Karen Irvine

Greater cognitive deterioration in women than men with Alzheimer's disease: A meta analysis

Studies reporting on the cognitive abilities of men and women with Alzheimers disease (AD) are surprisingly rare. We carried out a meta-analysis of neurocognitive data from 15 studies (n = 828 men; 1,238 women), which revealed a consistent male advantage on verbal and visuospatial tasks and tests of episodic and semantic memory. Moderator regression analyses showed that age, education level, and dementia severity did not significantly predict the male advantage. Reasons posited for this advantage include a reduction of estrogen in postmenopausal women, sex differences in AD pathology, and greater cognitive reserve in men.

Sex differences in cognitive impairment in Alzheimer’s disease

Sex differences in neurocognitive abilities have been extensively explored both in the healthy population and in many disorders. Until recently, however, little work has examined such differences in people with Alzheimers disease (AD). This is despite clear evidence that AD is more prevalent in women, and converging lines of evidence from brain imaging, post-mortem analyses, hormone therapy and genetics suggesting that AD affects men and women differently. We provide an overview of evidence attesting to the poorer cognitive profiles in women than in men at the same stage of AD. Indeed, men significantly outperform women in several cognitive domains, including: Language and semantic abilities, visuospatial abilities and episodic memory. These differences do not appear to be attributable to any differences in age, education, or dementia severity. Reasons posited for this female disadvantage include a reduction of estrogen in postmenopausal women, greater cognitive reserve in men, and the influence of the apolipoprotein E ε4 allele. Assessment of cognitive abilities contributes to the diagnosis of the condition and thus, it is crucial to identify the role of sex differences if potentially more accurate diagnoses and treatments are to emerge.

The naming profile in Alzheimer patients parallels that of elderly controls

Controversy exists as to whether semantic disruption in Alzheimers disease (AD) systematically impairs the naming of living things. Moreover, little is known about performance across more specific subcategories. We investigated picture naming in 28 AD patients and 24 controls. To deal with nonnormal distributions, we created 1,000 bootstrap hierarchical regressions and determined which variables (the “nuisance” variables familiarity, word frequency, age of acquisition and visual complexity; category; and control naming) best predicted AD patient naming. Nuisance variables combined, control naming, and category uniquely accounted for 39%, 36%, and 3% of patient naming variance, respectively. Finally, analysis of the AD naming profile across the 10 subcategories mirrored that of controls. Taken together, these findings indicate that while AD naming is, of course, quantitatively worse than that of controls, it does not qualitatively differ—that is, it is an exaggerated normal profile.

Feasibility study of a randomised controlled trial to investigate the effectiveness of using a humanoid robot to improve the social skills of children with autism spectrum disorder (Kaspar RCT): a study protocol

Introduction Interventions using robot-assisted therapy may be beneficial for the social skills development of children with autism spectrum disorder (ASD); however, randomised controlled trials (RCTs) are lacking. The present research aims to assess the feasibility of conducting an RCT evaluating the effectiveness of a social skills intervention using Kinesics and Synchronisation in Personal Assistant Robotics (Kaspar) with children with ASD. Methods and analysis Forty children will be recruited. Inclusion criteria are the following: aged 5–10 years, confirmed ASD diagnosis, IQ over 70, English-language comprehension, a carer who can complete questionnaires in English and no current participation in a private social communication intervention. Children will be randomised to receive an intervention with a therapist and Kaspar, or with the therapist only. They will receive two familiarisation sessions and six treatment sessions for 8 weeks. They will be assessed at baseline, and at 10 and 22 weeks after baseline. The primary outcome of this study is to evaluate whether the predetermined feasibility criteria for a full-scale trial are met. The potential primary outcome measures for a full-scale trial are the Social Communication Questionnaire and the Social Skills Improvement System. We will conduct a preliminary economic analysis. After the study has ended, a sample of 20 participants and their families will be invited to participate in semistructured interviews to explore the feasibility and acceptability of the study’s methods and intervention. Ethics and dissemination Parents/carers will provide informed consent, and children will give assent, where appropriate. Care will be taken to avoid pressure or coercion to participate. Aftercare is available from the recruiting NHS Trust, and a phased withdrawal protocol will be followed if children become excessively attached to the robot. The results of the study will be disseminated to academic audiences and non-academic stakeholders, for example, families of children with ASD, support groups, clinicians and charities. Trial registration number ISRCTN registry (ISRCTN14156001); Pre-results.

