Genetic and inflammatory effects on childhood trauma and cognitive functioning in patients with schizophrenia and healthy participants.

Recent studies have reported a negative association between exposure to childhood trauma, including physical neglect, and cognitive functioning in patients with schizophrenia. Childhood trauma has been found to influence immune functioning, which may contribute to the risk of schizophrenia and cognitive symptoms of the disorder. In this study, we aimed to test the hypothesis that physical neglect is associated with cognitive ability, and that this association is mediated by a combined latent measure of inflammatory response, and moderated by higher genetic risk for schizophrenia. The study included 279 Irish participants, comprising 102 patients and 177 healthy participants. Structural equation modelling was used to perform mediation and moderation analyses. Inflammatory response was measured via basal plasma levels of IL-6, TNF-α, and CRP, and cognitive performance was assessed across three domains: full-scale IQ, logical memory, and the emotion recognition task. Genetic variation for schizophrenia was estimated using a genome-wide polygenic score based on genome-wide association study summary statistics. The results showed that inflammatory response mediated the association between physical neglect and all measures of cognitive functioning, and explained considerably more variance than any of the inflammatory markers alone. Furthermore, genetic risk for schizophrenia was observed to moderate the direct pathway between physical neglect and measures of non-social cognitive functioning in both patient and healthy participants. However, genetic risk did not moderate the mediated pathway associated with inflammatory response. Therefore, we conclude that the mediating role of inflammatory response and the moderating role of higher genetic risk may independently influence the association between adverse early life experiences and cognitive function in patients and healthy participants.

Psychological intervention for a person living with amblyopia: a case study from home-based integrated care.

Amblyopia is a common developmental disability resulting in reduced visual acuity and gaze stability; it occurs in approximately 5% of the general population. Here, we present the case of an 18-year-old girl diagnosed with amblyopia. Subsequent to her diagnosis of amblyopia, she developed a depressive episode with co-morbid anxiety symptoms. She was treated with low intensity psychological intervention, Problem Management Plus, as home-based intervention. This intervention was associated both subjectively and objectively utilising psychometric measures (i.e. psychiatric interview, depression, anxiety and stress scale, general health questionnaire) with a significant amelioration of her mental state. This case provides preliminary evidence for the effectiveness of Problem Management Plus intervention and suggests that this intervention should be considered for other individuals with similar clinical presentations.

In vivo hippocampal subfield volumes in bipolar disorder-A mega-analysis from The Enhancing Neuro Imaging Genetics through Meta-Analysis Bipolar Disorder Working Group.

The hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder (BD). Here we, the Enhancing NeuroImaging Genetics through Meta-Analysis Bipolar Disorder workinggroup, study hippocampal subfield volumetry in BD. T1-weighted magnetic resonance imaging scans from 4,698 individuals (BD = 1,472, healthy controls [HC] = 3,226) from 23 sites worldwide were processed with FreeSurfer. We used linear mixed-effects models and mega-analysis to investigate differences in hippocampal subfield volumes between BD and HC, followed by analyses of clinical characteristics and medication use. BD showed significantly smaller volumes of the whole hippocampus (Cohen's d = -0.20), cornu ammonis (CA)1 (d = -0.18), CA2/3 (d = -0.11), CA4 (d = -0.19), molecular layer (d = -0.21), granule cell layer of dentate gyrus (d = -0.21), hippocampal tail (d = -0.10), subiculum (d = -0.15), presubiculum (d = -0.18), and hippocampal amygdala transition area (d = -0.17) compared to HC. Lithium users did not show volume differences compared to HC, while non-users did. Antipsychotics or antiepileptic use was associated with smaller volumes. In this largest study of hippocampal subfields in BD to date, we show widespread reductions in nine of 12 subfields studied. The associations were modulated by medication use and specifically the lack of differences between lithium users and HC supports a possible protective role of lithium in BD.

Early life Adversity, functional connectivity and cognitive performance in Schizophrenia: The mediating role of IL-6.

