Simon S.Y. Lui

Meta-analysis of neuropsychological measures of executive functioning in children and adolescents with high-functioning autism spectrum disorder

Existing literature on the profile of executive dysfunction in autism spectrum disorder showed inconsistent results. Age, comorbid attention‐deficit/hyperactivity disorder (ADHD) and cognitive abilities appeared to play a role in confounding the picture. Previous meta‐analyses have focused on a few components of executive functions. This meta‐analysis attempted to delineate the profile of deficit in several components of executive functioning in children and adolescents with high‐functioning autism spectrum disorder (HFASD). Ninety‐eight English published case‐control studies comparing children and adolescents with HFASD with typically developing controls using well‐known neuropsychological measures to assess executive functions were included. Results showed that children and adolescents with HFASD were moderately impaired in verbal working memory (g = 0.67), spatial working memory (g = 0.58), flexibility (g = 0.59), planning (g = 0.62), and generativity (g = 0.60) except for inhibition (g = 0.41). Subgroup analysis showed that impairments were still significant for flexibility (g = 0.57–0.61), generativity (g = 0.52–0.68), and working memory (g = 0.49–0.56) in a sample of autism spectrum disorder (ASD) subjects without comorbid ADHD or when the cognitive abilities of the ASD group and the control group were comparable. This meta‐analysis confirmed the presence of executive dysfunction in children and adolescents with HFASD. These deficits are not solely accounted for by the effect of comorbid ADHD and the general cognitive abilities. Our results support the executive dysfunction hypothesis and contribute to the clinical understanding and possible development of interventions to alleviate these deficits in children and adolescents with HFASD. Autism Res 2017, 10: 911–939.

Witnessed Presence and the YUTPA Framework

The Temporal Experience of Pleasure Scale (TEPS) is a self-report instrument that assesses pleasure experience. Initial scale development and validation in the United States yielded a two-factor solution comprising anticipatory and consummatory pleasure. However, a four-factor model that further parsed anticipatory and consummatory pleasure experience into abstract and contextual components was a better model fit in China. In this study, we tested both models using confirmatory factor analysis in an American and a Chinese sample and examined the configural measurement invariance of both models across culture. We also examined the temporal stability of the four-factor model in the Chinese sample. The results indicated that the four-factor model of the TEPS was a better fit than the two-factor model in the Chinese sample. In contrast, both models fit the American sample, which also included many Asian American participants. The four-factor model fit both the Asian American and Chinese samples equally well. Finally, the four-factor model demonstrated good measurement and structural invariance across culture and time, suggesting that this model may be applicable in both cross-cultural and longitudinal studies.

Altered corticostriatal functional connectivity in individuals with high social anhedonia

BACKGROUND Dysregulation of the striatum and altered corticostriatal connectivity have been associated with psychotic disorders. Social anhedonia has been identified as a predictor for the development of schizophrenia spectrum disorders. The aim of the present study was to examine corticostriatal functional connectivity in individuals with high social anhedonia. METHOD Twenty-one participants with high social anhedonia score and 30 with low social anhedonia score measured by the Chinese version of the Revised Social Anhedonia Scale were recruited from university undergraduates (age 17-21 years) to undergo resting-state functional MRI scans. Six subdivisions of the striatum in each hemisphere were defined as seeds. Voxel-wise functional connectivity analyses were conducted between each seed and the whole brain voxels, followed by repeated-measures ANOVA for the group effect. RESULTS Participants with high social anhedonia showed hyper-connectivity between the ventral striatum and the anterior cingulate cortex and the insula, and between the dorsal striatum and the motor cortex. Hypo-connectivity in participants with high social anhedonia was also observed between the ventral striatum and the posterior cingulate cortex. Partial correlation analyses further showed that the functional connectivity between the ventral striatum and the prefrontal cortex was associated with pleasure experience and emotional suppression. CONCLUSIONS Our findings suggest that altered corticostriatal connectivity can be found in participants with high levels of social anhedonia. Since social anhedonia has been considered a predictor for schizophrenia spectrum disorders, our results may provide novel evidence on the early changes in brain functional connectivity in at-risk individuals.

