Aberrant connectivity in the hippocampus, bilateral insula and temporal poles precedes treatment resistance in first-episode psychosis: a prospective resting-state functional magnetic resonance imaging study with connectivity concordance mapping.

Functional connectivity resting-state functional magnetic resonance imaging has been proposed to predict antipsychotic treatment response in schizophrenia. However, only a few prospective studies have examined baseline resting-state functional magnetic resonance imaging data in drug-naïve first-episode schizophrenia patients with regard to subsequent treatment response. Data-driven approaches to conceptualize and measure functional connectivity patterns vary broadly, and model-free, voxel-wise, whole-brain analysis techniques are scarce. Here, we apply such a method, called connectivity concordance mapping to resting-state functional magnetic resonance imaging data acquired from an Asian sample (n = 60) with first-episode psychosis, prior to pharmaceutical treatment. Using a longitudinal design, 12 months after the resting-state functional magnetic resonance imaging, we measured and classified patients into two groups based on psychometric testing: treatment responsive and treatment resistant. Next, we compared the two groups' connectivity concordance maps that were derived from the resting-state functional magnetic resonance imaging data at baseline. We have identified consistently higher functional connectivity in the treatment-resistant group in a network including the left hippocampus, bilateral insula and temporal poles. These data-driven novel findings can help researchers to consider new regions of interest and facilitate biomarker development in order to identify treatment-resistant schizophrenia patients early, in advance of treatment and at the time of their first psychotic episode.

Modeling the effects of treatment resistance and anticholinergic burden on cognitive function domains in patients with schizophrenia.

The contribution of anticholinergic burden to cognitive function in patients with treatment resistant schizophrenia (TRS) is uncertain. This case-control study aims to comprehensively examine the association between treatment resistance and cognitive functions and the contribution of anticholinergic burden in patients with schizophrenia. Anticholinergic burden of all patients was calculated using the Anticholinergic Cognitive Burden scale. Exploratory Factor Analysis of 11 cognitive assessments identified four cognitive domains: verbal memory, attention and general cognitive functions, visual memory and processing speed, and executive function. Two structural equation models (SEM) examined the relationship of TRS and these cognitive functions with, and without considering anticholinergic burden. A total of 288 participants were included (TRS N=111, non-TRS N=177). Patients with TRS performed poorer than the non-TRS group only in the executive function domain. Anticholinergic burden contributed significantly to the attention and general cognitive functions, visual memory and processing speed, and executive function. The impact of TRS on executive function was no longer significant after adding anticholinergic burden to the SEM. Results suggested that anticholinergic burden contributes to a wide range of cognitive function impairment in patients with schizophrenia and is likely to be part of the apparent differences of cognitive function between TRS and non-TRS.

Age-related differences in the impact of resilience on mental health outcomes during the COVID-19 pandemic in Hong Kong.

OBJECTIVE: This study investigated changes in mental health in Hong Kong over two years and examined the role of resilience and age in mitigating the negative effects of public health emergencies, particularly the COVID-19 pandemic. METHODS: Complete data of interest from two telephone surveys conducted in 2020 (n = 1182) and 2021 (n = 1108) were analysed. Participants self-reported depressive and anxiety symptoms using the Patient Health Questionnaire 4-item version (PHQ), psychotic-like experiences (PLEs) using three items from the Prodromal Questionnaire Brief (PQB), and resilience using the Connor-Davidson Resilience Scale 2-item version (CD-RISC-2). RESULTS: We observed an increase in the percentage of participants with high depressive and anxiety symptoms and PLEs from 1.6% to 6.5% between 2020 and 2021. The likelihood of having high depressive and anxiety symptoms or PLEs depended on resilience and age, with no significant between-year differences. Resilience and age interaction effects were significant when comparing the high PHQ-high PQB group to the low PHQ-low PQB group only in 2021 but not in 2020. CONCLUSIONS: This study provides valuable insights into the impact of the COVID-19 pandemic on mental health in Hong Kong, emphasising the age-dependent nature of resilience in mitigating negative effects. Future research should explore the mechanisms by which resilience promotes mental health and well-being and identify ways to enhance resilience among older individuals during public health crises.

Development of an individualized risk calculator of treatment resistance in patients with first-episode psychosis (TRipCal) using automated machine learning: a 12-year follow-up study with clozapine prescription as a proxy indicator.