OBJECTIVE: Exposure to childhood trauma (CT) is associated with cognitive impairment in schizophrenia, and deficits in social cognition in particular. Here, we sought to test whether IL-6 mediated the association between CT and social cognition both directly, and sequentially via altered default mode network (DMN) connectivity. METHODS: Three-hundred-and-eleven participants (104 patients and 207 healthy participants) were included, with MRI data acquired in a subset of n = 147. CT was measured using the childhood trauma questionnaire (CTQ). IL-6 was measured in both plasma and in toll like receptor (TLR) stimulated whole blood. The CANTAB emotion recognition task (ERT) was administered to assess social cognition, and cortical connectivity was assessed based on resting DMN connectivity. RESULTS: Higher IL-6 levels, measured both in plasma and in toll-like receptor (TLR-2) stimulated blood, were significantly correlated with higher CTQ scores and lower cognitive and social cognitive function. Plasma IL-6 was further observed to partly mediate the association between higher CT scores and lower emotion recognition performance (CTQ total: ßindirect -0.0234, 95% CI: -0.0573 to -0.0074; CTQ physical neglect: ßindirect = -0.0316, 95% CI: -0.0741 to -0.0049). Finally, sequential mediation was observed between plasma IL-6 levels and DMN connectivity in mediating the effects of higher CTQ on lower social cognitive function (ßindirect = -0.0618, 95% CI: -0.1523 to -0.285). CONCLUSION: This work suggests that previous associations between CT and social cognition may be partly mediated via an increased inflammatory response. IL-6's association with changes in DMN activity further suggest at least one cortical network via which CT related effects on cognition may be transmitted.

A 52-week prophylactic randomised control trial of omega-3 polyunsaturated fatty acids in bipolar disorder.

OBJECTIVES: Previous work suggests supplementation with omega-3 polyunsaturated fatty acids (PUFAs) may improve mood symptoms in bipolar disorder (BD) although findings remain unclear. In this study, we assess the efficacy of omega-3 PUFA administration for prophylaxis in BD using a clinical trial design over 52-weeks (ClinicalTrials.gov Identifier: NCT04210804). METHODS: Individuals with BD (n = 80) were randomised to receive placebo (n = 40) or 1 g eicosapentaenoic acid (EPA) plus 1 g docosahexaenoic acid (DHA; n = 40) adjunctively for 52-weeks. The primary outcome measure comprised the number of mood episode relapses including hospital admissions and medication changes experienced. Secondary outcome measures included time to first mood episode relapse and change in psychometric measures of depression and elation (Hamilton Depression Rating Scale and Young Mania Rating Scale). RESULTS: No significant differences in the number of mood episode relapses (U = 490.00, p = 0.14) or the number of individuals requiring admission to hospital (χ2  = 0.67, p = 0.41) or medication adjustment in the omega-3 PUFA compared to the placebo group were noted. Time to relapse was not significantly different between groups (Log Rank χ2  = 0.41, p = 0.52). Change in Young Manic Rating Scale (F(3.12, 152.86) = 2.71, p = 0.05) was significantly different between treatment groups over 12-months, with scores at 9-months and 12-months significantly lower than those at 3-months in the omega-3 group and not in the placebo group. Change in Hamilton Depression Rating Scale, Global Clinical Impression and Global Assessment of Functioning were not different between groups. CONCLUSIONS: Despite a minor reduction in hypomania scores in the omega-3 PUFA group compared to placebo, we find little evidence that the supplementation of omega-3-PUFAs exhibits prophylactic benefit in BD.

Childhood trauma, parental bonding, and social cognition in patients with schizophrenia and healthy adults.

OBJECTIVE: This study investigated associations between childhood trauma, parental bonding, and social cognition (i.e., Theory of Mind and emotion recognition) in patients with schizophrenia and healthy adults. METHODS: Using cross-sectional data, we examined the recollections of childhood trauma experiences and social cognitive abilities in 74 patients with schizophrenia and 116 healthy adults. RESULTS: Patients had significantly higher scores compared with healthy participants on childhood trauma, and lower scores on parental bonding and social cognitive measures. Physical neglect was found to be the strongest predictor of emotion recognition impairments in both groups. Optimal parental bonding attenuated the impact of childhood trauma on emotion recognition. CONCLUSION: The present study provides evidence of an association between physical neglect and emotion recognition in patients with schizophrenia and healthy individuals and shows that both childhood trauma and parental bonding may influence social cognitive development. Psychosocial interventions should be developed to prevent and mitigate the long-term effects of childhood adversities.

