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Many studies have reported correlations between measures of aggression and indices of serotonergic function, but most have studied patient or offender populations and relatively few have investigated plasma concentrations of the serotonin precursor tryptophan. This study investigates the relationship between plasma concentrations of tryptophan and trait hostility, depression and anxiety in male healthy volunteers. Sixty-seven healthy male volunteers gave blood samples and completed trait questionnaires. Plasma tryptophan was positively correlated with the Buss-Durkee Hostility Inventory Total score and Motor Aggression subscale, but not with the Attitudinal Hostility subscale or with trait anxiety or depression. In conclusion, there is evidence for an association between high concentrations of plasma tryptophan and aggressive behaviour in men, presumably mediated by some aspect of central serotonergic function, which seems unlikely to be explained by high trait anxiety or depression. [ABSTRACT FROM AUTHOR]

Abstract Background Smoking is the leading cause of preventable death worldwide and has been shown to increase the risk of multiple diseases including coronary artery disease (CAD). We sought to identify genes whose levels of expression in whole blood correlate with self-reported smoking status. Methods Microarrays were used to identify gene expression changes in whole blood which correlated with self-reported smoking status; a set of significant genes from the microarray analysis were validated by qRT-PCR in an independent set of subjects. Stepwise forward logistic regression was performed using the qRT-PCR data to create a predictive model whose performance was validated in an independent set of subjects and compared to cotinine, a nicotine metabolite. Results Microarray analysis of whole blood RNA from 209 PREDICT subjects (41 current smokers, 4 quit ≤ 2 months, 64 quit > 2 months, 100 never smoked; NCT00500617) identified 4214 genes significantly correlated with self-reported smoking status. qRT-PCR was performed on 1,071 PREDICT subjects across 256 microarray genes significantly correlated with smoking or CAD. A five gene (CLDND1, LRRN3, MUC1, GOPC, LEF1) predictive model, derived from the qRT-PCR data using stepwise forward logistic regression, had a cross-validated mean AUC of 0.93 (sensitivity=0.78; specificity=0.95), and was validated using 180 independent PREDICT subjects (AUC=0.82, CI 0.69-0.94; sensitivity=0.63; specificity=0.94). Plasma from the 180 validation subjects was used to assess levels of cotinine; a model using a threshold of 10 ng/ml cotinine resulted in an AUC of 0.89 (CI 0.81-0.97; sensitivity=0.81; specificity=0.97; kappa with expression model = 0.53). Conclusion We have constructed and validated a whole blood gene expression score for the evaluation of smoking status, demonstrating that clinical and environmental factors contributing to cardiovascular disease risk can be assessed by gene expression.

Abstract Background Alterations in gene expression in peripheral blood cells have been shown to be sensitive to the presence and extent of coronary artery disease (CAD). A non-invasive blood test that could reliably assess obstructive CAD likelihood would have diagnostic utility. Results Microarray analysis of RNA samples from a 195 patient Duke CATHGEN registry case:control cohort yielded 2,438 genes with significant CAD association (p < 0.05), and identified the clinical/demographic factors with the largest effects on gene expression as age, sex, and diabetic status. RT-PCR analysis of 88 CAD classifier genes confirmed that diabetic status was the largest clinical factor affecting CAD associated gene expression changes. A second microarray cohort analysis limited to non-diabetics from the multi-center PREDICT study (198 patients; 99 case: control pairs matched for age and sex) evaluated gene expression, clinical, and cell population predictors of CAD and yielded 5,935 CAD genes (p < 0.05) with an intersection of 655 genes with the CATHGEN results. Biological pathway (gene ontology and literature) and statistical analyses (hierarchical clustering and logistic regression) were used in combination to select 113 genes for RT-PCR analysis including CAD classifiers, cell-type specific markers, and normalization genes. RT-PCR analysis of these 113 genes in a PREDICT cohort of 640 non-diabetic subject samples was used for algorithm development. Gene expression correlations identified clusters of CAD classifier genes which were reduced to meta-genes using LASSO. The final classifier for assessment of obstructive CAD was derived by Ridge Regression and contained sex-specific age functions and 6 meta-gene terms, comprising 23 genes. This algorithm showed a cross-validated estimated AUC = 0.77 (95% CI 0.73-0.81) in ROC analysis. Conclusions We have developed a whole blood classifier based on gene expression, age and sex for the assessment of obstructive CAD in non-diabetic patients from a combination of microarray and RT-PCR data derived from studies of patients clinically indicated for invasive angiography. Clinical trial registration information PREDICT, Personalized Risk Evaluation and Diagnosis in the Coronary Tree, http://www.clinicaltrials.gov, NCT00500617

Background: England's primary care service for psychological therapy (Improving Access to Psychological Therapies [IAPT]) treats anxiety and depression, with a target recovery rate of 50%. Identifying the characteristics of patients who achieve recovery may assist in optimizing future treatment. This naturalistic cohort study investigated pre-therapy characteristics as predictors of recovery and improvement after IAPT therapy., Methods: In a cohort of patients attending an IAPT service in South London, we recruited 263 participants and conducted a baseline interview to gather extensive pre-therapy characteristics. Bayesian prediction models and variable selection were used to identify baseline variables prognostic of good clinical outcomes. Recovery (primary outcome) was defined using (IAPT) service-defined score thresholds for both depression (Patient Health Questionnaire [PHQ-9]) and anxiety (Generalized Anxiety Disorder [GAD-7]). Depression and anxiety outcomes were also evaluated as standalone (PHQ-9/GAD-7) scores after therapy. Prediction model performance metrics were estimated using cross-validation., Results: Predictor variables explained 26% (recovery), 37% (depression), and 31% (anxiety) of the variance in outcomes, respectively. Variables prognostic of recovery were lower pre-treatment depression severity and not meeting criteria for obsessive compulsive disorder. Post-therapy depression and anxiety severity scores were predicted by lower symptom severity and higher ratings of health-related quality of life (EuroQol questionnaire [EQ5D]) at baseline., Conclusion: Almost a third of the variance in clinical outcomes was explained by pre-treatment symptom severity scores. These constructs benefit from being rapidly accessible in healthcare services. If replicated in external samples, the early identification of patients who are less likely to recover may facilitate earlier triage to alternative interventions.