About 15-40% of patients with schizophrenia are treatment resistance (TR) and require clozapine. Identifying individuals who have higher risk of development of TR early in the course of illness is important to provide personalized intervention. A total of 1400 patients with FEP enrolled in the early intervention for psychosis service or receiving the standard psychiatric service between July 1, 1998, and June 30, 2003, for the first time were included. Clozapine prescriptions until June 2015, as a proxy of TR, were obtained. Premorbid information, baseline characteristics, and monthly clinical information were retrieved systematically from the electronic clinical management system (CMS). Training and testing samples were established with random subsampling. An automated machine learning (autoML) approach was used to optimize the ML algorithm and hyperparameters selection to establish four probabilistic classification models (baseline, 12-month, 24-month, and 36-month information) of TR development. This study found 191 FEP patients (13.7%) who had ever been prescribed clozapine over the follow-up periods. The ML pipelines identified with autoML had an area under the receiver operating characteristic curve ranging from 0.676 (baseline information) to 0.774 (36-month information) in predicting future TR. Features of baseline information, including schizophrenia diagnosis and age of onset, and longitudinal clinical information including symptoms variability, relapse, and use of antipsychotics and anticholinergic medications were important predictors and were included in the risk calculator. The risk calculator for future TR development in FEP patients (TRipCal) developed in this study could support the continuous development of data-driven clinical tools to assist personalized interventions to prevent or postpone TR development in the early course of illness and reduce delay in clozapine initiation.

Comorbidity of autism spectrum and attention deficit/hyperactivity disorder symptoms and their associations with 1-year mental health outcomes in adolescents and young adults.

Autism spectrum (ASD) and attention deficit/hyperactivity disorders (ADHD) share genetic, neurological, and behavioural features. However, related research in Asia is limited. We collected self-reported ASD and ADHD symptoms from 2186 Hong Kong adolescents and young adults aged 15-24 years, among whom, 1200 provided 1-year data on mental health-related outcomes. Comparative and network analyses were performed. Rating scale cutoff scores were used to divide participants into ASD, ADHD, comorbid, and control groups. The prevalence rates of ASD, ADHD, and comorbidities in Hong Kong were 13.3 %, 10.6 %, and 2.7 %, respectively. Compared with the control group, the comorbid group experienced more psychotic-like experiences (PLEs), the ASD group had poorer functioning, and the ADHD group had higher depression and anxiety symptoms and a lower quality of life after 1 year. The ability to switch attention, preference for routines and difficulty with change, and problems with organisation and planning were positively associated with depressive symptoms, forgetfulness and working memory issues with anxiety symptoms, and heightened sensory input and difficulties in sustaining attention and task completion with PLEs after 1 year. Our findings provide insight into support strategies to address the needs of young Asians to improving their well-being and long-term outcomes.

Evaluation of a Low-Intensity Online Intervention (LiON) for Reducing Distress and Mental Health Symptoms in Young People.

PURPOSE: Enhancing young people's mental health is crucial given that most adult mental disorders develop before age 24 years. However, it is unclear whether low-intensity interventions delivered online can be effective. This study aimed to provide preliminary evidence on whether a low-intensity online intervention (LiON) can effectively lower young people's distress levels and mental health symptoms. METHODS: We compared the preintervention and postintervention changes in distress level and severity of depression and anxiety symptoms in 137 young people aged 15-24 years who used the LiON service with the three-month changes in a 1:1 propensity score-matched control group of community young people who did not use the service. They participated in one of the following modules for the first time: (1) sleep and relaxation, (2) stress-coping, and (3) problem-solving. RESULTS: Participants who received LiON intervention (mean age 22.88 [standard deviation 3.67] years, 65.7% female) showed significantly greater reductions in distress level (Cohen's f2: 0.079), as well as the severity of depressive symptoms (Cohen's f2: 0.056) and anxiety symptoms (Cohen's f2: 0.044) compared to the control group. DISCUSSION: The findings suggest that the LiON intervention has the potential to effectively reduce distress and mental health symptoms in young people. Future research should aim to confirm these findings through randomized controlled trials and explore the cost-effectiveness of the intervention.

Age-matched versus non-age-matched comparison of clinical and functional differences between delusional disorder and schizophrenia: a systematic review.

