Bridge centrality network structure of negative symptoms in people with schizophrenia.

Negative symptoms are complex psychopathology. Although evidence generally supported the NIMH five consensus domains, research seldom examined measurement invariance of this model, and domain-specific correspondence across multiple scales. This study aimed to examine the interrelationship between negative symptom domains captured by different rating scales, and to examine the domain-specific correspondence across multiple scales. We administered the Brief Negative Symptom Scale (BNSS), the Self-evaluation of Negative Symptoms (SNS), and the Scale for Assessment of Negative Symptoms (SANS) to 204 individuals with schizophrenia. We used network analysis to examine the interrelationship between negative symptom domains. Besides regularized partial correlation network, we estimated bridge centrality indices to investigate domain-specific correspondence, while taking each scale as an independent community. The regularized partial correlation network showed that the SNS nodes clustered together, whereas the SANS and the BNSS nodes intermingled together. The SANS attention domain lied at the periphery of the network according to the Fruchterman-Reingold algorithm. The SANS anhedonia-asociality (strength = 1.48; EI = 1.48) and the SANS affective flattening (strength = 1.06; EI = 1.06) had the highest node strength and EI. Moreover, the five nodes of the BNSS bridged the nodes of the SANS and the SNS. BNSS blunted affect (strength = 0.76; EI = 0.76) and SANS anhedonia-asociality (strength = 0.76; EI = 0.74) showed the highest bridge strength and bridge EI. The BNSS captures negative symptoms and bridges the symptom domains measured by the SANS and the SNS. The three scales showed domain-specific correspondence.

The benefits of emotionally salient cues on event-based prospective memory in bipolar patients and schizophrenia patients.

Prospective memory (PM) refers to the ability to remember to carry out a delayed intention in the future. Evidence suggests that emotionally salient cues can enhance PM functions in healthy population, but whether the benefit exists in schizophrenia and bipolar patients remains unclear. This study aimed to examine and compare the potential enhancement effect of emotional PM cues in schizophrenia patients and bipolar patients. Twenty-eight clinically stable schizophrenia participants, 26 euthymic bipolar participants and 29 controls completed a computerized PM task involving PM cues with different types of valences (i.e., positive, neutral and negative). All the three groups showed better PM performance when negative PM cues were presented compared with positive and neutral PM cues. The sizes of the enhancement effects of negative PM cues were large (all Cohen's d ≥ 1.00) and comparable across three groups. Our findings suggested that patients with schizophrenia and bipolar disorders could benefit from negative PM cues to an extent similar to healthy individuals, thus extended the notion of psychosis continuum to the important area of emotion-cognition interaction.

Minimum inhibitory concentration and killing properties of rifampicin against canine Staphylococcus pseudintermedius isolates from dogs in the southeast USA.

BACKGROUND: Meticillin-resistant (MR) staphylococcal pyoderma in dogs has led to increased use of alternate antibiotics such as rifampicin (RFP). However, little information exists regarding its pharmacodynamics in MR Staphylococcus pseudintermedius. HYPOTHESIS/OBJECTIVES: To determine the minimum inhibitory concentration (MIC) and killing properties of RFP for canine Staphylococcus pseudintermedius isolates. METHODS: The MIC of RFP was determined using the ETEST® for 50 meticillin-susceptible (MS) and 50 MR S. pseudintermedius isolates collected from dogs. From these isolates, two MS isolates (RFP MIC of 0.003 and 0.008 µg/mL, respectively) and two MR isolates (RFP MIC of 0.003 and 0.012 µg/mL, respectively) were subjected to time-kill studies. Mueller-Hinton broth was supplemented with RFP at 0, 0.5, 1, 2, 4, 8, 16 and 32 times the MIC for 0, 2, 4, 10, 16 and 24 h. The number of viable colony forming units in each sample was determined using a commercial luciferase assay kit. RESULTS: The MIC50 and MIC90 were the same for MS and MR isolates, at 0.004 µg/mL and 0.008 µg/mL, respectively. Rifampicin kill curves were not indicative of concentration-dependency, suggesting time-dependent activity. Two isolates (MS 0.003 and 0.008 µg/mL) exhibited bacteriostatic activity, whereas two others (MR 0.003 and 0.012 µg/mL) exhibited bactericidal activity. CONCLUSIONS AND CLINICAL IMPORTANCE: This study demonstrated that MS and MR S. pseudintermedius isolates were equally susceptible to rifampicin and that dosing intervals should be designed for time-dependent efficacy. These data can support pharmacokinetic studies of RFP in dogs with susceptible infections caused by S. pseudintermedius.

