John Francis William Deakin

The University of Manchester · Institute of Health Sciences

Background: Clozapine-induced hypersalivation (CIH) is a common side effect of clozapine treatment and is disliked by clozapine patients, potentially threatening adherence to clozapine treatment. We proposed a trial of alternative medications, hyoscine and glycopyrrolate, for the treatment of CIH and the primary objective of the feasibility study...

Despite growing interest in the beneficial effects of positive touch experiences throughout our lives, and individual differences in how these experiences are perceived, there is not yet available a contemporary self-report measure of touch experiences and attitudes, for which the factor structure has been validated. This article describes four stu...

Cognitive dysfunction is common in depression during both acute episodes and remission. Vortioxetine is a novel multimodal antidepressant that has improved cognitive function including executive function in depressed patients in randomised placebo-controlled clinical trials. However, it is unclear whether vortioxetine is able to target directly the...

The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have...

Evidence suggests that disturbances in neurobiological mechanisms of reward and inhibitory control maintain addiction and provoke relapse during abstinence. Abnormalities within the dopamine system may contribute to these disturbances and pharmacologically targeting the D3 dopamine receptor (DRD3) is therefore of significant clinical interest. We u...

Naltrexone is an opioid receptor antagonist used in the management of alcohol dependence. Although the endogenous opioid system has been implicated in emotion regulation, the effects of mu-opioid receptor blockade on brain systems underlying negative emotional processing are not clear in addiction. Individuals meeting criteria for alcohol dependenc...

Appendix S1: Advantage of the Bayesian system‐based analysis and potential biological explanation of the results. Table S1: Haplotype frequencies in the CNR1 gene (using the nominally significant SNPs in haploblock 1: rs806366, rs4707436, rs1049353, rs806369), and statistical results of interaction effects between recent negative life events (RLE)...

Supplementary Information for Workman et al., 2017, Psychological Medicine.

Background A high proportion of patients with remitted major depressive disorder (MDD) will experience recurring episodes, whilst some develop resilience and remain in recovery. The neural basis of resilience to recurrence is elusive. Abnormal resting-state connectivity of the subgenual cingulate cortex (sgACC) was previously found in cross-section...

Current understanding and treatment of depression is limited to the monoaminergic theory with little knowledge of the involvement of other cellular processes. Genome-wide association studies, however, implicate several novel single-nucleotide polymorphisms with weak but replicable effects and unclarified mechanisms. We investigated the effect of rs...

Objectives We aimed to set up a robust multi-centre clinical fMRI and neuropsychological platform to investigate the neuropharmacology of brain processes relevant to addiction ? reward, impulsivity and emotional reactivity. Here we provide an overview of the fMRI battery, carried out across three centres, characterizing neuronal response to the tas...

Background: Working memory (WM) deficits are a core feature of schizophrenia. Electrophysiological studies suggest that impaired early visual processing may contribute to impaired WM in the visual domain. Abnormal N-methyl-D-aspartate (NMDA) receptor function has been implicated both in WM and in early visual processing deficits in schizophrenia....

One of the main effects of the endocannabinoid system in the brain is stress adaptation with presynaptic endocannabinoid receptor 1 (CB1 receptors) playing a major role. In the present study, we investigated whether the effect of the CB1 receptor coding CNR1 gene on migraine and its symptoms is conditional on life stress. In a cross-sectional Europ...

Supplementary Information for Zahn et al., 2015, European Psychiatry.

Objective: The relationship between migraine and psychological distress has been consistently reported in cross-sectional and longitudinal studies. We hypothesized that a stable tendency to perseverative thoughts such as rumination would mediate the relationship between migraine and psychological distress. Design and Main Outcomes Measures: Self-r...

Supplementary Information for Workman et al., 2016, Neuropsychopharmacology.

C-tactile afferents (CTs) are slowly conducting nerve fibres, present only in hairy skin. They are optimally activated by slow, gentle stroking touch, such as those experienced during a caress. CT-stimulation activates affective processing brain regions, alluding to their role in affective touch perception. We tested a theory that CT-activating tou...