Background: It has been widely suggested that delusional disorder (DD) differs from schizophrenia (SZ). However, whether the two disorders are truly distinct from each other is inconclusive as an older age of onset is closely linked to a better prognosis in psychotic disorders. In order to delineate the potential influence of age on outcomes, we undertook a systematic review on the clinical and functional differences between DD and SZ in age-matched and non-age-matched cohorts. Methods: Electronic databases were retrieved up to May 2022. Included studies were analyzed with reference to statements about clinical, cognitive and functional differences between DD and SZ. Results: Data synthesized from 8 studies showed (1) extensive effects of age on positive, general psychopathological symptoms and functioning, but (2) consistent differences between the two disorders in terms of negative symptoms and hospitalizations regardless of age matching. Conclusion: There is currently insufficient evidence to conclude whether DD is completely distinct from SZ, but our review showed support for the confounding effect of age in comparisons of psychotic disorders with different ages of onset. Future studies shall take note of other possible confounding variables, methods of age-matching and the importance of longitudinal information in deducing whether the two disorders differ from each other in course and outcome.

Functional and clinical outcomes of delusional disorder and schizophrenia patients after first episode psychosis: a 4-year follow-up study.

BACKGROUND: Literature has typically associated delusional disorder with a poorer prognosis relative to schizophrenia, without considering the confounding effect of age despite the differential age of onset. This study therefore aims to investigate the diagnostic stability, clinical, functional, and neurocognitive differences of Chinese first-episode psychosis age-matched patients with delusional disorder and schizophrenia at four years. METHODS: 71 delusional disorder and 71 age-matched schizophrenia patients were followed up for four years after their initial episode. Their symptoms, insight in psychosis, side effects of medication, medication compliance, functioning, and neurocognitive performance were assessed at four years. RESULTS: At four years, 65% of DD patients maintained the same diagnosis, while the rest shifted to SZ. Only those without a diagnostic shift were included in the analysis. Delusional disorder patients (n = 46) experienced greater general psychopathology and poorer insight, but better attitude towards medication than schizophrenia patients (n = 71). Social and occupational functioning, quality of life, and cognitive functioning, however, were similar in delusional disorder and schizophrenia patients. CONCLUSIONS: Results indicate that delusional disorder is less diagnostically stable than schizophrenia. Their outcomes in a Chinese population were largely similar at four years after removing the confounding age factor, implying that delusional disorder and schizophrenia may not be as distinct as previously thought.

Resilient, undercontrolled, and overcontrolled personality types in Hong Kong youths and the association with mental health outcomes.

OBJECTIVE: This study aimed to investigate the relationship between RUO types and mental health in a youth sample in Hong Kong. BACKGROUND: Previous research has found that Resilient, Undercontrolled, and Overcontrolled (RUO) personality types derived from Big Five personality traits are associated with mental health outcomes. Most studies, however, have predominantly been conducted in Western societies. METHOD: Clinical diagnostic interviews and self-rated measures of psychological constructs, covering resilience, rumination, self-esteem and more, were administered to 860 youths aged 15 to 24 recruited from an ongoing epidemiological youth mental health study in Hong Kong. RESULTS: Three personality clusters were identified. The first (mean age = 19.6, 63.3% female) and second (mean age = 19.5, 60.7% female) cluster both have characteristics of the under- and overcontrolled personalities. The third personality type resembled the resilient profile in RUO typology (mean age = 19.6, 50.5% female) and showed the lowest prevalence of poor mental health. CONCLUSIONS: The results suggest that the replicability of the RUO profiles was only partial in a Hong Kong sample predominantly Chinese. The resilient profile was replicated but not the undercontrolled and overcontrolled profiles proposed by previous studies. The findings of the current study implicated that culturally contextual considerations are necessary when relating mental health to personality.

COVID-19 exposure and psychosis: A comparison of clinical, functional, and cognitive profiles in remitted patients with psychosis.

The impact of Coronavirus Disease 2019 (COVID-19) on psychiatric care in remitted patients with first-episode psychosis (FEP) remains unknown. This study compared the demographic, clinical, functional, and cognitive profiles of patients recruited before and during the pandemic. The results showed that COVID patients were significantly older, smokers, alcohol users, experienced more stressors, with better functioning than pre-COVID patients. The former also had fewer severe negative and general psychopathological symptoms, more impaired insight, poorer medication compliance, and worse cognitive performance. Our findings highlighted a timely need to improve awareness into the illness and treatment in FEP patients experiencing pandemic related stressors.