Contact dermatitis: a comparative and translational review of the literature.

BACKGROUND: Contact dermatitis (CD) is an inflammatory skin condition induced by direct contact with a specific chemical. Irritant CD (ICD) is a nonspecific inflammatory cutaneous reaction to an irritating agent. Allergic CD (ACD) is an immune-mediated antigen-specific skin reaction to an allergenic chemical. OBJECTIVES AND METHODS: The biomedical literature (human, basic science, veterinary) was reviewed to evaluate the current state of knowledge regarding CD. RESULTS: The incidence of human CD remains unclear, but represents up to 90-95% of all occupational skin diseases. The prevalence of CD has not been established in veterinary medicine. The pathogenesis of CD is not fully understood, but involves a complex cascade of events between resident skin cells, relocated immune cells, pro-inflammatory cytokines and chemokines. The main difference between ICD and ACD is that ACD is an antigen-specific reaction to an allergenic irritating agent whereas ICD is not antigen-specific. To date, there is no fully validated diagnostic test available for CD. Thus, its clinical diagnosis relies on the patient's history, clinical examination, dermatological tests and, in some cases, research-based assays. The most important factor in CD management is the identification and avoidance of the culprit irritant or allergen. In addition, various topical and systemic therapies can be considered. CONCLUSION AND CLINICAL RELEVANCE: CD is a relatively common occupational skin disease in human beings, but the prevalence in veterinary medicine is undefined. It can lead to debilitating clinical signs. Further research in human medicine and even more so in veterinary patients, will be required in order to allow for an evidence-based approach in its diagnosis and management.

Whole-exome sequencing in a Chinese sample provides preliminary evidence for the link between rare/low-frequency immune-related variants and early-onset schizophrenia.

Rare and low-frequency variants contribute to schizophrenia (SCZ), and may influence its age-at-onset (AAO). We examined the association of rare or low-frequency deleterious coding variants in Chinese patients with SCZ. We collected DNA samples in 197 patients with SCZ spectrum disorder and 82 healthy controls (HC), and performed exome sequencing. The AAO variable was ascertained in the majority of SCZ participants for identify the early-onset (EOS, AAO<=18) and adult-onset (AOS, AAO>18) subgroups. We examined the overall association of rare/low-frequency, damaging variants in SCZ versus HC, EOS versus HC, and AOS versus HC at the gene and gene-set levels using Sequence Kernel Association Test. The quantitative rare-variant association test of AAO was conducted. Resampling was used to obtain empirical p-values and to control for family-wise error rate (FWER). In binary-trait association tests, we identified 5 potential candidate risk genes and 10 gene ontology biological processes (GOBP) terms, among which PADI2 reached FWER-adjusted significance. In quantitative rare-variant association tests, we found marginally significant correlations of AAO with alterations in 4 candidate risk genes, and 5 GOBP pathways. Together, the biological and functional profiles of these genes and gene sets supported the involvement of perturbations of neural systems in SCZ, and altered immune functions in EOS.

Combined oestrogen and progesterone for preventing miscarriage.

