Early effects of fluoxetine on emotional processing: implications for adolescent depression

Depression in adolescence is a major health problem, associated with poor psychological function and key risk factors both for later illness and suicidal behaviours. The antidepressant fluoxetine is commonly used in this population and it is shown to have a favourable benefit-to-risk profile. However, controversy still exists about the use of antidepressants in young people and there is little research focusing on underlying mechanisms of wanted and unwanted actions in this group. This doctoral thesis aims to investigate, for the first time, the acute effects of fluoxetine on emotional processing, using a combination of behavioural and neuroimaging techniques. The aim is to achieve a greater understanding of the mechanisms underlying fluoxetine use in depressed adolescents, in light of differences seen in their clinical presentation and response to antidepressant drugs. In the first study (Chapter Two), a single dose of fluoxetine was shown to decrease the recognition of anger in a sample of young adult volunteers, an effect not previously seen in acute studies of older participants. This effect may be particularly relevant for the treatment of adolescent depression, in which symptoms of anger and irritability are often prominent. Beyond this, fluoxetine was shown to increase the recognition of positive vs. negative facial information, and also exerted an anxiolytic-like influence, eliminating the emotion-potentiated startle effect. However, no influence was seen in measures of attentional vigilance to threat. In an attempt to overcome methodological limitations of this study, a paradigm was developed that is particularly sensitive to the detection of automatic biases towards threatening information (Chapter Three). Chapter Four describes a neuroimaging study with depressed adolescents, in which a single dose of fluoxetine was found to reduce amygdala activity in response to anger. Early changes in amygdala activity to fear correlated with decreased symptoms of anxiety and depression in the first 7-10 days of treatment. Chapter Five explores the effects of acute fluoxetine in a sample of high trait anger males. This study replicated the finding that fluoxetine acts to increase the recognition of positive information, whilst showing preliminary evidence for a reduction in attentional vigilance to angry faces. Overall, fluoxetine was found to decrease the processing of anger across studies. This effect was seen alongside a broader influence on positive vs. negative information and anxiolytic-like properties. Together, these results indicate that fluoxetine has direct effects on processes that are especially relevant to adolescent depression and suggest a potential cognitive mechanism for the efficacy of this particular antidepressant in adolescent patients.</p

Early effects of fluoxetine on emotional processing: implications for adolescent depression

Depression in adolescence is a major health problem, associated with poor psychological function and key risk factors both for later illness and suicidal behaviours. The antidepressant fluoxetine is commonly used in this population and it is shown to have a favourable benefit-to-risk profile. However, controversy still exists about the use of antidepressants in young people and there is little research focusing on underlying mechanisms of wanted and unwanted actions in this group. This doctoral thesis aims to investigate, for the first time, the acute effects of fluoxetine on emotional processing, using a combination of behavioural and neuroimaging techniques. The aim is to achieve a greater understanding of the mechanisms underlying fluoxetine use in depressed adolescents, in light of differences seen in their clinical presentation and response to antidepressant drugs. In the first study (Chapter Two), a single dose of fluoxetine was shown to decrease the recognition of anger in a sample of young adult volunteers, an effect not previously seen in acute studies of older participants. This effect may be particularly relevant for the treatment of adolescent depression, in which symptoms of anger and irritability are often prominent. Beyond this, fluoxetine was shown to increase the recognition of positive vs. negative facial information, and also exerted an anxiolytic-like influence, eliminating the emotion-potentiated startle effect. However, no influence was seen in measures of attentional vigilance to threat. In an attempt to overcome methodological limitations of this study, a paradigm was developed that is particularly sensitive to the detection of automatic biases towards threatening information (Chapter Three). Chapter Four describes a neuroimaging study with depressed adolescents, in which a single dose of fluoxetine was found to reduce amygdala activity in response to anger. Early changes in amygdala activity to fear correlated with decreased symptoms of anxiety and depression in the first 7-10 days of treatment. Chapter Five explores the effects of acute fluoxetine in a sample of high trait anger males. This study replicated the finding that fluoxetine acts to increase the recognition of positive information, whilst showing preliminary evidence for a reduction in attentional vigilance to angry faces. Overall, fluoxetine was found to decrease the processing of anger across studies. This effect was seen alongside a broader influence on positive vs. negative information and anxiolytic-like properties. Together, these results indicate that fluoxetine has direct effects on processes that are especially relevant to adolescent depression and suggest a potential cognitive mechanism for the efficacy of this particular antidepressant in adolescent patients.This thesis is not currently available in OR