Impact of Conventional Beliefs and Social Stigma on Attitude Towards Access to Mental Health Services in Pakistan.

This study aims to explore the role of conventional beliefs and social stigma on attitude towards access to mental health services. From 50 caregivers data were collected by Perceived Public Stigma Scale and an in-depth semi-structured interview. The majority (86%) of patients having significant symptoms of major mental illness visited traditional healer prior to engagement with the mental health services. However a significant positive finding, related to carers predominantly perceiving that individuals with mental health difficulties were trustworthy, capable of engagement in employment and were comfortable with having them as their friends were identified.

Computerised working memory-based cognitive remediation therapy does not affect Reading the Mind in The Eyes test performance or neural activity during a Facial Emotion Recognition test in psychosis.

Working memory-based cognitive remediation therapy (CT) for psychosis has recently been associated with broad improvements in performance on untrained tasks measuring working memory, episodic memory and IQ, and changes in associated brain regions. However, it is unclear whether these improvements transfer to the domain of social cognition and neural activity related to performance on social cognitive tasks. We examined performance on the Reading the Mind in the Eyes test (Eyes test) in a large sample of participants with psychosis who underwent working memory-based CT (N = 43) compared to a control group of participants with psychosis (N = 35). In a subset of this sample, we used functional magnetic resonance imaging (fMRI) to examine changes in neural activity during a facial emotion recognition task in participants who underwent CT (N = 15) compared to a control group (N = 15). No significant effects of CT were observed on Eyes test performance or on neural activity during facial emotion recognition, either at p < 0.05 family-wise error or at a p < 0.001 uncorrected threshold, within a priori social cognitive regions of interest. This study suggests that working memory-based CT does not significantly impact an aspect of social cognition which was measured behaviourally and neurally. It provides further evidence that deficits in the ability to decode mental state from facial expressions are dissociable from working memory deficits, and suggests that future CT programmes should target social cognition in addition to working memory for the purposes of further enhancing social function.

Neuropsychiatric syndromes of multiple sclerosis.

Neuropsychiatric signs and symptoms occur frequently in individuals with multiple sclerosis (MS), either as the initial presenting complaint prior to a definitive neurological diagnosis or more commonly with disease progression. However, the pathogenesis of these comorbid conditions remains unclear and it remains difficult to accurately elucidate if neuropsychiatric symptoms or conditions are indicators of MS illness severity. Furthermore, both the disease process and the treatments of MS can adversely impact an individual's mental health. In this review, we discuss the common neuropsychiatric syndromes that occur in MS and describe the clinical symptoms, aetiology, neuroimaging findings and management strategies for these conditions.

Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression.

BACKGROUND: Trials evaluating efficacy of omega-3 highly unsaturated fatty acids (HUFAs) in major depressive disorder report discrepant findings. AIMS: To establish the reasons underlying inconsistent findings among randomised controlled trials (RCTs) of omega-3 HUFAs for depression and to assess implications for further trials. METHOD: A systematic bibliographic search of double-blind RCTs was conducted between January 1980 and July 2014 and an exploratory hypothesis-testing meta-analysis performed in 35 RCTs including 6665 participants receiving omega-3 HUFAs and 4373 participants receiving placebo. RESULTS: Among participants with diagnosed depression, eicosapentaenoic acid (EPA)-predominant formulations (>50% EPA) demonstrated clinical benefits compared with placebo (Hedge's G = 0.61, P<0.001) whereas docosahexaenoic acid (DHA)-predominant formulations (>50% DHA) did not. EPA failed to prevent depressive symptoms among populations not diagnosed for depression. CONCLUSIONS: Further RCTs should be conducted on study populations with diagnosed or clinically significant depression of adequate duration using EPA-predominant omega-3 HUFA formulations.

Response inhibition and serotonin in autism: a functional MRI study using acute tryptophan depletion.