Clozapine dosing patterns and clinical outcomes in patients with treatment resistant schizophrenia.

Clozapine is the only medication found to be effective for patients with treatment resistant schizophrenia-spectrum disorders (TRS) and its prescription patterns may impact on their outcomes. The study aims to explore the impact of clozapine dosing frequency, dose level and presence of pharmacological augmentation on the clinical, social and cognitive outcomes in patients with TRS. Patients with TRS and on clozapine were interviewed. Daily defined dose (DDD) and anticholinergic burden were calculated. Patients were categorized in three ways: the single daily dose (SDD) and multiple daily dose (MDD), ≤300 mg/day (LD) and >300 mg/day (HD) of clozapine, and clozapine monotherapy (MT) and augmentation therapy (AT). The impact of these clozapine prescription patterns and their interaction on patient outcomes were examined with ANOVA. Of 124 patients on clozapine, 98 patients (79%) had SDD, 59 patients (47.6%) received LD, and 58 patients (46.8%) had MT. Patients in the LD group had significantly better cognitive functions. Though no significant effect of clozapine dosing frequency on outcomes, among patients on LD, those on MDD had better processing speed, short-term and visual memory. Patients with MT had better motivation. Among patients on HD, those with MT had better motivation and vocational functioning. These results provide guidance to the clozapine prescription in a naturalistic setting to achieve optimizing outcomes for patients with TRS in social and cognitive functions. Further longitudinal studies are needed to verify the results.

Effects of a culturally adapted counselling service for low-income ethnic minorities experiencing mental distress: a pragmatic randomised clinical trial.

BACKGROUND: Culturally competent early mental health interventions for ethnic minorities (EMs) with no formal diagnoses are needed. OBJECTIVES: To determine whether 8-12 weeks culturally adapted counselling (CAC) is better than waiting (waitlist (WL) group) to reduce depressive and anxiety symptoms and stress levels among EMs with elevated mental distress. METHODS: Hong Kong EMs with mild and above-mild mental distress were randomly assigned to CAC or WL in this pragmatic, randomised, WL-controlled trial. The CAC group received the intervention after randomisation and the WL group received the intervention after 8-12 weeks (T1). The prespecified primary outcomes were depressive and anxiety symptoms and stress levels measured by the Depression, Anxiety and Stress subscales of the Depression, Anxiety and Stress Scale (DASS-D, DASS-A and DASS-S, respectively) at postintervention (T1, 8-12 weeks). FINDINGS: A total of 120 participants were randomly assigned to either CAC (n=60) or WL (n=60), of whom 110 provided primary outcome data. At T1, CAC led to significantly lower depressive and anxiety symptom severity and stress levels compared with waiting, with unstandardised regression coefficients of -8.91 DASS-D points (95% CI -12.57 to -5.25; d=-0.90),-6.33 DASS-A points (95% CI -9.81 to -2.86; d=-0.68) and -8.60 DASS-S points (95% CI -12.14 to -5.06; d=-0.90). CONCLUSIONS: CAC clinically outperformed WL for mild and above-mild levels of mental distress in EMs. CLINICAL IMPLICATIONS: Making CAC routinely available for EMs in community settings can reduce healthcare burden. TRIAL REGISTRATION NUMBER: NCT04811170.

Spurious Autobiographical Memory of Psychosis: A Mechanistic Hypothesis for the Resolution, Persistence, and Recurrence of Positive Symptoms in Psychotic Disorders.