The development of drugs to improve cognition in patients with schizophrenia is a major unmet clinical need. A number of promising compounds failed in recent clinical trials, a pattern linked to poor translation between preclinical and clinical stages of drug development. Seeking proof of efficacy in early Phase 1 studies in surrogate patient popul...

Several studies indicate that 5-HTTLPR mediates the effect of childhood adversity in the development of depression, while results are contradictory for recent negative life events. For childhood adversity the interaction with genotype is strongest for sexual abuse, but not for other types of childhood maltreatment; however, possible interactions wi...

Rationale Working memory impairments in schizophrenia have been attributed to dysfunction of the dorsolateral prefrontal cortex (DLPFC) which in turn may be due to low DLPFC dopamine innervation. Conventional antipsychotic drugs block DLPFC D2 receptors, and this may lead to further dysfunction and working memory impairments. Aripiprazole is a D2 r...

Intravenous infusion of lanicemine (formerly AZD6765), a low trapping non-selective N-methyl-. D-aspartate (NMDA) receptor antagonist, induces antidepressant effects with a similar time course to ketamine. We investigated whether a single dose lanicemine infusion would reproduce the previously reported decrease in subgenual anterior cingulate corte...

Alterations in the folate pathway have been related to both major depression and cognitive inflexibility; however, they have not been investigated in the genetic background of ruminative response style, which is a form of perseverative cognition and a risk factor for depression. In the present study, we explored the association of rumination (measu...

Importance Patients with remitted major depressive disorder (MDD) were previously found to display abnormal functional magnetic resonance imaging connectivity (fMRI) between the right superior anterior temporal lobe (RSATL) and the subgenual cingulate cortex and adjacent septal region (SCSR) when experiencing self-blaming emotions relative to emot...

Cognitive models predict that vulnerability to major depressive disorder (MDD) is due to a bias to blame oneself for failure in a global way resulting in excessive self-blaming emotions, decreased self-worth, hopelessness and depressed mood. Clinical studies comparing the consistency and coherence of these symptoms in order to probe the predictions...

Standard functional magnetic resonance imaging (fMRI) analyses cannot assess the potential of a neuroimaging signature as a biomarker to predict individual vulnerability to major depression (MD). Here, we use machine learning for the first time to address this question. Using a recently identified neural signature of guilt-selective functional disc...

Objectives Immune mechanisms have been implicated in the pathogenesis of schizophrenia. This has lead to clinical trials of re-purposing drugs with off-target anti-inflammatory actions. They include the antibiotic minocycline and simvastatin (HMP-Co reductase inhibitor), which decrease microglial activation, and ondansetron a 5-HT3-receptor antago...

Although 5-HTTLPR has been shown to influence the risk of life stress-induced depression in the majority of studies, others have produced contradictory results, possibly due to weak effects and/or sample heterogeneity. In the present study we investigated how age, type and intensity of life-stressors modulate the effect of 5-HTTLPR on depression an...

One influential view is that vulnerability to major depressive disorder (MDD) is associated with a proneness to experience negative emotions in general. In contrast, blame attribution theories emphasise the importance of blaming oneself rather than others for negative events. Our previous exploratory study provided support for the attributional hyp...

Objectives. Immune mechanisms have been implicated in the pathogenesis of schizophrenia. This has lead to clinical trials of re-purposing drugs with off-target anti-inflammatory actions. They include the antibiotic minocycline and simvastatin (HMP-Co reductase inhibitor), which decrease microglial activation, and ondansetron a 5-HT3-receptor antago...

Background: Prosocial emotions related to self-blame are important in guiding human altruistic decisions. These emotions are elevated in major depressive disorder (MDD), such that MDD has been associated with guilt-driven pathological hyper-altruism. However, the impact of such emotional impairments in MDD on different types of social decision-mak...

