The nature and neurobiology of fear and anxiety: State of the science and opportunities for accelerating discovery

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 151, P. 105237 - 105237

Published: May 18, 2023

Language: Английский

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The immunological perspective of major depressive disorder: unveiling the interactions between central and peripheral immune mechanisms

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Jan. 19, 2025

Major depressive disorder is a prevalent mental disorder, yet its pathogenesis remains poorly understood. Accumulating evidence implicates dysregulated immune mechanisms as key contributors to disorders. This review elucidates the complex interplay between peripheral and central components underlying pathology. Peripherally, systemic inflammation, gut dysregulation, dysfunction in organs including gut, liver, spleen adipose tissue influence brain function through neural molecular pathways. Within nervous system, aberrant microglial astrocytes activation, cytokine imbalances, compromised blood-brain barrier integrity propagate neuroinflammation, disrupting neurotransmission, impairing neuroplasticity, promoting neuronal injury. The crosstalk immunity creates vicious cycle exacerbating neuropathology. Unraveling these multifaceted immune-mediated provides insights into major disorder's pathogenic basis potential biomarkers targets. Modulating both responses represent promising multidimensional therapeutic strategy.

Language: Английский

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Antidepressant mechanisms of ketamine: a review of actions with relevance to treatment-resistance and neuroprogression

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Aug. 8, 2023

Concurrent with recent insights into the neuroprogressive nature of depression, ketamine shows promise in interfering several factors, and has been suggested to reverse neuropathological patterns seen depression. These come at a time great need for novel approaches, as prevalence is rising current treatment options remain inadequate large number people. The rapidly growing literature on ketamine's antidepressant potential yielded multiple proposed mechanisms action, many which have implications recently elucidated aspects depressive pathology. This review aims provide reader an understanding pathology how act it. Literature was identified through PubMed Google Scholar, reference lists retrieved articles. When reviewing evidence pathology, picture emerges four elements interacting each other facilitate progressive worsening, namely stress, inflammation, neurotoxicity neurodegeneration. Ketamine acts all these levels rapid potent reductions symptoms. Converging suggests that works increase stress resilience stress-induced dysfunction, modulate systemic inflammation neuroinflammation, attenuate neurotoxic processes glial synaptogenesis rather than Still, much remains be revealed about research lacking durability effect. findings discussed herein calls more longitudinal approaches when determining efficacy its relation could relevant considerations clinical implementation.

Language: Английский

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Nucleus accumbens in the pathogenesis of major depressive disorder: A brief review

Brain Research Bulletin, Journal Year: 2023, Volume and Issue: 196, P. 68 - 75

Published: March 7, 2023

Major depressive disorder (MDD) is the most prevalent mental characterized by anhedonia, loss of motivation, avolition, behavioral despair and cognitive abnormalities. Despite substantial advancements in pathophysiology MDD recent years, pathogenesis this not fully understood. Meanwhile,the treatment with currently available antidepressants inadequate, highlighting urgent need for clarifying developing novel therapeutics. Extensive studies have demonstrated involvement nuclei such as prefrontal cortex (PFC), hippocampus (HIP), nucleus accumbens (NAc), hypothalamus, etc., MDD. NAc,a region critical reward motivation,dysregulation its activity seems to be a hallmark mood disorder. In paper, we present review NAc related circuits, cellular molecular mechanisms underlying share an analysis gaps current research possible future directions.

Language: Английский

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Distinct and shared patterns of brain plasticity during electroconvulsive therapy and treatment as usual in depression: an observational multimodal MRI-study

Translational Psychiatry, Journal Year: 2023, Volume and Issue: 13(1)

Published: Jan. 10, 2023

Abstract Electroconvulsive therapy (ECT) is a highly effective treatment for depression. Previous studies point to ECT-induced volume increase in the hippocampi and amygdalae, cortical thickness. However, it unclear if these neuroplastic changes are associated with response. This observational study aimed address this research question by comparing neuroplasticity between patients depression receiving ECT that respond as usual (TAU-responders). Twenty ECT-patients (16 major depressive disorder (MDD), 4 depressed bipolar disorder), 20 TAU-responders (20 MDD) healthy controls (HC) were scanned twice multimodal magnetic resonance imaging (structure: MP2RAGE; perfusion: arterial spin labeling). before after an ECT-index series (ECT-group). during episode following remission or Volumes cerebral blood flow (CBF) of global mean thickness compared groups. There was significant group × time interaction hippocampal amygdalar volumes, CBF Hippocampal enlargements observed ECT-group but neither nor HC. Increase not The co-occurrence both may shared mechanism antidepressant case subcortical increase.

