scholarly journals Investigation of reward learning and feedback sensitivity in non-clinical participants with a history of early life stress

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260444
Author(s):  
Matthew Paul Wilkinson ◽  
Chloe Louise Slaney ◽  
Jack Robert Mellor ◽  
Emma Susan Jane Robinson
Keyword(s):  
Reversal Learning ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Learning Task ◽  
Reward Learning ◽  
Feedback Sensitivity ◽  
History Of ◽  
A Current ◽  
Probabilistic Reversal Learning

Early life stress (ELS) is an important risk factor for the development of depression. Impairments in reward learning and feedback sensitivity are suggested to be an intermediate phenotype in depression aetiology therefore we hypothesised that healthy adults with a history of ELS would exhibit reward processing deficits independent of any current depressive symptoms. We recruited 64 adults with high levels of ELS and no diagnosis of a current mental health disorder and 65 controls. Participants completed the probabilistic reversal learning task and probabilistic reward task followed by depression, anhedonia, social status, and stress scales. Participants with high levels of ELS showed decreased positive feedback sensitivity in the probabilistic reversal learning task compared to controls. High ELS participants also trended towards possessing a decreased model-free learning rate. This was coupled with a decreased learning ability in the acquisition phase of block 1 following the practice session. Neither group showed a reward induced response bias in the probabilistic reward task however high ELS participants exhibited decreased stimuli discrimination. Overall, these data suggest that healthy participants without a current mental health diagnosis but with high levels of ELS show deficits in positive feedback sensitivity and reward learning in the probabilistic reversal learning task that are distinct from depressed patients. These deficits may be relevant to increased depression vulnerability.

scholarly journals Investigation of reward learning and feedback sensitivity in non-clinical participants with a history of early life stress

2020 ◽  
Author(s):  
Matthew P Wilkinson ◽  
Jack R Mellor ◽  
Emma S J Robinson
Keyword(s):  
Mental Health ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Learning Ability ◽  
Reward Learning ◽  
Induced Response ◽  
Model Free ◽  
Feedback Sensitivity ◽  
History Of

AbstractBackgroundEarly life stress (ELS) is an important risk factor for the development of depression. Impairments in reward learning and feedback sensitivity have been suggested. to be an intermediate phenotype in depression aetiology. We therefore hypothesised that healthy adults with a history of ELS would have impairments in reward learning and feedback sensitivity.MethodsWe recruited 64 adult participants with high levels of ELS and no diagnosis of a current mental health disorder in addition to 65 controls. Participants completed two online reward learning tasks: the probabilistic reversal learning task (PRLT) and probabilistic reward task (PRT). Participants also completed depression, anhedonia, social status and stress scales with PRLT data being additionally analysed utilising a reinforcement learning model.ResultsParticipants with high levels of ELS showed decreased positive feedback sensitivity (PFS) in the PRLT compared to controls. High ELS participants also tended towards possessing a decreased model-free learning rate which strengthened in subsequent analysis. This was coupled with a decreased learning ability in the acquisition phase of block 1 following the practice session. Neither groups of participants showed a reward induced response bias in the PLT however high ELS participants exhibited decreased discrimination ability between stimuli; this was however accounted for by depression symptomology in further analysis.ConclusionsThese data suggest that healthy participants without a mental health diagnosis and high levels of ELS show deficits in PFS and reward learning in the PRLT that are distinct from depressed patients. These deficits may be relevant to an increased vulnerability to depression.

scholarly journals Comparison of conventional and rapid-acting antidepressants in a rodent probabilistic reversal learning task

2020 ◽  
Vol 4 ◽  
pp. 239821282090717 ◽  
Author(s):  
Matthew P. Wilkinson ◽  
John P. Grogan ◽  
Jack R. Mellor ◽  
Emma S. J. Robinson
Keyword(s):  
Reinforcement Learning ◽  
Reversal Learning ◽  
Antidepressant Treatment ◽  
Learning Task ◽  
Reward Processing ◽  
Reward Learning ◽  
Feedback Sensitivity ◽  
Rule Changes ◽  
Reinforcement Learning Model ◽  
Probabilistic Reversal Learning

Deficits in reward processing are a central feature of major depressive disorder with patients exhibiting decreased reward learning and altered feedback sensitivity in probabilistic reversal learning tasks. Methods to quantify probabilistic learning in both rodents and humans have been developed, providing translational paradigms for depression research. We have utilised a probabilistic reversal learning task to investigate potential differences between conventional and rapid-acting antidepressants on reward learning and feedback sensitivity. We trained 12 rats in a touchscreen probabilistic reversal learning task before investigating the effect of acute administration of citalopram, venlafaxine, reboxetine, ketamine or scopolamine. Data were also analysed using a Q-learning reinforcement learning model to understand the effects of antidepressant treatment on underlying reward processing parameters. Citalopram administration decreased trials taken to learn the first rule and increased win-stay probability. Reboxetine decreased win-stay behaviour while also decreasing the number of rule changes animals performed in a session. Venlafaxine had no effect. Ketamine and scopolamine both decreased win-stay probability, number of rule changes performed and motivation in the task. Insights from the reinforcement learning model suggested that reboxetine led animals to choose a less optimal strategy, while ketamine decreased the model-free learning rate. These results suggest that reward learning and feedback sensitivity are not differentially modulated by conventional and rapid-acting antidepressant treatment in the probabilistic reversal learning task.