Background and Objectives: Disentangling brain aging from disease-related neurodegeneration in patients with multiple sclerosis (PwMS) is increasingly topical. The brain-age paradigm offers a window into this problem but may miss disease-specific effects. In this study, we investigated whether a disease-specific model might complement the brain-age gap (BAG) by capturing aspects unique to MS., Methods: In this retrospective study, we collected 3D T1-weighted brain MRI scans of PwMS to build (1) a cross-sectional multicentric cohort for age and disease duration (DD) modeling and (2) a longitudinal single-center cohort of patients with early MS as a clinical use case. We trained and evaluated a 3D DenseNet architecture to predict DD from minimally preprocessed images while age predictions were obtained with the DeepBrainNet model. The brain-predicted DD gap (the difference between predicted and actual duration) was proposed as a DD-adjusted global measure of MS-specific brain damage. Model predictions were scrutinized to assess the influence of lesions and brain volumes while the DD gap was biologically and clinically validated within a linear model framework assessing its relationship with BAG and physical disability measured with the Expanded Disability Status Scale (EDSS)., Results: We gathered MRI scans of 4,392 PwMS (69.7% female, age: 42.8 ± 10.6 years, DD: 11.4 ± 9.3 years) from 15 centers while the early MS cohort included 749 sessions from 252 patients (64.7% female, age: 34.5 ± 8.3 years, DD: 0.7 ± 1.2 years). Our model predicted DD better than chance (mean absolute error = 5.63 years, R 2 = 0.34) and was nearly orthogonal to the brain-age model (correlation between DD and BAGs: r = 0.06 [0.00-0.13], p = 0.07). Predictions were influenced by distributed variations in brain volume and, unlike brain-predicted age, were sensitive to MS lesions (difference between unfilled and filled scans: 0.55 years [0.51-0.59], p < 0.001). DD gap significantly explained EDSS changes ( B = 0.060 [0.038-0.082], p < 0.001), adding to BAG (Δ R 2 = 0.012, p < 0.001). Longitudinally, increasing DD gap was associated with greater annualized EDSS change ( r = 0.50 [0.39-0.60], p < 0.001), with an incremental contribution in explaining disability worsening compared with changes in BAG alone (Δ R 2 = 0.064, p < 0.001)., Discussion: The brain-predicted DD gap is sensitive to MS-related lesions and brain atrophy, adds to the brain-age paradigm in explaining physical disability both cross-sectionally and longitudinally, and may be used as an MS-specific biomarker of disease severity and progression.

Context: There are limited comparative studies between one anastomosis gastric bypass (OAGB) versus Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on body composition and musculoskeletal health., Objective: To compare changes in body composition, areal bone mineral density (aBMD), muscle strength, and physical function in the first year following OAGB, RYGB and SG within a UK-based healthcare setting., Methods: This is a secondary analysis of the BARI-LIFESTYLE trial in 119 adults (77% women; mean±SD, age: 45.9±10.3 years; BMI: 43.6±5.5 kg/m2) who underwent OAGB (n=19), RYGB (n=39) and SG (n=61). Body composition and aBMD by dual energy x-ray absorptiometry, handgrip strength, sit-to-stand (STS) test and 6-minute walking test (6MWT) were assessed pre-surgery and at 12 months post-surgery., Results: OAGB, RYGB, and SG exhibited similar reductions in body weight, body fat and lean mass (within-group comparisons, p<0.001). All surgery types were associated with reductions in aBMD at the total hip, femoral neck, and lumbar spine, which were more pronounced after OAGB and RYGB compared to SG (all p<0.03), though no difference between OAGB and RYGB. Despite reductions in absolute handgrip strength, relative handgrip strength, STS test and 6MWT improved post-surgery (all p<0.02), with no differences by surgical procedure., Conclusion: OAGB, RYGB, and SG resulted in comparable weight loss, changes in body composition and improvements in relative muscle strength and physical function. OAGB and RYGB, compared with SG, led to greater BMD reductions at clinically relevant sites. Future long-term studies should explore whether these BMD reductions translate into a greater fracture risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Visual snow syndrome (VSS) is associated with functional connectivity (FC) dysregulation of visual networks (VNs). We hypothesized that mindfulness-based cognitive therapy, customized for visual symptoms (MBCT-vision), can treat VSS and modulate dysfunctional VNs., Methods: An open-label feasibility study for an 8-week MBCT-vision treatment program was conducted. Primary (symptom severity; impact on daily life) and secondary (WHO-5; CORE-10) outcomes at Week 9 and Week 20 were compared with baseline. Secondary MRI outcomes in a subcohort compared resting-state functional and diffusion MRI between baseline and Week 20., Results: Twenty-one participants (14 male participants, median 30 years, range 22-56 years) recruited from January 2020 to October 2021. Two (9.5%) dropped out. Self-rated symptom severity (0-10) improved: baseline (median [interquartile range (IQR)] 7 [6-8]) vs Week 9 (5.5 [3-7], P = 0.015) and Week 20 (4 [3-6], P < 0.001), respectively. Self-rated impact of symptoms on daily life (0-10) improved: baseline (6 [5-8]) vs Week 9 (4 [2-5], P = 0.003) and Week 20 (2 [1-3], P < 0.001), respectively. WHO-5 Wellbeing (0-100) improved: baseline (median [IQR] 52 [36-56]) vs Week 9 (median 64 [47-80], P = 0.001) and Week 20 (68 [48-76], P < 0.001), respectively. CORE-10 Distress (0-40) improved: baseline (15 [12-20]) vs Week 9 (12.5 [11-16.5], P = 0.003) and Week 20 (11 [10-14], P = 0.003), respectively. Within-subject fMRI analysis found reductions between baseline and Week 20, within VN-related FC in the i) left lateral occipital cortex (size = 82 mL, familywise error [FWE]-corrected P value = 0.006) and ii) left cerebellar lobules VIIb/VIII (size = 65 mL, FWE-corrected P value = 0.02), and increases within VN-related FC in the precuneus/posterior cingulate cortex (size = 69 mL, cluster-level FWE-corrected P value = 0.02)., Conclusions: MBCT-vision was a feasible treatment for VSS, improved symptoms and modulated FC of VNs. This study also showed proof-of-concept for intensive mindfulness interventions in the treatment of neurological conditions., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the North American Neuro-Opthalmology Society.)

