The effects of pramipexole on motivational vigour during a saccade task: a placebo-controlled study in healthy adults.

Motivation allows us to energise actions when we expect reward and is reduced in depression. This effect, termed motivational vigour, has been proposed to rely on central dopamine, with dopaminergic agents showing promise in the treatment of depression. This suggests that dopaminergic agents might act to reduce depression by increasing the effects of reward or by helping energise actions. The aim of the current study was to investigate whether the dopamine agonist pramipexole enhanced motivational vigour during a rewarded saccade task. In addition, we asked whether the effects of pramipexole on vigour differ between reward contingent on performance and guaranteed reward. Healthy adult participants were randomised to receive either pramipexole (n = 19) or placebo (controls n = 18) for 18 days. The vigour of saccades was measured twice, once before the administration of study medication (Time 1) and after taking it for 12-15 days (Time 2). To separate motivation by contingency vs. reward, saccadic vigour was separately measured when (1) rewards were contingent on performance (2) delivered randomly with matched frequency, (3) when reward was guaranteed, (4) when reward was not present at all. Motivation increased response vigour, as expected. Relative to placebo, pramipexole also increased response vigour. However, there was no interaction, meaning that the effects of reward were not modulated by drug, and there was no differential drug effect on contingent vs. guaranteed rewards. The effect of pramipexole on vigour could not be explained by a speed/accuracy trade-off, nor by autonomic arousal as indexed by pupillary dilation. Chronic D2 stimulation increases general vigour, energising movements in healthy adults irrespective of extrinsic reward.

Personal reformulation during the clinical associate psychologist apprenticeship: Exploratory mixed methods evaluation.

OBJECTIVES: Clinical associate psychologists (CAPs) train under the auspices of the apprenticeship programme and are a new addition to the psychological workforce. This project sought to evaluate whether a "personal reformulation" (PR) was helpful in terms of personal and professional development during the apprenticeship. METHODS: A mixed methods evaluation containing a longitudinal quantitative element and a "Big Q" qualitative element with a single cohort of N = 18 CAPs. A PR consists of a 2-hr one-to-one session and a follow-up session with a cognitive analytic psychotherapist. During a PR, a sequential diagrammatic reformulation is produced to aid recognition and revision of potentially problematic relationship patterns at work. Two outcome measures concerning reflective capacity and professional quality of life were completed at the start of the apprenticeship, pre-PR and at 3-month PR follow-up. The semi-structured interviews (n = 11) conducted at the follow-up were analysed using reflexive thematic analysis. RESULTS: Quantitative changes were limited to significant increases to general confidence and 8/12 apprentices had a reliable increase in confidence in communication. Qualitatively, five overarching themes were found: (1) gaining insight, (2) wellbeing, (3) nature of the space, (4) being an apprentice, and (5) moving forward. CONCLUSIONS: PRs were generally found to be emotionally challenging, but relatively large amounts of insight are possible from a very brief intervention that can contribute to personal and professional development during clinical training. More controlled research needs to be conducted and wider applications and evaluations of PRs in different professions would be welcome.

Autism and autistic traits in those who died by suicide in England.

BACKGROUND: Autism and autistic traits are risk factors for suicidal behaviour. AIMS: To explore the prevalence of autism (diagnosed and undiagnosed) in those who died by suicide, and identify risk factors for suicide in this group. METHOD: Stage 1: 372 coroners' inquest records, covering the period 1 January 2014 to 31 December 2017 from two regions of England, were analysed for evidence that the person who died had diagnosed autism or undiagnosed possible autism (elevated autistic traits), and identified risk markers. Stage 2: 29 follow-up interviews with the next of kin of those who died gathered further evidence of autism and autistic traits using validated autism screening and diagnostic tools. RESULTS: Stage 1: evidence of autism (10.8%) was significantly higher in those who died by suicide than the 1.1% prevalence expected in the UK general alive population (odds ratio (OR) = 11.08, 95% CI 3.92-31.31). Stage 2: 5 (17.2%) of the follow-up sample had evidence of autism identified from the coroners' records in stage 1. We identified evidence of undiagnosed possible autism in an additional 7 (24.1%) individuals, giving a total of 12 (41.4%); significantly higher than expected in the general alive population (1.1%) (OR = 19.76, 95% CI 2.36-165.84). Characteristics of those who died were largely similar regardless of evidence of autism, with groups experiencing a comparably high number of multiple risk markers before they died. CONCLUSIONS: Elevated autistic traits are significantly over-represented in those who die by suicide.

PAX-D: study protocol for a randomised placebo-controlled trial evaluating the efficacy and mechanism of pramipexole as add-on treatment for people with treatment resistant depression.