F7. SEX DIFFERENCES IN THE ASSOCIATION BETWEEN SELF-REPORTS OF CHILDHOOD ADVERSITIES AND SCHIZOTYPAL PERSONALITY TRAITS

Abstract Background While it has been repeatedly documented that people with schizophrenia report higher levels of adverse events in childhood (emotional, physical and sexual abuse), this has not been extensively examined in healthy individuals who score highly on schizotypal personality traits. The continuum hypothesis of psychosis and schizophrenia suggests it is important to assess the relationship in those who are healthy but who experience some psychotic-like symptoms. Of course, it is problematic to rely upon the veracity of events that anyone might recall from their childhood, but this is likely to be compounded by the presence of well-documented memory and executive problems, as well as symptoms such as delusional thinking, in some adults with psychosis. One advantage of examining healthy participants is that recall is not affected by the condition itself or memory- and executive-function problems. As there is evidence that the expression of psychotic disorders differ between males and females, the etiological mechanisms and pathways to the development and experience of psychotic symptoms may equally differ. Indeed, sex differences in the association between childhood trauma and psychotic symptoms have been noted. The aim of this present study was to investigate any links between childhood trauma and psychotic-like symptoms in healthy individuals. Based on previous research the expectation is that associations will be found between self-reports of childhood trauma and schizotypal personality traits. These associations would be expected to differ between males and females. Methods The sample consisted of 320 participants (221 females, 99 males) with a mean age of 28.24 (SD 12.76). Childhood traumatic events were assessed by three sub-scales (Physical Punishment; Emotional Abuse; and Sexual Events) of the Early Trauma Inventory Self Report-Short Form (ETISR-SF; Bremner et al., 2007). Schizotypal personality traits were assessed using the Five Factor Schizotypal Inventory (FFSI; Edmundson et al., 2011). This consists of nine subscales (Interpersonal Suspiciousness; Social Anhedonia; Social Isolation and Withdrawal; Physical Anhedonia; Social Anxiousness; Social Discomfort; Odd and Eccentric; Aberrant Ideas; and Aberrant Perceptions) which were constructed as schizotypic variants of respective facets of the five factor personality model. Results The relationship between childhood trauma and schizotypy was examined using Spearman’s bivariate correlation analyses. Males showed significant positive correlations (ranging from .28 to .39) between Emotional Abuse and seven out of nine schizotypal sub-scales. The other two childhood trauma scales were not associated with any schizotypal sub-scales in males. Females showed significant positive correlations (ranging from .19 to .34) between Physical Punishment and eight out of nine schizotypal sub-scales. Additionally, females showed significant positive correlations (ranging from .26 to .35) between Emotional Abuse and all schizotypal sub-scales. Sexual Events positively correlated with two schizotypal sub-scales (Aberrant Ideas and Aberrant Perceptions) in females. Discussion From the results of this study it appears that emotional abuse was linked to the expression of psychotic-like symptoms in both sexes across a wide array of symptomatology. Therefore, any effect of emotional abuse should not be considered sex or symptom specific. By contrast, physical abuse appeared to be sex specific – affecting only females – but not symptom specific. Finally, sexual abuse appeared to have a specific link with disorganized thoughts and hallucination-like experiences in females.

Sex differences in the association between childhood adversities and schizotypal personality traits

Patients with psychosis report higher levels of adverse events in childhood. This relationship has not been extensively examined in healthy individuals who score highly on schizotypal personality traits. This study examined the association between different childhood traumas and psychosis-like traits in a general population sample, as well as differences in those links between men and women. Participants completed an online survey including measures of physical, emotional, and sexual abuse, and schizotypal personality traits. Results showed that the experience of emotional abuse was associated with a range of both positive and negative psychosis-like traits in both sexes. Sex differences emerged in the association between physical abuse and schizotypal personality traits. Although men reported more physical abuse in early life than women, this type of trauma was only associated with schizotypal traits in women and not in men. Additionally, women scored higher than men in sexual abuse; however, sexual abuse did not explicitly predict any schizotypal traits in the presence of the other two types of abuse. A simple linear or dose-response relationship between different types of trauma and psychosis-like traits was not supported. The importance of emotional abuse on schizotypy was highlighted in both sexes.