scholarly journals Automaticity as a Vulnerability to Depression: Daily Mood-Reactive Rumination and Early-Life Stress in People With- and Without Depression History

2021 ◽  
Author(s):  
Kristján Helgi Hjartarson ◽  
Ivar Snorrason ◽  
Laura Francina Bringmann ◽  
Ragnar P. Ólafsson
Keyword(s):  
Negative Affect ◽  
Life Stress ◽  
Early Life ◽  
Negative Mood ◽  
Early Life Stress ◽  
Conscious Awareness ◽  
Depression Vulnerability ◽  
Negative Thinking ◽  
History Of ◽  
Mood Reactivity

Depressive rumination has been conceptualized as a mental habit that is initiated automatically without conscious awareness, intent or control in response to negative mood. However, it is unknown whether depression vulnerability is characterized by elevated levels of mood-reactive rumination at the level of short-term dynamics. Using mobile ecological momentary assessment, formerly depressed individuals with a recurrent history of depression (n = 94) and non-clinical controls (n = 55) recorded in-the-moment affect and rumination ten times daily over six days, after completing measures of trait ruminative brooding, early-life stress, and habitual characteristics of negative thinking (e.g., automaticity, lack of conscious awareness, intent, and control). Momentary fluctuations in negative affect were prospectively associated with greater rumination at the next sampling occasion in formerly depressed participants whereas this pattern was not observed in non-clinical controls. In formerly depressed participants, the degree of mood-reactivity was moderated by habitual characteristics of negative thinking, which interacted with a history of early-life stress in predicting greater mood-reactive rumination. It was not, however, associated with depression course nor with the frequency of trait ruminative brooding. Mood-reactive rumination may be a vulnerability marker for depression, triggered in response to negative affect with a high degree of automaticity, making it difficult to control. It might constitute a risk independent of the depressive course and originate in early-life stress. Future studies may need to go beyond frequency and target the mood-reactivity and automaticity of ruminative thinking to reduce depression vulnerability

scholarly journals Combined dexamethasone/corticotropin-releasing factor test in chronic fatigue syndrome

2007 ◽  
Vol 38 (7) ◽  
pp. 963-973 ◽  
Author(s):  
F. Van Den Eede ◽  
G. Moorkens ◽  
W. Hulstijn ◽  
B. Van Houdenhove ◽  
P. Cosyns ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Life Stress ◽  
Early Life ◽  
Low Dose ◽  
Early Life Stress ◽  
Chronic Fatigue ◽  
Corticotropin Releasing Factor ◽  
Fatigue Syndrome ◽  
History Of ◽  
Cortisol Responses

BackgroundStudies of hypothalamic–pituitary–adrenal (HPA) axis function in chronic fatigue syndrome (CFS) point to hypofunction, although there are negative reports. Suggested mechanisms include a reduced hypothalamic or supra-hypothalamic stimulus to the HPA axis and enhanced sensitivity to the negative feedback of glucocorticoids. The aim of the current study was to investigate HPA axis function in CFS with the dexamethasone/corticotropin-releasing factor (Dex/CRF) test, in analogy with research in affective disorders.MethodThirty-four well-characterized female CFS patients and 25 healthy control subjects participated in the low-dose Dex/CRF test. Current major depressive episode was an exclusion criterion. History of early-life stress (ELS) was assessed with the Structured Trauma Interview.ResultsSalivary cortisol responses after 0.5 mg Dex were lower in CFS patients than in controls (before 100 μg CRF, p=0.038; after 100 μg CRF, p=0.015). A secondary analysis revealed an influence of early-life stress and of oestrogen intake. After removal of the 10 participants who were taking an oral oestrogen, patients without a history of ELS showed lower cortisol responses than patients with ELS and controls (before CRF, p=0.005; after CRF, p=0.008).ConclusionsCFS is globally associated with reduced cortisol responses in the combined low-dose Dex/CRF test, but this effect is only clearly present in CFS patients without a history of ELS. This study provides further support for an enhanced glucocorticoid negative feedback and/or a reduced central HPA axis drive in CFS. Furthermore, it demonstrates that ELS is an important variable to consider in CFS research.

