Neurobiology and systems biology of stress resilience

Physiological Reviews, Год журнала: 2024, Номер 104(3), С. 1205 - 1263

Опубликована: Март 14, 2024

Stress resilience is the phenomenon that some people maintain their mental health despite exposure to adversity or show only temporary impairments followed by quick recovery. Resilience research attempts unravel factors and mechanisms make possible harness its insights for development of preventative interventions in individuals at risk acquiring stress-related dysfunctions. Biological has been lagging behind psychological social sciences but seen a massive surge recent years. At same time, progress this field hampered methodological challenges related finding suitable operationalizations study designs, replicating findings, modeling animals. We embed review behavioral, neuroimaging, neurobiological, systems biological findings adults critical methods discussion. find preliminary evidence hippocampus-based pattern separation prefrontal-based cognitive control functions protect against pathological fears aftermath singular, event-type stressors [as found fear-related disorders, including simpler forms posttraumatic stress disorder (PTSD)] facilitating perception safety. Reward system-based pursuit savoring positive reinforcers appear more generalized dysfunctions anxious-depressive spectrum resulting from severe longer-lasting (as depression, comorbid anxiety, PTSD). Links between preserved functioning these neural under neuroplasticity, immunoregulation, gut microbiome composition, integrity barrier blood-brain are beginning emerge. On basis, avenues pointed out.

Язык: Английский

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Inflammation as a mediator between adverse childhood experiences and adult depression: A meta-analytic structural equation model

Journal of Affective Disorders, Год журнала: 2024, Номер 357, С. 85 - 96

Опубликована: Апрель 25, 2024

Exposure to adverse childhood experiences (ACEs) confers a higher risk of developing depression in adulthood, yet the mediation inflammation remains under debate. To test this model, we conducted systematic review and two-stage structural equation modelling meta-analysis studies reporting correlations between ACEs before age 18, inflammatory markers severity adulthood. Scopus, Pubmed, Medline, PsycInfo, CINAHL were searched up 2 October 2023. Twenty-two data on C-reactive protein (CRP, n = 12,935), interleukin-6 (IL-6, 4108), tumour necrosis factor-α (TNF-α, 2256) composite measures (n 1674) included. Unadjusted models revealed that CRP (β 0.003, 95 % LBCI 0.0002 0.0068), IL-6 0.001 0.006), 0.009, 0.004 0.018) significantly mediated association adult depression. The effects no longer survived after adjusting for BMI; however, serial model BMI sequentially 0.002, 0.0005 0.0046), accounting 14.59 9.94 variance depressive symptoms, respectively. Due cross-sectional nature assessment findings should be approached with caution; results suggest complex interactions psychoneuroimmunological metabolic factors underlie adulthood

Язык: Английский

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The kinase RIPK3 promotes neuronal survival by suppressing excitatory neurotransmission during central nervous system viral infection

Immunity, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Omega-3 fatty acids for inflamed depression – A match/mismatch study

Brain Behavior and Immunity, Год журнала: 2024, Номер 118, С. 192 - 201

Опубликована: Март 1, 2024

Despite decades of research on the pathophysiology depression, development new therapeutic interventions has been slow, and no biomarkers treatment response have clinically implemented. Several lines evidence suggest that clinical biological heterogeneity among patients with major depressive disorder (MDD) hampered progress in field. MDD low-grade inflammation – "inflamed depression" is a subtype depression may be associated superior antidepressant to anti-inflammatory compounds. Omega-3 fatty acid eicosapentaenoic (EPA) properties, preliminary data it particularly efficacious inflamed depression. In this study we tested hypothesis add-on EPA greater efficacy high baseline high-sensitivity C-reactive protein (hs-CRP) compared low hs-CRP. All subjects received 2.2 g EPA, 400 mg docosahexaenoic 800 other acids/day for 8 weeks, added stable ongoing treatment. The primary outcome was change 17-item Hamilton Depression Rating Scale (HAMD-17). Patients raters were blind hs-CRP status. an intention-to-treat analysis including all at least one post visit (n = 101), cut-off ≥1 mg/L, but not ≥3 improvement HAMD-17 total score. addition general effect ≥ 1 adjuvant improved symptoms putatively related such as fatigue sleep difficulties. This adds mounting delineation MDD-subgroups based relevant predict interventions.