INTRODUCTION: Clinical depression is usually treated in primary care with psychological therapies and antidepressant medication. However, when patients do not respond to at least two or more antidepressants within a depressive episode, they are considered to have treatment resistant depression (TRD). Previous small randomised controlled trials suggested that pramipexole, a dopamine D2/3 receptor agonist, may be effective for treating patients with unipolar and bipolar depression as it is known to influence motivational drive and reward processing. PAX-D will compare the effects of pramipexole vs placebo when added to current antidepressant medication for people with TRD. Additionally, PAX-D will investigate the mechanistic effect of pramipexole on reward sensitivity using a probabilistic decision-making task. METHODS AND ANALYSIS: PAX-D will assess effectiveness in the short- term (during the first 12 weeks) and in the longer-term (48 weeks) in patients with TRD from the UK. The primary outcome will be change in self-reported depressive symptoms from baseline to week 12 post-randomisation measured using the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). Performance on the decision-making task will be measured at week 0, week 2 and week 12. Secondary outcomes include anhedonia, anxiety and health economic measures including quality of life, capability, well-being and costs. PAX-D will also assess the adverse effects of pramipexole including impulse control difficulties. DISCUSSION: Pramipexole is a promising augmentation agent for TRD and may be a useful addition to existing treatment regimes. PAX-D will assess its effectiveness and test for a potential mechanism of action in patients with TRD. TRIAL REGISTRATION NUMBER: ISRCTN84666271.

An evaluation of the mental health impact of SARS-CoV-2 on patients, general public and healthcare professionals: A systematic review and meta-analysis.

BACKGROUND: The global impact of COVID-19 pandemic continues to affect the lives of billions of people with recurrent waves. Healthcare systems are struggling to manage pre-existing patient care and recurring covid-19 demands. As a result, we evaluated the mental health impact using systematic review and meta-analysis. METHODS: A comprehensive search was undertaken from April 2020 to 22nd January 2021 using multiple electronic databases. A systematic review protocol was developed and published on PROSPERO registration; CRD42020181481. A random-effects model was used to compute pooled estimates of anxiety, depression, PTSD, insomnia and suicidal thoughts. FINDINGS: Our search yielded 11,295 studies and of those 287 met the inclusion criteria. The meta-analysis of 206 studies revealed minimal differences in prevalence of anxiety, depression, and PTSD among HCPs compared with the public during the pandemic but higher prevalence of suicidal thoughts/ideation or self-harm (11% vs 5.8%) and lower prevalence of wellbeing (28.2% vs 52.6%) among the public compared to HCPs. INTERPRETATION: The pandemic has led to a high mental health burden especially amongst HCPs and higher suicidal ideation and lower wellbeing in general public which warrants further investigation and management globally. These findings highlight an emerging critical public health issue that requires urgent solutions.

Experience of mental health diagnosis and perceived misdiagnosis in autistic, possibly autistic and non-autistic adults.

Previous research shows that autistic people have high levels of co-occurring mental health conditions. Yet, a number of case reports have revealed that mental health conditions are often misdiagnosed in autistic individuals. A total of 420 adults who identified as autistic, possibly autistic or non-autistic completed an online survey consisting of questions regarding mental health diagnoses they received, whether they agreed with those diagnoses and if not why. Autistic and possibly autistic participants were more likely to report receiving mental health diagnoses compared to non-autistic participants, but were less likely to agree with those diagnoses. Thematic analysis revealed the participants' main reasons for disagreement were that (1) they felt their autism characteristics were being confused with mental health conditions by healthcare professionals and (2) they perceived their own mental health difficulties to be resultant of ASC. Participants attributed these to the clinical barriers they experienced, including healthcare professionals' lack of autism awareness and lack of communication, which in turn prevented them from receiving appropriate support. This study highlights the need for autism awareness training for healthcare professionals and the need to develop tools and interventions to accurately diagnose and effectively treat mental health conditions in autistic individuals.

Psychometric evaluation of the hope, agency and opportunity (HAO); a brief measure of mental health recovery.

BACKGROUND: The development of safe and effective mental health services is a priority. This requires valid measures of personal recovery, yet these tools are not embedded in routine clinical practice. Brief "patient reported measures" are most likely to be acceptable to service-users and clinicians. The 4-item "Hope, Agency and Opportunity" (HAO) was co-produced to assess recovery outcomes and experience of mental health services. AIM: To evaluate the psychometric properties of the HAO. METHOD: A clinical sample from secondary healthcare services and a non-clinical sample were assessed at baseline and two weeks, on measures of personal recovery. RESULTS: Factor analysis indicated goodness of fit for the HAO with both clinical and non-clinical samples. The measure demonstrated acceptable internal consistency, moderate to strong construct validity and substantial test-retest reliability over two weeks. CONCLUSIONS: The HAO demonstrates satisfactory psychometric properties. Co-production of the measure confers clinical credibility. The brevity of the tool means it can be incorporated into routine clinical practice to drive improvements in service quality.

