Liliana Capitao

@ox.ac.uk

Department of Psychiatry
University of Oxford



              

https://researchid.co/lilianacapitao
5

Scopus Publications

199

Scholar Citations

3

Scholar h-index

4

Scholar i10-index

Scopus Publications

  • Angiotensin receptor blockade modulates resting state functional connectivity in the memory network rather than fear network – implications for posttraumatic stress disorder
    Lorika Shkreli, Caroline Nettekoven, Sirius Boessenkool, Marieke Martens, Nicola Filippini, Liliana Capitão, Phil Cowen, and Andrea Reinecke
    Elsevier BV

  • Acute neural effects of the mood stabiliser lamotrigine on emotional processing in healthy volunteers: a randomised control trial
    Marieke A. G. Martens, Tarek Zghoul, Evelyn Watson, Sebastian W. Rieger, Liliana P. Capitão, and Catherine J. Harmer
    Springer Science and Business Media LLC
    AbstractLamotrigine is an effective mood stabiliser, largely used for the management and prevention of depression in bipolar disorder. The neuropsychological mechanisms by which lamotrigine acts to relieve symptoms as well as its neural effects on emotional processing remain unclear. The primary objective of this current study was to investigate the impact of an acute dose of lamotrigine on the neural response to a well-characterised fMRI task probing implicit emotional processing relevant to negative bias. 31 healthy participants were administered either a single dose of lamotrigine (300 mg, n = 14) or placebo (n = 17) in a randomized, double-blind design. Inside the 3 T MRI scanner, participants completed a covert emotional faces gender discrimination task. Brain activations showing significant group differences were identified using voxel-wise general linear model (GLM) nonparametric permutation testing, with threshold free cluster enhancement (TFCE) and a family wise error (FWE)-corrected cluster significance threshold of p < 0.05. Participants receiving lamotrigine were more accurate at identifying the gender of fearful (but not happy or angry) faces. A network of regions associated with emotional processing, including amygdala, insula, and the anterior cingulate cortex (ACC), was significantly less activated in the lamotrigine group compared to the placebo group across emotional facial expressions. A single dose of lamotrigine reduced activation in limbic areas in response to faces with both positive and negative expressions, suggesting a valence-independent effect. However, at a behavioural level lamotrigine appeared to reduce the distracting effect of fear on face discrimination. Such effects may be relevant to the mood stabilisation effects of lamotrigine.

  • Effects of ulotaront on brain circuits of reward, working memory, and emotion processing in healthy volunteers with high or low schizotypy
    Francesca Perini, Jadwiga Maria Nazimek, Shane Mckie, Liliana P. Capitão, Jessica Scaife, Deepa Pal, Michael Browning, Gerard R. Dawson, Hiroyuki Nishikawa, Una Campbell,et al.
    Springer Science and Business Media LLC
    AbstractUlotaront, a trace amine-associated receptor 1 (TAAR1) and serotonin 5-HT1A receptor agonist without antagonist activity at dopamine D2 or the serotonin 5-HT2A receptors, has demonstrated efficacy in the treatment of schizophrenia. Here we report the phase 1 translational studies that profiled the effect of ulotaront on brain responses to reward, working memory, and resting state connectivity (RSC) in individuals with low or high schizotypy (LS or HS). Participants were randomized to placebo (n = 32), ulotaront (50 mg; n = 30), or the D2 receptor antagonist amisulpride (400 mg; n = 34) 2 h prior to functional magnetic resonance imaging (fMRI) of blood oxygen level-dependent (BOLD) responses to task performance. Ulotaront increased subjective drowsiness, but reaction times were impaired by less than 10% and did not correlate with BOLD responses. In the Monetary Incentive Delay task (reward processing), ulotaront significantly modulated striatal responses to incentive cues, induced medial orbitofrontal responses, and prevented insula activation seen in HS subjects. In the N-Back working memory task, ulotaront modulated BOLD signals in brain regions associated with cognitive impairment in schizophrenia. Ulotaront did not show antidepressant-like biases in an emotion processing task. HS had significantly reduced connectivity in default, salience, and executive networks compared to LS participants and both drugs reduced this difference. Although performance impairment may have weakened or contributed to the fMRI findings, the profile of ulotaront on BOLD activations elicited by reward, memory, and resting state is compatible with an indirect modulation of dopaminergic function as indicated by preclinical studies. This phase 1 study supported the subsequent clinical proof of concept trial in people with schizophrenia.Clinical trial registration: Registry# and URL: ClinicalTrials.gov NCT01972711, https://clinicaltrials.gov/ct2/show/NCT01972711

