The association between negative attention biases and symptoms of depression in a community sample of adolescents

Adolescence is a vulnerable time for the onset of depression. Recent evidence from adult studies suggests not only that negative attention biases are correlated with symptoms of depression, but that reducing negative attention biases through training can in turn reduce symptomology. The role and plasticity of attention biases in adolescent depression, however, remains unclear. This study examines the association between symptoms of depression and attention biases, and whether such biases are modifiable, in a community sample of adolescents. We report data from 105 adolescents aged 13-17 who completed a dot-probe measure of attention bias before and after a single session of visual search-based cognitive bias modification training. This is the first study to find a significant association between negative attention biases and increased symptoms of depression in a community sample of adolescents. Contrary to expectations, we were unable to manipulate attention biases using a previously successful cognitive bias modification task. There were no significant effects of the training on positive affect and only modest effects of the training, identified in post-hoc analyses, were observed on negative affect. Our data replicate those from the adult literature, which suggest that adolescent depression is a disorder associated with negative attention biases, although we were unable to modify attention biases in our study. We identify numerous parameters of our methodology which may explain these null training effects, and which could be addressed in future cognitive bias modification studies of adolescent depression

Salivary cortisol response to infant distress in pregnant women with depressive symptoms.

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

The association between negative attention biases and symptoms of depression in a community sample of adolescents

Adolescence is a vulnerable time for the onset of depression. Recent evidence from adult studies suggests not only that negative attention biases are correlated with symptoms of depression, but that reducing negative attention biases through training can in turn reduce symptomology. The role and plasticity of attention biases in adolescent depression, however, remains unclear. This study examines the association between symptoms of depression and attention biases, and whether such biases are modifiable, in a community sample of adolescents. We report data from 105 adolescents aged 13-17 who completed a dot-probe measure of attention bias before and after a single session of visual search-based cognitive bias modification training. This is the first study to find a significant association between negative attention biases and increased symptoms of depression in a community sample of adolescents. Contrary to expectations, we were unable to manipulate attention biases using a previously successful cognitive bias modification task. There were no significant effects of the training on positive affect and only modest effects of the training, identified in post-hoc analyses, were observed on negative affect. Our data replicate those from the adult literature, which suggest that adolescent depression is a disorder associated with negative attention biases, although we were unable to modify attention biases in our study. We identify numerous parameters of our methodology which may explain these null training effects, and which could be addressed in future cognitive bias modification studies of adolescent depression

Effects of prenatal depressive symptoms on maternal and infant cortisol reactivity.

Prenatal depression is associated with adverse offspring outcomes, and the prevailing mechanistic theory to account for mood-associated effects implicates alterations of the maternal and foetal hypothalamic-pituitary adrenal (HPA) axes. Recent research suggests that depression may be associated with a failure to attenuate cortisol reactivity during early pregnancy. The aim of the current study is to investigate whether this effect continues into mid and late gestation. A further aim is to test whether maternal prenatal cortisol reactivity directly predicts infant cortisol reactivity. One hundred three pregnant women were recruited during either the second or third trimester. Depressive symptoms were assessed by self-report, and maternal salivary cortisol responses to a stressor (infant distress film) were measured. Approximately 2 months after birth, mothers (n = 88) reported postnatal depression and infant salivary cortisol responses to inoculation were measured. Prenatal depression was not associated with cortisol reactivity to acute stress in mid and late pregnancy. Similarly, neither prenatal depression nor maternal prenatal cortisol reactivity predicted infant cortisol reactivity to inoculation at 2 months. If the effects of prenatal depression on foetal and infant development are mediated by alterations of the maternal and foetal HPA axes, then early pregnancy may be a particularly vulnerable period. Alternatively, changes to HPA reactivity may not be as central to this association as previously thought

Short-term serotonergic but not noradrenergic antidepressant administration reduces attentional vigilance to threat in healthy volunteers

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

Pharmacological targeting of cognitive impairment in depression: recent developments and challenges in human clinical research

Impaired cognition is often overlooked in the clinical management of depression, despite its association with poor psychosocial functioning and reduced clinical engagement. There is an outstanding need for new treatments to address this unmet clinical need, highlighted by our consultations with individuals with lived experience of depression. Here we consider the evidence to support different pharmacological approaches for the treatment of impaired cognition in individuals with depression, including treatments that influence primary neurotransmission directly as well as novel targets such as neurosteroid modulation. We also consider potential methodological challenges in establishing a strong evidence base in this area, including the need to disentangle direct effects of treatment on cognition from more generalised symptomatic improvement and the identification of sensitive, reliable and objective measures of cognition

Associations of maternal and paternal antenatal mood with offspring anxiety disorder at age 18 years.