Язык: Английский

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Transcriptomic profiles in major depressive disorder: the role of immunometabolic and cell-cycle-related pathways in depression with different levels of inflammation

Molecular Psychiatry, Год журнала: 2024, Номер unknown

Опубликована: Сен. 13, 2024

Abstract Transcriptomic profiles are important indicators for molecular mechanisms and pathways involved in major depressive disorder (MDD) its different phenotypes, such as immunometabolic depression. We performed whole-transcriptome pathway analyses on 139 individuals from the observational, case-control, BIOmarkers DEPression (BIODEP) study, 105 with MDD 34 controls. divided participants based levels of inflammation, measured by serum high-sensitivity C-reactive protein (CRP), n = 39 ‘not inflamed’ (CRP < 1 mg/L), 31 ‘elevated CRP’ (1–3 35 ‘low-grade inflammation’ (>3 mg/L). whole-blood RNA sequencing using Illumina NextSeq 550 statistical Deseq2 package R statistics (RUV-corrected) subsequent Ingenuity Pathway Analysis. Immunometabolic were activated CRP > mg/L, although surprisingly 1–3 group showed stronger immune activation than 3 group. The main identified comparison between controls cell-cycle-related, which may be protective against abnormalities this ‘non-inflamed’ depressed further exposure response to antidepressants ( 47 non-responders, 37 responders, 22 unmedicated), specific immunomodulatory neuroprotective responders (especially vs. non-responders), could relevant treatment response. In subgroup analyses, we found that transcriptional profile is independent levels, inhibition cell-cycle-related mg/L present only those who currently depressed, not responders. study demonstrates transcriptomic associated (CRP-based treatment-based) while shedding light potential prevent or facilitate an individual’s trajectory toward depression and/or treatment-non-responsive recognition integration these will a precision-medicine approach MDD.

Язык: Английский

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Depression in adolescence and young adulthood: the difficulty to integrate motivational/emotional systems

Frontiers in Psychology, Год журнала: 2025, Номер 15

Опубликована: Янв. 6, 2025

Depression is presented as a multi-factorial bio-psycho-social expression that has evolved primarily an effect of stressors related to the motivational/emotional systems regulate BrainMind in our relationship with conspecifics. These may be caused by two sources threat, firstly, loss bonding caregiver and later partner and/or group which relates SEPARATION (PANIC/GRIEF) system, secondly, social defeat competition dominance. The sexual maturity drives individual dominance, even if latter often occurs before maturity, e.g., chickens, dogs, non-human primates, humans. evolutionarily conserved mechanism mammals terminate both separation anxiety, so protect vulnerable brain from consequences prolonged stress when predictable. Adolescence Young adulthood are particularly susceptible these types threat because human developmental characteristics summarized term neoteny. This refers slowing down growth development, resulting period dependence on caring/protective adult persistence juvenile throughout life. Therefore, neoteny makes transition childhood more dramatic, making integration system dynamics dominance stressful source depression. Stress HPA-Hypothalamic-Pituitary-Adrenal axis articulates other systems, mainly autonomic nervous immune-inflammatory system. believed one most significant components depressive processes, connected prodromes its activation childhood, under pressure environmental relational can lead learned helplessness. recurrence it easier for activated life, could make contribution establishment disease. possible children's identification processes their parents' personalities through observational learning considered.