FACTORS INFLUENCING RECRUITMENT TO A UK RANDOMISED CONTROLLED TREATMENT TRIAL; THE ROLE OF PATIENT-PREFERENCE

Background Recruitment to target is a major challenge for randomised controlled treatment trials (RCTs) in psychiatry. Strong patient preference may hamper recruitment of protocol-eligible participants, thereby compromising statistical power and limiting the external validity and generalisability of study findings to target populations. The Optimal Treatment in OCD (OTO) is a UK non-placebo feasibility trial of CBT and sertraline (two standard treatments) and their combination, randomly allocated, designed to ascertain the optimal community-based treatment for OCD. OTO aims to provide information about relevant design issues, to optimise feasibility of the definitive trial. Aim To identify the factors influencing recruitment to the RCT. Methods The study was approved by the relevant NHS ethics committee. Adult OCD outpatients were recruited at three UK centres. They were identified from routine referrals, primary healthcare services, community mental health clinics, other clinics attracting high levels of OCD, trust databases of patients likely to be suffering with OCD and the use of promotional materials. Patients subjected to screening were given detailed information about the treatments. Flexible and responsive clinical support was offered for the trial duration. Those eligible candidates declining to consent to participate were asked for their reasons. We report the data from one centre. Results 86 individuals satisfied the trial eligibility criteria. Of these, only 24 (27.9%) agreed to participate in the study. Of the remaining 62 (72.1%) who refused to participate, 35 (56.5%) gave treatment-related reasons. The commonest treatment-related reason was refusal to take pharmacological treatment (N=17; 27.4% all refusers). 12 of these individuals refused medication in general, while 5 refused sertraline. Another 8 (12.9% all refusers), showed a clear preference for CBT. However, 10 (16.1% all refusers) declined because they were reluctant to discontinue ongoing medication prior to randomisation. Conclusions and Future Directions Treatment–related preferences constituted a major obstacle to the recruitment of UK OCD patients to a non-placebo RCT of standard pharmacotherapy and CBT, to the extent that only 27.9% eligible patients were actually randomised. Over 40% (40.3%) of those refusing to enter the study gave as the reason a reluctance to receive pharmacotherapy or a bias toward receiving CBT, while 16.1% refused washout. These choices occurred despite patients being informed of the current evidence suggesting equivalent clinical effectiveness for CBT and SSRI and being offered clinical support during the washout phase. Trial designs that account for patient preference e.g. ‘patient-preference RCT’ ‘or ‘comprehensive cohort’ designs (Brewin & Bradley, 1989) or omit washout may increase recruitment but have methodological limitations. RCTs should gather information on the effect of pre-randomisation preference on outcomes to inform better trial design (Torgerson, Klaber-Moffett & Russell, 1996). New approaches to overcome public prejudice toward psychopharmacology are also needed to support robust trial design in psychiatry.

OPTIMAL TREATMENT FOR OCD (OTO): A RANDOMISED CONTROLLED FEASIBILITY TRIAL COMPARING THE CLINICAL AND COST EFFECTIVENESS OF COGNITIVE BEHAVIOURAL THERAPY (CBT) AND SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRI) AND THEIR COMBINATION IN THE MANAGEMENT OF OBSESSIVE COMPULSIVE DISORDER

Background Established treatments for Obsessive Compulsive Disorder (OCD) include cognitive behavioural psychotherapy (CBT) and selective serotonin reuptake inhibitor (SSRI) medication. Combining CBT with SSRI may be superior to either monotherapy, but few studies have addressed this question in adults with OCD. Aim Optimal Treatment for OCD (OTO) is a feasibility study aimed to inform the design of a definitive trial of sufficient size to provide accurate information about the cost-effectiveness of each treatment approach. Design The study took place at three centres. Participants were community-based service-users aged 18-65y with OCD of at least moderate severity and a duration of symptoms >1 year. Out of 258 potential participants, 66 were screened and 49 entered the study and were randomly assigned to CBT (n=16), SSRI (n=18) or SSRI+ CBT (combination; n=15). Sertraline (50-200mg/d) was given as the SSRI for 52 weeks. Sixteen hours’ manualised individual CBT was delivered over 8 weeks with 4 additional hour-long follow-up sessions. Regular assessments were made by researchers ‘blinded’ to the treatment allocation for 52 weeks. A preliminary health economic evaluation was made using standardised measures of resource use and the EQ-5D-3L. Results At baseline the mean total Y-BOCS across all groups was 26.7 (SD =5.9). 29 patients completed 16 weeks of treatment, with adequate adherence to allocated treatments. At week 16, for participants remaining in the study, there was evidence of improvement (all patients’ mean total YBOCS =18.4 (8.9)). Combination treatment (n=13) was associated with the largest improvement, sertraline (n=7) the next largest and CBT (n=9) the smallest. Symptomatic improvement continued to 52 weeks, but participant discontinuation made it not possible to perform further reliable between-treatment comparisons. Compared to sertraline monotherapy, the mean costs were higher for the CBT monotherapy, and the combined group. The mean QALY score was greater for sertraline monotherapy when compared with CBT monotherapy and when compared with the combined group. Eleven of a total of 288 adverse events were considered to be severe. Three serious adverse events were reported. One was a suicide attempt, which was considered to be possibly related to treatment, and 2 were hospital admissions for termination of pregnancy which were not related. Conclusions SSRI with CBT may offer the most clinically effective treatment (especially over CBT), and SSRI monotherapy the most cost-effective treatment. Implications If the superiority of SSRI in OCD were to be replicated in a future study, there would be potential for large cost savings to health services. However the small size of the current study means that the conclusions drawn have to be treated with caution, and further research would thereby be of value. Our study confirms that a definitive study can be conducted.