It has been suggested that the restricted, stereotyped and repetitive behaviours typically found in autism are underpinned by deficits of inhibitory control. The biological basis of this is unknown but may include differences in the modulatory role of neurotransmitters, such as serotonin, which are implicated in the condition. However, this has never been tested directly. We therefore assessed the modifying role of serotonin on inhibitory brain function during a Go/No-Go task in 14 adults with autism and normal intelligence and 14 control subjects that did not differ in gender, age and intelligence. We undertook a double-blind, placebo-controlled, crossover trial of acute tryptophan depletion using functional magnetic resonance imaging. Following sham, adults with autism relative to controls had reduced activation in key inhibitory regions of inferior frontal cortex and thalamus, but increased activation of caudate and cerebellum. However, brain activation was modulated in opposite ways by depletion in each group. Within autistic individuals depletion upregulated fronto-thalamic activations and downregulated striato-cerebellar activations toward control sham levels, completely 'normalizing' the fronto-cerebellar dysfunctions. The opposite pattern occurred in controls. Moreover, the severity of autism was related to the degree of differential modulation by depletion within frontal, striatal and thalamic regions. Our findings demonstrate that individuals with autism have abnormal inhibitory networks, and that serotonin has a differential, opposite, effect on them in adults with and without autism. Together these factors may partially explain the severity of autistic behaviours and/or provide a novel (tractable) treatment target.

Uncinate fasciculus microstructural organisation and emotion recognition in schizophrenia: controlling for hit rate bias.

Introduction: Schizophrenia (SCZ) is a complex neurodevelopmental disorder characterised by functional and structural brain dysconnectivity and disturbances in perception, cognition, emotion, and social functioning. In the present study, we investigated whether the microstructural organisation of the uncinate fasciculus (UF) was associated with emotion recognition (ER) performance. Additionally, we investigated the usefulness of an unbiased hit rate (UHR) score to control for response biases (i.e., participant guessing) during an emotion recognition task (ERT). Methods: Fifty-eight individuals diagnosed with SCZ were included. The CANTAB ERT was used to measure social cognition. Specific ROI manual tract segmentation was completed using ExploreDTI and followed the protocol previously outlined by Coad et al. (2020). Results: We found that the microstructural organisation of the UF was significantly correlated with physical neglect and ER outcomes. Furthermore, we found that the UHR score was more sensitive to ERT subscale emotion items than the standard HR score. Finally, given the association between childhood trauma (in particular childhood neglect) and social cognition in SCZ, a mediation analysis found evidence that microstructural alterations of the UF mediated an association between childhood trauma and social cognitive performance. Discussion: The mediating role of microstructural alterations in the UF on the association between childhood trauma and social cognitive performance suggests that early life adversity impacts both brain development and social cognitive outcomes for people with SCZ. Limitations of the present study include the restricted ability of the tensor model to correctly assess multi-directionality at regions where fibre populations intersect.

The impact of badmouthing of medical specialties to medical students.

OBJECTIVES: This study aimed to evaluate the proportion of Irish medical students exposed to 'badmouthing' of different specialities and to ascertain: the degree of criticism of specialities based on the seniority of clinical or academic members of staff; if 'badmouthing' influenced student career choice in psychiatry; and attitudes of medical students towards psychiatry as a speciality and career choice. METHODS: Medical students in three Irish universities were invited to complete an online survey to determine the frequency and effect of non-constructive criticism on choice of medical specialty. The online questionnaire was distributed to Royal College of Surgeons in Ireland (RCSI), University of Galway (UoG) and University College Dublin (UCD) in the academic year 2020-2021. RESULTS: General practice (69%), surgery (65%) and psychiatry (50%) were the most criticised specialties. Criticism was most likely to be heard from medical students. 46% of students reported reconsidering a career in psychiatry due to criticism from junior doctors. There was a positive perception of psychiatry with 27% of respondents considering psychiatry as a first-choice specialty. CONCLUSIONS: Criticism of psychiatry by doctors, academics and student peers negatively influences students' career choice, which could be contributing to recruitment difficulties in psychiatry.

Corpus callosum microstructural organization mediates the effects of physical neglect on social cognition in schizophrenia.

Exposure to early life adversity is associated with both increased risk of developing schizophrenia and poorer performance on measures of social cognitive functioning. In this study, we examined whether interleukin-6 (IL-6) and Corpus Callosum (CC) microstructure mediated the association between childhood physical neglect and social cognition. Fifty-eight patients with a diagnosis of schizophrenia were included. The CANTAB emotion recognition task (unbiased hit rate) was used to assess social cognition. We found that the microstructural organization of the CC significantly mediated the association between physical neglect and emotion recognition. Furthermore, in a sequential mediation analysis that also considered the role of inflammatory response, the association between physical neglect, and lower emotion recognition performance was sequentially mediated by higher IL-6 and lower fractional anisotropy of the CC. This mediating effect of IL-6 was only present when simultaneously considering the effects of CC microstructural organization and remained significant while controlling for the effects of sex, BMI and medication dosage (but not age). Overall, the findings suggest that the association between physical neglect and poorer emotion recognition in schizophrenia occurs, at least in part, via its association with white matter microstructure.