Язык: Английский

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<strong>Metastability demystified — the foundational past, the pragmatic present, and the potential future</strong>

Опубликована: Июль 21, 2023

Healthy brain functioning depends on balancing stable integration between areas for effective coordinated functioning, with bursts of desynchronisation to allow subsystems reconfigure and express functional specialisation. Metastability, a concept originated in statistical physics dynamical systems theory, has been proposed as key signature that characterises this balance. Building principle, the neuroscience literature employed markers metastability investigate various aspects function including cognitive performance, healthy ageing, meditation, sleep, responses pharmacological challenges, characterise psychiatric conditions or disorders consciousness. However, body work often uses notion heuristically, sometimes inaccurately, making it hard uninitiated navigate vast literature, interpret findings, foster further development theoretical experimental methodologies. In paper we provide comprehensive review its applications neuroscience, covering scientific historical foundations practical estimators used estimate empirical data. We also critical analysis recent developments, clarifying common misconceptions paving road future developments.

Язык: Английский

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Inflammatory processes in the prefrontal cortex induced by systemic immune challenge: Focusing on neurons

Brain Behavior & Immunity - Health, Год журнала: 2023, Номер 34, С. 100703 - 100703

Опубликована: Ноя. 9, 2023

Peripheral immune challenge induces neurobiological alterations in the brain and related neuropsychiatric symptoms both humans other mammals. One of best known physiological effects systemic inflammation is sickness behavior. However, addition to this depression-like state, there are cognitive outcomes peripherally induced neuroinflammation that can be linked dysfunction higher-order cortical areas, such as prefrontal cortex (PFC). As activity PFC largely based on balanced interplay excitatory pyramidal cells inhibitory interneurons, it may hypothesized neuroinflammatory processes result a shift excitatory/inhibitory balance, which common hallmark several conditions. Indeed, many data suggest strongly associated with molecular functional changes neurons leading disturbances their synaptic networks. Different experimental approaches cause some incongruence reviewed data. commonly agreed acute leads balance by proinflammatory signaling at borders parenchyma. These cellular altered local brain-wide network inducing top-down control goal-directed behavior cognition regulated PFC. Lipopolysaccharide (LPS)-treated rodents most widely used models neuroinflammation, so majority come from studies utilizing LPS model. This limit general interpretation regarding neuronal peripheral activation. In addition, biological variables (e.g., sex, age) influence challenge, not only nature severity Therefore, would desirable investigate inflammation-related using well, focus targeted fine-tuning affected cell types via mechanisms nervous systems.

Язык: Английский

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Inflammation as an aetiological trigger for depressive symptoms in a prospective cohort of patients with inflammatory bowel disease

Journal of Psychosomatic Research, Год журнала: 2024, Номер 177, С. 111592 - 111592

Опубликована: Янв. 10, 2024

Inflammatory bowel disease (IBD) is often comorbid with mood disorders and depressive symptoms. The aetiology of symptoms in IBD, however, remains largely unknown. Consistent the inflammatory hypothesis depression, aim this study was to explore prospective associations between biomarkers a cohort IBD patients without previous clinical diagnosis disorder.

Язык: Английский

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Inflammatory hypotheses of sleep disturbance - depression link: Update and research agenda

Brain Behavior & Immunity - Health, Год журнала: 2023, Номер 31, С. 100647 - 100647

Опубликована: Июнь 22, 2023

Studies in human and experimental animal models support a role of inflammation the aetiology depression, yet precise played by sleep disturbance (i.e., difficulties falling or maintaining sleep) is poorly understood. Consistent evidence from prospective epidemiological studies suggests as predictor major depression episodes recurrence. In parallel, up to 20% individuals with have low-grade peripheral CRP>3 mg/l), preliminary longitudinal showed that may even predict levels inflammation. Therefore, it possible increase inflammation, which turn contribute mediate) onset - worsening depression. Alternatively, serve vulnerability factor risk developing depressive symptoms when facing an immune challenge. The aim this review was summarise state science on contributing depression-related A research agenda also proposed advance study psychoneuroimmunology

Язык: Английский

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