Psychotic disorders are complex disorders with multiple etiologies. While increased dopamine synthesis capacity has been proposed to underlie psychotic episodes, dopamine-independent processes are also involved (less responsive to dopamine receptor-blocking medications). The underlying mechanism(s) of the reduction in antipsychotic responsiveness over time, especially after repeated relapses, remain unclear. Despite the consistent evidence of dopamine overactivity and hippocampal volume loss in schizophrenia, few accounts have been provided based on the interactive effect of dopamine on hippocampal synapse plasticity mediating autobiographical memory processes. The present hypothesis builds upon previous works showing the potential effects of dopamine overactivity on hippocampal-mediated neuroplasticity underlying autobiographical memory, alongside known patterns of autobiographical memory dysfunction in psychosis. We propose that spurious autobiographical memory of psychosis (SAMP) produced during active psychosis may be a key mechanism mediating relapses and treatment non-responsiveness. In a hyperdopaminergic state, SAMP is expected to be generated at an increased rate during active psychosis. Similar to other memories, it will undergo assimilation, accommodation, and extinction processes. However, if SAMP fails to integrate with existing memory, a discontinuity in autobiographical memory may result. Inadequate exposure to normalizing experiences and hyposalience due to overmedication or negative symptoms may also impede the resolution of SAMP. Residual SAMP is hypothesized to increase the propensity for relapse and treatment non-responsiveness. Based on recent findings on the role of dopamine in facilitating hippocampal synapse plasticity and autobiographical memory formation, the SAMP hypothesis is consistent with clinical observations of DUP effects, including the repetition of contents in psychotic relapses as well as the emergence of treatment non-responsiveness after repeated relapses. Clinical implications of the hypothesis highlight the importance of minimizing active psychosis, integrating psychosis memory, avoiding over-medication, and fostering normalizing experiences.

Unveiling common psychological characteristics of proneness to aggression and general psychopathology in a large community youth cohort.

Elevated aggression in individuals with psychiatric disorders is frequently reported yet aggressive acts among people with mental illness are often intertwined with proneness to aggression and other risk factors. Evidence has suggested that both general psychopathology and proneness to aggression may share common psychological characteristics. This study aims to investigate the complex relationship between general psychopathology, proneness to aggression, and their contributing factors in community youth. Here, we first examined the association between proneness to aggression and the level of general psychopathology in 2184 community youths (male: 41.2%). To identify common characteristics, we trained machine learning models using LASSO based on 230 features covering sociodemographic, cognitive functions, lifestyle, well-being, and psychological characteristics to predict levels of general psychopathology and proneness to aggression. A subsequent Gaussian Graph Model (GGM) was fitted to understand the relationships between the general psychopathology, proneness to aggression, and selected features. We showed that proneness to aggression was associated with a higher level of general psychopathology (discovery: r = 0.56, 95% CI: [0.52-0.59]; holdout: r = 0.60, 95% CI: [0.54-0.65]). The LASSO model trained on the discovery dataset for general psychopathology was able to predict proneness to aggression in the holdout dataset with a moderate correlation coefficient of 0.606. Similarly, the model trained on the proneness to aggression in the discovery dataset was able to predict general psychopathology in the holdout dataset with a correlation coefficient of 0.717. These results suggest that there is substantial shared information between the two outcomes. The GGM model revealed that isolation and impulsivity factors were directly associated with both general psychopathology and proneness to aggression. These results revealed shared psychological characteristics of general psychopathology and proneness to aggression in a community sample of youths.

The emergence of primary negative symptoms: relevance of timing?

Negative symptoms are an important symptom dimension in schizophrenia that are often least responsive to antipsychotic medications. We revisit the current practice of identifying 'primary' negative symptoms and suggest that its concept would benefit from a further elaboration of their timing of emergence in relation to the dynamic neurobiological changes to enhance their utility in clinical decision-making and research.

Evaluating a pilot community-based FITMIND exercise programme for psychosis in Hong Kong.

BACKGROUND: Exercise interventions can improve clinical symptoms and cognition in patients with psychosis in addition to their physical health. However, their benefits may not be maximally generalised to those who cannot access gymnasium facilities, which were commonly required previously. This study evaluated a 12-week community exercise programme named FITMIND, which aims to help patients with psychosis establish exercise habits through easy-to-learn aerobic exercise and yoga, with the support of trained volunteers. METHOD: This study analysed the profiles of 49 patients with psychosis who were referred by the case manager of the early psychosis programme in the public hospital in Hong Kong or enrolled in the programme through the project website. The outcome measures were working memory, physical activity (PA) participation, quality of life, and mood symptoms. RESULTS: At baseline, seven participants (14.3%) met the recommendation of the PA for severe mental illnesses. After the 12-week programme, participants demonstrated significant improvement in vigorous-intensity PA, moderate-to-vigorous PA, compliance with international guidelines for PA, and mood symptoms. CONCLUSION: The FITMIND exercise programme is a feasible community-based intervention that can improve PA participation and mood in patients with psychosis. Further systematic studies are needed to examine the long-term beneficial effects of the programme.