  • Acute neural effects of fluoxetine on emotional regulation in depressed adolescents
    Liliana P. Capitão, Robert Chapman, Nicola Filippini, Lucy Wright, Susannah E. Murphy, Anthony James, Philip J. Cowen, and Catherine J. Harmer
    Cambridge University Press (CUP)
    AbstractBackgroundAdolescent major depressive disorder (MDD) is associated with disrupted processing of emotional stimuli and difficulties in cognitive reappraisal. Little is known however about how current pharmacotherapies act to modulate the neural mechanisms underlying these key processes. The current study therefore investigated the neural effects of fluoxetine on emotional reactivity and cognitive reappraisal in adolescent depression.MethodsThirty-one adolescents with MDD were randomised to acute fluoxetine (10 mg) or placebo. Seventeen healthy adolescents were also recruited but did not receive any treatment for ethical reasons. During functional magnetic resonance imaging (fMRI), participants viewed aversive images and were asked to either experience naturally the emotional state elicited (‘Maintain’) or to reinterpret the content of the pictures to reduce negative affect (‘Reappraise’). Significant activations were identified using whole-brain analysis.ResultsNo significant group differences were seen when comparing Reappraise and Maintain conditions. However, when compared to healthy controls, depressed adolescents on placebo showed reduced visual activation to aversive pictures irrespective of the condition. The depressed adolescent group on fluoxetine showed the opposite pattern, i.e. increased visuo-cerebellar activity in response to aversive pictures, when compared to depressed adolescents on placebo.ConclusionsThese data suggest that depression in adolescence may be associated with reduced visual processing of aversive imagery and that fluoxetine may act to reduce avoidance of such cues. This could reflect a key mechanism whereby depressed adolescents engage with negative cues previously avoided. Future research combining fMRI with eye-tracking is nonetheless needed to further clarify these effects.

  • Multispecies probiotic administration reduces emotional salience and improves mood in subjects with moderate depression: A randomised, double-blind, placebo-controlled study
    Rita Baião, Liliana P. Capitão, Cameron Higgins, Michael Browning, Catherine J. Harmer, and Philip W. J. Burnet
    Cambridge University Press (CUP)
    Abstract Background The potential antidepressant properties of probiotics have been suggested, but their influence on the emotional processes that may underlie this effect is unclear. Methods Depressed volunteers (n = 71) were recruited into a randomised double-blind, placebo-controlled study to explore the effects of a daily, 4-week intake of a multispecies probiotic or placebo on emotional processing and cognition. Mood, anxiety, positive and negative affect, sleep, salivary cortisol and serum C-reactive peptide (CRP) were assessed before and after supplementation. Results Compared with placebo, probiotic intake increased accuracy at identifying faces expressing all emotions (+12%, p < 0.05, total n = 51) and vigilance to neutral faces (mean difference between groups = 12.28 ms ± 6.1, p < 0.05, total n = 51). Probiotic supplementation also reduced reward learning (−9%, p < 0.05, total n = 51), and interference word recall on the auditory verbal learning task (−18%, p < 0.05, total n = 50), but did not affect other aspects of cognitive performance. Although actigraphy revealed a significant group × night-time activity interaction, follow up analysis was not significant (p = 0.094). Supplementation did not alter salivary cortisol or circulating CRP concentrations. Probiotic intake significantly reduced (−50% from baseline, p < 0.05, n = 35) depression scores on the Patient Health Questionnaire-9, but these did not correlate with the changes in emotional processing. Conclusions The impartiality to positive and negative emotional stimuli or reward after probiotic supplementation have not been observed with conventional antidepressant therapies. Further studies are required to elucidate the significance of these changes with regard to the mood-improving action of the current probiotic.

  • The Effect of the 5-HT<inf>4</inf> Agonist, Prucalopride, on a Functional Magnetic Resonance Imaging Faces Task in the Healthy Human Brain
    Angharad N. de Cates, Marieke A. G. Martens, Lucy C. Wright, Cassandra D. Gould van Praag, Liliana P. Capitão, Daisy Gibson, Philip J. Cowen, Catherine J. Harmer, and Susannah E. Murphy
    Frontiers Media SA
    Depression is a common and often recurrent illness with significant negative impact on a global scale. Current antidepressants are ineffective for up to one third of people with depression, many of whom experience persistent symptomatology. 5-HT4 receptor agonists show promise in both animal models of depression and cognitive deficit. We therefore studied the effect of the 5-HT4 partial agonist prucalopride (1 mg daily for 6 days) on the neural processing of emotional faces in 43 healthy participants using a randomised placebo-controlled design. Participants receiving prucalopride were more accurate at identifying the gender of emotional faces. In whole brain analyses, prucalopride was also associated with reduced activation in a network of regions corresponding to the default mode network. However, there was no evidence that prucalopride treatment produced a positive bias in the neural processing of emotional faces. Our study provides further support for a pro-cognitive effect of 5-HT4 receptor agonism in humans. While our current behavioural and neural investigations do not suggest an antidepressant-like profile of prucalopride in humans, it will be important to study a wider dose range in future studies.

  • Effect of the NMDA receptor partial agonist, d-cycloserine, on emotional processing and autobiographical memory
    Runsen Chen, Liliana P. Capitão, Philip J. Cowen, and Catherine J. Harmer
    Cambridge University Press (CUP)
    Abstract Background Studies suggest that d-cycloserine (DCS) may have antidepressant potential through its interaction with the glycine site of the N-methyl-D-aspartate receptor; however, clinical evidence of DCS's efficacy as a treatment for depression is limited. Other evidence suggests that DCS affects emotional learning which may also be relevant for the treatment of depression and anxiety. The aim of the present investigation was to assess the effect of DCS on emotional processing in healthy volunteers and to further characterise its effects on emotional and autobiographical memory. Methods Forty healthy volunteers were randomly allocated to a single dose of 250 mg DCS or placebo in a double-blind design. Three hours later, participants performed an Emotional Test Battery [including Facial Expression Recognition Task (FERT), Emotional Categorisation Task (ECAT), Emotional Recall Task (EREC), Facial Dot-Probe Task (FDOT) and Emotional Recognition Memory Task (EMEM)] and an Autobiographical Memory Test (AMT). Also, participants performed the FERT, EREC and AMT tasks again after 24 h in order to assess longer lasting effects of a single dose of DCS. Results DCS did not significantly affect the FERT, EMEM and FDOT performance but significantly increased emotional memory and classification for positive words v. negative words. Also, DCS enhanced the retrieval of more specific autobiographical memories, and this effect persisted at 24 h. Conclusions These findings support the suggestion that low-dose DCS increases specific autobiographical memory retrieval and positive emotional memory. Such effects make it an intriguing agent for further investigation in clinical depression, which is characterised by decreased autobiographical memory specificity and increased negative bias in memory recall. It also underscores the potential role of DCS as an adjunct to cognitive behavioural therapy in depression.