Differential functional connectivity within an emotion regulation neural network among individuals resilient and susceptible to the depressogenic effects of early life stress

2012 ◽  
Vol 43 (3) ◽  
pp. 507-518 ◽  
Author(s):  
J. M. Cisler ◽  
G. A. James ◽  
S. Tripathi ◽  
T. Mletzko ◽  
C. Heim ◽  
...  
Keyword(s):  
Neural Network ◽  
Emotion Regulation ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Local Network ◽  
Network Organization ◽  
Local Connectivity ◽  
History Of ◽  
Global Connectivity

BackgroundEarly life stress (ELS) is a significant risk factor for depression. The effects of ELS exposure on neural network organization have not been differentiated from the effect of depression. Furthermore, many individuals exposed to ELS do not develop depression, yet the network organization patterns differentiating resiliency versus susceptibility to the depressogenic effects of ELS are not clear.MethodWomen aged 18–44 years with either a history of ELS and no history of depression (n = 7), a history of ELS and current or past depression (n = 19), or a history of neither ELS nor depression (n = 12) underwent a resting-state 3-T functional magnetic resonance imaging (fMRI) scan. An emotion regulation brain network consisting of 21 nodes was described using graph analyses and compared between groups.ResultsGroup differences in network topology involved decreased global connectivity and hub-like properties for the right ventrolateral prefrontal cortex (vlPFC) and decreased local network connectivity for the dorsal anterior cingulate cortex (dACC) among resilient individuals. Decreased local connectivity and increased hub-like properties of the left amygdala, decreased hub-like properties of the dACC and decreased local connectivity of the left vlPFC were observed among susceptible individuals. Regression analyses suggested that the severity of ELS (measured by self-report) correlated negatively with global connectivity and hub-like qualities for the left dorsolateral PFC (dlPFC).ConclusionsThese preliminary results suggest functional neural connectivity patterns specific to ELS exposure and resiliency versus susceptibility to the depressogenic effects of ELS exposure.

scholarly journals Differential Effects of Two Early Life Stress Paradigms on Cerebellar-Dependent Delay Eyeblink Conditioning

2020 ◽  
Author(s):  
Alexandra B. Moussa-Tooks ◽  
William P. Hetrick ◽  
John T. Green
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Eyeblink Conditioning ◽  
Early Life Stress ◽  
Learning Task ◽  
Neural Circuitry ◽  
Learning Curves ◽  
Robust Learning ◽  
Atypical Development

AbstractEarly life stress paradigms have become prominent in the animal literature to model atypical development. Currently, two models have prevailed within the literature: (1) limited bedding or nesting and (2) maternal separation or deprivation. Both models have produced aberrations spanning behavior and neural circuitry. Surprisingly, these two models have yet to be directly compared. The current study utilized delay eyeblink conditioning, an associative learning task with a well-defined cerebellar circuit, to compare the behavioral effects of standard limited bedding (postnatal day 2-9, n=15) and maternal separation (60 minutes per day during postnatal day 2-14, n=13) early life stress paradigms. Animals in all groups exhibited robust learning curves. Surprisingly, facilitated conditioning was observed in the maternal separation group. Rats that underwent limited bedding did not differ from the control or maternal separation groups on any conditioning measures. This study contributes to a clearer understanding of early life stress paradigms and the claims made about their mechanisms, which if better clarified can be properly leveraged to increase translational value.

scholarly journals Maternal Separation Early in Life Alters the Expression of Genes Npas4 and Nr1d1 in Adult Female Mice: Correlation with Social Behavior

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Yuliya A. Ryabushkina ◽  
Vasiliy V. Reshetnikov ◽  
Natalya P. Bondar
Keyword(s):  
Prefrontal Cortex ◽  
Social Behavior ◽  
Adult Female ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Dorsal Hippocampus ◽  
Early Life Stress ◽  
Female Mice ◽  
History Of

Early-life stress affects neuronal plasticity of the brain regions participating in the implementation of social behavior. Our previous studies have shown that brief and prolonged separation of pups from their mothers leads to enhanced social behavior in adult female mice. The goal of the present study was to characterize the expression of genes (which are engaged in synaptic plasticity) Egr1, Npas4, Arc, and Homer1 in the prefrontal cortex and dorsal hippocampus of adult female mice with a history of early-life stress. In addition, we evaluated the expression of stress-related genes: glucocorticoid and mineralocorticoid receptors (Nr3c1 and Nr3c2) and Nr1d1, which encodes a transcription factor (also known as REVERBα) modulating sociability and anxiety-related behavior. C57Bl/6 mice were exposed to either maternal separation (MS, 3 h once a day) or handling (HD, 15 min once a day) on postnatal days 2 through 14. In adulthood, the behavior of female mice was analyzed by some behavioral tests, and on the day after the testing of social behavior, we measured the gene expression. We found increased Npas4 expression only in the prefrontal cortex and higher Nr1d1 expression in both the prefrontal cortex and dorsal hippocampus of adult female mice with a history of MS. The expression of the studied genes did not change in HD female mice. The expression of stress-related genes Nr3c1 and Nr3c2 was unaltered in both groups. We propose that the upregulation of Npas4 and Nr1d1 in females with a history of early-life stress and the corresponding enhancement of social behavior may be regarded as an adaptation mechanism reversing possible aberrations caused by early-life stress.

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