BACKGROUND: Historically, oestrogen and progesterone were each commonly used to save threatened pregnancies. In the 1940s it was postulated that their combined use would be synergistic and thereby led to the rationale of combined therapy for women who risked miscarriage. OBJECTIVES: To determine the efficacy and safety of combined oestrogen and progesterone therapy to prevent miscarriage. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (23 June 2013) CENTRAL (OVID) (The Cochrane Library 2013, Issue 6 of 12), MEDLINE (OVID) (1946 to June Week 2 2013), OLDMEDLINE (1946 to 1965), Embase (1974 to Week 25 2013), Embase Classic (1947 to 1973), CINAHL (1994 to 23 June 2013) and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials that assessed the effectiveness of combined oestrogen and progesterone for preventing miscarriage. We included one stratified randomised trial and one quasi-randomised trials. Cluster-randomised trials were eligible for inclusion but none were identified. We excluded studies published only as abstracts.We included studies that compared oestrogen and progesterone versus placebo or no intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and assessed trial quality. Two review authors extracted data. Data were checked for accuracy. MAIN RESULTS: Two trials (281 pregnancies and 282 fetuses) met our inclusion criteria. However, the two trials had significant clinical and methodological heterogeneity such that a meta-analysis combining trial data was considered inappropriate.One trial (involving 161 pregnancies) was based on women with a history of diabetes. It showed no statistically significant difference between using combined oestrogen and progestogen and using placebo for all our proposed primary outcomes, namely, miscarriage (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.32 to 2.80), perinatal death (RR 0.94, 95% CI 0.53 to 1.69) and preterm birth (less than 34 weeks of gestation) (RR 0.91, 95% CI 0.80 to 1.04). In terms of this review's secondary outcomes, use of combined oestrogen and progestogen was associated with an increased risk of maternal cancer in the reproductive system (RR 6.65, 95% CI 1.56 to 28.29). However, for the outcome of cancer other than that of the reproductive system in mothers, there was no difference between groups. Similarly, there were no differences between the combined oestrogen and progestogen group versus placebo for other secondary outcomes reported: low birthweight of less than 2500 g, genital abnormalities in the offspring, abnormalities other than genital tract in the offspring, cancer in the reproductive system in the offspring, or cancer other than of the reproductive system in the offspring.The second study was based on pregnant women who had undergone in-vitro fertilisation (IVF). This study showed no difference in the rate of miscarriage between the combined oestrogen and progesterone group and the no treatment group (RR 0.66, 95% CI 0.23 to 1.85). The study did not report on this review's other primary outcomes (perinatal death or rates of preterm birth), nor on any of our proposed secondary outcomes. AUTHORS' CONCLUSIONS: There is an insufficient evidence from randomised controlled trials to assess the use of combined oestrogen and progesterone for preventing miscarriages. We strongly recommend further research in this area.

Early-onset schizophrenia is associated with immune-related rare variants in a Chinese sample.

Background: Rare variants are likely to contribute to schizophrenia (SCZ), given the large discrepancy between the heritability estimated from twin and GWAS studies. Furthermore, the nature of the rare-variant contribution to SCZ may vary with the "age-at-onset" (AAO), since early-onset has been suggested as being indicative of neurodevelopment deviance. Objective: To examine the association of rare deleterious coding variants in early- and adult-onset SCZ in a Chinese sample. Method: Exome sequencing was performed on DNA from 197 patients with SCZ spectrum disorder and 82 healthy controls (HC) of Chinese ancestry recruited in Hong Kong. We also gathered AAO information in the majority of SCZ samples. Patients were classified into early-onset (EOS, AAO<18) and adult-onset (AOS, AAO>18). We collapsed the rare variants to improve statistical power and examined the overall association of rare variants in SCZ versus HC, EOS versus HC, and AOS versus HC at the gene and gene-set levels by Sequence Kernel Association Test. The quantitative rare-variant association test of AAO was also conducted. We focused on variants which were predicted to have a medium or high impact on the protein-encoding process as defined by Ensembl. We applied a 100000-time permutation test to obtain empirical p-values, with significance threshold set at p < 1e -3 to control family-wise error rates. Moreover, we compared the burden of targeted rare variants in significant risk genes and gene sets in cases and controls. Results: Based on several binary-trait association tests (i.e., SCZ vs HC, EOS vs HC and AOS vs HC), we identified 7 candidate risk genes and 20 gene ontology biological processes (GOBP) terms, which exhibited higher burdens in SCZ than in controls. Based on quantitative rare-variant association tests, we found that alterations in 5 candidate risk genes and 7 GOBP pathways were significantly correlated with AAO. Based on biological and functional profiles of the candidate risk genes and gene sets, our findings suggested that, in addition to the involvement of perturbations in neural systems in SCZ in general, altered immune responses may be specifically implicated in EOS. Conclusion: Disrupted immune responses may exacerbate abnormal perturbations during neurodevelopment and trigger the early onset of SCZ. We provided evidence of rare variants increasing SCZ risk in the Chinese population.

Pathway-Specific Polygenic Scores Improve Cross-Ancestry Prediction of Psychosis and Clinical Outcomes.