  • The knowns and unknowns of SSRI treatment in young people with depression and anxiety: efficacy, predictors, and mechanisms of action
    Susannah E Murphy, Liliana P Capitão, Sophie L C Giles, Philip J Cowen, Argyris Stringaris, and Catherine J Harmer
    Elsevier BV
    The use of SSRIs for the treatment of depression and anxiety in young people is increasing. However, the effects of SSRIs in adolescence, a time when there are substantial changes in neural, cognitive, and social functioning, are not well understood. Here, we review evidence from clinical trials about the benefits and risks of SSRIs in young people and consider their mechanisms of action, as shown through human experimental work and animal models. We emphasise key outstanding questions about the effects of SSRIs in youth, identified through gaps in the literature and in consultation with young people with lived experience. It is crucial to characterise the mechanisms underpinning risks and benefits of SSRIs in this age group to progress the field, and to narrow the chasm between the widespread use of SSRIs in youth and the science on which this use is based.

  • Hydrocortisone as an adjunct to brief cognitive-behavioural therapy for specific fear: Endocrine and cognitive biomarkers as predictors of symptom improvement
    Susann Steudte-Schmiedgen, Emily Fay, Liliana Capitao, Clemens Kirschbaum, and Andrea Reinecke
    SAGE Publications
    Background: Glucocorticoid (GC) administration prior to exposure-based cognitive-behavioural therapy (CBT) has emerged as a promising approach to facilitate treatment outcome in anxiety disorders. Further components relevant for improved CBT efficacy include raised endogenous GCs and reductions in information-processing biases to threat. Aims: To investigate hydrocortisone as an adjunct to CBT for spider fear and the modulating role of threat bias change and endogenous short-term and long-term GCs for treatment response. Methods: Spider-fearful individuals were randomized to receiving either 20 mg of hydrocortisone ( n = 17) or placebo ( n = 16) one hour prior to single-session predominantly computerised exposure-based CBT. Spider fear was assessed using self-report and behavioural approach measures at baseline, 1-day and 1-month follow-up. Threat processing was assessed at baseline and 1-day follow-up. Cortisol and cortisone were analysed from hair and saliva samples at baseline. Results/outcomes: Self-report, behavioural and threat processing indices improved following CBT. Hydrocortisone augmentation resulted in greater improvement of self-report spider fear and stronger increase in speed when approaching a spider, but not on threat bias. Neither threat bias nor endogenous GCs predicted symptom change, and no interactive effects with hydrocortisone emerged. Preliminary evidence indicated higher hair cortisone as predictor of a stronger threat bias reduction. Conclusions/interpretation: Our data extend earlier findings by suggesting that GC administration boosts the success of exposure therapy for specific fear even with a low-level therapist involvement. Future studies corroborating our result of a predictive hair GC relationship with threat bias change in larger clinical samples are needed.

  • A single, clinically relevant dose of the GABA<inf>B</inf> agonist baclofen impairs visuomotor learning
    Ainslie Johnstone, Ioana Grigoras, Pierre Petitet, Liliana P. Capitão, and Charlotte J. Stagg
    Wiley
    Baclofen is a GABAB agonist prescribed as a treatment for spasticity in stroke, brain injury and multiple sclerosis patients, who are often undergoing concurrent motor rehabilitation. Decreasing GABAergic inhibition is a key feature of motor learning and so there is a possibility that GABA agonist drugs, such as baclofen, could impair these processes, potentially impacting rehabilitation. Here, we examined the effect of 10 mg of baclofen, in 20 young healthy individuals, and found that the drug impaired retention of visuomotor learning with no significant effect on motor sequence learning. Overall baclofen did not alter transcranial magnetic stimulation‐measured GABAB inhibition, although the change in GABAB inhibition correlated with aspects of visuomotor learning retention. Further work is needed to investigate whether taking baclofen impacts motor rehabilitation in patients.

  • Neural effects of a single dose of fluoxetine on resting-state functional connectivity in adolescent depression
    Liliana P Capitão, Robert Chapman, Nicola Filippini, Lucy Wright, Susannah E Murphy, Anthony James, Phil J Cowen, and Catherine J Harmer
    SAGE Publications
    Fluoxetine is commonly prescribed in adolescent depression, but the neural mechanisms underlying its action remain poorly understood. Here, we used resting-state functional magnetic resonance imaging to investigate the effects of a single dose of fluoxetine vs. placebo in adolescents with major depressive disorder. In contrast with previous studies in adults that have demonstrated an acute effect of antidepressants on activity within the default mode network, a single dose of fluoxetine did not alter activity in this network in adolescent depression. There were unexpected group activity differences in the motor network, which should be clarified in future research.

