Rates and correlates of medication non-adherence behaviors and attitudes in adult patients with early psychosis.

PURPOSE: Literature on antipsychotic medication adherence in early psychosis primarily assessed adherence behaviors and focused on young patients. There is a paucity of research investigating negative medication attitude and its determinants in the early illness course, particularly in older-aged sample. We aimed to examine prevalence and correlates of medication non-adherence behaviors and negative medication attitudes separately in adult patients with early psychosis. METHODS: One hundred ninety-nine Chinese early psychosis patients aged 26-55 years who had received three-year treatment for first psychotic episode in Hong Kong were examined. Assessments encompassing socio-demographics, premorbid adjustment, clinical and treatment profiles, self-stigma and therapeutic alliance were conducted. Patients were evaluated with Medication Compliance Questionnaire, which is a modified Chinese-translated version of Medication Adherence Rating Scale and includes items measuring adherence behaviors and attitudes towards medications. RESULTS: Rates of medication non-adherence and negative attitude towards medications were 38.7% and 50.8%, respectively. Multivariate regression analysis showed that more severe positive symptoms, greater self-stigma and negative medication attitude were independently associated with medication non-adherence. Negative attitude towards medications was significantly associated with younger age, higher educational attainment, diagnosis of other psychotic disorders, poorer insight, greater self-stigma and less satisfaction with communication with healthcare staff, which represented an index reflecting suboptimal therapeutic alliance. CONCLUSION: Antipsychotic non-adherence and negative medication attitudes are frequently observed in adult early psychosis patients. Our findings indicate that poor insight, elevated self-stigma and suboptimal therapeutic alliance may constitute potential treatment targets for promoting medication adherence and rectifying negative medication attitudes in the early illness stage.

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.

Association between the pharmacological treatment of bipolar disorder and risk of traumatic injuries: a self-controlled case series study.

BACKGROUND: Patients with bipolar disorder (BPD) are prone to engage in risk-taking behaviours and self-harm, contributing to higher risk of traumatic injuries requiring medical attention at the emergency room (ER).We hypothesize that pharmacological treatment of BPD could reduce the risk of traumatic injuries by alleviating symptoms but evidence remains unclear. This study aimed to examine the association between pharmacological treatment and the risk of ER admissions due to traumatic injuries. METHODS: Individuals with BPD who received mood stabilizers and/or antipsychotics were identified using a population-based electronic healthcare records database in Hong Kong (2001-2019). A self-controlled case series design was applied to control for time-invariant confounders. RESULTS: A total of 5040 out of 14 021 adults with BPD who received pharmacological treatment and had incident ER admissions due to traumatic injuries from 2001 to 2019 were included. An increased risk of traumatic injuries was found 30 days before treatment [incidence rate ratio (IRR) 4.44 (3.71-5.31), p < 0.0001]. After treatment initiation, the risk remained increased with a smaller magnitude, before returning to baseline [IRR 0.97 (0.88-1.06), p = 0.50] during maintenance treatment. The direct comparison of the risk during treatment to that before and after treatment showed a significant decrease. After treatment cessation, the risk was increased [IRR 1.34 (1.09-1.66), p = 0.006]. CONCLUSIONS: This study supports the hypothesis that pharmacological treatment of BPD was associated with a lower risk of ER admissions due to traumatic injuries but an increased risk after treatment cessation. Close monitoring of symptoms relapse is recommended to clinicians and patients if treatment cessation is warranted.

Nervous system-wide analysis of Hox regulation of terminal neuronal fate specification in Caenorhabditis elegans.

Hox genes encode evolutionarily conserved transcription factors that specify regional identities along the anterior-posterior (A-P) axis. Although some Hox genes are known to regulate the differentiation of certain neurons, to what extent Hox genes are involved in the terminal specification of the entire nervous system is unclear. Here, we systematically mapped the expression of all six Hox genes in C. elegans nervous system and found Hox expression in 97 (32%) of the 302 neurons in adult hermaphrodites. Our results are generally consistent with previous high-throughput expression mapping and single-cell transcriptomic studies. Detailed analysis of the fate markers for these neurons revealed that Hox genes regulate the differentiation of 29 (25%) of the 118 classes of C. elegans neurons. Hox genes not only regulate the specification of terminal neuronal fates through multiple mechanisms but also control subtype diversification along the A-P axis. The widespread involvement of Hox genes in neuronal differentiation indicates their roles in establishing complex nervous systems.