Language: Английский

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The association of hypogonadism with depression and its treatments

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 10, 2023

According to World Health Organization estimates, 5% of the adult population worldwide suffers from depression. In addition affective, psychomotor and cognitive symptoms which characterize this mood disorder, sexual dysfunction has been frequently reported among men suffering The most common manifestations are decreased libido, erectile orgasmic disorder. addition, epidemiological studies have documented a reduction testosterone concentrations in with depression and, for these reasons, depressive disorders appear as one possible cause male functional hypogonadism. Moreover, some largely used antidepressant medications can or worsen complaints, thus its treatments rise several andrological-relevant issues. other way round, hypogonadism manifest depressed mood, anxiety, insomnia, memory impairment which, if mild, may respond replacement therapy (TRT). However, prevalence depression, hypogonadal men, is not known. Severe do TRT, while effect treating major on hypogonadism, investigated. Overall, clinical relevance each condition other, well physiopathological underpinnings their relationship, still be clarified. present review summarizes current evidence influence hypothalamic-pituitary-testis axis; association between depression; reciprocal effects respective treatments.

Language: Английский

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Hydrogen Sulfide Prevents LPS-Induced Depression-like Behavior through the Suppression of NLRP3 Inflammasome and Pyroptosis and the Improvement of Mitochondrial Function in the Hippocampus of Mice

Biology, Journal Year: 2023, Volume and Issue: 12(8), P. 1092 - 1092

Published: Aug. 5, 2023

Hydrogen sulfide (H2S) has been implicated to have antidepressive effects. We sought investigate the prevention effects of H2S donor NaHS on depression-like behavior induced by lipopolysaccharide (LPS) in mice and its potential mechanisms. Sucrose preference, force swimming, open field, elevate zero maze were used evaluate behavior. NF-κB NLRP3 inflammasome activation mitochondrial function hippocampus determined. It was found that LPS prevented pretreatment. caused as evidenced increased phosphorylated-p65 levels NLRP3, ASC, caspase-1, mature IL-1β hippocampus, which also blocked NaHS. GSDMD-N TUNEL-positive cells Abnormal morphology LPS-treated mice. Mitochondrial membrane ATP production reduced, ROS pretreatment improved impaired reduced Our data indicate prevents LPS-induced behaviors inhibiting pyroptosis improving hippocampus.

Language: Английский

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A theory of the neural mechanisms underlying negative cognitive bias in major depression

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 15

Published: March 12, 2024

The widely acknowledged cognitive theory of depression, developed by Aaron Beck, focused on biased information processing that emphasizes the negative aspects affective and conceptual information. Current attempts to discover neurological mechanism underlying such bias have successfully identified various brain regions associated with severally functions as emotion, attention, rumination, inhibition control. However, neurobiological mechanisms how individuals in depression develop this selective toward is still under question. This paper introduces a framework centered around frontal-limbic circuit, specifically analyzing synthesizing activity functional connectivity within amygdala, hippocampus, medial prefrontal cortex. Firstly, possible explanation positive feedback loop contributes persistent hyperactivity amygdala at an automatic level established. Building upon this, two hypotheses are presented: hypothesis 1 revolves bidirectional amygdalohippocampal projection facilitating amplification emotions memories while concurrently contributing impediment retrieval opposing hippocampus attractor network. Hypothesis 2 highlights involvement ventromedial cortex establishment through generalization emotional conjunction hippocampus. primary objective study improve complement existing pathological models pushing frontiers current understanding neuroscience disorders, eventually successful recovery from debilitating disorders.

Language: Английский

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

Frontiers in Psychology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 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.

Language: Английский

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The mediating effect of the amygdala-frontal circuit on the association between depressive symptoms and cognitive function in Alzheimer’s disease

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 23, 2024

Abstract Depressive symptoms occur commonly in Alzheimer’s disease (AD). Although abnormalities the amygdala-frontal circuit have been linked to emotional dysregulation and cognitive impairment, neurological basis underlying these associations AD patients with depressive (ADD) is unclear. We aimed investigate relationship between function ADD. recruited 60 ADD, without (ADND), healthy controls (HC). Functional connectivity (FC) maps of bilateral amygdala were compared. Fractional anisotropy (FA) connected by uncinate fasciculus (UF) was calculated using automated fiber quantification (AFQ). In addition, mediation analysis performed explore effects on function. found decreased FC inferior frontal gyrus (IFG) ADD group compared ADND HC groups. Moreover, FA left UF (nodes 64–97) significantly lower than group. Notably, amygdala-based IFG mediated mediating ranging 15 18%. Our study first demonstrate effect functional microstructural The findings suggest that may underlie providing potential targets for treatment strategies.

Language: Английский

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