  • ENIGMA MDD: seven years of global neuroimaging studies of major depression through worldwide data sharing
    Lianne Schmaal, Elena Pozzi, Tiffany C. Ho, Laura S. van Velzen, Ilya M. Veer, Nils Opel, Eus J. W. Van Someren, Laura K. M. Han, Lybomir Aftanas, André Aleman,et al.
    Springer Science and Business Media LLC
    AbstractA key objective in the field of translational psychiatry over the past few decades has been to identify the brain correlates of major depressive disorder (MDD). Identifying measurable indicators of brain processes associated with MDD could facilitate the detection of individuals at risk, and the development of novel treatments, the monitoring of treatment effects, and predicting who might benefit most from treatments that target specific brain mechanisms. However, despite intensive neuroimaging research towards this effort, underpowered studies and a lack of reproducible findings have hindered progress. Here, we discuss the work of the ENIGMA Major Depressive Disorder (MDD) Consortium, which was established to address issues of poor replication, unreliable results, and overestimation of effect sizes in previous studies. The ENIGMA MDD Consortium currently includes data from 45 MDD study cohorts from 14 countries across six continents. The primary aim of ENIGMA MDD is to identify structural and functional brain alterations associated with MDD that can be reliably detected and replicated across cohorts worldwide. A secondary goal is to investigate how demographic, genetic, clinical, psychological, and environmental factors affect these associations. In this review, we summarize findings of the ENIGMA MDD disease working group to date and discuss future directions. We also highlight the challenges and benefits of large-scale data sharing for mental health research.

  • A single administration of the antibiotic, minocycline, reduces fear processing and improves implicit learning in healthy volunteers: analysis of the serum metabolome
    Shi Yu Chan, Liliana Capitão, Fay Probert, Corinna Klinge, Sebastian Hoeckner, Catherine J. Harmer, Philip J. Cowen, Daniel C. Anthony, and Philip W. J. Burnet
    Springer Science and Business Media LLC
    AbstractMinocycline has shown therapeutic promise in pre-clinical animal models and early phase clinical trials for a variety of psychiatric disorders. Previous studies on minocycline have shown its ability to suppress microglia activity and reduce inflammatory cytokine levels, and its amelioration of depressive-like behaviour in animals and humans. However, the underlying mechanisms that lead to minocycline’s psychotropic effects are not clear. In this study, we investigated the psychological and biochemical effects of an acute dose of minocycline or placebo in 40 healthy adult volunteers. Psychological changes in emotional processing, implicit learning, and working memory were assessed. Plasma inflammatory markers, measured with enzyme-linked immunosorbent assays, and serum metabolites, measured with proton nuclear magnetic resonance combined with multi-variate analysis techniques, were also studied. Results showed that minocycline administration decreased fear misclassification and increased contextual learning, which suggested that reducing negative biases and improving cognition, respectively, may underlie the antidepressant actions of this agent. An examination of serum metabolites revealed higher levels of lipoproteins, particularly cholesterol, in the minocycline group. Minocycline also decreased circulating concentrations of the inflammatory marker C-Reactive Peptide, which is consistent with previous research. These effects highlight two important psychological mechanisms that may be relevant to the efficacy of minocycline reported in clinical trials, and also suggest a possible largely unexplored lipid-related biochemical pathway for the action of this drug.

  • Precision biomarkers for mood disorders based on brain imaging
    Runsen Chen, Zaixu Cui, Liliana Capitão, Gang Wang, Theodore D Satterthwaite, and Catherine Harmer
    BMJ
    Identification of biomarkers could facilitate earlier diagnosis and better treatment, say Runsen Chen and colleagues

  • A single administration of ‘microbial’ D-alanine to healthy volunteers augments reaction to negative emotions: A comparison with D-serine
    Liliana P Capitão, Jessica Forsyth, Mia A Thomaidou, Mark D Condon, Catherine J Harmer, and Philip WJ Burnet
    SAGE Publications
    Background: Activation of the glutamate N-methyl-D-aspartate receptor with its co-agonist D-serine has been shown to improve subjective mood in healthy volunteers. D-alanine is another potent N-methyl-D-aspartate receptor co-agonist which arises from the natural breakdown of host gut microbes, and is predominantly sequestered in the pituitary. This may suggest that D-alanine influences the neuroendocrine stress response which may then impact on emotion. Aims: The current study explored the effects of D-serine and D-alanine on emotional processing, cognition and the levels of the stress hormone cortisol in healthy volunteers. Methods: In a double-blind, placebo-controlled randomised study, participants ( n=63) received a single oral dose of either D-serine, D-alanine (60 mg/kg) or placebo and then performed the Emotional Test Battery and N-back task (two hours post-administration) and provided saliva samples at fixed intervals. Results: Subjects administered with D-alanine were faster at identifying facial expressions of fear, surprise and anger, and at categorising negative self-referential words. Participants on D-alanine also showed a trend to recall more words than placebo in a memory task. D-serine did not have any meaningful effects in any of the tasks. Neither amino acid had a significant effect on salivary cortisol or working memory. Conclusion: This study is the first to suggest that D-alanine can modulate emotional cognitive processing after a single dose. The lack of findings for D-serine nevertheless contrasts a previous study, emphasising a need for further investigation to clarify discrepancies. A better understanding of the physiological actions of D-amino acids would be beneficial in evaluating their therapeutic potential.