Psychotic disorders are debilitating conditions with disproportionately high public health burden. Genetic studies indicate high heritability, but current polygenic scores (PGS) account for only a fraction of variance in psychosis risk. PGS often show poor portability across ancestries, performing significantly worse in non-European populations. Pathway-specific PGS (pPGS), which restrict PGS to genomic locations within distinct biological units, could lead to increased mechanistic understanding of pathways that lead to risk and improve cross-ancestry prediction by reducing noise in genetic predictors. This study examined the predictive power of genome-wide PGS and nine pathway-specific pPGS in a unique Chinese-ancestry sample of deeply-phenotyped psychosis patients and non-psychiatric controls. We found strong evidence for the involvement of schizophrenia-associated risk variants within "nervous system development" (p=2.5e-4) and "regulation of neuron differentiation" pathways (p=3.0e-4) in predicting risk for psychosis. We also found the "ion channel complex" pPGS, with weights derived from GWAS of bipolar disorder, to be strongly associated with the number of inpatient psychiatry admissions a patient experiences (p=1.5e-3) and account for a majority of the signal in the overall bipolar PGS. Importantly, although the schizophrenia genome-wide PGS alone explained only 3.7% of the variance in liability to psychosis in this Chinese ancestry sample, the addition of the schizophrenia-weighted pPGS for "nervous system development" and "regulation of neuron differentiation" increased the variance explained to 6.9%, which is on-par with the predictive power of PGS in European ancestry samples. Thus, not only can pPGS provide greater insight into mechanisms underlying genetic risk for disease and clinical outcomes, but may also improve cross-ancestry risk prediction accuracy.

Emotion-behaviour decoupling and experiential pleasure deficits predict negative symptoms and functional outcome in first-episode schizophrenia patients.

BACKGROUND: Emotion-behaviour decoupling refers to the failure to translate emotion into motivated behaviour, and is a putative marker for schizophrenia. The heterogeneity of experiential pleasure and emotion expressivity deficits has been reported in schizophrenia patients. These three constructs are believed to contribute to negative symptoms, but very few studies have examined their predictive ability for clinical and functional outcome of schizophrenia. This study aimed to clarify whether these three constructs influence clinical and functional outcome of schizophrenia. METHOD: At baseline, 127 first-episode schizophrenia patients completed a behavioural paradigm for emotion-behaviour decoupling, and self-report scales for experiential pleasure and emotion expressivity deficits. Cluster-analysis was applied to characterize schizophrenia subgroups based on these three constructs. At end-point (mean follow-up = 5.37 years, SD = 1.03 years), 85 schizophrenia patients were reassessed using the Clinical Assessment Interview for Negative Symptoms (CAINS) and a clinician-rated social functioning scale. RESULTS: Cluster 1 (n = 74) did not show emotion-behaviour decoupling, and had intact experiential pleasure and emotion expressivity. Cluster 2 (n = 29) showed emotion-behaviour decoupling and experiential pleasure deficits. Cluster 3 (n = 24) showed emotion expressivity deficits. At endpoint, the three clusters differed significantly in CAINS MAP factor (p = 0.016) and social functioning (p = 0.019), but not CAINS EXP factor. Specifically, Cluster 2 (n = 18) showed more severe negative symptoms of CAINS MAP factor (p = 0.046) and poorer social functioning (p = 0.022) than Cluster 1 (n = 49). Cluster 3 (n = 18) did not differ from Cluster 1 and Cluster 2 in negative symptoms and social functioning. DISCUSSION: Emotion-behaviour decoupling and experiential pleasure deficits predicted clinical and functional outcome of schizophrenia.

Structural network alterations and their association with neurological soft signs in schizophrenia: Evidence from clinical patients and unaffected siblings.

BACKGROUND: Grey matter abnormalities and neurological soft signs (NSS) have been found in schizophrenia patients and their unaffected relatives. Evidence suggested that NSS are associated with grey matter morphometrical alterations in multiple regions in schizophrenia. However, the association between NSS and structural abnormalities at network level remains largely unexplored, especially in the schizophrenia and unaffected siblings. METHOD: We used source-based morphometry (SBM) to examine the association of structural brain network characteristics with NSS in 62 schizophrenia patients, 25 unaffected siblings, and 60 healthy controls. RESULTS: Two components, namely the IC-5 (superior temporal gyrus, inferior frontal gyrus and insula network) and the IC-10 (parahippocampal gyrus, fusiform, thalamus and insula network) showed significant grey matter reductions in schizophrenia patients compared to healthy controls and unaffected siblings. Further association analysis demonstrated separate NSS-related grey matter covarying patterns in schizophrenia, unaffected siblings and healthy controls. Specifically, NSS were negatively associated with IC-1 (hippocampus, caudate and thalamus network) and IC-5 in schizophrenia, but with IC-3 (caudate, superior and middle frontal cortices network) in unaffected siblings and with IC-5 in healthy controls. CONCLUSION: Our results confirmed the key cortical and subcortical network abnormalities and NSS-related grey matter covarying patterns in the schizophrenia and unaffected siblings. Our findings suggest that brain regions implicating genetic liability to schizophrenia are partly separated from brain regions implicating neural abnormalities.

