Papers by Tarun Limbachya
Threat minus safe reaction time and accuracy vs trait anxiety scores in Study 2 (r and p values r... more Threat minus safe reaction time and accuracy vs trait anxiety scores in Study 2 (r and p values reported in legend).
SSRN Electronic Journal, 2018
Background: The legal framework for governing involuntary treatment in England and Wales is set o... more Background: The legal framework for governing involuntary treatment in England and Wales is set out in the Mental Health Act (1983) which gives health professionals power, in certain circumstances, to detain, assess and treat people considered to have a ‘mental disorder’, in the interest of their own health and safety or for public safety. It is accompanied by a Code of Practice and other statutory safeguards that aim to preserve service users’ human rights. While some people find psychiatric inpatient treatment helpful and necessary, there are growing concerns that services are failing to protect service users’ human rights. Aims: To deepen an understanding of how service users’ human rights are respected on psychiatric inpatient wards. Key research questions were: what are voluntary and involuntary inpatient service users’ experiences of staff respecting their human rights; what are voluntary and involuntary inpatient service users’ experiences of being informed about their rights...
Studying the effects of experimentally induced anxiety in healthy volunteers may increase our und... more Studying the effects of experimentally induced anxiety in healthy volunteers may increase our understanding of the mechanisms underpinning anxiety disorders. Experimentally induced stress (via threat of unpredictable shock) improves accuracy at withholding a response on the sustained attention to response task (SART), and in separate studies improves accuracy to classify fearful faces, creating an affective bias. Integrating these findings, participants at two public science engagement events (<i>n</i> = 46, <i>n</i> = 55) were recruited to explore the effects of experimentally induced stress on an affective version of the SART. We hypothesized that we would see an improved accuracy at withholding a response to affectively congruent stimuli (i.e. increased accuracy at withholding a response to fearful 'no-go' distractors) under threat of shock. Induced anxiety slowed reaction time, and at the second event quicker responses were made to fearful stimuli. However, we did not observe improved inhibition overall during induced anxiety, and there was no evidence to suggest an interaction between induced anxiety and stimulus valence on response accuracy. Indeed Bayesian analysis provided decisive evidence against this hypothesis. We suggest that the presence of emotional stimuli might make the safe condition more anxiogenic, reducing the differential between conditions and knocking out any threat-potentiated improvement.
Biological Psychiatry, 2018
Background: Cognitive dysfunction is a core symptom dimension in bipolar disorder, and a strong p... more Background: Cognitive dysfunction is a core symptom dimension in bipolar disorder, and a strong predictor of functional outcomes. Cognitive remediation (CR) produces significant, durable effects on cognition in patients with schizophrenia (SZ) (Wykes et al., 2011) and bipolar disorder (BD) (Lewandowski et al., 2017). However, not all patients respond robustly to CR. "Cortical reserve" may predict response to CR in patients with SZ (Keshavan et al., 2011); this association has not been tested in BD. We examined the effects of baseline cortical reserve on CR treatment response in patients with BD. Methods: Patients with BD were randomized to a 24-week CR or a dose matched active control. Patients who received an MRI scan at baseline (n¼34) were included in this report. We examined total intracranial volume (eICV) and total brain volume (TBV) as measures of cortical reserve. Cognitive and clinical assessments were administered at baseline and posttreatment. Responders were defined using a 90% CI of composite change method (Gasto, 2006). Results: Groups differed on proportion of responders (CR ¼ 75%; Control ¼ 33%). Comparison of baseline structural measures showed significantly reduced eICV and TBV in non-responders (F(1, 20)¼ 7.84, p¼ 0.01 and F(1, 20)¼ 7.62, p¼0.01, respectively. After controlling for sex, age, and baseline cognition these findings remained unchanged. Conclusions: Given the lengthy and intensive nature of CR programs and the unmet need for cognitive treatments in psychosis, identifying predictors of treatment response will allow selection of candidates likely to benefit from treatment and individualized tailoring of treatments to best meet patients' needs.