  • Prebiotic supplementation does not affect reading and cognitive performance in children: A randomised placebo-controlled study
    Liliana P Capitão, Rita Baião, Hee K Baek, Nils Kappelmann, Rachel Sharman, Christopher-James Harvey, Paul Montgomery, and Philip WJ Burnet
    SAGE Publications
    Based on the emerging interest in the effects of gut microbiota on cognition, this proof-of-concept study assessed how children aged 7 to 9 with low reading scores responded to the ingestion of a 3-month prebiotic supplement versus a placebo. As a secondary aim, the effects of the prebiotic on cognition, sleep, behaviour, mood, anxiety, and cortisol were assessed. In this sample, the prebiotic did not affect any of the outcome measures.

  • A single dose of fluoxetine reduces neural limbic responses to anger in depressed adolescents
    Liliana P. Capitão, Robert Chapman, Susannah E. Murphy, Christopher-James Harvey, Anthony James, Philip J. Cowen, and Catherine J. Harmer
    Springer Science and Business Media LLC
    Depression in adolescence is frequently characterised by symptoms of irritability. Fluoxetine is the antidepressant with the most favourable benefit:risk ratio profile to treat adolescent depression, but the neural mechanisms underlying antidepressant drugs in the young brain are still poorly understood. Previous studies have characterised the neural effects of long-term fluoxetine treatment in depressed adolescents, but these are limited by concurrent mood changes and a lack of placebo control. There is also recent evidence suggesting that fluoxetine reduces the processing of anger in young healthy volunteers, which is consistent with its effect for the treatment of irritability in this age group, but this remains to be investigated in depressed adolescents. Here we assessed the effects of a single, first dose of 10 mg fluoxetine vs. placebo on neural response to anger cues using fMRI in a sample of adolescents with Major Depressive Disorder (MDD) who had been recently prescribed fluoxetine. As predicted, adolescents receiving fluoxetine showed reduced activity in response to angry facial expressions in the amygdala-hippocampal region relative to placebo. Activity in the dorsal anterior cingulate cortex (dACC) was also increased. No changes in symptoms were observed. These results demonstrate, for the first time in depressed adolescents, that fluoxetine has immediate neural effects on core components of the cortico-limbic circuitry prior to clinical changes in mood. The effect on anger is consistent with our previous work and could represent a key mechanism through which fluoxetine may act to alleviate irritability symptoms in adolescent depression.

  • Co-Production: An Ethical Model for Mental Health Research?
    Sapfo Lignou, Liliana Capitao, Julia Madeleine Hamer-Hunt, and Ilina Singh
    Informa UK Limited

  • Psychoeducation for psychiatric inpatients following remission of a manic episode in bipolar I disorder: A randomized controlled trial
    Runsen Chen, Xuequan Zhu, Liliana P Capitão, Huijun Zhang, Jiong Luo, Xue Wang, Yingjun Xi, Xiuping Song, Yancun Feng, Liuzhong Cao,et al.
    Wiley
    The aim of the present study was to evaluate the effectiveness of psychoeducation for bipolar I inpatients following remission of a manic episode in a Chinese population.

  • Acute fluoxetine modulates emotional processing in young adult volunteers
    L. P. Capitão, S. E. Murphy, M. Browning, P. J. Cowen, and C. J. Harmer
    Cambridge University Press (CUP)
    BackgroundFluoxetine is generally regarded as the first-line pharmacological treatment for young people, as it is believed to show a more favourable benefit:risk ratio than other antidepressants. However, the mechanisms through which fluoxetine influences symptoms in youth have been little investigated. This study examined whether acute administration of fluoxetine in a sample of young healthy adults altered the processing of affective information, including positive, sad and anger cues.MethodA total of 35 male and female volunteers aged between 18 and 21 years old were randomized to receive a single 20 mg dose of fluoxetine or placebo. At 6 h after administration, participants completed a facial expression recognition task, an emotion-potentiated startle task, an attentional dot-probe task and the Rapid Serial Visual Presentation. Subjective ratings of mood, anxiety and side effects were also taken pre- and post-fluoxetine/placebo administration.ResultsRelative to placebo-treated participants, participants receiving fluoxetine were less accurate at identifying anger and sadness and did not show the emotion-potentiated startle effect. There were no overall significant effects of fluoxetine on subjective ratings of mood.ConclusionsFluoxetine can modulate emotional processing after a single dose in young adults. This pattern of effects suggests a potential cognitive mechanism for the greater benefit:risk ratio of fluoxetine in adolescent patients.

  • Anxiety increases breakthrough of threat stimuli in continuous flash suppression
    Liliana P. Capitão, Stacey J. V. Underdown, Samuel Vile, Eunice Yang, Catherine J. Harmer, and Susannah E. Murphy
    American Psychological Association (APA)
    Trait anxiety is associated with an excessive processing of danger-related stimuli, predisposing individuals to quickly detect threatening cues. Early, automatic mechanisms are believed to be responsible for the production of these cognitive biases; however, limitations in the paradigms most commonly used to achieve visual suppression or attentional unawareness have left open the possibility of strategic mechanisms influencing these early stages of information processing. Establishing whether symptoms of anxiety are associated with truly automatic biases in processing is an essential step in determining their etiology and in developing targeted cognitive interventions. We addressed this question using continuous flash suppression (CFS), a novel and robust method of visual suppression capable of rendering a stimulus invisible from awareness for extended durations. We specifically investigated the degree to which trait anxiety influenced the suppression of threatening, positive, and neutral faces. Forty-nine individuals, with no reported history of psychological problems and varying levels of anxiety, were recruited. Higher trait anxiety scores were associated with an increased speed to detect fearful compared with happy faces. These results indicate that the bias toward threatening information associated with symptoms of anxiety operates, at least partly, at an early stage of information processing. This suggests that cognitive interventions for anxiety may benefit from directly targeting such early and potentially preconscious processes.