Long-term effects of discontinuation from antipsychotic maintenance following first-episode schizophrenia and related disorders: a 10 year follow-up of a randomised, double-blind trial

BACKGROUND The long-term consequences of discontinuing antipsychotic medication after successful treatment of first-episode psychosis are not well studied. We assess the relation between early maintenance therapy decisions in first-episode psychosis and the subsequent clinical outcome at 10 years. METHODS This is a 10 year follow-up study, spanning Sept 5, 2003, to Dec 30, 2014, of a randomised, double-blind trial in seven centres in Hong Kong in which 178 patients with first-episode psychosis with full positive symptom resolution after at least 1 year of antipsychotic treatment were given maintenance treatment (n=89; oral quetiapine 400 mg daily) or early treatment discontinuation (n=89; placebo) for 12 months. After the trial, patients received naturalistic treatment. Overall this cohort of patients will have received about 3 years of treatment before entering the follow-up phase of the study: about 2 years of maintenance treatment before study entry and 1 year of treatment in the trial. The primary outcome of this follow-up was the proportion of patients in each group (including those for whom direct follow-up was not available) with good or poor long-term clinical outcomes at 10 years, with poor outcome defined as a composite of persistent psychotic symptoms, a requirement for clozapine treatment, or death by suicide. The randomised trial was registered with ClinicalTrials.gov, number NCT00334035, and the follow-up study was registered with ClinicalTrials.gov, number NCT01926340. FINDINGS Poor 10 year clinical outcome occurred in 35 (39%) of 89 patients in the discontinuation group and 19 (21%) of 89 patients in the maintenance treatment group (risk ratio 1·84, 95% CI 1·15-2·96; p=0·012). Suicide was the only serious adverse event that occurred in the follow-up phase (four [4%] patients in the early discontinuation group vs two [2%] in the maintenance group). INTERPRETATION In patients with first-episode psychosis with a full initial response to treatment, medication continuation for at least the first 3 years after starting treatment decreases the risk of relapse and poor long-term clinical outcome. FUNDING Food and Health Bureau, Research Grants Council of Hong Kong, and AstraZeneca.

The effects of working memory training on enhancing hedonic processing to affective rewards in individuals with high social anhedonia

Anhedonia is a core feature of the negative symptoms of schizophrenia and is less responsive to antipsychotic medication. Little is known whether anhedonia could be alleviated by cognitive training. The present study aimed to examine whether hedonic deficits observed in individuals with high social anhedonia could be reduced by working memory (WM) training. Thirty-four individuals with high social anhedonia were randomly assigned to either a WM training group or a control group. The WM training group received 20 sessions of dual n-back task training for four weeks. The affective incentive delay task was administered in all participants before the training and one month later. The results showed that individuals who received the WM training showed significant improvement in WM performance (F(19, 304)=55.80, p<0.001) and they also showed significant improvement in approach sensitivity to rewards (p=0.004). These preliminary findings suggest that hedonic processing could be improved through WM training in individuals with high social anhedonia. These results may have important implications for the development of non-pharmacological interventions to alleviate anhedonia in patients with schizophrenia.

Distinct structural neural patterns of trait physical and social anhedonia: evidence from cortical thickness, subcortical volumes and inter-regional correlations.

Anhedonia is an enduring trait accounting for the reduced capacity to experience pleasure. Few studies have investigated the brain structural features associated with trait anhedonia. In this study, the relationships between cortical thickness, volume of subcortical structures and scores on the Chapman physical and social anhedonia scales were examined in a non-clinical sample (n=72, 35 males). FreeSurfer was used to examine the cortical thickness and the volume of six identified subcortical structures related to trait anhedonia. We found that the cortical thickness of the superior frontal gyrus and the volume of the pallidum in the left hemisphere were correlated with anhedonia scores in both physical and social aspects. Specifically, positive correlations were found between levels of social anhedonia and the thickness of the postcentral and the inferior parietal gyri. Cortico-subcortical inter-correlations between these clusters were also observed. Our findings revealed distinct correlation patterns of neural substrates with trait physical and social anhedonia in a non-clinical sample. These findings contribute to the understanding of the pathologies underlying the anhedonia phenotype in schizophrenia and other psychiatric disorders.