Delusions of Vampirism in an Adolescent and Treatment With Clozapine: A Case Report.

This case describes delusions of vampirism among several other psychotic symptoms in a 15-year-old who has a diagnosis of schizophrenia, with these delusions first presenting when he was 13 years of age. Delusions of vampirism can be associated with a strong desire to suck human blood but these delusional beliefs were not acted upon here. This is the first report of delusions of vampirism in childhood to date. The introduction of the antipsychotic medication clozapine after failed treatment trials with two other antipsychotic agents has been associated with a significant amelioration in symptomatology and an improvement in functioning.

Impact factor and future directions for the Irish Journal of Psychological Medicine.

Impact factor (IF) is a concept dating back over half a century, created to evaluate the impact of a journal within a particular scientific field. In spite of limitations, IF remains a widely used metric for journals to establish the average number of citations for articles published in a journal. The Irish Journal of Psychological Medicine (IJPM) recently received an IF of 5.1, the first IF for the journal. We believe that this is a reflection of the hard work and dedication of our authors, reviewers, publishers and editorial board. The IJPM is the official research journal of the College of Psychiatrists of Ireland, and while psychiatry is the primary discipline of the journal, the current multidisciplinary approach will continue into the future. The journal has a strong Irish and international readership; while the journal will continue to publish research with an Irish focus, the editorial team are aware of the importance of ongoing global contributions to ensure the journal maintains high-quality publications of an international standard. This is an exciting time to be involved in mental health research, and the journal will continue to publish cutting edge themes with the goal of improving mental healthcare in Ireland and beyond.

Impulsivity, suicidal thoughts, psychological distress, and religiosity in adolescents and young adults.

Background: Impulsivity is associated with suicidal acts and ideation, whereas higher religious commitment has been identified as a potential protective factor linked to lower suicidal ideation. Objectives: We examined the extent to which higher religious commitment is associated with lower suicidal ideation and whether religious commitment modifies the relationship between impulsivity and suicidal ideation. Methods: Adolescent and young adult males, with a prior history of suicidal act and ideations, completed standardized questionnaires [i.e., Beck Scale for Suicidal Ideation (BSS), Barratt Impulsivity Scale-II (BIS-II), Depression Anxiety Stress Scale (DASS), and Religious Commitment Inventory-10 (RCI-10)], to assess impulsivity, suicidal ideation, distress, and religious commitment. Regression and mediation analyses were performed to investigate the relationships among impulsivity, religious commitment, and suicidal ideation. Results: Of the 747 study participants (mean age 18.8 years, SD = 4.1), 151 (20.2%) had a history of suicidal acts and 177 (23.7%) had a history of suicidal ideation. Non-planning impulsivity (predictor) was inversely associated with religious commitment (r = -0.33, p < 0.01), and religious commitment (mediator) was inversely related to suicidal ideation (outcome) (r = -0.32, p < 0.01). These findings remained statistically significant when controlling for either religious commitment or non-planning impulsivity, as appropriate. Higher religious commitment reduced the association between non-planning impulsivity and suicidal ideation (p < 0.01). Conclusion: The findings highlight the potential for cultivating spirituality to buffer against higher suicidal ideation, and thus could be considered as an additional therapeutic strategy for individuals with higher levels of impulsivity and co-morbid suicidal ideation.

A longitudinal evaluation of the impact of the COVID-19 pandemic on a cohort of patients treated with clozapine.