  • Variation in serotonin transporter expression modulates fear-evoked hemodynamic responses and theta-frequency neuronal oscillations in the amygdala
    Christopher Barkus, Samantha J. Line, Anna Huber, Liliana Capitao, Joao Lima, Katie Jennings, John Lowry, Trevor Sharp, David M. Bannerman, and Stephen B. McHugh
    Elsevier BV
    Background Gene association studies detect an influence of natural variation in the 5-hydroxytryptamine transporter (5-HTT) gene on multiple aspects of individuality in brain function, ranging from personality traits through to susceptibility to psychiatric disorders such as anxiety and depression. The neural substrates of these associations are unknown. Human neuroimaging studies suggest modulation of the amygdala by 5-HTT variation, but this hypothesis is controversial and unresolved, and difficult to investigate further in humans. Methods We used a mouse model in which the 5-HTT is overexpressed throughout the brain and recorded hemodynamic responses (using a novel in vivo voltammetric monitoring method, analogous to blood oxygen level–dependent functional magnetic resonance imaging) and local field potentials during Pavlovian fear conditioning. Results Increased 5-HTT expression impaired, but did not prevent, fear learning and significantly reduced amygdala hemodynamic responses to aversive cues. Increased 5-HTT expression was also associated with reduced theta oscillations, which were a feature of aversive cue presentation in controls. Moreover, in control mice, but not those with high 5-HTT expression, there was a strong correlation between theta power and the amplitude of the hemodynamic response. Conclusions Direct experimental manipulation of 5-HTT expression levels throughout the brain markedly altered fear learning, amygdala hemodynamic responses, and neuronal oscillations.

  • Aversive prediction error signals in the amygdala
    S. B. McHugh, C. Barkus, A. Huber, L. Capitao, J. Lima, J. P. Lowry, and D. M. Bannerman
    Society for Neuroscience
    Prediction error signals are fundamental to learning. Here, in mice, we show that aversive prediction signals are found in the hemodynamic responses and theta oscillations recorded from the basolateral amygdala. During fear conditioning, amygdala responses evoked by footshock progressively decreased, whereas responses evoked by the auditory cue that predicted footshock concomitantly increased. Unexpected footshock evoked larger amygdala responses than expected footshock. The magnitude of the amygdala response to the footshock predicted behavioral responses the following day. The omission of expected footshock led to a decrease below baseline in the amygdala response suggesting a negative aversive prediction error signal. Thus, in mice, amygdala activity conforms to temporal difference models of aversive learning.

  • MRI amygdala volume in Williams Syndrome
    Liliana Capitão, Adriana Sampaio, Cassandra Sampaio, Cristiana Vasconcelos, Montse Férnandez, Elena Garayzábal, Martha E. Shenton, and Óscar F. Gonçalves
    Elsevier BV
    One of the most intriguing characteristics of Williams Syndrome individuals is their hypersociability. The amygdala has been consistently implicated in the etiology of this social profile, particularly given its role in emotional and social behavior. This study examined amygdala volume and symmetry in WS individuals and in age and sex matched controls. Magnetic resonance imaging scans were obtained on a GE 1.5-T magnet with 1.5-mm contiguous slices and were used to measure whole gray matter, white matter and cerebrospinal fluid volumes, as well as amygdala volume (right and left). Results revealed significantly reduced intracranial volume in individuals with WS, compared with controls. There were no differences between groups in absolute amygdalae volume, although there was a relative increase in amygdalae volumes, when adjusted for total intracranial content. There were no inter-hemispheric differences in amygdalae volumes in both groups. These results suggest a relative increase in amygdala volume in WS compared with healthy controls that likely reflects abnormal neurodevelopmental processes of midline brain structures.

  • Williams syndrome hypersociability: A neuropsychological study of the amygdala and prefrontal cortex hypotheses
    Liliana Capitão, Adriana Sampaio, Montse Férnandez, Nuno Sousa, Ana Pinheiro, and Óscar F. Gonçalves
    Elsevier BV
    Individuals with Williams syndrome display indiscriminate approach towards strangers. Neuroimaging studies conducted so far have linked this social profile to structural and/or functional abnormalities in WS amygdala and prefrontal cortex. In this study, the neuropsychological hypotheses of amygdala and prefrontal cortex involvement in WS hypersociability was explored using three behavioral tasks--facial emotional recognition task, a social approach task and a go no/go task. Thus, a group 15 individuals with Williams syndrome was compared to two groups of normal developing individuals--a group of 15 individuals matched for chronological age (CA) and 15 individuals matched for mental age (MA), and sex. Individuals with WS present a specific impairment in recognizing negative facial expressions and do not display impairments in response inhibition when compared with typically developing groups. Although these findings partially support the amygdala contribution to WS hypersociability, we found that general cognitive functioning predicted this performance. Additionally, individuals with WS did not differ from both CA and MA groups in the recognition of angry facial expressions, a finding suggesting that they are actually able to identify stimuli associated with social threat. Overall, the results seem to indicate that this social profile must be understood within a developmental framework.

