What Role Does the Prefrontal Cortex Play in the Processing of Negative and Positive Stimuli in Adolescent Depression?

Kaya, Mehmet; McCabe, Ciara

doi:10.3390/brainsci9050104

Cited by 15 publications

(9 citation statements)

References 77 publications

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“…This is in keeping with the meta-analysis and first quantitative review of emotional reactivity in depression that found consistent reductions in both positive and negative reactivity, which supported our previous study. 19,22 Interestingly, we did not find brain differences between the groups in the ventral striatum, which is consistent with our previous study examining young people at familial risk of depression but no personal depression experiences 20 nor did we find any relationship between anhedonia and the ventral striatum. This suggests that perhaps striatal differences (in this task) are only detectable after having experienced clinical depression and is thus a state rather than a trait marker of depression.…”

Section: Assessing Anticipation Effort and Consummationsupporting

confidence: 92%

Dimensional anhedonia and the adolescent brain: reward and aversion anticipation, effort and consummation

Rzepa

McCabe

2019

BJPsych open

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Background Given the heterogeneity of depression the Research Domain Criteria Framework suggests a dimensional approach to understanding the nature of mental illness. Neural reward function has been suggested as underpinning the symptom of anhedonia in depression but how anhedonia is related to aversion processing is unclear. Aims To assess how the dimensional experience of anhedonia and depression severity relate to reward and aversion processing in the human brain. Method We examined adolescents and emerging adults (n = 84) in the age range 13–21 years. Using a dimensional approach we examined how anhedonia and depression related to physical effort to gain reward or avoid aversion and neural activity during the anticipation, motivation/effort and consummation of reward and aversion. Results As anhedonia increased physical effort to gain reward decreased. As anhedonia increased neural activity decreased during effort to avoid in the precuneus and insula (trend) and increased in the caudate during aversive consummation. We found participants with depression symptoms invested less physical effort than controls and had blunted neural anticipation of reward and aversion in the precuneus, insula and prefrontal cortex and blunted neural activity during effort for reward in the putamen. Conclusions We show for the first time that both physical effort and neural activity during effort correlate with anhedonia in adolescents and that amotivation might be a specific deficit of anhedonia irrespective of valence. Future work will assess if these neural mechanisms can be used to predict blunted approach and avoidance in adolescents at risk of depression.

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Section: Assessing Anticipation Effort and Consummationsupporting

confidence: 92%

Dimensional anhedonia and the adolescent brain: reward and aversion anticipation, effort and consummation

Rzepa

McCabe

2019

BJPsych open

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“…Depression is associated with lower PFC activity, and reduced PFC function is a suggested risk factor for development of depression (Hare & Duman, 2020; Kaya & McCabe, 2019). Tobacco use is associated with altered nicotinic acetylcholine receptor availability in the PFC (Brody et al, 2016; Feduccia et al, 2012) which are integral to its function, especially in the dorsolateral PFC (DLPFC; Croxson et al, 2011; Yang et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Prefrontally Modulated Vagal Tone Inhibits Inflammatory Responses to Prevent Telomere Damage in Healthy Participants