OBJECTIVES: We previously demonstrated that three months into the COVID-19 pandemic, the impact on individuals with treatment-resistant psychotic disorders was modest. Here, we examined and compared the psychological and social impact of the COVID-19 pandemic on the same patient cohort 12 months after their initial study engagement. METHODS: Semi-structured interviews were conducted with 54 individuals (85.7% response rate) between June 12 and July 29, 2021, 12 months after their initial interviews. Participants' subjective experience of the impact of the COVID-19 pandemic on anxiety symptoms, social and vocational functioning was measured utilising the same Likert scales at both time points. Anxiety symptoms were additionally measured using subjective (Beck Anxiety Inventory) and objective (Hamilton Anxiety Rating Scale (HARS)) psychometric instruments. Paired t-tests or Wilcoxon ranked tests compared parametric or non-parametric data over time. Free-text responses pertaining to participants' perspectives on the impact of COVID-19 were grouped into themes. RESULTS: A minor increase in anxiety symptoms was demonstrated utilising the HARS (1.9 points, z = 3.017, p = 0.003), with a minimal increase in depressive symptoms noted using Likert ratings (0.8 points, z = 2.119, p = 0.034). Five themes were identified with the most prevalent being (i) positivity regarding vaccination, (ii) social isolation from family members and (iii) looking forward to post-COVID-19 'normality'. However, negative views pertaining to the psychosocial impact of COVID-19 and vaccination were additionally reported. CONCLUSIONS: No significant overall clinical change in symptomatology or functioning over time was noted.The study demonstrated that positive views regarding vaccination and optimism for the future were evident for some participants.

Alcohol use is associated with affective and interoceptive network alterations in bipolar disorder.

INTRODUCTION: Alcohol use in bipolar disorder (BD) is associated with mood lability and negative illness trajectory, while also impacting functional networks related to emotion, cognition, and introspection. The adverse impact of alcohol use in BD may be explained by its additive effects on these networks, thereby contributing to a poorer clinical outcome. METHODS: Forty BD-I (DSM-IV-TR) and 46 psychiatrically healthy controls underwent T1 and resting state functional MRI scanning and the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) to assess alcohol use. Functional images were decomposed using spatial independent component analysis into 14 resting state networks (RSN), which were examined for effect of alcohol use and diagnosis-by-alcohol use accounting for age, sex, and diagnosis. RESULTS: Despite the groups consuming similar amounts of alcohol (BD: mean score ± SD 3.63 ± 3; HC 4.72 ± 3, U = 713, p = .07), for BD participants, greater alcohol use was associated with increased connectivity of the paracingulate gyrus within a default mode network (DMN) and reduced connectivity within an executive control network (ECN) relative to controls. Independently, greater alcohol use was associated with increased connectivity within an ECN and reduced connectivity within a DMN. A diagnosis of BD was associated with increased connectivity of a DMN and reduced connectivity of an ECN. CONCLUSION: Affective symptomatology in BD is suggested to arise from the aberrant functionality of networks subserving emotive, cognitive, and introspective processes. Taken together, our results suggest that during euthymic periods, alcohol can contribute to the weakening of emotional regulation and response, potentially explaining the increased lability of mood and vulnerability to relapse within the disorder.

Dysfunctional schema modes as determinants of psychiatric comorbidities: a study in a cohort of people with epilepsy.

INTRODUCTION AND AIMS: Symptomatology of epilepsy and its' associated alteration in brain processes, stigma of experiencing seizures, and adverse sequelae of anti-epileptics have been demonstrated to impact behaviour and exacerbate psychopathology. This study examines the role of dysfunctional schema modes in People with Epilepsy (PWE) and their association with psychiatric symptoms. METHODS: Semi-structured interviews were conducted with 108 PWE treated with anti-epileptics for at least one year and with no history or mental disorder or psycho-active substance use. Clinical symptoms were measured utilising the Symptom Checklist-90 (SCL-90) with schema modes measured utilising the Schema Mode Inventory (SMI). RESULTS: Maladaptive coping and child schema modes were significantly higher in individuals from lower socio-economic status group (p < 0.01), with several maladaptive schema modes more prevalent in males. Hostility symptoms were increased in individuals from lower socio-economic classes and were more prevalent early in disease course. Several psychological symptoms including somatisation, interpersonal, obsession, depression, paranoia, hostility, phobia, anxiety, and psychoticism, were predicted by various maladaptive schema modes (p < 0.001). CONCLUSION: This study highlights the impact of maladaptive schemas, suggesting that PWE might benefit from the introduction of appropriate psychotherapeutic interventions such as schema-focused therapy, particularly if from lower socio-economic classes or in the early stages of theirdisease course.