RECENT SCHOLAR PUBLICATIONS

  • “Raging hearts”: Recalling an Anger Incident Increases Heart Rate Variability in Men Prone to Anger
    L Capitao, C Fagundes, M Verbecke, A Stavropoulou-Deli, D Folloni, ...
    OSF 2025

  • Acute neural effects of the mood stabiliser lamotrigine on emotional processing in healthy volunteers: a randomised control trial
    MAG Martens, T Zghoul, E Watson, SW Rieger, LP Capito, CJ Harmer
    Translational Psychiatry 14 (1), 211 2024

  • “Invisible Dangers”: unconscious processing of angry vs fearful faces and its relationship to subjective anger
    A Pelliet, M Nogueira, C Fagundes, S Capela, F Saraiva, E Pulcu, ...
    OSF 2024

  • “Invisible Dangers”: preconscious detection of fearful vs angry faces influences the subjective experience of anger
    A Pelliet, M Nogueira, C Fagundes, S Capela, F Saraiva, E Pulcu, ...
    OSF 2024

  • An experimental medicine study of the effects of nicardipine on emotional processing in healthy volunteers with mood instability
    L Colbourne, L Atkinson, L Capitao, A Gillespie, M Martens, C Harmer, ...
    Neuroscience Applied 3, 104181 2024

  • " Unseen Threats": preconscious detection of fearful vs angry faces influences the subjective experience of anger
    M Nogueira, A Pelliet, C Fagundes, S Capela, F Saraiva, E Pulcu, ...
    Neuroscience Applied 3, 105214 2024

  • Uncovering the invisible: early adversity's role in adolescent emotion processing
    M Nogueira, SS Sousa, P Oliveira, I Soares, A Mesquita, LP Capito
    Neuroscience Applied 3, 104509 2024

  • A single dose of lamotrigine induces a positive memory bias in healthy volunteers
    T Zghoul, PA Hortelano, A Kaltenboeck, L Wright, G Goodwin, L Capito, ...
    medRxiv, 2023.12. 06.23299597 2023

  • Effects of ulotaront on brain circuits of reward, working memory, and emotion processing in healthy volunteers with high or low schizotypy
    F Perini, JM Nazimek, S Mckie, LP Capito, J Scaife, D Pal, M Browning, ...
    Schizophrenia 9 (1), 49 2023

  • Acute neural effects of fluoxetine on emotional regulation in depressed adolescents
    LP Capito, R Chapman, N Filippini, L Wright, SE Murphy, A James, ...
    Psychological Medicine 53 (10), 4799-4810 2023

  • Multispecies probiotic administration reduces emotional salience and improves mood in subjects with moderate depression: a randomised, double-blind, placebo-controlled study
    R Baio, LP Capito, C Higgins, M Browning, CJ Harmer, PWJ Burnet
    Psychological Medicine 53 (8), 3437-3447 2023

  • Effects of ulotaront on brain circuits of reward, working memory, and emotion processing in healthy volunteers with high or low schizotypy
    L Capitao, J Scaife, D Pal, M Browning, CJ Harmer
     2023

  • The Effect of the 5-HT4 Agonist, Prucalopride, on a Functional Magnetic Resonance Imaging Faces Task in the Healthy Human Brain
    AN de Cates, MAG Martens, LC Wright, CD Gould van Praag, LP Capito, ...
    Frontiers in Psychiatry 13, 859123 2022

  • Effect of the NMDA receptor partial agonist, d-cycloserine, on emotional processing and autobiographical memory
    R Chen, LP Capito, PJ Cowen, CJ Harmer
    Psychological medicine 51 (15), 2657-2665 2021

  • Active Ingredients for Addressing Youth Anxiety and Depression 2. The knowns and unknowns of SSRI treatment in young people with depression and anxiety: Efficacy, predictors
    SE Murphy, LP Capitao, SLC Giles, PJ Cowen, A Stringaris, CJ Harmer
    The Lancet Psychiatry 2021

  • The knowns and unknowns of SSRI treatment in young people with depression and anxiety: efficacy, predictors, and mechanisms of action
    SE Murphy, LP Capito, SLC Giles, PJ Cowen, A Stringaris, CJ Harmer
    The Lancet Psychiatry 8 (9), 824-835 2021

  • Hydrocortisone as an adjunct to brief cognitive-behavioural therapy for specific fear: Endocrine and cognitive biomarkers as predictors of symptom improvement
    S Steudte-Schmiedgen, E Fay, L Capitao, C Kirschbaum, A Reinecke
    Journal of Psychopharmacology 35 (6), 641-651 2021

  • A single, clinically relevant dose of the GABAB agonist baclofen impairs visuomotor learning
    A Johnstone, I Grigoras, P Petitet, LP Capito, CJ Stagg
    The Journal of physiology 599 (1), 307-322 2021

  • Neural effects of a single dose of fluoxetine on resting-state functional connectivity in adolescent depression
    LP Capito, R Chapman, N Filippini, L Wright, SE Murphy, A James, ...
    Journal of Psychopharmacology 34 (12), 1461-1465 2020

  • Precision biomarkers for mood disorders based on brain imaging
    R Chen, Z Cui, L Capito, G Wang, TD Satterthwaite, C Harmer
    bmj 371 2020

