illness.

This study aimed to examine the subjective awareness of everyday dysexecutive function and the 'objective' executive function in individuals with schizotypal personality features. Forty-nine individuals with schizotypal personality disorder (SPD) proneness (25 negative schizotypy and 24 non-negative schizotypy were identified using cluster analysis) and 44 non-SPD individuals completed a battery of 'objective' executive function tests and a self-reported Dysexecutive Questionnaire (DEX) on everyday executive problems. The findings showed that individuals with SPD proneness including negative schizotypy and non-negative schizotypy did not have significant worse performance than non-SPD in most of 'objective' executive function tests, but self-reported significantly disproportionate more dysexecutive problems than non-SPD. Furthermore. SPD proneness, especially negative schizotypy was found to give undependable estimation on their everyday dysexecutive function while non-negative schizotypy was not. The current findings suggest that the subjective awareness of dysexecutive function may precede actual 'objective' executive function impairments in a subtype of SPD (non-negative schizotypy) and the subjective complaint of the daily dysexecutive behavior in SPD proneness, especially negative schizotypy might result from their unreliable estimation of executive function. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Executive dysfunctions have been consistently demonstrated in patients with schizophrenia. This study aimed to investigate deficits in specific executive functioning components, namely working memory and inhibition, in schizophrenia. In study 1, a set of neurocognitive function tests was administered to 41 patients with schizophrenia and 25 healthy controls to capture specific components of executive functioning, including semantic inhibition (the Stroop-like paradigm and the Chinese Version of the Hayling Sentence Completion Test (HSC)), working memory (the spatial n-back), and response inhibition (the stop signal task (SST)). Results showed that schizophrenia patients did significantly worse than controls under both working memory and inhibition demands in the Stroop-like paradigm. In particular, patients were impaired when inhibiting a semantically associated response; and performance was correlated with negative symptoms. In study 2, we employed a modified semantic inhibitory error monitoring paradigm to examine whether patients with schizophrenia (n = 11) were impaired in semantic inhibitory error monitoring or not as compared to 11 healthy controls. The results suggested that patients with schizophrenia in this study remained intact in semantic inhibition error monitoring. There was no difference in the semantic inhibitory monitoring performance between healthy controls and patients with schizophrenia. Taken together, these results suggested impaired working memory context maintenance and semantic inhibition in schizophrenia patients, and these impairments were related to clinical symptoms of schizophrenia. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Schizophrenia and normal aging have both been associated with structural and physiological changes in the prefrontal and temporal cortex and impairments in prospective memory (PM). This study aimed to compare PM performance in patients with schizophrenia, healthy older, and healthy younger individuals. Computerized event- and time-based PM tasks were administered to 30 patients with schizophrenia, 30 healthy older adults, and 30 healthy younger adults. The healthy older adults and patients with schizophrenia demonstrated deficits in time-based PM when compared with the healthy younger adults. However, only healthy older adults were found to be impaired in event-based PM when compared with the healthy younger adults. These findings suggest that patients with schizophrenia show a similar pattern of performance on one type but not another type of PM and provide only partial support for the accelerated aging hypothesis of schizophrenia.

Although there is a consensus that patients with schizophrenia have certain deficits in perceiving and expressing facial emotions, previous studies of facial emotion perception in schizophrenia do not present consistent results. The objective of this study was to explore facial emotion perception deficits in Chinese patients with schizophrenia and their non-psychotic first-degree relatives. Sixty-nine patients with schizophrenia, 56 of their first-degree relatives (33 parents and 23 siblings), and 92 healthy controls (67 younger healthy controls matched to the patients and siblings, and 25 older healthy controls matched to the parents) completed a set of facial emotion perception tasks, including facial emotion discrimination, identification, intensity, valence, and corresponding face identification tasks. The results demonstrated that patients with schizophrenia performed significantly worse than their siblings and younger healthy controls in accuracy in a variety of facial emotion perception tasks, whereas the siblings of the patients performed as well as the corresponding younger healthy controls in all of the facial emotion perception tasks. Patients with schizophrenia also showed significantly reduced speed than younger healthy controls, while siblings of patients did not demonstrate significant differences with both patients and younger healthy controls in speed. Meanwhile, we also found that parents of the schizophrenia patients performed significantly worse than the corresponding older healthy controls in accuracy in terms of facial emotion identification, valence, and the composite index of the facial discrimination, identification, intensity and valence tasks. Moreover, no significant differences were found between the parents of patients and older healthy controls in speed after controlling the years of education and IQ. Taken together, the results suggest that facial emotion perception deficits may serve as potential endophenotypes for schizophrenia.

