[Show abstract][Hide abstract] ABSTRACT: The Hypothalamic-Pituitary-Adrenal (HPA) axis has been proposed as a potential underlying biological mechanism linking prenatal depression with adverse offspring outcomes. However, it is unknown whether the reactivity of this system to stress is altered in pregnant women experiencing depression. The objective of this study was to investigate whether salivary cortisol response to a distressed infant film is enhanced in pregnant women with symptoms of depression compared with non-depressed controls. Salivary cortisol and subjective mood responses to the film were measured in 53 primiparous women, between 11 and 18 weeks gestation. Both groups showed similar increases in state anxiety in response to the film, but there was a significantly increased cortisol response in women experiencing symptoms of depression. Depression during pregnancy is associated with increased reactivity of the HPA axis. This is consistent with altered HPA axis functioning being a key mechanism by which prenatal mood disturbance can impact upon fetal development.
Archives of Women s Mental Health 10/2014; 18(2). DOI:10.1007/s00737-014-0473-0 · 2.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
[Show abstract][Hide abstract] ABSTRACT: Maternal antenatal anxiety is associated with an increased risk of behavioral disturbances in offspring. Recent work has suggested that the effect of maternal antenatal anxiety on infant temperament at 6 months is moderated by the serotonin transporter polymorphism 5-HTTLPR, with carriers of the short allele more susceptible to the adverse behavioral outcomes of maternal antenatal anxiety. These findings, however, are yet to be replicated and extended beyond infancy. The aim of the current study was to assess this same potential moderator (5-HTTLPR) in a large population-based cohort study, and to determine whether or not the effects persist into childhood and early adolescence.
Data from the Avon Longitudinal Study of Children and Parents (ALSPAC) cohort (N = 3,946) were used to assess whether the 5-HTTLPR genotype moderated the association between self-reported maternal antenatal anxiety (Crown Crisp Index) in pregnancy, and child temperament at 6 months (Infant Temperament Questionnaire), and also later behavioral and emotional problems on the Strengths and Difficulties Questionnaire from age 4 to 13 years.
We found no evidence to suggest that the 5-HTTLPR polymorphism moderated the effects of maternal antenatal anxiety on infant temperament at 6 months or infant behavioral and emotional problems from childhood through to adolescence.
Our results, based on a large prospective community sample that assessed children from infancy to early adolescence, provide a thorough test of, but no evidence for, a genetic moderation of the effects of maternal antenatal anxiety by 5-HTTLPR.
Journal of the American Academy of Child and Adolescent Psychiatry 05/2013; 52(5):519-26. DOI:10.1016/j.jaac.2013.02.010 · 7.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Parental depression is a risk factor for psychiatric problems in children and adolescents. Exciting scientific developments have elucidated potential early mechanisms of intergenerational risk transmission and new models of intervention may help to prevent some childhood problems. However, caution is needed in interpreting such associations as causal and in targeting interventions appropriately.
The British journal of psychiatry: the journal of mental science 02/2013; 202(2):84-5. DOI:10.1192/bjp.bp.112.115659 · 7.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Investigating pharmacological modulation of brain activity using magnetic resonance imaging (MRI) presents an exciting opportunity to bridge the gap between preclinical and clinical studies, and holds the potential to be a useful tool in the discovery and development of novel therapeutic agents. Most functional MRI studies to date have utilized the blood oxygen level dependent (BOLD) contrast mechanism. Although this has some advantages over other techniques and is widely available, BOLD has two significant limitations for the study of drug effects; it is an indirect measurement of neuronal function, and produces only a relative (non-quantitative) measure of blood dynamics. Here we describe the various experimental manipulations that have been used to reduce the impact of these limitations, and discuss new ways of collecting and analysing imaging data that allow us to assess functional connectivity of the brain. We recommend some complementary techniques (such as arterial spin labelling and magnetoencephalography) that, if used in conjunction with BOLD functional MRI, will increase the interpretability and thus the utility of MRI for pharmacology research.
Journal of Psychopharmacology 09/2011; 25(9):1168-74. DOI:10.1177/0269881110372547 · 3.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A tendency to orient attention toward threatening stimuli may be involved in the etiology of anxiety disorders. In keeping with this, both psychological and pharmacological treatments of anxiety reduce this negative attentional bias. It has been hypothesized, but not proved, that psychological interventions may alter the function of prefrontal regions supervising the allocation of attentional resources.