MOST CITED SCHOLAR PUBLICATIONS

  • ENIGMA MDD: seven years of global neuroimaging studies of major depression through worldwide data sharing
    L Schmaal, E Pozzi, T C. Ho, LS Van Velzen, IM Veer, N Opel, ...
    Translational psychiatry 10 (1), 172 2020
    Citations: 187

  • Aversive prediction error signals in the amygdala
    SB McHugh, C Barkus, A Huber, L Capitao, J Lima, JP Lowry, ...
    Journal of Neuroscience 34 (27), 9024-9033 2014
    Citations: 98

  • The knowns and unknowns of SSRI treatment in young people with depression and anxiety: efficacy, predictors, and mechanisms of action
    SE Murphy, LP Capito, SLC Giles, PJ Cowen, A Stringaris, CJ Harmer
    The Lancet Psychiatry 8 (9), 824-835 2021
    Citations: 81

  • Crenas e atitudes dos profissionais face violncia conjugal: estudos com profissionais de sade, polcias e professores
    C Machado, M Matos, RMM Saavedra, OFS Cruz, CMV Antunes, ...
    Ordem dos Mdicos 2009
    Citations: 66

  • Anxiety increases breakthrough of threat stimuli in continuous flash suppression.
    LP Capito, SJV Underdown, S Vile, E Yang, CJ Harmer, SE Murphy
    Emotion 14 (6), 1027 2014
    Citations: 65

  • MRI amygdala volume in Williams Syndrome
    L Capitao, A Sampaio, C Sampaio, C Vasconcelos, M Fernandez, ...
    Research in Developmental Disabilities 32 (6), 2767-2772 2011
    Citations: 56

  • Williams syndrome hypersociability: A neuropsychological study of the amygdala and prefrontal cortex hypotheses
    L Capito, A Sampaio, M Frnandez, N Sousa, A Pinheiro, OF Gonalves
    Research in Developmental Disabilities 32 (3), 1169-1179 2011
    Citations: 42

  • Multispecies probiotic administration reduces emotional salience and improves mood in subjects with moderate depression: a randomised, double-blind, placebo-controlled study
    R Baio, LP Capito, C Higgins, M Browning, CJ Harmer, PWJ Burnet
    Psychological Medicine 53 (8), 3437-3447 2023
    Citations: 41

  • Psychoeducation for psychiatric inpatients following remission of a manic episode in bipolar I disorder: A randomized controlled trial
    R Chen, X Zhu, LP Capito, H Zhang, J Luo, X Wang, Y Xi, X Song, ...
    Bipolar Disorders 21 (1), 76-85 2019
    Citations: 41

  • Acute fluoxetine modulates emotional processing in young adult volunteers
    LP Capito, SE Murphy, M Browning, PJ Cowen, CJ Harmer
    Psychological medicine 45 (11), 2295-2308 2015
    Citations: 39

  • Variation in serotonin transporter expression modulates fear-evoked hemodynamic responses and theta-frequency neuronal oscillations in the amygdala
    C Barkus, SJ Line, A Huber, L Capitao, J Lima, K Jennings, J Lowry, ...
    Biological psychiatry 75 (11), 901-908 2014
    Citations: 39

  • Experincias adversas e funcionamento actual: um estudo com jovens portugueses
     Maia, C Guimares, E Magalhes, L Capito, M Campos, S Capela
    Associao Portuguesa de Psicologia 2006
    Citations: 30

  • Maus-tratos na infncia, psicopatologia e satisfao com a vida: um estudo com jovens portugueses
     Maia, C Guimares, C Carvalho, L Capito, S Carvalho, S Capela
    Universidade do Minho 2007
    Citations: 28

  • A single dose of fluoxetine reduces neural limbic responses to anger in depressed adolescents
    LP Capito, R Chapman, SE Murphy, CJ Harvey, A James, PJ Cowen, ...
    Translational psychiatry 9 (1), 30 2019
    Citations: 27

  • Co-production: an ethical model for mental health research?
    S Lignou, L Capitao, JM Hamer-Hunt, I Singh
    The American Journal of Bioethics 19 (8), 49-51 2019
    Citations: 26

  • A single administration of the antibiotic, minocycline, reduces fear processing and improves implicit learning in healthy volunteers: analysis of the serum metabolome
    SY Chan, L Capito, F Probert, C Klinge, S Hoeckner, CJ Harmer, ...
    Translational Psychiatry 10 (1), 148 2020
    Citations: 16

  • A single, clinically relevant dose of the GABAB agonist baclofen impairs visuomotor learning
    A Johnstone, I Grigoras, P Petitet, LP Capito, CJ Stagg
    The Journal of physiology 599 (1), 307-322 2021
    Citations: 14

  • Precision biomarkers for mood disorders based on brain imaging
    R Chen, Z Cui, L Capito, G Wang, TD Satterthwaite, C Harmer
    bmj 371 2020
    Citations: 12

  • The Effect of the 5-HT4 Agonist, Prucalopride, on a Functional Magnetic Resonance Imaging Faces Task in the Healthy Human Brain
    AN de Cates, MAG Martens, LC Wright, CD Gould van Praag, LP Capito, ...
    Frontiers in Psychiatry 13, 859123 2022
    Citations: 11

  • Effect of the NMDA receptor partial agonist, d-cycloserine, on emotional processing and autobiographical memory
    R Chen, LP Capito, PJ Cowen, CJ Harmer
    Psychological medicine 51 (15), 2657-2665 2021
    Citations: 10