Different trajectories of neurological soft signs progression between treatment-responsive and treatment-resistant schizophrenia patients.

Schizophrenia patients exhibit subtle and non-localizing neurological abnormalities, known as neurological soft signs (NSS). Life-span evidence suggests that NSS vary along the course of schizophrenia. An association between NSS and treatment response has been proposed, suggesting that NSS reflect the underlying neuropathology development in schizophrenia. However, few studies have investigated the relationship between NSS and treatment resistance in first-episode schizophrenia patients. We conducted a longitudinal study on 52 first-episode schizophrenia patients, who were assessed at baseline, the sixth month, and the fifth year using the abridged version of the Cambridge Neurological Inventory. The trajectories of NSS between 29 treatment-responsive patients (with full symptomatic remission) and 23 treatment-resistant patients (who received clozapine) were compared using mixed model ANOVA. We also controlled for the effect of age and estimated IQ, using a mixed ANCOVA model. Although the two schizophrenia groups had comparable NSS at the baseline, their trajectories of NSS differed significantly. Compared with their treatment-responsive counterparts, treatment-resistant schizophrenia patients had worsening of NSS over time. Our findings support the potential utility of NSS in identifying treatment resistance in first-episode schizophrenia. Progressive worsening of NSS in treatment-resistant schizophrenia patients may reflect the development of underlying neuropathology. Further studies using large samples of treatment-resistant schizophrenia patients are needed.

Two-dimensional ultrasound measurement of thyroid gland volume: a new equation with higher correlation with 3-D ultrasound measurement.

This study aimed to develop a new two-dimensional (2-D) ultrasound thyroid volume estimation equation using three-dimensional (3-D) ultrasound as the standard of reference, and to compare the thyroid volume estimation accuracy of the new equation with three previously reported equations. 2-D and 3-D ultrasound examinations of the thyroid gland were performed in 150 subjects with normal serum thyrotropin (TSH, thyroid-stimulating hormone) and free thyroxine (fT4) levels (63 men and 87 women, age range: 17 to 71 y). In each subject, the volume of both thyroid lobes was measured by 3-D ultrasound. On 2-D ultrasound, the craniocaudal (CC), lateromedial (LM) and anteroposterior (AP) dimensions of the thyroid lobes were measured. The equation was derived by correlating the volume of the thyroid lobes measured with 3-D ultrasound and the product of the three dimensions measured with 2-D ultrasound using linear regression analysis, in 75 subjects without thyroid nodule. The accuracy of thyroid volume estimation of the new equation and the three previously reported equations was evaluated and compared in another 75 subjects (without thyroid nodule, n = 30; with thyroid nodule, n = 45). It is suggested that volume of thyroid lobe may be estimated as: volume of thyroid lobe = 0.38.(CC.LM.AP) + 1.76. Result showed that the new equation (16.9% to 36.1%) had a significantly smaller thyroid volume estimation error than the previously reported equations (20.8% to 54.9%) (p < 0.05). There was a significantly larger thyroid volume estimation error when thyroid glands with nodules were examined (p < 0.05). With the use of the appropriate thyroid volume equation, 2-D ultrasound can be a useful alternative in thyroid volume measurement when 3-D ultrasound is not available.

Theory of mind performances in first-episode schizophrenia patients: An 18-month follow-up study.

This study examined the change of Theory of Mind (ToM) performances in patients with first-episode schizophrenia over an 18-month period since illness onset. A computerised behavioural task was utilised to assess the affective and cognitive facets of visual-based ToM. Patients' ToM performances were standardised using the norms of gender-stratified, age- and IQ-matched controls. The results showed that schizophrenia patients exhibited poorer second-order affective and cognitive ToM at baseline, but their ToM ability improved after 18 months of follow-up. Our findings do not support a longitudinal dissociation of affective from cognitive ToM in schizophrenia.

Surveillance of drug abuse in Hong Kong by hair analysis using LC-MS/MS.