Background: There is substantial variation in patient symptoms following psychological therapy for depression and anxiety. However, reliance on endpoint outcomes ignores additional interindividual variation during therapy. Knowing a patient's likely symptom trajectories could guide clinical decisions. We aimed to identify latent classes of patients with similar symptom trajectories over the course of psychological therapy and explore associations between baseline variables and trajectory class., Methods: Patients received high-intensity psychological treatment for common mental health problems at National Health Service Improving Access to Psychological Therapies services in South London ( N = 16 258). To identify trajectories, we performed growth mixture modelling of depression and anxiety symptoms over 11 sessions. We then ran multinomial regressions to identify baseline variables associated with trajectory class membership., Results: Trajectories of depression and anxiety symptoms were highly similar and best modelled by four classes. Three classes started with moderate-severe symptoms and showed (1) no change, (2) gradual improvement, and (3) fast improvement. A final class (4) showed initially mild symptoms and minimal improvement. Within the moderate-severe baseline symptom classes, patients in the two showing improvement as opposed to no change tended not to be prescribed psychotropic medication or report a disability and were in employment. Patients showing fast improvement additionally reported lower baseline functional impairment on average., Conclusions: Multiple trajectory classes of depression and anxiety symptoms were associated with baseline characteristics. Identifying the most likely trajectory for a patient at the start of treatment could inform decisions about the suitability and continuation of therapy, ultimately improving patient outcomes.

Background: Olfactory impairments and anosmia from COVID-19 infection typically resolve within 2-4 weeks, although in some cases, symptoms persist longer. COVID-19-related anosmia is associated with olfactory bulb atrophy, however, the impact on cortical structures is relatively unknown, particularly in those with long-term symptoms., Methods: In this exploratory, observational study, we studied individuals who experienced COVID-19-related anosmia, with or without recovered sense of smell, and compared against individuals with no prior COVID-19 infection (confirmed by antibody testing, all vaccine naïve). MRI Imaging was carried out between the 15th July and 17th November 2020 at the Queen Square House Clinical Scanning Facility, UCL, United Kingdom. Using functional magnetic resonance imaging (fMRI) and structural imaging, we assessed differences in functional connectivity (FC) between olfactory regions, whole brain grey matter (GM) cerebral blood flow (CBF) and GM density., Findings: Individuals with anosmia showed increased FC between the left orbitofrontal cortex (OFC), visual association cortex and cerebellum and FC reductions between the right OFC and dorsal anterior cingulate cortex compared to those with no prior COVID-19 infection ( p  < 0.05, from whole brain statistical parametric map analysis). Individuals with anosmia also showed greater CBF in the left insula, hippocampus and ventral posterior cingulate when compared to those with resolved anosmia ( p  < 0.05, from whole brain statistical parametric map analysis)., Interpretation: This work describes, for the first time to our knowledge, functional differences within olfactory areas and regions involved in sensory processing and cognitive functioning. This work identifies key areas for further research and potential target sites for therapeutic strategies., Funding: This study was funded by the National Institute for Health and Care Research and supported by the Queen Square Scanner business case., Competing Interests: XG is a founder, shareholder and CEO of Gold Standard Phantoms, a company providing calibration and test objects for MRI. ED’A received funding from the H2020 Research and Innovation Action Grants Human Brain Project 785907 and 945539 (SGA2 and SGA3), and from the MNL Project “Local Neuronal Microcircuits” of the Centro Fermi (Rome, Italy). CGWK received funding from the H2020 Research and Innovation Action Grants Human Brain Project 945539 (SGA3), from the MS Society (#77), from Wings for Life (#169111), BRC (#BRC704/CAP/CGW), MRC (#MR/S026088/1), Ataxia UK. CGWK is a shareholder in Queen Square Analytics Ltd. RLB reports receiving consulting fees from Pfizer, Eli-Lilly, Gila Therapeutics Inc., and ViiV Healthcare and consulting fees, lecture fees from Novo Nordisk and participating in clinical trials for Novo Nordisk. RLB receives National Institute for Health and Care Research Professorship funding RP-2015-06-005 and JW is funded under this funding too. JM receives UCL/UCLH National Institute for Health and Care Research BRC funding., (© 2023 The Authors.)

Retinoic acid, the active metabolite of vitamin A, is important for vertebrate cognition and hippocampal plasticity, but few studies have examined its role in invertebrate learning and memory, and its actions in the invertebrate central nervous system are currently unknown. Using the mollusc Lymnaea stagnalis , we examined operant conditioning of the respiratory behavior, controlled by a well-defined central pattern generator (CPG), and used citral to inhibit retinoic acid signaling. Both citral- and vehicle-treated animals showed normal learning, but citral-treated animals failed to exhibit long-term memory at 24 h. Cohorts of citral- or vehicle-treated animals were dissected into semi-intact preparations, either 1 h after training, or after the memory test 24 h later. Simultaneous electrophysiological recordings from the CPG pacemaker cell (right pedal dorsal 1; RPeD1) and an identified motorneuron (VI) were made while monitoring respiratory activity (pneumostome opening). Activity of the CPG pneumostome opener interneuron (input 3 interneuron; IP3) was also monitored indirectly. Vehicle-treated conditioned preparations showed significant changes in network parameters immediately after learning, such as reduced motorneuron bursting activity (from IP3 input), delayed pneumostome opening, and decoupling of coincident IP3 input within the network. However, citral-treated preparations failed to exhibit these network changes and more closely resembled naïve preparations. Importantly, these citral-induced differences were manifested immediately after training and before any overt changes in the behavioral response (memory impairment). These studies shed light on where and when retinoid signaling might affect a central pattern-generating network to promote memory formation during conditioning of a homeostatic behavior. NEW & NOTEWORTHY We provide novel evidence for how conditioning-induced changes in a CPG network are disrupted when retinoid signaling is inhibited. Inhibition of retinoic acid signaling prevents long-term memory formation following operant conditioning, but has no effect on learning. Simultaneous electrophysiological and behavioral analyses indicate network changes immediately following learning, but these changes are prevented with inhibition of retinoid signaling, before any overt changes in behavior. These data suggest sites for retinoid actions during memory formation.