Ask

Sütterlin

2022

Preprint

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Background: Accumulated senescent cells are proposed to be one of the main drivers of age-related pathology through disruption of tissue structure and function. We recently proposed the Neuro-Immuno-Senescence Integrative Model (NISIM; Ask et al., 2018) which relates prefrontally modulated vagal tone and subsequent balance between vagal and sympathetic input to the spleen to inflammatory responses leading to generation of reactive oxygen species and oxidative telomere damage. The NISIM is based on converging evidence and argues for the existence of a prefrontal cortex-autonomic nervous system-spleen (PAS) axis, suggesting that the inflammation that induces reactive oxygen species-generation is downstream of this axis. Aim: In this study, we aim to assess inflammation as a mediator in the relationship between prefrontally modulated vagal tone and leukocyte telomere length to test the hypothesis that PAS axis dysregulation accelerates cellular aging. We also assess the relationship between a recently proposed index of vagal immunomodulation (vagal tone/inflammation ratio; NIM index; Gidron et al., 2018) and telomere length, and compare results between the NIM index and vagal tone as predictors of telomere length. Methods: This study uses participant data from a large nationally representative longitudinal study since 1974 with a total of 45,000 Norwegian residents so far. A sub-sample of 1372 participants from which vagal tone, C Reactive Protein, and leukocyte telomere length could be obtained were included in the study. Relationships were analyzed with hierarchical multiple linear regression using either vagal tone and C Reactive Protein or the NIM index to predict telomere length. Sleeping problems, tobacco use status, alcohol use status, time since last meal, and symptoms of depression were included as control variables. Results: In the mediation analysis, vagal tone was a significant positive predictor of telomere length, while C Reactive Protein was a significant negative predictor of telomere length. This relationship remained significant when individually controlling for some but not all confounding variables. The NIM index was a significant positive predictor of telomere length. This relationship remained significant when controlling for all confounding variables except one. In a reduced dataset excluding all participants where confounders were present, the NIM index remained a significant predictor of telomere length. Conclusion: This is the first study suggesting that PAS axis activity is associated with telomere length thus supporting the NISIM. Results indicate that the NIM index is a more sensitive indicator of PAS axis activity than vagal tone and C Reactive Protein in isolation. Clinical relevance and suggestions for future research are discussed.

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“…The prefrontal cortex is one of the most important cortical areas among the network of regions being involved in the pathogenesis of depression that plays a main role in the ability to process positive and negative emotions (Harms et al., 2017; Kaya & McCabe, 2019). Thus, the observed increase in levels of Fkbp5 in this brain area should not be surprising and may underlie a condition of potential increased vulnerability to stress.…”

Section: Discussionmentioning

confidence: 99%

High‐fat diet during adulthood interacts with prenatal stress, affecting both brain inflammatory and neuroendocrine markers in male rats

Berry

Mazzelli

Musillo

et al. 2021

Eur J of Neuroscience

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Prenatal stress (PNS) affects foetal programming and, through an interaction with subsequent challenges, can increase vulnerability to mood and metabolic disorders. We have previously shown that, following PNS, adult male rats are characterized by increased vulnerability to a metabolic stressor experienced at adulthood (8‐week‐high‐fat diet—HFD). In this study, we specifically assessed whether PNS might interact with an adult metabolic challenge to induce an inflammatory phenotype. Changes in the expression levels of inflammatory (Il‐1β, Tnf‐α, Il‐6) and of stress response mediators (Nr3c1, Fkbp5) as well as of mood and metabolic regulators (Bdnf, Ghs‐R) were investigated in the hippocampus, prefrontal cortex and hypothalamus, brain regions involved in the pathogenesis of depression and prone to inflammation in response to stress. Overall, PNS reduced the expression of Bdnf and Tnf‐α, while HFD administered at adulthood counteracted this effect suggesting that PNS impinges upon the same pathways regulating responses to a metabolic challenge at adulthood. Furthermore, HFD and PNS affected the expression of both Nr3c1 and Fkbp5, two neuroendocrine mediators involved in the response to stress, metabolic challenges and in the modulation of the emotional profile (as shown by the correlation between Fkbp5 and the time spent in the open arms of the elevated plus‐maze). Overall, these results indicate that the same metabolic and neuroendocrine effectors engaged by PNS are affected by metabolic challenges at adulthood, providing some mechanistic insight into the well‐known comorbidity between mood and metabolic disorders.

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What Role Does the Prefrontal Cortex Play in the Processing of Negative and Positive Stimuli in Adolescent Depression?

Cited by 15 publications

References 77 publications

Dimensional anhedonia and the adolescent brain: reward and aversion anticipation, effort and consummation

Dimensional anhedonia and the adolescent brain: reward and aversion anticipation, effort and consummation

Prefrontally Modulated Vagal Tone Inhibits Inflammatory Responses to Prevent Telomere Damage in Healthy Participants

High‐fat diet during adulthood interacts with prenatal stress, affecting both brain inflammatory and neuroendocrine markers in male rats

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