Sensory gating deficit, as reflected by P50 suppression, has been demonstrated in schizophrenia. Despite extensive evidence of the irreversible effects of typical neuroleptics on this deficit, recent studies of atypical neuroleptics have produced inconsistent findings on the reversibility of P50 suppression in schizophrenia. As the majority of these studies were limited by either their cross-sectional design or the recruitment of patients on multiple medications, the current study was designed to examine the effects of different neuroleptic medications on the P50 sensory gating index in patients with first-episode, never-medicated schizophrenia. P50-evoked potential recordings were obtained from 62 normal controls when they entered the study and from 65 patients with first-episode, never-medicated schizophrenia at baseline and after six weeks of different neuroleptic treatments (sulpiride [n=24], risperidone [n=24] and clozapine [n=17]). The first-episode, never-medicated schizophrenia patients had impaired sensory gating relative to the normal controls (mean=94.19% [SD=61.31%] versus mean=41.22% [SD=33.82%]). The test amplitude S2 was significantly higher in the schizophrenia patients than in the normal controls. The conditioning amplitude S1 and the positive symptom scores were related to the P50 gating ratios in schizophrenia at baseline. There was no change in P50 sensory gating (P>0.10) and a significant improvement in the clinical ratings (P>0.10) after six-week neuroleptic treatment for schizophrenia. P50 sensory gating was not significant for the patients who received sulpiride, risperidone or clozapine at baseline (F=1.074, df=2, 62, P=0.348) or at endpoint (F=0.441, df=2, 62, p=0.646). Our findings indicate that there is P50 sensory gating impairment in first-episode, never-medicated schizophrenia and that treatment with typical and atypical antipsychotics has no significant impact on such gating in this illness.

While a number of studies have shown that individuals with schizophrenia are impaired on various types of prospective memory, few studies have examined the relationship between subjective and objective measures of this construct in this clinical group. The purpose of the current study was to explore the relationship between computer-based prospective memory tasks and the corresponding subjective complaints in patients with schizophrenia, individuals with schizotypal personality features, and healthy volunteers. The findings showed that patients with schizophrenia demonstrated significantly poorer performance in all domains of memory function except visual memory than individuals with schizotypal personality disorder and healthy controls. More importantly, there was a significant interaction effect of prospective memory type and group. Although patients with schizophrenia were found to show significantly poorer performance on computer-based measures of prospective memory than controls, their level of subjective complaint was not found to be significantly higher. While subjective complaints of prospective memory were found to associate significantly with self-reported executive dysfunctions, significant relationships were not found between these complaints and performance on a computer-based task of prospective memory and other objective measures of memory. Taken together, these findings suggest that subjective and objective measures of prospective memory are two distinct domains that might need to be assessed and addressed separately.

Background We sought to investigate the clinical features of and risk factors for recurrent major depression (MD) with history of postpartum episodes (PPD) in Han Chinese women and the differences between first-onset postpartum MD (MD that has its first lifetime depressive episode in the postpartum period) and first-onset non-postpartum MD (MD with history of PPD and has its first lifetime depressive episode in a period other than postpartum). Methods Data were derived from the China, Oxford and Virginia Commonwealth University Experimental Research on Genetic Epidemiology (CONVERGE) study (N=6017 cases) and analyzed in two steps. We first examined the clinical features of and risk factors for MD patients with (N=981) or without (N=4410) a history of PPD. We then compared the differences between first-onset postpartum MD (N=583) and first-onset non-postpartum MD (N=398) in those with a history of PPD. Linear, logistic and multinomial logistic models were employed to measure the associations. Results A history of PPD was associated with more guilt feelings, greater psychiatric comorbidity, higher neuroticism, earlier onset and more chronicity (OR 0.2–2.8). Severe premenstrual symptoms (PMS) and more childbirths increased the risk of PPD, as did a family history of MD, childhood sexual abuse, stressful life events and lack of social support (OR 1.1–1.3). In the MD with history of PPD subsample, first-onset postpartum MD was associated with fewer recurrent major depressive episodes, less psychiatric comorbidity, lower neuroticism, less severe PMS and fewer disagreements with their husbands (OR 0.5–0.8), but more childbirths (OR 1.2). Limitations Data were obtained retrospectively through interview and recall bias may have affected the results. Conclusions MD with history of PPD in Han Chinese women is typically chronic and severe, with particular risk factors including severe PMS and more childbirths. First-onset postpartum MD and first-onset non-postpartum MD can be partly differentiated by their clinical features and risk factors, but are not clearly distinctive.