The current study examined the effects of a cognitive training regime on attention. Participants were randomly assigned to one of two training conditions: "attend-threat" training, which increases negative attentional bias, or "avoid-threat" training, which reduces it. The behavioral effects of training were assessed using a sample of 24 healthy participants. Functional magnetic resonance imaging data were collected in a further 29 healthy volunteers using a protocol that allowed the influence of both stimuli valence and attention to be discriminated.
Cognitive training induced the expected attentional biases in healthy volunteers. Further, the training altered lateral frontal activation to emotional stimuli, with these areas responding specifically to violations of the behavioral rules learned during training. Connectivity analysis confirmed that the identified lateral frontal regions were influencing attention as indexed by activity in visual association cortex.
Our results indicate that frontal control over the processing of emotional stimuli may be tuned by psychological interventions in a manner predicted to regulate levels of anxiety. This directly supports the proposal that psychological interventions may influence attention via an effect on the prefrontal cortex.
[Show abstract][Hide abstract] ABSTRACT: Selective serotonin reuptake inhibitors (SSRIs) are effective in the treatment of depression and a range of anxiety disorders [1;2]. Preclinical models have been relatively successful at elucidating the key neurochemical effects of these serotonergic agents; however, a lack of understanding exists of the functional mechanisms by which these drugs exert their effects on mood and anxiety. Elucidating the link between the neurochemical effects of these drugs and their therapeutic action is an essential step in further understanding some of the current limitations of SSRIs, and in developing novel agents that are more selectively designed to target the symptoms they treat. An increasingly popular experimental method within psychopharmacological research is the use of functional neuroimaging techniques to investigate the pharmacological modulation of task-induced brain activity by psychoactive drugs. Such an approach offers an exciting opportunity to investigate the mechanisms of drug action and, in this way, bridge the gap between preclinical and clinical studies. Applying this approach to the study of SSRIs has highlighted that direct modulation of activity in neural areas involved in emotional processing may represent a key functional mechanism through which these agents exert their antidepressant clinical effects. This review summarises the cognitive and neuroimaging evidence suggesting the critical role that disruptions in emotion-related processing play in depression and anxiety disorders. It then examines the functional neuroimaging evidence, from both patient and healthy volunteer studies, to suggest that the amelioration of such disruptions is a key mechanism through which SSRIs exert their therapeutic effects.
Current pharmaceutical design 04/2010; 16(18):1990-7. DOI:10.2174/138161210791293051 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We have previously demonstrated that antidepressant medication facilitates the processing of positive affective stimuli in healthy volunteers. These early effects of antidepressants may be an important component in the therapeutic effects of antidepressant treatment in patients with depression and anxiety.
Here we used functional magnetic resonance imaging in a double-blind, randomised, placebo-controlled between-groups design to investigate the effects of short-term (7-10 days) treatment with the selective serotonin reuptake inhibitor, citalopram, on the amygdala response to positive and negative facial expressions in healthy volunteers.
Citalopram was associated with increased amygdala activation to happy faces relative to placebo control, without changes in levels of mood or anxiety.
These early, direct effects of antidepressant administration on emotional processing are consistent with a cognitive neuropsychological model of antidepressant action.
[Show abstract][Hide abstract] ABSTRACT: Selective serotonin reuptake inhibitors (SSRIs) are typically thought to have a delay of several weeks in the onset of their clinical effects. However, recent reports suggest they may have a much earlier therapeutic onset. A reduction in amygdala responsivity has been implicated in the therapeutic action of SSRIs.
To investigate the effect of a single dose of an SSRI on the amygdala response to emotional faces.
Twenty-six healthy volunteers were randomised to receive a single oral dose of citalopram (20 mg) or placebo. Effects on the processing of facial expressions were assessed 3 h later using functional magnetic resonance imaging.
Volunteers treated with citalopram displayed a significantly reduced amygdala response to fearful facial expressions compared with placebo.
Such an immediate effect of an SSRI on amygdala responses to threat supports the idea that antidepressants have an earlier onset of therapeutically relevant effects than conventionally thought.