Would Adults with Autism be less likely to Bury the Survivors? An Eye Movement Study of Anomalous Text Reading.

In a single eye movement experiment we investigated the effects of context on the time course of local and global anomaly processing during reading in adults with Autism Spectrum Disorder (ASD). In one condition short paragraph texts contained anomalous target words. Detection of the anomaly was only possible through evaluation of word meaning in relation to the global context of the whole paragraph (Passage Level Anomalies). In another condition the anomaly could be detected via computation of a local thematic violation within a single sentence embedded in the paragraph (Sentence Level Anomalies). For the sentence level anomalies the ASD group, in contrast with the typically developing (TD) group, showed early detection of the anomaly as indexed by regressive eye movements from the critical target word upon fixation. Conversely, for the passage level anomalies, and in contrast with the ASD group, the TD group showed early detection of the anomaly, with increased regressive eye movements once the critical word had been fixated. The reversal of the pattern of regression path data for the two groups, for the sentence and passage level anomalies, is discussed in relation to cognitive accounts of ASD.

Processing of Written Irony in Autism Spectrum Disorder: An Eye-Movement Study.

Previous research has suggested that individuals with Autism Spectrum Disorders (ASD) have difficulties understanding others communicative intent and with using contextual information to correctly interpret irony. We recorded the eye movements of typically developing (TD) adults ASD adults when they read statements that could either be interpreted as ironic or non-ironic depending on the context of the passage. Participants with ASD performed as well as TD controls in their comprehension accuracy for speaker's statements in both ironic and non-ironic conditions. Eye movement data showed that for both participant groups, total reading times were longer for the critical region containing the speaker's statement and a subsequent sentence restating the context in the ironic condition compared to the non-ironic condition. The results suggest that more effortful processing is required in both ASD and TD participants for ironic compared with literal non-ironic statements, and that individuals with ASD were able to use contextual information to infer a non-literal interpretation of ironic text. Individuals with ASD, however, spent more time overall than TD controls rereading the passages, to a similar degree across both ironic and non-ironic conditions, suggesting that they either take longer to construct a coherent discourse representation of the text, or that they take longer to make the decision that their representation of the text is reasonable based on their knowledge of the world.

Cognitive perspective-taking during scene perception in autism spectrum disorder: evidence from eye movements.

The present study examined how eye movements during scene viewing are modulated by adopting psychological perspectives in both adults with autism spectrum disorders (ASD) and typically developing adults. In the current study, participants viewed house scenes with either non-perspective-taking (look for valuable items/features of the house that need fixing) or perspective-taking instructions (imagine that you are a burglar/repairman) while their eye movements were recorded. The eye movement measures revealed that for the "look for the valuable items" and burglar perspective task, the ASD group showed typical relevance effects (the preference to look at schema-relevant compared with schema-irrelevant targets) in their eye movements. However, we found subtle processing differences between the groups that were related to initial orienting to and processing of schema-relevant items for the "look for the features that need fixing" and the repairman perspective-taking task. There was an absence of a relevance effect for the ASD group for the repairman perspective and its non-perspective-taking equivalent instruction showing that the identification of items relevant to those schemas was more difficult for the ASD group. The present findings suggest that resolving ambiguity may be a defining feature of complex information processing deficits in ASD.

Eye movements reveal no immediate "WOW" ("which one's weird") effect in autism spectrum disorder.

Autism spectrum disorder (ASD) and typically developed (TD) adult participants viewed pairs of scenes for a simple "spot the difference" (STD) and a complex "which one's weird" (WOW) task. There were no group differences in the STD task. In the WOW task, the ASD group took longer to respond manually and to begin fixating the target "weird" region. Additionally, as indexed by the first-fixation duration into the target region, the ASD group failed to "pick up" immediately on what was "weird". The findings are discussed with reference to the complex information processing theory of ASD (Minshew & Goldstein, 1998 ).

Eye Movement Sequences during Simple versus Complex Information Processing of Scenes in Autism Spectrum Disorder.

Minshew and Goldstein (1998) postulated that autism spectrum disorder (ASD) is a disorder of complex information processing. The current study was designed to investigate this hypothesis. Participants with and without ASD completed two scene perception tasks: a simple "spot the difference" task, where they had to say which one of a pair of pictures had a detail missing, and a complex "which one's weird" task, where they had to decide which one of a pair of pictures looks "weird". Participants with ASD did not differ from TD participants in their ability to accurately identify the target picture in both tasks. However, analysis of the eye movement sequences showed that participants with ASD viewed scenes differently from normal controls exclusively for the complex task. This difference in eye movement patterns, and the method used to examine different patterns, adds to the knowledge base regarding eye movements and ASD. Our results are in accordance with Minshew and Goldstein's theory that complex, but not simple, information processing is impaired in ASD.