BackgroundOur prior study in Han Chinese women has shown that women with a history of childhood sexual abuse (CSA) are at increased risk for developing major depression (MD). Would this relationship be found in our whole data set?MethodThree levels of CSA (non-genital, genital, and intercourse) were assessed by self-report in two groups of Han Chinese women: 6017 clinically ascertained with recurrent MD and 5983 matched controls. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression.ResultsWe confirmed earlier results by replicating prior analyses in 3,950 new recurrent MD cases. There were no significant differences between the two data sets. Any form of CSA was significantly associated with recurrent MD (OR 4.06, 95% confidence interval (CI) [3.19-5.24]). This association strengthened with increasing CSA severity: non-genital (OR 2.21, 95% CI 1.58-3.15), genital (OR 5.24, 95% CI 3.52-8.15) and intercourse (OR 10.65, 95% CI 5.56-23.71). Among the depressed women, those with CSA had an earlier age of onset, longer depressive episodes. Recurrent MD patients those with CSA had an increased risk for dysthymia (OR 1.60, 95%CI 1.11-2.27) and phobia (OR 1.41, 95%CI 1.09-1.80). Any form of CSA was significantly associated with suicidal ideation or attempt (OR 1.50, 95% CI 1.20-1.89) and feelings of worthlessness or guilt (OR 1.41, 95% CI 1.02-2.02). Intercourse (OR 3.47, 95%CI 1.66-8.22), use of force and threats (OR 1.95, 95%CI 1.05-3.82) and how strongly the victims were affected at the time (OR 1.39, 95%CI 1.20-1.64) were significantly associated with recurrent MD.ConclusionsIn Chinese women CSA is strongly associated with recurrent MD and this association increases with greater severity of CSA. Depressed women with CSA have some specific clinical traits. Some features of CSA were associated with greater likelihood of developing recurrent MD.

Background The prevalence of major depressive disorder (MDD) is higher in those with low levels of educational attainment, the unemployed and those with low social status. However the extent to which these factors cause MDD is unclear. Most of the available data comes from studies in developed countries, and these findings may not extrapolate to developing countries. Examining the relationship between MDD and socio economic status in China is likely to add to the debate because of the radical economic and social changes occurring in China over the last 30 years. Principal findings We report results from 3,639 Chinese women with recurrent MDD and 3,800 controls. Highly significant odds ratios (ORs) were observed between MDD and full time employment (OR = 0.36, 95% CI = 0.25–0.46, logP = 78), social status (OR = 0.83, 95% CI = 0.77–0.87, logP = 13.3) and education attainment (OR = 0.90, 95% CI = 0.86–0.90, logP = 6.8). We found a monotonic relationship between increasing age and increasing levels of educational attainment. Those with only primary school education have significantly more episodes of MDD (mean 6.5, P-value = 0.009) and have a clinically more severe disorder, while those with higher educational attainment are likely to manifest more comorbid anxiety disorders. Conclusions In China lower socioeconomic position is associated with increased rates of MDD, as it is elsewhere in the world. Significantly more episodes of MDD occur among those with lower educational attainment (rather than longer episodes of disease), consistent with the hypothesis that the lower socioeconomic position increases the likelihood of developing MDD. The phenomenology of MDD varies according to the degree of educational attainment: higher educational attainment not only appears to protect against MDD but alters its presentation, to a more anxious phenotype.