Aberrant responses within homeostatic, hedonic and cognitive systems contribute to poor appetite control in those with an overweight phenotype. The hedonic system incorporates limbic and meso-limbic regions involved in learning and reward processing, as well as cortical regions involved in motivation, decision making and gustatory processing. Equally important within this complex, multifaceted framework are the cognitive systems involved in inhibitory control and valuation of food choices. Regions within these systems display insulin receptors and pharmacologically increasing central insulin concentrations using intranasal administration (IN-INS) has been shown to significantly reduce appealing food cue responsiveness and also food intake. In this work we describe a placebo-controlled crossover pharmacological functional magnetic resonance imaging (fMRI) study that looks at how IN-INS (160 IU) affects anticipatory and consummatory responses to sweet stimuli and importantly how these responses differ between healthy normal weight and overweight male individuals. This work shows that age matched normal weight and overweight (not obese) individuals respond similarly to both the anticipation and receipt of sweet stimuli under placebo conditions. However, increased central insulin concentrations produce marked differences between groups when anticipating sweet stimuli within the prefrontal cortex and midbrain as well as observed differences in the amygdala during consummatory responses., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Progress towards stratified care for anxiety and depression will require the identification of new predictors. We collected data on retrospectively self-reported therapeutic outcomes in adults who received psychological therapy in the UK in the past ten years. We aimed to replicate factors associated with traditional treatment outcome measures from the literature., Methods: Participants were from the Genetic Links to Anxiety and Depression (GLAD) Study, a UK-based volunteer cohort study. We investigated associations between retrospectively self-reported outcomes following therapy, on a five-point scale (global rating of change; GRC) and a range of sociodemographic, clinical and therapy-related factors, using ordinal logistic regression models (n = 2890)., Results: Four factors were associated with therapy outcomes (adjusted odds ratios, OR). One sociodemographic factor, having university-level education, was associated with favourable outcomes (OR = 1.37, 95%CI: 1.18, 1.59). Two clinical factors, greater number of reported episodes of illness (OR = 0.95, 95%CI: 0.92, 0.97) and higher levels of personality disorder symptoms (OR = 0.89, 95%CI: 0.87, 0.91), were associated with less favourable outcomes. Finally, reported regular use of additional therapeutic activities was associated with favourable outcomes (OR = 1.39, 95%CI: 1.19, 1.63). There were no statistically significant differences between fully adjusted multivariable and unadjusted univariable odds ratios., Conclusion: Therapy outcome data can be collected quickly and inexpensively using retrospectively self-reported measures in large observational cohorts. Retrospectively self-reported therapy outcomes were associated with four factors previously reported in the literature. Similar data collected in larger observational cohorts may enable detection of novel associations with therapy outcomes, to generate new hypotheses, which can be followed up in prospective studies., (© 2022. The Author(s).)

Despite evidence that formula very low-energy diets (VLED) and low-energy diets (LED) are both effective and safe as treatments for obesity and type 2 diabetes, these diets remain underutilized in the United Kingdom. The aim of this study was to explore UK dietitians' attitudes and experiences of using formula VLED and LED. A cross-sectional survey was disseminated between September 2019 and April 2020 through websites, social media platforms and dietetic networks using snowball sampling. In total, 241 dietitians responded to the online survey with 152 participants included in the final analysis (female [94.1%], mean age 40.8 years [SD 9.5]; median 12 years [interquartile range 8, 22] within dietetic practice). One hundred and nine (71.7%) participants reported currently using VLED/LED in clinical practice and 43 (28.3%) did not. Those with lower motivation and confidence in implementing VLED/LED in clinical practice were less likely to use them. Cost and adherence were the two highest reported barriers to use. Dietitians perceived VLED/LED were effective, but concerns remained about long-term effectiveness, particularly for some patient groups. Dietitians also reported that further education, funding and service infrastructure, including access to clinic space and administrative support, were required to help embed VLED/LED into routine clinical practice. With clinical services now regularly offering VLED/LED programmes in the United Kingdom, dietitians are ideally placed to provide long-term support. However, understanding, reporting and addressing the potential barriers (funding/infrastructure and education) appear to be key requirements in increasing the delivery of VLED/LED programmes nationally., (© 2022 The Authors. Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Background: Anxiety and depression are common, debilitating and costly. These disorders are influenced by multiple risk factors, from genes to psychological vulnerabilities and environmental stressors, but research is hampered by a lack of sufficiently large comprehensive studies. We are recruiting 40,000 individuals with lifetime depression or anxiety and broad assessment of risks to facilitate future research., Methods: The Genetic Links to Anxiety and Depression (GLAD) Study (www.gladstudy.org.uk) recruits individuals with depression or anxiety into the NIHR Mental Health BioResource. Participants invited to join the study (via media campaigns) provide demographic, environmental and genetic data, and consent for medical record linkage and recontact., Results: Online recruitment was effective; 42,531 participants consented and 27,776 completed the questionnaire by end of July 2019. Participants' questionnaire data identified very high rates of recurrent depression, severe anxiety, and comorbidity. Participants reported high rates of treatment receipt. The age profile of the sample is biased toward young adults, with higher recruitment of females and the more educated, especially at younger ages., Discussion: This paper describes the study methodology and descriptive data for GLAD, which represents a large, recontactable resource that will enable future research into risks, outcomes, and treatment for anxiety and depression., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: This study investigates whether sexual minority patients have poorer treatment outcomes than heterosexual patients in England's Improving Access to Psychological Therapies (IAPT) services. These services provide evidence-based psychological interventions for people with depression or anxiety., Method: National routinely collected data were analyzed for a cohort who had attended at least 2 treatment sessions and were discharged between April 2013-March, 2015. Depression, anxiety and functional impairment were compared for 85,831 women (83,482 [97.2%] heterosexual; 1,285 [1.5%] lesbian; 1,064 [1.2%] bisexual) and 47,092 men (44,969 [95.5%] heterosexual; 1,734 [3.7%] gay; 389 [0.8%] bisexual). Linear and logistic models were fitted adjusting for baseline scores, and sociodemographic and treatment characteristics., Results: Compared to heterosexual women, lesbian and bisexual women had higher final-session severity for depression, anxiety, and functional impairment and increased risk of not attaining reliable recovery in depression/anxiety or functioning (aORs 1.3-1.4) and reliable improvement in depression/anxiety or functioning (aORs 1.2-1.3). Compared to heterosexual and gay men, bisexual men had higher final-session severity for depression, anxiety, and functioning and increased risk of not attaining reliable recovery for depression/anxiety or functioning (aORs 1.5-1.7) and reliable improvement in depression/anxiety or functioning (aORs 1.3-1.4). Gay and heterosexual men did not differ on treatment outcomes. Racial minority lesbian/gay or bisexual patients did not have significantly different outcomes to their White lesbian/gay or bisexual counterparts., Conclusions: The reasons for treatment outcome inequities for bisexual patients and lesbian women (e.g., 30-70% increased risk of not recovering) need investigation. Health services should address these inequalities. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