Clinical and psychological correlates of insight dimensions in patients with early psychosis.

AIM: To investigate correlates of insight dimensions in Chinese adult patients with early psychosis. METHODS: Insight dimensions including awareness of mental disorder (AMD), illness consequences (AIC) and medication effect (AME) were measured. A wide array of variables encompassing demographics, premorbid adjustment, onset profiles, symptomatology, treatment characteristics and psychological factors were comprehensively assessed. RESULTS: Of 130 participants, 53.1%, 47.7% and 56.2% were categorized with good AMD, AIC and AME, respectively. Good AMD was associated with female gender, fewer positive and disorganization symptoms, more severe depression and greater self-stigma. Good AIC was related to female gender, more severe depression and greater self-stigma. Younger age of onset, fewer positive symptoms and greater service satisfaction associated with good AME. CONCLUSIONS: Poor insight is prevalent in early psychosis. Differential relationships of insight dimensions with other illness variables underscore the importance of multidimensional approach in insight evaluation, and suggest potential treatment target for insight enhancement.

Sex differences in symptom severity, cognition and psychosocial functioning among individuals with at-risk mental state for psychosis.

AIM: Sex differences are well documented in schizophrenia, but have been much less studied in at-risk mental state (ARMS) for psychosis. We aimed to examine sex differences in symptomatology, cognition, social and role functioning in individuals with ARMS, with specific focus on clarifying relationships between sex, negative symptoms and functioning. METHODS: One hundred and seventy-seven Chinese participants aged 15-40 years with ARMS were recruited from a specialized early intervention service in Hong Kong. ARMS status was verified by Comprehensive Assessment of At-Risk Mental State. Assessments encompassing symptom profiles, a brief battery of cognitive tests and social and role functioning were conducted. Brief Negative Symptom Scale was adapted to measure negative symptoms at the level of five core domains. RESULTS: Males with ARMS exhibited significantly poorer social functioning and more severe asociality of negative symptoms than female counterparts. Mediation analysis revealed that sex difference in social functioning became statistically insignificant when asocality was included in the model, indicating that asociality mediated the relationship between sex and social functioning. No sex differences were observed in other core domains of negative symptoms, other symptom dimensions, cognitive measures and role functioning. CONCLUSIONS: This study suggests that sex differences in ARMS may be less pronounced that those observed in established psychotic disorders. Our findings of differential pattern of asociality between sexes and its mediating role on sex difference in social functioning underscore the importance in investigating negative symptoms at a separable domain-level. Further research is required to identify sex-specific predictors of longitudinal outcomes in at-risk populations.

A multifaceted approach in promoting positive mental health culture in Hong Kong secondary schools: The Mindshift educational networking programme.

AIM: Many young people with mental health problems refuse to seek help because of stigma and leave the problem untreated. Previous research suggests that contact interventions with education could improve the stigma of mental illness in young people, thereby encouraging help-seeking in distress. The current study examined the effectiveness of a multifaceted programme, the Mindshift educational networking programme (MENP), in promoting a positive mental health culture in Hong Kong secondary schools. METHODS: The MENP provided activities at school, teacher and student levels to 14 Hong Kong secondary schools. School activities included visits, mental health talks and support for capstone projects. While teachers participated in workshops and regional seminars, students received ambassador training workshops, contact opportunities with people with psychosis and attachment programmes. The impact of MENP was evaluated by changes in students' knowledge, attitudes and behaviours toward people with psychosis and mental illness before and after the programme, as well as by teachers' feedback on the programme. RESULTS: This study analysed data from 55 students and 20 teachers. It was found that the MENP improved students' knowledge of mood symptoms (p = .03), acceptance of people with psychosis (p = .04) and intended behaviour toward people with mental illness (p = .02). The feedback of the teachers on the programme was positive. CONCLUSIONS: The results support the application of the multifaceted approach to promote a positive mental health culture in schools. The findings call on the government to implement the programme in schools in Hong Kong by providing financial support to relevant organizations.