Very few studies have examined physical and social anhedonia across the spectrum of schizophrenia. In the present study, we recruited three groups of participants (n=84 in each group): patients with schizophrenia, schizotypy and non-schizotypy as assessed by the Schizotypal Personality Questionnaire (SPQ). All participants completed the self-reported trait anhedonia scales (the Revised Physical Anhedonia Scale and the Social Anhedonia Scale). The clinical symptoms of schizophrenia patients were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Scale for Assessment of Negative Symptoms (SANS). We found that the three groups differed in both physical and social anhedonia. The schizotypy group reported higher levels of physical anhedonia than the non-schizotypy group, and the patient group reported higher levels of physical anhedonia than the schizotypy group. For social anhedonia, the non-schizotypy group differed significantly from both the schizotypy and the patient group, while no significant difference was found between the last two groups. Our findings show that individuals with schizotypy exhibits similar social but not physical anhedonia compared with patients with schizophrenia, which further suggests that decreased pleasure experiences in the social environment may be a valuable target for identification and early intervention in high-risk populations.

The purpose of the current study was to explore the association of auditory P50 sensory gating (P50) and prepulse inhibition (PPI) of schizophrenia with polymorphisms in the CHRNA7 and COMT genes. One hundred and fourty patients with schizophrenia participated in this study. They were administered the tests P50 and PPI. Moreover, three single nucleotide polymorphisms (SNPs) (rs2337980, rs1909884 and rs883473) in CHRNA7 and three SNPs (rs4680, rs737865 and rs165599) in COMT were selected to be genotyped by polyacrylamide gel microarray techniques. P50 index showed significant reduction in S2 amplitude between wild-type and mutation groups in the COMT rs4680. S1 amplitude of mutation group in the COMT rs737865 was also lower compared to wild-type group. PPI index revealed a shorter pulse latency of mutation group in the rs4680. The suppression ratio of mutation group was lower in COMT rs165599. Negative findings were shown between comparisons in all the CHRNA7 SNPs. We find that P50 and PPI may be influenced by COMT rs4680 polymorphisms in schizophrenia; more excitingly, we find that P50 might be influenced by COMT rs737865 polymorphisms and PPI may be influenced by COMT rs165599 polymorphisms in schizophrenia, and their mutations are associated with the reduction of the risk of P50 or PPI defects in schizophrenia. Futher studies with a larger number of subjects are needed to verify the present findings.

The α7 nicotinic acetylcholine receptor (nAChR) is associated with cognitive and P50 auditory gating deficits in schizophrenia, and α7 nAChR agonists can potentially reverse these deficits. The authors examined multiple dosages of tropisetron, a partial agonist at the nAChR, for short-term effects on cognition and P50 deficits in schizophrenia.In a randomized double-blind design, 40 nonsmoking patients with schizophrenia who had P50 ratios greater than 0.5 and were stabilized on 3-6 mg/day of risperidone were randomly assigned to receive placebo (N=10) or oral tropisetron at 5 mg/day (N=10), 10 mg/day (N=10), or 20 mg/day (N=10). The authors measured P50 inhibitory gating and administered the Chinese-language version of the Repeatable Battery for the Assessment of Neuropsychological Status at baseline and after 10 days of treatment.After 10 days of treatment, all three daily doses of tropisetron significantly improved overall cognitive deficits, with 10 mg showing the greatest improvement for the immediate memory index score and 20 mg for the delayed memory index score on the cognitive battery. The P50 deficits were also improved, and that improvement was significantly correlated with cognitive improvement. Two patients in the 20 mg/day group dropped out because of adverse effects, but the other dosages were well tolerated.The improvement of cognition with tropisetron appeared to be associated with normalization in P50 deficits. Thus, α7 nAChR agonists appear to be a promising therapeutic approach for the treatment of cognitive deficits that are related to abnormal P50 suppression in schizophrenia.