OBJECTIVE: Maternal antenatal depression and anxiety are associated with increased risk of childhood behavioural and emotional problems in offspring; it remains unclear to what extent this is due to a maternal biological impact on foetal development. Here, we compare associations between maternal and paternal antenatal depression and anxiety with offspring anxiety disorders, thus controlling for some genetic and shared environmental factors. METHODS: We used data from the ALSPAC population cohort including measures of antenatal parental depression and anxiety. At 18 years, offspring completed the CIS-R interview, yielding diagnoses for anxiety disorders. Results were adjusted for confounding variables including parental postnatal depression and anxiety. RESULTS: Children of women with antenatal depression (18 weeks gestation), had an increased risk of anxiety disorders at 18 years of age (11.1% vs. 6.2%; adj. OR 1.75 (1.19, 2.58); p=0.01). Children of women with antenatal anxiety had increased risk of co-morbid anxiety and depression (adj. OR 1.39 (1.06, 1.82); p=0.02). No such associations were found with paternal antenatal depression or anxiety. LIMITATIONS: There was a high attrition rate from the original cohort to the CIS-R completion at 18 years postpartum. Parental mood was only assessed together at one time point during the antenatal period. CONCLUSIONS: The differences in the association between maternal and paternal mood during pregnancy and child outcomes supports the hypothesis that foetal programming may account, at least in part, for this association. We highlight the potential opportunity for preventative intervention by optimising antenatal mental health

Effect of acute citalopram on self-referential emotional processing and social cognition in healthy volunteers

This study was funded by the UK National Productivity Investment Fund awarded to C.H. through the GW4 BioMed Medical Research Council Doctoral Training Partnership. This study was supported by the National Institute for Health Research (NIHR) Oxford Health Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR or the Department of Health. ICMJE forms are in the supplementary material, available online at https://doi.org/10.1192/bjo.2020.107.Peer reviewedPublisher PD

No moderating effect of 5-HTTLPR on associations between antenatal anxiety and infant behavior.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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

5-HT₄ Receptor Agonist Effects on Functional Connectivity in the Human Brain:Implications for Procognitive Action

Background: Cognitive deficits are often comorbid with mood disorders and can cause significant functional impairment even after resolution of the primary mood symptoms. We do not currently have pharmacological treatments that adequately address these deficits. 5-HT4 receptor agonists show promise as potential procognitive agents in animal and early human translational studies. Optimal cognitive performance in humans is directly associated with appropriate functional connectivity between specific resting-state neural networks. However, so far the effect of 5-HT4 receptor agonism on resting-state functional connectivity (rsFC) in the brain in humans is unknown.Methods: We collected resting-state functional magnetic resonance imaging scans from 50 healthy volunteers, of whom 25 received 6 days × 1 mg prucalopride (a highly selective 5-HT4 receptor agonist) and 25 received placebo in a randomized double-blind design.Results: Network analyses identified that participants in the prucalopride group had enhanced rsFC between the central executive network and the posterior/anterior cingulate cortex. Seed analyses also showed greater rsFC between the left and right rostral anterior cingulate cortex and the left lateral occipital cortex, and reduced rsFC between the hippocampus and other default mode network regions.Conclusions: Similar to other potentially procognitive medications, low-dose prucalopride in healthy volunteers appeared to enhance rsFC between regions involved in cognitive networks and reduce rsFC within the default mode network. This suggests a mechanism for the behavioral cognitive enhancement previously seen with 5-HT4 receptor agonists in humans and supports the potential for 5-HT4 receptor agonists to be used in clinical psychiatric populations