Aberrant Learned Irrelevance in Patients with First-Episode Schizophrenia-Spectrum Disorder.

Emerging evidence has indicated disrupted learned irrelevance (LIrr), a form of selective attention deficit that may contribute to psychotic symptom formation, in schizophrenia. However, previous research mostly focused on chronic patients. There is a paucity of studies on LIrr in first-episode schizophrenia-spectrum disorder (i.e., schizophrenia and schizophreniform disorder; FES), which were limited by small sample size and have produced mixed results. The current study examined a LIrr effect and its relationship with positive symptom severity in 40 briefly-medicated FES patients and 42 demographically-matched healthy controls using a well-validated computerized LIrr paradigm which has been applied in chronic schizophrenia sample. Positive symptoms were assessed by Positive and Negative Syndrome Scale (PANSS) and Psychotic Symptom Rating Scales (PSYRATS). Our results showed that controls demonstrated intact LIrr, with significantly faster learning about previously predictive (relevant) than previously non-predictive (irrelevant) cues. Lack of such normal attention bias towards predictive over non-predictive cues was observed in FES patients, indicating their failure to distinguish between relevant and irrelevant stimuli. Nonetheless, we failed to reveal any significant correlations between learning scores, in particular learning scores for non-predictive cues, and positive symptom measures in FES patients. Learning scores were also not associated with other symptom dimensions, cognitive functions and antipsychotic dose. In conclusion, our findings indicate aberrant LIrr with impaired allocation of attention to relevant versus irrelevant stimuli in briefly-medicated FES patients. Further prospective research is warranted to clarify the longitudinal trajectory of such selective attention deficit and its association with positive symptoms and treatment response in the early course of illness.

Relationship between stressful life events, stigma and life satisfaction with the willingness of disclosure of psychotic illness: A community study in Hong Kong.

AIM: The preference of and potential barriers to disclosure of psychotic illness vary across cultures. Studying its patterns and correlates can guide the design of future culture-specific intervention and public education approaches to improve willingness to disclose and thereby reducing the duration of untreated psychosis (DUP). METHODS: A population-based, random telephone survey was conducted with a total of 1514 respondents in Hong Kong in January 2018. Cross-sectional data on willingness to disclose psychotic illness, life satisfaction, stigmatizing attitude and recent experience of stressful life events (SLEs) were analysed against age and gender using structural equation modelling (SEM). RESULTS: Unwillingness to disclose to anyone was reported by 12% of the participants. Family was reported as the preferred disclosure candidate by most respondents. Our model, which showed a good fit to the data demonstrated that stigmatizing attitude and life satisfaction were directly associated with willingness to disclose illness. Younger age was correlated with more recent experience of SLEs, lower life satisfaction and less willingness to disclose illness. Women's disclosure willingness was positively associated with their life satisfaction, which was sensitive to recent exposure to single SLE. In contrast, men's was negatively associated with their stigmatizing attitude, which increased significantly upon exposure to two or more recent SLEs. CONCLUSION: Encouraging the public to help their family to seek treatment should be a focal point of a successful mental health public education campaign. Cultural-specific and integrated interventions should be developed targeting the vulnerable groups including people with high recent life stress, particularly woman and those with younger age.

Psychiatric comorbidity in individuals at-risk for psychosis: Relationships with symptoms, cognition and psychosocial functioning.