The British journal of psychiatry: the journal of mental science 07/2009; 194(6):535-40. DOI:10.1192/bjp.bp.108.056093 · 7.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Risky decision-making involves weighing good and bad outcomes against their probabilities in order to determine the relative values of candidate actions. Although human decision-making sometimes conforms to rational models of how this weighting is achieved, irrational (or nonnormative) patterns of risky choice, including shifts between risk-averse and risk-seeking choices involving equivalent-value gambles (the "reflection effect"), are frequently observed. In the present experiment, we investigated the role of serotonin in decision-making under conditions of uncertainty. Fifteen healthy adult volunteers received a treatment of 3 g per day of the serotonin precursor, tryptophan, in the form of dietary supplements over a 14-day period, whereas 15 age- and IQ-matched control volunteers received a matched placebo substance. At test, all participants completed a risky decision-making task involving a series of choices between two simultaneously presented gambles, differing in the magnitude of their possible gains, the magnitude of their possible losses, and the probabilities with which these outcomes were delivered. Tryptophan supplements were associated with alterations in the weighting of gains and small losses perhaps reflecting reduced loss-aversion, and a marked and significant diminution of the reflection effect. We conclude that serotonin activity plays a significant role in nonnormative risky decision-making under conditions of uncertainty.
[Show abstract][Hide abstract] ABSTRACT: Anxiety is associated with threat-related biases in information processing such as heightened attentional vigilance to potential threat. Such biases are an important focus of psychological treatments for anxiety disorders. Selective serotonin reuptake inhibitors (SSRIs) are effective in the treatment of a range of anxiety disorders. The aim of this study was to assess the effect of an SSRI on the processing of threat in healthy volunteers. A selective noradrenergic reuptake inhibitor (SNRI), which is not generally used in the treatment of anxiety, was used as a contrast to assess the specificity of SSRI effects on threat processing. Forty-two healthy volunteers were randomly assigned to 7 d double-blind intervention with the SSRI citalopram (20 mg/d), the SNRI reboxetine (8 mg/d), or placebo. On the final day, attentional and interpretative bias to threat was assessed using the attentional probe and the homograph primed lexical decision tasks. Citalopram reduced attentional vigilance towards fearful faces but did not affect the interpretation of ambiguous homographs as threatening. Reboxetine had no significant effect on either of these measures. Citalopram reduces attentional orienting to threatening stimuli, which is potentially relevant to its clinical use in the treatment of anxiety disorders. This finding supports a growing literature suggesting that an important mechanism through which pharmacological agents may exert their effects on mood is by reversing the cognitive biases that characterize the disorders that they treat. Future studies are needed to clarify the neural mechanisms through which these effects on threat processing are mediated.
The International Journal of Neuropsychopharmacology 09/2008; 12(2):169-79. DOI:10.1017/S1461145708009164 · 4.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We previously found that children of parents with depression showed impaired performance on a task of emotional categorisation.
To test the hypothesis that children of parents with depression would show abnormal neural responses in the anterior cingulate cortex, a brain region involved in the integration of emotional and cognitive information.
Eighteen young people (mean age 19.8 years) with no personal history of depression but with a biological parent with a history of major depression (FH+ participants) and 16 controls (mean age 19.9 years) underwent functional magnetic resonance imaging while completing an emotional counting Stroop task.
Controls showed significant activation in the pregenual anterior cingulate cortex to both positive and negative words during the emotional Stroop task. This activation was absent in FH+ participants.
Our findings show that people at increased familial risk of depression demonstrate impaired modulation of the anterior cingulate cortex in response to emotionally valenced stimuli.
The British Journal of Psychiatry 06/2008; 192(5):356-61. DOI:10.1192/bjp.bp.107.043398 · 7.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The serotonin precursor L-tryptophan (TRP) is available as a nutritional supplement and is licensed as an antidepressant in a number of countries. However, evidence of its efficacy as the primary treatment for depression is limited, and the direct action of TRP on the symptoms of depression and anxiety has not been well-characterised.
The present study assessed whether TRP induces cognitive changes opposite to the negative biases found in depression and characteristic of those induced by serotonergic antidepressants in healthy volunteers.
Thirty eight healthy volunteers were randomised to receive 14 days double-blind intervention with TRP (1 g 3x a day) or placebo. On the final day, emotional processing was assessed using four tasks: facial expression recognition, emotion-potentiated startle, attentional probe and emotional categorisation and memory.
TRP increased the recognition of happy facial expressions and decreased the recognition of disgusted facial expressions in female, but not male, volunteers. TRP also reduced attentional vigilance towards negative words and decreased baseline startle responsivity in the females.
These findings provide evidence that TRP supplementation in women induces a positive bias in the processing of emotional material that is reminiscent of the actions of serotonergic antidepressants. This highlights a key role for serotonin in emotional processing and lends support to the use of TRP as a nutritional supplement in people with mild depression or for prevention in those at risk. Future studies are needed to clarify the effect of tryptophan on these measures in men.