“Invisible Dangers”: preconscious detection of fearful vs angry faces influences the subjective experience of anger

Anger can profoundly disrupt psychological and social well-being when experienced intensely. Yet, our understanding of the cognitive mechanisms (both conscious and preconscious) underlying anger and their connection to subjective experience remains limited. This preliminary study investigated the relationship between preconscious detection of angry faces (vs happy and fear) and the subjective experience of anger. Thirty participants were administered a robust measure of preconscious processing - Continuous Flash Suppression -, followed by an anger induction protocol. Results showed a significantly quicker detection of fearful than happy faces and a trend for a faster anger detection over happiness, aligning with prior research suggesting a preconscious prioritization of threat stimuli. Our protocol was effective in eliciting subjective anger, but no significant association emerged between detection of angry faces and state anger symptoms following the anger induction. Interestingly, however, participants showing faster detection of fear relative to anger displayed increased state anger post-induction. This finding suggests that a preferential detection of fearful vs slower detection of angry faces could ultimately contribute to an increased predisposition to experience anger following an anger-inducing event, hence shedding light on the early cognitive mechanisms influencing subjective emotional experiences. Future work is needed to further explore this effect

Data

Questionnaire and fMRI behavioural data for the 7 day prucalopride stud

Qualtrics template files

The Master Template file includes the following questionnaires: • BDI (Beck Depression Inventory - 21Q)* • EPQ (Eysenck Personality Questionnaire 90Q)* • Locus of Control (29Q)* • STAI-T (State-Trait Anxiety Inventory - Trait 20Q)* • STAI-S (State-Trait Anxiety Inventory - State 20Q)* • PANAS (Positive and Negative Affect Scale 20Q)* • SHAPS (Snaith-Hamilton Pleasure Scale 14Q)* • VAS (Visual Analogue Scales -combined 6Q) • VAS (Visual Analogue Scales -individual 16Q) • EHI (Edinburgh Handedness Inventory) • BIS (Barratt Impulsiveness Scale 30Q) • AGQ (Buss Perry Aggression Questionnaire 29Q) • ASEC (Anti-depressant Side Effect Checklist 18Q) • PHQ-9 (Patient Health Questionnaire 9Q) • GAD-7 (Generalised Anxiety Disorder 7Q) • BFNE (Brief Fear of Negative Evaluation 8Q) • FPES (Fear of Positive Evaluation 10Q) • BFIN (Big Five Inventory 8Q) • RESES (Rosenberg Self Esteem 10Q) • DAS24 (Derriford Appearance - short 24Q) • STAXI-S (State-Trait Anger Expression Inventory - State) • STAXI-T (State-Trait Anger Expression Inventory - Trait) • STAXI-AEC (State-Trait Anger Expression Inventory - Anger Expression and Control) • AMI (Apathy Motivation Index 18Q) • Epworth Sleepiness Scale (8Q) • HADS (Hospital Anxiety and Depression Scale 14Q) • PDQ (Perceived Deficits Questionnaire 20Q) • QUIP (Questionnaire for Impulsive-compulsive disorders in Parkinson's 15Q) • UDPRS Part I nM-EDL (Unified Parkinson's disease rating scale) Part 1 - Non Motor Aspects Experiences of Daily Living (7Q) • UDPRS Part II M-EDL (Unified Parkinson's disease rating scale) Part 2 - Non Motor Aspects Experiences of Daily Living (13Q) • PDQ (Perceived Deficits Questionnaire 20Q) • RBDSQ (REM Sleep Behaviour Disorder Screening 16Q) • BADS (behavioural activation for depression scale 25Q) • EROS (environmental reward observation scale 10Q) • MSPSS (multidimension scale of perceived social support 12Q) * = with scoring To use, download the file, then on qualtrics choose to Create a Project from Existing, select From a File and then navigate to select the Master Template file. This will be added to your library, and you can then rename it and remove or add questionnaires to suit your study. If you would like to to help add to the Master Template, feel free to do the above, and then add additional blocks of questions, and re-upload here (keeping the same file name as the download). The UDPRS III Motor Examination template is seperate, as an examiner rated scale - all the others are completed by participants