This study aimed to characterise three nasal drug delivery devices to evaluate their propensity to deliver human insulin solutions to the nasal cavity for redistribution to the central nervous system. Brain delivery was evaluated using functional magnetic resonance imaging to measure regional cerebral blood flow. Intranasal insulin administration has been hypothesised to exploit nose-to-brain pathways and deliver drug directly to the brain tissue whilst limiting systemic exposure. Three nasal pump-actuator configurations were compared for delivery of 400 IU/mL insulin solution by measuring droplet size distribution, plume geometry, spray pattern and in vitro deposition in a nasal cast. The device with optimal spray properties for nose to brain delivery (spray angle between 30° and 45°; droplet size between 20 and 50 μm) also favoured high posterior-superior deposition in the nasal cast and was utilised in a pharmacological magnetic resonance imaging study. Functional magnetic resonance imaging in healthy male volunteers showed statistically significant decreases in regional cerebral blood flow within areas dense in insulin receptors (bilateral amygdala) in response to intranasally administered insulin (160 IU) compared to saline (control). These changes correspond to the expected effects of insulin in the brain and were achieved using a simple nasal spray device and solution formulation. We recommend that a thorough characterisation of nasal delivery devices and qualitative/quantitative assessment of the administered dose is reported in all studies of nose to brain delivery so that responses can be evaluated with respect to posology and comparison between studies is facilitated., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Multidisciplinary team meetings (MDTM) provide a regular forum for cancer teams to convene and discuss the diagnostic and treatment aspects of patient care. For some rare cancers, MDTMs may also occur at national level to pool expertise and to ensure more consistent decision-making. One such national MDTM exists in the UK for patients with a diagnosis of Ewing's sarcoma of the bone-the National Ewing's MDT (NEMDT). This study explored the patient perspective of this rare cancer national MDTM using focus group and survey methodology. Study participants used their experience to provide several recommendations: that their views should always inform the decision-making process, these views should be presented by someone who has met them such as a specialist nurse, MDT recommendations should be provided to them in plain English, and tools to improve patient choice and enhance communication should be implemented. These patient-centred recommendations will be used to improve the NEMDT but may be valid to inform quality improvement processes for other similar national panels., (© 2018 John Wiley & Sons Ltd.)

Background: Lesbian, gay and bisexual individuals experience more anxiety and depression than heterosexual people. Little is known about their comparative treatment response to psychological interventions., Aims: To compare sociodemographic/clinical characteristics and treatment outcomes across sexual orientation groups, for adults receiving primary care psychological interventions from Improving Access to Psychological Therapies (IAPT) services in London, adjusting for possible confounders., Method: Data from 188 lesbian women, 222 bisexual women, 6637 heterosexual women, 645 gay men, 75 bisexual men and 3024 heterosexual men were analysed from pre-treatment and last treatment sessions. Males and females were analysed separately., Results: Before treatment, lesbian and bisexual women were more likely to report clinical levels of impairment (Work and Social Adjustment Scale) than heterosexual women; there were no significant differences in depression (PHQ-9) or anxiety (GAD-7). Bisexual men were more likely to meet depression caseness than gay men but less likely to meet anxiety caseness than gay or heterosexual men. Compared with heterosexual women, lesbian and bisexual individuals showed smaller reductions in depression and impairment, controlling for age, ethnicity, employment, baseline symptoms, number of sessions and intervention type. Bisexual women experienced significantly smaller reductions in anxiety than heterosexual women and were less likely to show recovery or reliable recovery. There were no significant differences in treatment outcomes between gay, bisexual and heterosexual men., Conclusions: Reasons for poorer outcomes in lesbian and bisexual women require investigation, for example lifetime trauma or stigma/discrimination regarding gender or sexual orientation in everyday life or within therapy services.

Background: A substantial number of patients do not benefit from first line psychological therapies for the treatment of depression and anxiety. Currently, there are no clear predictors of treatment outcomes for these patients. The PROMPT project aims to establish an infrastructure platform for the identification of factors that predict outcomes following psychological treatment for depression and anxiety. Here we report on the first year of recruitment and describe the characteristics of our sample to date., Methods: One hundred and forty-seven patients awaiting treatment within an Improving Access to Psychological Therapies (IAPT) service were recruited between February 2014 and February 2015 (representing 48 % of those eligible). Baseline assessments were conducted to collect information on a variety of clinical, psychological and social variables including a diagnostic interview using the Mini International Neuropsychiatric Interview (MINI)., Results: Our initial findings showed that over a third of our sample were not presenting to IAPT services for the first time, and 63 % had been allocated to receive higher intensity IAPT treatments. Approximately half (46 %) were taking prescribed psychotropic medication (most frequently antidepressants). Co-morbidity was common: 72 % of the sample met criteria for 2 or more current MINI diagnoses. Our initial data also indicated that 16 % met criteria for borderline personality disorder and 69 % were at high risk of personality disorder. Sixty-one percent scored above the screening threshold for bipolarity. Over half of participants (55 %) reported experiencing at least one stressful life event in the previous 12 months, whilst 67 % reported experiencing at least one form of childhood trauma., Conclusions: Our results to date highlight the complex nature of patients seen within an urban IAPT service, with high rates of psychiatric comorbidity, personality disorder, bipolarity and childhood trauma. Whilst there are significant challenges associated with researching IAPT populations, we have also confirmed the feasibility of undertaking such research.