Facial emotion perception impairments in schizophrenia patients with comorbid antisocial personality disorder

Impairment in facial emotion perception is believed to be associated with aggression. Schizophrenia patients with antisocial features are more impaired in facial emotion perception than their counterparts without these features. However, previous studies did not define the comorbidity of antisocial personality disorder (ASPD) using stringent criteria. We recruited 30 participants with dual diagnoses of ASPD and schizophrenia, 30 participants with schizophrenia and 30 controls. We employed the Facial Emotional Recognition paradigm to measure facial emotion perception, and administered a battery of neurocognitive tests. The Life History of Aggression scale was used. ANOVAs and ANCOVAs were conducted to examine group differences in facial emotion perception, and control for the effect of other neurocognitive dysfunctions on facial emotion perception. Correlational analyses were conducted to examine the association between facial emotion perception and aggression. Patients with dual diagnoses performed worst in facial emotion perception among the three groups. The group differences in facial emotion perception remained significant, even after other neurocognitive impairments were controlled for. Severity of aggression was correlated with impairment in perceiving negative-valenced facial emotions in patients with dual diagnoses. Our findings support the presence of facial emotion perception impairment and its association with aggression in schizophrenia patients with comorbid ASPD.

Effect of emotional cues on prospective memory performance in patients with schizophrenia and major depressive disorder

Prospective memory (PM) is the ability to remember to carry out future intentions when prompted by a cue, and previous studies have suggested that emotional PM cues may enhance PM performance. This study examined the influence of emotional cues on PM performance in patients with schizophrenia and major depressive disorder. All participants were required to respond to emotional or neutral PM cues while completing a working memory task. Healthy participants showed improved PM performance with positive and negative cues. Patients with major depressive disorder were not impaired in PM performance and showed significant improvement in PM performance when cued by negative but not positive cues. Patients with schizophrenia had impaired PM performance irrespective of cue emotionality. In addition, the majority of patients with schizophrenia failed to show an emotional enhancement effect, and only those who had normal arousal ratings for negative PM cues showed emotional enhancement effect. These findings show for the first time that patients with schizophrenia exhibit PM impairments even with emotional cues, and suggest that arousal may be a critical factor for schizophrenia patients to utilize emotional cues to facilitate execution of future actions. In patients with major depressive disorder, our findings suggest that the negative bias in attention and retrospective memory may also extend to memory for future actions. These novel findings have both theoretical and clinical implications.

Negative symptom dimensions differentially impact on functioning in individuals at-risk for psychosis

a Department of Psychiatry, The University of Hong Kong, Queen Mary Hospital, Hong Kong b State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong c Department of Psychiatry, Queen Mary Hospital, Hong Kong d Department of Psychiatry, Pamela Youde Nethersole Eastern Hospital, Hong Kong e Department of Psychiatry, Kwai Chung Hospital, Hong Kong f Department of Psychiatry, Kowloon Hospital, Hong Kong g Department of Psychiatry, United Christian Hospital, Hong Kong h Department of Psychiatry, Tai Po Hospital, Hong Kong i Department of Psychiatry, Alice Ho Miu Ling Nethersole Hospital, Hong Kong j Department of Psychiatry, Castle Peak Hospital, Hong Kong

Revisiting the persistent negative symptoms proxy score using the Clinical Assessment Interview for Negative Symptoms

OBJECTIVE The present study aimed to validate a severity cut-off of negative symptoms for persistent negative symptoms (PNS) identification using the Clinical Assessment Interview for Negative Symptoms (CAINS). METHOD A total of 206 patients with schizophrenia were recruited and divided into the PNS group (n = 57) and the Non-PNS group (n = 149) using PNS criteria based on the SANS and the SAPS. To determine the appropriate cut-offs on the CAINS in identifying PNS, Receiver Operating Characteristic (ROC) curve analysis was conducted in the PNS and Non-PNS groups. RESULTS Our results showed that the cutoffs for identifying PNS on the CAINS total score, the Motivation and Pleasure (MAP) subscale score and the Expression (EXP) subscale score were 25, 17, and 5 respectively. Area Under the Curve (AUC) analysis indicated excellent discrimination of the PNS group from the Non-PNS group using the cut-off for the CAINS total score. However, discrimination was somewhat better for the MAP subscale score than the EXP subscale score. The Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of the MAP subscale were 81.54% and 97.16%. CONCLUSION We found that the cut-off scores derived from the CAINS to identify PNS are comparable to existing scales. The CAINS offers an alternative means in identifying PNS patients in clinical trials that overcomes methodological and conceptual limitations of older scales.