Trials, 2019
Background: Poor recruitment is the most common reason for premature discontinuation of randomise... more Background: Poor recruitment is the most common reason for premature discontinuation of randomised controlled trials (RCTs). An RCT of medication versus psychological therapy for generalised anxiety disorder (GAD) was discontinued prematurely by the UK National Institute of Health Research funders because of recruitment failure. In order to inform future research studies, this article explores the reasons for poor recruitment and aspects which could have been improved. Methods: The trial recruited participants via psychological well-being practitioners (PWPs) employed within local Improving Assess to Psychological Therapies (IAPT) services at four sites in England. For this study, we initially examined the recruitment data to identify reasons why potential participants were reluctant to participate in the trial. We then investigated reasons the PWPs did not identify more potential participants. Finally, we performed retrospective analyses of a computerised clinical records system used by the IAPT services in this study. These analyses aimed to establish the number of potential participants who had not been approached about the trial as well as whether there were additional factors affecting the numbers of people who might be eligible to take part. Data were obtained for all patients assessed during the period from the date on which recruitment commenced until the closure of the trial. Results: Three quarters of those patients identified as possibly suitable for the trial declined to take part; the great majority did so because they did not want to be randomly assigned to receive medication. Our retrospective database analyses showed that only around 12% of potentially eligible patients for the trial were identified by the PWPs at the pilot sites. The results also indicated that only 5% of those noted at entry to the IAPT services to have a score of at least 10 on the GAD-7 questionnaire (a self-completed questionnaire with high sensitivity and specificity for GAD) would have been eligible for the trial. Conclusions: Our findings suggest that poor recruitment to RCTs can be significantly affected by participants' treatment preferences and by factors influencing the recruiting clinicians. It may also be important not to include too many restrictions on inclusion criteria for pragmatic trials aiming for generalisable results.
Neuropsychopharmacology, 2019
Standard depression treatments, including antidepressant medication and cognitive behavioural the... more Standard depression treatments, including antidepressant medication and cognitive behavioural therapy (CBT), are ineffective for many patients. Prefrontal transcranial direct current stimulation (tDCS) has been proposed as an alternative treatment, but has shown inconsistent efficacy for depression, and its mechanisms are poorly understood. We recruited unmedicated patients with major depressive disorder (N = 71 approached; N = 39 randomised) for a mechanistic, double-blind, randomized controlled trial consisting of eight weekly sessions of prefrontal tDCS administered to the left prefrontal cortex prior to CBT. We probed (1) whether tDCS improved the efficacy of CBT relative to sham stimulation; and (2) whether neural measures predicted clinical response. We found a modest and non-significant effect of tDCS on clinical outcome over and above CBT (active: 50%; sham: 31.6%; odds ratio: 2.16, 95% CI = 0.59-7.99), but a strong relationship, predicted a priori, between baseline activation during a working memory task in the stimulated prefrontal region and symptom improvement. Repeating our analyses of symptom outcome splitting the sample according to this biomarker revealed that tDCS was significantly superior to sham in individuals with high left prefrontal cortex activation at baseline; we also show 86% accuracy in predicting clinical response using this measure. Exploratory analyses revealed several other regions where activation at baseline was associated with subsequent response to CBT, irrespective of tDCS. This mechanistic trial revealed variable, but predictable, clinical effects of prefrontal tDCS combined with CBT for depression. We have discovered a potential explanation for this variability: individual differences in baseline activation of the region stimulated. Such a biomarker could potentially be used to pre-select patients for trials and, eventually, in the clinic.
Royal Society Open Science, 2017
Studying the effects of experimentally induced anxiety in healthy volunteers may increase our und... more Studying the effects of experimentally induced anxiety in healthy volunteers may increase our understanding of the mechanisms underpinning anxiety disorders. Experimentally induced stress (via threat of unpredictable shock) improves accuracy at withholding a response on the sustained attention to response task (SART), and in separate studies improves accuracy to classify fearful faces, creating an affective bias. Integrating these findings, participants at two public science engagement events ( n = 46, n = 55) were recruited to explore the effects of experimentally induced stress on an affective version of the SART. We hypothesized that we would see an improved accuracy at withholding a response to affectively congruent stimuli (i.e. increased accuracy at withholding a response to fearful ‘no-go’ distractors) under threat of shock. Induced anxiety slowed reaction time, and at the second event quicker responses were made to fearful stimuli. However, we did not observe improved inhi...
Biological Psychiatry, 2017
Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) has ... more Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) has recently shown efficacy as a treatment for depression. We combined tDCS with psychological therapy to determine whether tDCS of the DLPFC could enhance therapeutic outcome in depression.
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Papers by Tarun Limbachya