Sensory gating deficits have been found in patients with schizophrenia and their unaffected relatives. However, the underlying neurobiological mechanism of this deficit remains unclear. Pre-clinical studies have implicated adenosine in sensory gating deficits in schizophrenia. Therefore, the current study investigated a possible relationship between peripheral adenosine A2A receptor (ADORA2A) and sensory gating indices (P50 measures) in medication-free schizophrenia (n = 31) and healthy (n = 21) groups. The effects of six-week antipsychotic treatment were examined. At baseline, schizophrenia patients showed impaired sensory gating compared to healthy controls. However, there was no significant difference in ADORA2A gene expression among groups. In addition, ADORA2A expression was not correlated with sensory gating at any time point. Following treatment, we found a significant upregulation of ADORA2A expression. Intriguingly, we observed a significant positive association between ADORA2A upregulation and baseline P50 amplitudes in the schizophrenia group. A main finding of the current pilot study is the upregulation of ADORA2A expression following treatment with antipsychotics. In addition, this upregulation was predicted by baseline P50 amplitude, an observation that awaits replication in an expanded sample.

Although a number of studies have found prospective memory (PM) impairment in patients with schizophrenia, very little is known about the PM performance in non-psychotic relatives of these patients. The current study aimed to explore the PM performance in non-psychotic first-degree relatives of these patients. Two groups of participants (26 non-psychotic first-degree relatives of schizophrenia patients and 26 healthy comparison participants) were administered three PM tasks (time-, event-, and activity-based) and a set of neurocognitive tests. Results showed that the relatives performed significantly worse than the comparisons on most indices of the PM tasks, with a similar pattern of impairment found in other neurocognitive measures. Together with findings from previous studies, results of the current study suggest that PM may be a potential endophenotype for schizophrenia.

This study examined anticipatory and consummatory pleasure in schizophrenia patients with and without negative symptoms. Negative symptom patients experienced less anticipatory pleasure than non-negative symptom patients; only one facet of consummatory pleasure was unaffected in negative schizophrenia. Greater pleasure deficits were correlated with more severe positive and negative symptoms.

Prospective memory (PM) refers to the ability to execute a delayed intention and is different from retrospective memory (RM) in its nature and underlying mechanism (e.g., intention formation, maintenance, detection of PM cue and intention execution). Although preliminary studies have found PM impairment in patients with schizophrenia, the nature and magnitude of this problem in this clinical group is not yet fully known. The current study aimed to further clarify the nature of this impairment in schizophrenia. Fifty-four patients with schizophrenia and fifty-four healthy volunteers matched on demographic variables, IQ and executive functions took part in the study. Time-, event-, and activity-based PM tasks and a set of neurocognitive tests were administered to the participants. Results showed that patients with schizophrenia performed significantly worse on all sub-types of PM tasks, even after controlling for neurocognitive functions such as working memory, verbal memory, visual memory, and executive function. These findings suggest PM deficit is a primary deficit rather than a secondary consequence of neurocognitive impairments in schizophrenia. Analysis found that PM deficits may be mainly due to the impairment of the cue detection and intention retrieval stage.

Objective To investigate the risk factors that contribute to smoking in female patients with major depressive disorder (MDD) and the clinical features in depressed smokers. Methods We examined the smoking status and clinical features in 6120 Han Chinese women with MDD (DSM-IV) between 30 and 60 years of age across China. Logistic regression was used to determine the association between clinical features of MDD and smoking status and between risk factors for MDD and smoking status. Results Among the recurrent MDD patients there were 216(3.6%) current smokers, 117 (2.0%) former smokers and 333(5.6%) lifetime smokers. Lifetime smokers had a slightly more severe illness, characterized by more episodes, longer duration, more comorbid illness (panic and phobias), with more DSM-IV A criteria and reported more symptoms of fatigue and suicidal ideation or attempts than never smokers. Some known risk factors for MDD were also differentially represented among smokers compared to non-smokers. Smokers reported more stressful life events, were more likely to report childhood sexual abuse, had higher levels of neuroticism and an increased rate of familial MDD. Only neuroticism was significantly related to nicotine dependence. Conclusions Although depressed women smokers experience more severe illness, smoking rates remain low in MDD patients. Family history of MDD and environmental factors contribute to lifetime smoking in Chinese women, consistent with the hypothesis that the association of smoking and depression may be caused by common underlying factors.