The aim of this study is to reveal the habits of drug abusers in hair samples from drug rehabilitation units in Hong Kong. With the application of liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology, a total of 1771 hair samples were analyzed during the period of hair testing service (January 2012 to March 2016) provided to 14 drug rehabilitation units including non-governmental organizations (NGOs), rehabilitation centers, and medical clinics. Hair samples were analyzed for abused drugs and their metabolites simultaneously, including ketamine, norketamine, cocaine, benzoylecgonine, cocaethylene, norcocaine, codeine, MDMA, MDA, MDEA, amphetamine, methamphetamine, morphine, 6-acetylmorphine, phencyclidine, and methadone. The results showed that ketamine (77.2%), cocaine (21.3%), and methamphetamine (16.5%) were the frequently detected drugs among those drug abusers, which is consistent with the reported data. In addition, the usage of multiple drugs was also observed in the hair samples. About 29% of drug-positive samples were detected with multiple drug use. Our studies prove that our locally developed hair drug-testing method and service can be a valid tool to monitor the use of abused drugs, and which could facilitate rehabilitation program management.

Cross Cultural Validation and Extension of the Clinical Assessment Interview for Negative Symptoms (CAINS) in the Chinese Context: Evidence from a Spectrum Perspective.

The Clinical Assessment Interview for Negative Symptoms (CAINS) was designed in accordance with the recent theory and research in social affective neuroscience and to address the psychometric and conceptual limitations of other instruments assessing negative symptoms. The present study aimed to provide a large-scale validation of the CAINS in China and examine its applicability and validity evidence across the schizophrenia spectrum. Using confirmatory factor analysis, our results replicated the original findings in the US development samples that the CAINS possesses a stable 2-factor structure, namely "motivation/pleasure" and "expression". We also found significant correlations between the CAINS and other negative symptom measures. The CAINS demonstrated good discriminant validity in differentiating negative symptoms in people with schizophrenia, nonpsychotic first-degree relatives and people with social anhedonia. People with schizophrenia exhibited significantly higher CAINS subscale scores than first-degree relatives and healthy controls. In addition, first-degree relatives had higher "motivation/pleasure" scores than healthy controls. The "motivation/pleasure" subscale scores of individuals with social anhedonia were also significantly higher than healthy controls.

Clustering of Schizotypal Features in Unaffected First-Degree Relatives of Schizophrenia Patients.

Meehl conceptualized schizotypy as the phenotypic manifestations of a neural integrative defect resulting from a schizophrenia diathesis. The majority of schizotypy studies recruited subjects from the general population and revealed a multidimensional construct. This 2-phase investigation first examined the clustering of schizotypy in 194 unaffected relatives of schizophrenia patients using the Chapman Psychosis Proneness scales and then directly compared the cognitive profiles of negative schizotypal individuals and positive schizotypal individuals with schizophrenia patients and controls. In the first phase, cluster analysis categorized 194 unaffected relatives of schizophrenia patients into positive schizotypy (n = 33), negative schizotypy (n = 66), mixed schizotypy (n = 27), and low schizotypy (n = 64). Positive schizotypal participants showed more self-report pleasure experiences than negative schizotypal participants, replicating earlier cluster analytic findings. In the second phase, 27 negative schizotypal individuals, 18 positive schizotypal individuals, 19 schizophrenia patients, and 29 controls were recruited. Although the groups were matched in terms of age, gender, and IQ, they differed significantly in cognitive profiles. While schizophrenia patients exhibited the broadest cognitive impairments, negative schizotypal participants exhibited visual memory, working memory, and verbal fluency impairments, and positive schizotypal participants exhibited logical memory, visual memory, working memory, and theory-of-mind impairments. Among people with familial risk of schizophrenia, individuals exhibiting positive rather than negative schizotypal features resembled schizophrenia patients in cognitive profiles. Using the psychometric-familial method to identify schizotypy, our findings support the heterogeneity of schizotypy as well as the potential utility of the positive schizotypy dimension in genetically high-risk individuals to predict the risk of developing schizophrenia.

Determination of hair ketamine cut-off value from Hong Kong ketamine users by LC-MS/MS analysis.