AIM: Psychiatric comorbidity frequently occurs with at-risk mental state (ARMS) for psychosis. Its relationships with psychopathology, cognition and functioning, however, remain to be further clarified. We aimed to examine prevalence and correlates of psychiatric comorbidity, and its associations with psychosocial functioning and subjective quality-of-life (QoL) in a representative sample of Chinese ARMS individuals. METHODS: One hundred ten help-seeking participants aged 15 to 40 years with ARMS were recruited from a specialized early psychosis service in Hong Kong. ARMS status was verified by comprehensive assessment of at-risk mental state (CAARMS). Comorbid Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition non-psychotic psychiatric disorders at baseline were ascertained using diagnostic interview and medical record review. Assessments encompassing symptom profiles, psychosocial functioning, subjective QoL and a brief cognitive battery were conducted. RESULTS: Forty-nine (44.5%) ARMS participants were diagnosed as having comorbid non-psychotic psychiatric disorders at baseline, primarily depressive and anxiety disorders. Binary multiple logistic regression analysis revealed that female gender, more severe depressive symptoms, higher suicidality and poorer global cognitive functioning were independently associated with comorbid diagnosis status. ARMS participants with psychiatric comorbidity displayed significantly more limited extended social networks and poorer subjective QoL than those without psychiatric comorbidity. CONCLUSION: Comorbid disorders were frequently observed in Chinese ARMS individuals, and were linked to poorer cognition and higher suicide risk. Our findings underscore a potential critical role of psychiatric comorbidity in determining social functioning and subjective QoL in at-risk individuals. Further longitudinal research is required to clarify trajectories of comorbid disorder status and its prospective impact on clinical and functional outcomes in ARMS populations.

Epistatic, synthetic, and balancing interactions among tubulin missense mutations affecting neurite growth in Caenorhabditis elegans.

Mutations in tubulins affect microtubule (MT) dynamics and functions during neuronal differentiation and their genetic interaction provides insights into the regulation of MT functions. We previously used Caenorhabditis elegans touch receptor neurons to analyze the cellular impact of tubulin mutations and reported the phenotypes of 67 tubulin missense mutations, categorized into three classes: loss-of-function (lf), antimorphic (anti), and neomorphic (neo) alleles. In this study, we isolated 54 additional tubulin alleles through suppressor screens in sensitized backgrounds that caused excessive neurite growth. These alleles included 32 missense mutations not analyzed before, bringing the total number of mutations in our collection to 99. Phenotypic characterization of these newly isolated mutations identified three new types of alleles: partial lf and weak neo alleles of mec-7/ß-tubulin that had subtle effects and strong anti alleles of mec-12/α-tubulin. We also discovered complex genetic interactions among the tubulin mutations, including the suppression of neo mutations by intragenic lf and anti alleles, additive and synthetic effects between mec-7 neo alleles, and unexpected epistasis, in which weaker neo alleles masked the effects of stronger neo alleles in inducing ectopic neurite growth. We also observed balancing between neo and anti alleles, whose respective MT-hyperstablizing and -destabilizing effects neutralized each other.

The role of dopamine dysregulation and evidence for the transdiagnostic nature of elevated dopamine synthesis in psychosis: a positron emission tomography (PET) study comparing schizophrenia, delusional disorder, and other psychotic disorders.

There have been few studies performed to examine the pathophysiological differences between different types of psychosis, such as between delusional disorder (DD) and schizophrenia (SZ). Notably, despite the different clinical characteristics of DD and schizophrenia (SZ), antipsychotics are deemed equally effective pharmaceutical treatments for both conditions. In this context, dopamine dysregulation may be transdiagnostic of the pathophysiology of psychotic disorders such as DD and SZ. In this study, an examination is made of the dopamine synthesis capacity (DSC) of patients with SZ, DD, other psychotic disorders, and the DSC of healthy subjects. Fifty-four subjects were recruited to the study, comprising 35 subjects with first-episode psychosis (11 DD, 12 SZ, 12 other psychotic disorders) and 19 healthy controls. All received an 18F-DOPA positron emission tomography (PET)/magnetic resonance (MR) scan to measure DSC (Kocc;30-60 value) within 1 month of starting antipsychotic treatment. Clinical assessments were also made, which included Positive and Negative Syndrome Scale (PANSS) measurements. The mean Kocc;30-60 was significantly greater in the caudate region of subjects in the DD group (ES = 0.83, corrected p = 0.048), the SZ group (ES = 1.40, corrected p = 0.003) and the other psychotic disorder group (ES = 1.34, corrected p = 0.0045), compared to that of the control group. These data indicate that DD, SZ, and other psychotic disorders have similar dysregulated mechanisms of dopamine synthesis, which supports the utility of abnormal dopamine synthesis in transdiagnoses of these psychotic conditions.