Objectives: Little data are available regarding coronary plaque composition and semi-quantitative scores in individuals with diabetes; the extent to which diabetes may affect the presence and extent of Coronary Artery Calcium (CAC) needs more evaluation. Considering that this information may be of great value in formulating preventive interventions in this population, we compared these findings in individuals with diabetes to those without., Methods: Multi-Detector Computed Tomographic (MDCT) images of 861 consecutive patients with diabetes who were referred to Los Angeles Biomedical Research Institute from January 2000 to September 2012, were evaluated using a 15-coronary segment model. All 861 patients underwent calcium scoring and from these; 389 had coronary CT angiography (CTA). CAC score was compared to 861 age, sex and ethnicity matched controls without diabetes after adjustment for Body Mass Index (BMI), family history of coronary artery disease, hyperlipidemia, hypertension and smoking. Segment Involvement Score (SIS; the total number of segments with any plaque), Segment Stenosis Score (SSS; the sum of maximal stenosis score per segment), Total Plaque Score (TPS; the sum of the plaque amount per segment) and plaque compositionwere compared to 389 age, sex and ethnicity matched controls without diabetes after adjustment for BMI, family history of coronary artery disease, hyperlipidemia, hypertension and smoking., Results: Diabetes was positively correlated to the presence and extent of CAC (P<0.0001 for both). SIS, SSS and TPS were significantly higher in those with diabetes (P<0.0001). Number of mixed and calcified plaques were significantly higher in those with diabetes (P = 0.018 and P<0.001 respectively) but there was no significant difference in the number of non-calcified plaques between the two groups (P = 0.398)., Conclusions: Patients with diabetes have higher CAC and semi-quantitative coronary plaque scores compared to the age, gender and ethnicity matched controls without diabetes after adjustment for cardiovascular risk factors. Since mixed plaque is associated with worse long-term clinical outcomes, these findings support more aggressive preventive measures in this population.

Unlabelled: The UK's Improving Access to Psychological Therapies (IAPT) initiative provides evidence-based psychological interventions for mild to moderate common mental health problems in a primary care setting. Predictors of treatment response are unclear. This study examined the impact of personality disorder status on outcome in a large IAPT service. We hypothesised that the presence of probable personality disorder would adversely affect treatment response., Method: We used a prospective cohort design to study a consecutive sample of individuals (n = 1249)., Results: Higher scores on a screening measure for personality disorder were associated with poorer outcome on measures of depression, anxiety and social functioning, and reduced recovery rates at the end of treatment. These associations were not confounded by demographic status, initial symptom severity nor number of treatment sessions. The presence of personality difficulties independently predicted reduced absolute change on all outcome measures., Conclusions: The presence of co-morbid personality difficulties adversely affects treatment outcome among individuals attending for treatment in an IAPT service. There is a need to routinely assess for the presence of personality difficulties on all individuals referred to IAPT services. This information will provide important prognostic data and could lead to the provision of more effective, personalised treatment in IAPT., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Cognitive behavioural interventions are effective in the treatment of chronic fatigue, chronic fatigue syndrome (sometimes known as ME or CFS/ME) and irritable bowel syndrome (IBS). Such interventions are increasingly being provided not only in specialist settings but in primary care settings such as Improving Access to Psychological Therapies (IAPT) services. There are no existing competences for the delivery of "low-intensity" or "high-intensity" cognitive behavioural interventions for these conditions., Aims: To develop "high-intensity" and "low-intensity" competences for cognitive behavioural interventions for chronic fatigue, CFS/ME and IBS., Method: The initial draft drew on a variety of sources including treatment manuals and other information from randomized controlled trials. Therapists with experience in providing cognitive behavioural interventions for CF, CFS/ME and IBS in research and clinical settings were consulted on the initial draft competences and their suggestions for minor amendments were incorporated into the final versions., Results: Feedback from experienced therapists was positive. Therapists providing low intensity interventions reported that the competences were also helpful in highlighting training needs., Conclusions: These sets of competences should facilitate the training and supervision of therapists providing cognitive behavioural interventions for chronic fatigue, CFS/ME and IBS. The competences are available online (see table of contents for this issue: http://journals.cambridge.org/jid&#95;BCP) or on request from the first author.

Background: Depression and anxiety are highly prevalent and represent a significant and well described public health burden. Whilst first line psychological treatments are effective for nearly half of attenders, there remain a substantial number of patients who do not benefit. The main objective of the present project is to establish an infrastructure platform for the identification of factors that predict lack of response to psychological treatment for depression and anxiety, in order to better target treatments as well as to support translational and experimental medicine research in mood and anxiety disorders., Methods/design: Predicting outcome following psychological therapy in IAPT (PROMPT) is a naturalistic observational project that began patient recruitment in January 2014. The project is currently taking place in Southwark Psychological Therapies Service, an Improving Access to Psychological Therapies (IAPT) service currently provided by the South London and Maudsley NHS Foundation Trust (SLaM). However, the aim is to roll-out the project across other IAPT services. Participants are approached before beginning treatment and offered a baseline interview whilst they are waiting for therapy to begin. This allows us to test for relationships between predictor variables and patient outcome measures. At the baseline interview, participants complete a diagnostic interview; are asked to give blood and hair samples for relevant biomarkers, and complete psychological and social questionnaire measures. Participants then complete their psychological therapy as offered by Southwark Psychological Therapies Service. Response to psychological therapy will be measured using standard IAPT outcome data, which are routinely collected at each appointment., Discussion: This project addresses a need to understand treatment response rates in primary care psychological therapy services for those with depression and/or anxiety. Measurement of a range of predictor variables allows for the detection of bio-psycho-social factors which may be relevant for treatment outcome. This will enable future clinical decision making to be based on the individual needs of the patient in an evidence-based manner. Moreover, the identification of individuals who fail to improve following therapy delivered by IAPT services could be utilised for the development of novel interventions.