Effort-based decision making in schizotypy and its relationship with amotivation and psychosocial functioning.

Introduction: Suboptimal effort-based decision-making with reduced willingness to expend effort for high-probability/high-value reward is observed in schizophrenia patients and is related to diminished motivation, but is understudied in schizotypy. This study aimed to examine effort-allocation in schizotypy individuals and its association with amotivation and psychosocial functioning. Methods: We recruited 40 schizotypy individuals and 40 demographically-matched healthy controls, based on Schizotypal Personality Questionnaire-Brief (SPQ-B) score (top and bottom 10% SPQ-B scores, respectively), from 2400 young people aged 15-24 years participating a population-based mental health survey in Hong Kong and examined effort-allocation using the Effort Expenditure for Reward Task (EEfRT). Negative / amotivation symptoms and psychosocial functioning were assessed by the Brief Negative Symptom Scale (BNSS) and the Social Functioning and Occupational Assessment Scale (SOFAS), respectively. Schizotypy individuals were categorized into high-amotivation and low-amotivation groups based on a median-split of BNSS amotivation domain score. Results: Our results showed no main group effect (in either two or three-group comparison) on effort task performance. Three-group comparison analyses on selected EEfRT performance indices revealed that high-amotivation schizotypy individuals displayed significantly less increase in effortful options from low-value to high-value reward (reward-difference score) and from low-probability/low-value to high-probability/high-value reward (probability/reward-difference score) than low-amotivation individuals and controls. Correlation analyses demonstrated trend-wise significance between BNSS amotivation domain score and several EEfRT performance indices in schizotypy group. Schizotypy individuals with poorer psychosocial functioning tended to exhibit smaller probability/reward-difference score relative to other two groups. Discussion: Our findings indicate subtle effort-allocation abnormalities in schizotypy individuals with high levels of diminished motivation, and suggest the link between laboratory-based effort-cost measures and real-world functional outcome.

Impact of early negative symptom patterns on the long-term outcomes of patients with first-episode schizophrenia-spectrum disorders: A 12-year follow up study.

Given the strong prognostic value of early negative symptoms (NS), understanding their associations with long-term outcomes of schizophrenia is essential. The study examined early NS patterns in trajectory, severity and variability and their association with 12-year outcomes. NS in the first 36 months after onset and the symptomatology, cognitive function, and functioning at 12 years were examined in 330 patients with first-episode schizophrenia spectrum disorders. The relationships and pathways between the outcomes at 12 years and the trajectory, severity, and variability of early NS were examined. We found that the prediction of trajectory of early NS to long-term outcomes was limited, whereas variability was negatively associated with the patient's long-term executive function, and severity was positively associated with long-term symptomatology and negatively associated with long-term functioning. Path modelling revealed that the severity and variability of early NS influenced patients' long-term functioning via cognitive function and/or clinical symptom pathways. Our findings support the notion that severity of early NS influences the prognosis of schizophrenia and the closer examination revealed that the severity and variability of early NS are differentially associated with long-term clinical symptoms, executive function, and functional outcomes via distinct pathways.

What Drives Animal Fluency Performance in Cantonese-Speaking Chinese Patients with Adult-Onset Psychosis?

Among the numerous studies investigating semantic factors associated with functioning in psychotic patients, most have been conducted on western populations. By contrast, the current cross-sectional study involved native Cantonese-speaking Chinese participants. Using the category fluency task, we compared performance between patients and healthy participants and examined clinical and sociodemographic correlates. First-episode psychosis patients (n = 356) and gender- and age-matched healthy participants (n = 35) were asked to generate as many 'animals' as they could in a minute. As expected, patients generated fewer correct responses (an average of 15.5 vs. 22.9 words), generated fewer clusters (an average of 3.7 vs. 5.4 thematically grouped nouns), switched less between clusters (on average 8.0 vs. 11.9 switches) and, interestingly, produced a larger percentage of Chinese zodiac animals than healthy participants (an average of 37.7 vs. 24.2). However, these significant group differences in the clusters and switches disappeared when the overall word production was controlled for. Within patients, education was the strongest predictor of category fluency performance (namely the number of correct responses, clusters, and switches). The findings suggest that an overall slowness in patients may account for the group differences in category fluency performance rather than any specific abnormality per se.