Opposing effects of an F-box protein and the HSP90 chaperone network on microtubule stability and neurite growth in Caenorhabditis elegans.

Molecular chaperones often work collaboratively with the ubiquitylation-proteasome system (UPS) to facilitate the degradation of misfolded proteins, which typically safeguards cellular differentiation and protects cells from stress. In this study, however, we report that the Hsp70/Hsp90 chaperone machinery and an F-box protein, MEC-15, have opposing effects on neuronal differentiation, and that the chaperones negatively regulate neuronal morphogenesis and functions. Using the touch receptor neurons (TRNs) of Caenorhabditis elegans, we find that mec-15(-) mutants display defects in microtubule formation, neurite growth, synaptic development and neuronal functions, and that these defects can be rescued by the loss of Hsp70/Hsp90 chaperones and co-chaperones. MEC-15 probably functions in a Skp-, Cullin- and F-box- containing complex to degrade DLK-1, which is an Hsp90 client protein stabilized by the chaperones. The abundance of DLK-1, and likely other Hsp90 substrates, is fine-tuned by the antagonism between MEC-15 and the chaperones; this antagonism regulates TRN development, as well as synaptic functions of GABAergic motor neurons. Therefore, a balance between the UPS and the chaperones tightly controls neuronal differentiation.

Prevalence and correlates of antipsychotic polypharmacy in Hong Kong.

BACKGROUND: Antipsychotic polypharmacy (APP) remains a common practice despite inconclusive empirical evidence of additional efficacy and potential exacerbation of side effects. Previous studies suggest APP rate is notably high in East Asia. This paper aims to investigate the prevalence and correlates of APP in Hong Kong. METHOD: This was a cross-sectional study of 728 patients with psychosis. The demographics and clinical information, including age, gender, diagnosis, hospitalization history, and medication were collected. Chi-square tests and logistic regression analyses were used to study correlates of APP. RESULTS: The APP rate for psychosis was 24.2% (n = 728) and that for schizophrenia was 26.0% (n = 611), both considerably lower than our previous local data and that from East Asian regions. The most widely used APP prescription fell within the atypical/atypical combination (i.e., Amisulpride/Clozapine and Paliperidone/Olanzapine), and Olanzapine was the most commonly prescribed antipsychotic. At least 75% of APP patients with psychosis took at least one type of atypical antipsychotics in their medical regimen. Typical/typical polypharmacy was associated with older age and use of antiparkinson drugs. Typical/atypical polypharmacy was associated with the use of antiparkinson drugs and anxiolytics, as well as inpatient status. Atypical/atypical polypharmacy was associated with younger age, inpatient status, and the use of mood stabilizers. CONCLUSION: Overall, our study highlights a relatively low APP rate in Hong Kong when compared to other countries in East Asia. Age, inpatient status and use of antiparkinson drugs, anxiolytics and mood stabilizers were associated with use of APP.

Medication adherence, knowledge about psychosis, and insight among patients with a schizophrenia-spectrum disorder.

This study aimed to explore the relationship between knowledge about psychosis, insight, and medication adherence among patients at an early stage of a schizophrenia-spectrum disorder. Eighty patients were recruited from a specialized outpatient clinic. Knowledge was assessed with the modified Knowledge About Schizophrenia Test (KAST). Medication adherence was determined with the Chinese abridged Medication Adherence Ratings Scale. Insight was measured with the abridged Scale to Assess Unawareness of Mental Disorder (SUMD). The KAST total score was correlated with the SUMD. A trend correlation between KAST subscores of cause and SUMD was found. The nonadherence rate was 43.8%. The medication-adherent patients had lower SUMD (z = -4.338, p < 0.0001) and higher KAST subscore of cause (z = -2.767, p = 0.006). These two variables explained 38.9% of the variance in adherence behavior, with SUMD being the mediator. This study highlights the importance of patients' understanding of etiology of the illness and its relationship with insight and medication adherence.