Unlabelled: Cognitive behaviour therapy (CBT) is an effective treatment for chronic fatigue syndrome (CFS; sometimes known as myalgic encephalomyelitis). However, only a minority of patients fully recover after CBT; thus, methods for improving treatment outcomes are required. This pilot study concerned a mindfulness-based cognitive therapy (MBCT) intervention adapted for people with CFS who were still experiencing excessive fatigue after CBT. The study aimed to investigate the acceptability of this new intervention and the feasibility of conducting a larger-scale randomized trial in the future. Preliminary efficacy analyses were also undertaken. Participants were randomly allocated to MBCT or waiting list. Sixteen MBCT participants and 19 waiting-list participants completed the study, with the intervention being delivered in two separate groups. Acceptability, engagement and participant-rated helpfulness of the intervention were high. Analysis of covariance controlling for pre-treatment scores indicated that, at post-treatment, MBCT participants reported lower levels of fatigue (the primary clinical outcome) than the waiting-list group. Similarly, there were significant group differences in fatigue at 2-month follow-up, and when the MBCT group was followed up to 6 months post-treatment, these improvements were maintained. The MBCT group also had superior outcomes on measures of impairment, depressed mood, catastrophic thinking about fatigue, all-or-nothing behavioural responses, unhelpful beliefs about emotions, mindfulness and self-compassion. In conclusion, MBCT is a promising and acceptable additional intervention for people still experiencing excessive fatigue after CBT for CFS, which should be investigated in a larger randomized controlled trial., Key Practitioner Message: Only about 30% of people with chronic fatigue syndrome (CFS) recover after cognitive behaviour therapy (CBT); thus, methods for improving treatment outcomes are needed. This is the first pilot randomized study to demonstrate that a mindfulness-based intervention was associated with reduced fatigue and other benefits for people with CFS who were still experiencing excessive fatigue after a course of CBT. Levels of acceptability, engagement in the intervention and rated helpfulness were high. A larger-scale randomized controlled trial is required., (Copyright © 2011 John Wiley & Sons, Ltd.)

Background: About 20% of major depressive episodes become chronic and medication-refractory and also appear to be less responsive to standard cognitive-behavioural therapy (CBT)., Aims: To test whether CBT developed from behavioural activation principles that explicitly and exclusively targets depressive rumination enhances treatment as usual (TAU) in reducing residual depression., Method: Forty-two consecutively recruited participants meeting criteria for medication-refractory residual depression were randomly allocated to TAU v. TAU plus up to 12 sessions of individual rumination-focused CBT. The trial has been registered (ISRCTN22782150)., Results: Adding rumination-focused CBT to TAU significantly improved residual symptoms and remission rates. Treatment effects were mediated by change in rumination., Conclusions: This is the first randomised controlled trial providing evidence of benefits of rumination-focused CBT in persistent depression. Although suggesting the internal validity of rumination-focused CBT for residual depression, the trial lacked an attentional control group so cannot test whether the effects were as a result of the specific content of rumination-focused CBT v. non-specific therapy effects.

Background: It is recommended that Mindfulness-Based Cognitive Therapy (MBCT) instructors should undertake MBCT themselves before teaching others., Aim: To investigate the impact of MBCT (modified for stress not depression) on trainee clinical psychologists., Method: Twenty trainees completed questionnaires pre- and post-MBCT., Results: There was a significant decrease in rumination, and increases in self-compassion and mindfulness. More frequent home practice was associated with larger decreases in stress, anxiety and rumination, and larger increases in empathic concern. Only first-year trainees showed a significant decrease in stress. Content analysis of written responses indicated that the most commonly reported effects were increased acceptance of thoughts/feelings (70%), increased understanding of what it is like to be a client (60%), greater awareness of thoughts/feelings/behaviours/bodily sensations (55%) and increased understanding of oneself and one's patterns of responding (55%). Participants reported increased metacognitive awareness and decentring in relation to negative thoughts. Eighty-five percent reported an impact on their clinical work by the end of the course., Conclusions: Trainee psychologists undergoing MBCT experienced many of the psychological processes/effects that they may eventually be helping to cultivate in clients using mindfulness interventions, and also benefits in their general clinical work.

The treatment of chronic and recurrent depression is a priority for the development of new interventions. The maintenance of residual symptoms following acute treatment for depression is a risk factor for both chronic depression and further relapse/recurrence. This open case series provides the first data on a cognitive-behavioural treatment for residual depression that explicitly targets depressive rumination. Rumination has been identified as a key factor in the onset and maintenance of depression, which is found to remain elevated following remission from depression. Fourteen consecutively recruited participants meeting criteria for medication--refractory residual depression [Paykel, E.S., Scott, J., Teasdale, J.D., Johnson, A.L., Garland, A., Moore, R. et al., 1999. Prevention of relapse in residual depression by cognitive therapy--a controlled trial. Archives of General Psychiatry 56, 829-835] were treated individually for up to 12 weekly 60-min sessions. Treatment specifically focused on switching patients from less helpful to more helpful styles of thinking through the use of functional analysis, experiential/imagery exercises and behavioural experiments. Treatment produced significant improvements in depressive symptoms, rumination and co-morbid disorders: 71% responded (50% reduction on Hamilton Depression Rating Scale) and 50% achieved full remission. Treating depressive rumination appears to yield generalised improvement in depression and co-morbidity. This study provides preliminary evidence that rumination-focused CBT may be an efficacious treatment for medication--refractory residual depression.

The hypothesis that trait anger is associated with an increased tendency to interpret ambiguous situations as anger-provoking was investigated in a reading time study. A total of 48 healthy volunteers read a series of short narrative passages and were asked to adopt the perspective of the main character, identified at the start of each passage. Reading times for key sentences, which described the main characters' angry or nonangry reactions to ambiguous anger-provoking situations, were recorded. Trait anger and impulsivity were negatively correlated with reading time for sentences describing both types of reaction, but anger was also correlated with relatively faster processing of sentences describing angry reactions. This study suggests that those with angrier dispositions are more likely to anticipate angry reactions from others.

The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.