Ketamine is one of the most frequent abused drugs in Hong Kong and South-East Asia, and the cases of ketamine abused have been reported worldwide. Hair has been commonly used as a specimen for the proof of chronic drug abused because of its non-invasiveness and long detection windows. The determinations of ketamine in hair with varieties of state-of-the-art instruments and detection methods have been developed in the past decade; however, the cut-off value for ketamine abuser has not been developed according to the international guidelines. The aim of this study is to propose a cut-off value for ketamine in hair by analyzing ketamine and its metabolite norketamine by LC-MS/MS method in a population of ketamine users in Hong Kong. The limit of detection (LOD) and limit of quantification (LOQ) for ketamine and norketamine were 20pg/mg and 100pg/mg, respectively. From 977 ketamine abusers, the cut-off value for ketamine in hair was proposed to be 400pg/mg of hair. This proposed cut-off value is the concentration of hair ketamine when over 90% of samples are being detected with the presence of norketamine, which is a proof of ketamine abuse. This value could be applied as a screening or occupational cut-off for reference.

Theory of mind impairments in patients with first-episode schizophrenia and their unaffected siblings.

BACKGROUND: Theory of mind (ToM) impairment has been consistently demonstrated in patients with schizophrenia, but whether ToM impairments exist in unaffected siblings of patients with schizophrenia remains unclear. Few studies have examined the affective and cognitive components of ToM in schizophrenia. This study aimed to examine whether ToM impairments exist in patients with first-episode schizophrenia and their unaffected siblings, and whether there is any dissociation between the affective and cognitive components of ToM. METHOD: We adopted a family-based case-control design. Participants were 41 patients with first-episode schizophrenia, 43 unaffected siblings, and 42 healthy controls. The Yoni Task which measures the participants' ability to understand first- and second-order affective versus cognitive ToM and the Faux Pas Task which taps into integration of the affective and cognitive components of ToM were administered. Multivariate and univariate ANCOVAs were used to examine the group differences in ToM, while controlling for other neurocognitive functions. RESULTS: Compared with controls, patients with schizophrenia and their unaffected siblings performed poorer on the Faux Pas Task (p<0.001), with siblings having intermediate performance between patients and controls. Patients with schizophrenia performed worse than controls on second-order affective condition of the Yoni Task (p=0.004), but their unaffected siblings did not (p=0.063). We did not find any significant Group-by-Condition interaction in the Yoni Task (p=0.358). CONCLUSION: Patients with first-episode schizophrenia and their unaffected siblings exhibit ToM impairments, but no dissociation between affective and cognitive component of ToM was found. Our findings support the notion that ToM deficit may be a trait marker of schizophrenia.

Course of neurological soft signs in first-episode schizophrenia: Relationship with negative symptoms and cognitive performances.

This prospective study examined the course of neurological soft signs (NSS) in patients with first-episode schizophrenia and its relationship with negative symptoms and cognitive functions. One hundred and forty-five patients with first-episode schizophrenia were recruited, 29 were classified as having prominent negative symptoms. NSS and neuropsychological measures were administered to all patients and 62 healthy controls at baseline. Patients were then followed-up prospectively at six-month intervals for up to a year. Patients with prominent negative symptoms exhibited significantly more motor coordination signs and total NSS than patients without prominent negative symptoms. Patients with prominent negative symptoms performed worse than patients without negative symptoms in working memory functions but not other fronto-parietal or fronto-temporal functions. Linear growth model for binary data showed that the prominent negative symptoms were stable over time. Despite general improvement in NSS and neuropsychological functions, the prominent negative symptoms group still exhibited poorer motor coordination and higher levels of NSS, as well as poorer working memory than patients without prominent negative symptoms. Two distinct subtypes of first-episode patients could be distinguished by NSS and prominent negative symptoms.

Re-visiting the nature and relationships between neurological signs and neurocognitive functions in first-episode schizophrenia: An invariance model across time.

The present study examined different types of neurological signs in patients with first-episode schizophrenia and their relationships with neurocognitive functions. Both cross-sectional and longitudinal designs were adopted with the use of the abridged Cambridge Neurological Inventory which comprises items capturing motor coordination, sensory integration and disinhibition. A total of 157 patients with first-episode schizophrenia were assessed at baseline and 101 of them were re-assessed at six-month interval. A structural equation model (SEM) with invariance model across time was used for data analysis. The model fitted well with the data at baseline assessment, X^2(21) = 21.78, p = 0.413, NFI = 0.95, NNFI = 1.00, CFI = 1.00, IFI = 1.00, RMSEA = 0.015. Subsequent SEM analysis with invariance model at six-month interval also demonstrated the same stable pattern across time and showed strong measurement invariance and structure invariance across time. Our findings suggest that neurological signs capture more or less the same construct captured by conventional neurocognitive tests in patients with schizophrenia. The measurement and structure of these relationships appear to be stable over time.