There is increasing evidence that genetic factors play a role in differential susceptibility to depression in response to severe or chronic adversity. Studies in animals suggest that nitric oxide (NO) signalling plays a key role in depression-like behavioural responses to stress. This study investigated whether genetic variation in the brain-expres...

Background Major depressive disorder (MDD) is associated with functional abnormalities in fronto-meso-limbic networks contributing to decision-making, affective and reward processing impairments. Such functional disturbances may underlie a tendency for enhanced altruism driven by empathy-based guilt observed in some patients. However, despite the r...

Significance Early and recent environmental stressors, such as maltreatment in childhood, or stressful life events in adulthood, are important risk factors for depression. Nevertheless, not all people who suffer from these will be depressed. The resilience or vulnerability to these stressors, and thus depression, is likely to reside in our genes. I...

Proneness to self-blaming moral emotions such as shame and guilt is increased in major depressive disorder (MDD), and may play an important role in vulnerability even after symptoms have subsided. Social psychologists have argued that shame-proneness is relevant for depression vulnerability and is distinct from guilt. Shame depends on the imagined...

The non-competitive N-methyl-D-aspartate receptor antagonist ketamine leads to transient psychosis-like symptoms and impairments in oculomotor performance in healthy volunteers. This study examined whether the adverse effects of ketamine on oculomotor performance can be reversed by the atypical antipsychotic risperidone. In this randomized double-b...

Major depressive disorder (MDD) is associated with abnormalities in financial reward processing. Previous research suggests that patients with MDD show reduced sensitivity to frequency of financial rewards. However, there is a lack of conclusive evidence from studies investigating the evaluation of financial rewards over time, an important aspect o...

The importance of differentiating between social concepts when appraising actions (e.g., understanding behavior as critical vs. fault-finding) and its contribution to vulnerability to major depressive disorder (MDD) is unknown. We predicted poor integration of differentiated conceptual knowledge when people with MDD appraise their social actions, c...

Rationale The increasing demand to develop more efficient compounds to treat cognitive impairments in schizophrenia has led to the development of experimental model systems. One such model system combines the study of surrogate populations expressing high levels of schizotypy with oculomotor biomarkers. Objectives We aimed (1) to replicate oculomot...

The cognitive impairment associated with schizophrenia is a major target for drug development but none of the drugs designed to address this problem has shown consistent efficacy. The most common causes for failure in the registration trials could be preempted by testing novel agents in milder forms of the disorder, such as schizotypy and assessing...

The catechol-o-methyltransferase (COMT) gene has been extensively investigated in depression with somewhat contradictory results but the role of impulsivity, as a possible intermediate phenotype in this disorder, has not been considered yet. In our study, four tagging SNPs in the COMT gene (rs933271, rs740603, rs4680, rs4646316) were genotyped in t...

Reduced hippocampal volume has been reported in depression and may be involved in the aetiology of depressive symptoms and vulnerability to depressive relapse. Neuroplasticity following antidepressant drug treatment in the hippocampus has been demonstrated in animal models but adaptive changes after such treatment have not been shown in humans. In...

AIMS: Pharmacological-challenge magnetic resonance imaging (phMRI) is powerful new tool enabling researchers to map the central effects of neuroactive drugs in vivo. To employ this technique pre-clinically, head movements and the stress of restraint are usually reduced by maintaining animals under general anaesthesia. However, interactions between...

Background: One widespread view holds that vulnerability to major depressive disorder (MDD) is linked to overall increases in negative emotionality. In contrast, cognitive attribution theories emphasize the importance of blaming oneself rather than others for negative events. Thus far, the contrasting predictions of these models have not been dire...

Increased amygdala response to negative emotions seen in functional MRI (fMRI) has been proposed as a biomarker for negative emotion processing bias underlying depressive symptoms and vulnerability to depressive relapse that are normalized by antidepressant drug treatment. The purpose of this study was to determine whether abnormal amygdala respons...