We aligned Incyte ESTs and publicly available sequences to the rat genome and analyzed rat chromosome 1q43-54, a region in which several quantitative trait loci (QTLs) have been identified, including renal disease, diabetes, hypertension, body weight, and encephalomyelitis. Within this region, which contains 255 Ensembl gene predictions, the aligned sequences clustered into 568 Incyte genes and gene fragments. Of the Incyte genes, 261 (46%) overlapped 184 (72%) of the Ensembl gene predictions, whereas 307 were unique to Incyte. The rat-to-human syntenic map displays rearrangement of this region on rat chr. 1 onto human chromosomes 9 and 10. The mapping of corresponding human disease phenotypes to either one of these chromosomes has allowed us to focus in on genes associated with disease phenotypes. As an example, we have used the syntenic information for the rat Rf-1 disease region and the orthologous human ESRD disease region to reduce the size of the original rat QTL to only 11.5 Mb. Using the syntenic information in combination with expression data from ESTs and microarrays, we have selected a set of 66 candidate disease genes for Rf-1. The combination of the results from these different analyses represents a powerful approach for narrowing the number of genes that could play a role in the development of complex diseases.

Rationale: According to cognitive theory, people who are aggressive expect angry responses to ambiguous situations. Increased aggression has been reported a few days or weeks following use of MDMA (ecstasy). This may relate to low 5-HT release, and so a 5-HT challenge may increase cognitive bias towards anger differentially in MDMA users and non-users., Objectives: To investigate whether: (1) measures of anger and aggression will correlate with processing time of angry material and with generation of aggressive responses and (2) tryptophan challenge in people abstinent from MDMA and controls will affect angry cognitive bias., Methods: Thirty-two current MDMA users abstinent for 3 weeks, 32 ex-users abstinent for longer than 1 year and 32 non-MDMA substance users were recruited. Trait measures were administered before and state measures before and 5 h after an amino acid drink, depleted or augmented with tryptophan. After the drink, subjects undertook a computer task, which involved reading ambiguous short stories. Reading times to a key sentence describing an angry or non-angry reaction were recorded and subjects wrote a continuing sentence for half the stories., Results: Subjects were faster to process angry than non-angry reactions, indicating the presence of angry cognitive bias. Trait anger and aggression were correlated with processing time of angry relative to non-angry reactions, particularly in the current users. Impulsivity was correlated with non-specific speed of response. Subjects wrote more aggressive sentences after an angry reaction. Tryptophan depletion tended to increase aggressive content. Trait aggression was correlated with aggressive content following non-angry reactions., Conclusions: Evidence of angry cognitive bias was shown in this group of substance users, which was not specific to MDMA use. People high on trait aggression were more likely to expect an angry reaction to an ambiguous situation and to generate more written aggression when this did not occur.

Rationale: Serotonergic pathways are thought to be important in mediating the effects of aversive events., Objective: To investigate the effects of buspirone, a 5-HT(1A) partial agonist, on habituation and extinction in an aversive classical conditioning model., Methods: Forty healthy male volunteers were randomly assigned to a single dose of buspirone (10 mg) or placebo. They filled in questionnaires of anxiety and depression at baseline and visual analogue scales of tension and anxiety before and at 60, 120 and 150 min after drug administration. Their skin conductance responses to auditory stimuli were measured on the conditioning model 2 h after drug intake., Results: There were no differences between groups on depression or anxiety. Buspirone decreased the amplitude of the skin conductance response and the number of spontaneous fluctuations in both the habituation and extinction phases but had no effect on skin conductance level. Buspirone also attenuated the unconditioned response to the white noise and the response to the first tone. Visual analogue ratings of tension and anxiety decreased after buspirone., Conclusions: Buspirone decreased physiological reactivity in an aversive classical conditioning model. It had anxiolytic effects on both conditioned and unconditioned anxiety. This might be due to its multiple actions on 5-HT receptors.

Background: Very few studies have examined the combination of drug and psychological treatment in generalised anxiety disorder (GAD). Theoretically, buspirone should be a useful drug to combine with a learning-based therapy., Methods: Sixty patients with GAD were randomly assigned to treatment with buspirone or placebo, combined with anxiety management training or non-directive therapy for a period of 8 weeks., Results: Forty-four patients with a mean Hamilton Anxiety Scale score of 28 completed treatment. There were no significant differences between treatment groups. All groups showed significant improvement after 8 weeks compared to baseline. There were no baseline differences between those who completed the trial and those who did not but patients given buspirone were more likely to drop out., Conclusions: A short course of psychological therapy, whether or not accompanied by active medication, was an effective treatment for patients diagnosed as having quite severe symptoms of GAD. CLINICAL IMPLICATIONS AND LIMITATIONS: Dropouts led to a sample size which may have been too small to detect group differences. Cognitive therapy may have been more effective.

Background: Menstrually related dysphoria is known to be associated with other affective disorders, notably major depressive disorder and puerperal depression. The relationship between premenstrual dysphoric disorder (PMDD) and maladaptive personality disorders and traits, however, is less established, at least in part because of the methodological and nosologic difficulties in the diagnosis of both PMDD and personality disorders. This study seeks to address this problem to elucidate the relationship between PMDD, other affective disturbances commonly experienced by women, and maladaptive personality., Method: Axis I and II disorders were examined using standardized instruments and stringent diagnostic criteria (DSM-IV and the International Personality Disorders Examination) in 34 women with DSM-IV PMDD and 22 healthy women without severe premenstrual mood changes., Results: Seventy-seven percent of the PMDD group had suffered from a past Axis I disorder in comparison with 17% of the control group. Two thirds of the parous women with PMDD had suffered from major depressive disorder in the puerperium. Personality disorder diagnoses were not highly represented in either group of women. The women with PMDD had significantly more obsessional personality traits (p < .001 ) but not absolute personality disorder diagnoses., Conclusion: Obsessional symptoms are known to cluster with the affective disorders and may reflect underlying temperamental and biological vulnerability. This study provides further evidence of the link between serotonergic dysregulation, personality vulnerability, and mood changes related to the female reproductive cycle.

Rationale: Reducing serotonin by the method of tryptophan depletion (TD) has led to increased aggression but experimental studies have not used female subjects., Objective: To evaluate the effects of TD on aggression in women in the late luteal phase of their menstrual cycle., Methods: Healthy women were recruited and randomly assigned to an amino acid drink either depleted or with a balanced amount of tryptophan. At 4.5 h later, they competed on the competitive reaction time task., Results: Women who had received the TD drink showed more behavioural aggression in response to provocation., Conclusion: Decreased serotonergic neurotransmission increases aggression in women as well as men.