scholarly journals The Role of HPA Axis and Allopregnanolone on the Neurobiology of Major Depressive Disorders and PTSD

2021 ◽  
Vol 22 (11) ◽  
pp. 5495
Author(s):  
Felipe Borges Almeida ◽  
Graziano Pinna ◽  
Helena Maria Tannhauser Barros
Keyword(s):  
Hpa Axis ◽  
Depressive Disorders ◽  
Post Traumatic Stress ◽  
Major Depressive ◽  
Physiological Adaptations ◽  
Suppression Test ◽  
Post Traumatic ◽  
Major Depressive Disorders ◽  
Cortisol Release

Under stressful conditions, the hypothalamic-pituitary-adrenal (HPA) axis acts to promote transitory physiological adaptations that are often resolved after the stressful stimulus is no longer present. In addition to corticosteroids (e.g., cortisol), the neurosteroid allopregnanolone (3α,5α-tetrahydroprogesterone, 3α-hydroxy-5α-pregnan-20-one) participates in negative feedback mechanisms that restore homeostasis. Chronic, repeated exposure to stress impairs the responsivity of the HPA axis and dampens allopregnanolone levels, participating in the etiopathology of psychiatric disorders, such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). MDD and PTSD patients present abnormalities in the HPA axis regulation, such as altered cortisol levels or failure to suppress cortisol release in the dexamethasone suppression test. Herein, we review the neurophysiological role of allopregnanolone both as a potent and positive GABAergic neuromodulator but also in its capacity of inhibiting the HPA axis. The allopregnanolone function in the mechanisms that recapitulate stress-induced pathophysiology, including MDD and PTSD, and its potential as both a treatment target and as a biomarker for these disorders is discussed.

scholarly journals Genes and hormones of the hypothalamic–pituitary–adrenal axis in post-traumatic stress disorder. What is their role in symptom expression and treatment response?

2021 ◽  
Author(s):  
Susanne Fischer ◽  
Tabea Schumacher ◽  
Christine Knaevelsrud ◽  
Ulrike Ehlert ◽  
Sarah Schumacher
Keyword(s):  
Hpa Axis ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Ptsd Symptoms ◽  
Post Traumatic Stress ◽  
Alternative Treatments ◽  
Hypothalamic Pituitary Adrenal ◽  
Post Traumatic

Abstract Background Less than half of all individuals with post-traumatic stress disorder (PTSD) remit spontaneously and a large proportion of those seeking treatment do not respond sufficiently. This suggests that there may be subgroups of individuals who are in need of augmentative or alternative treatments. One of the most frequent pathophysiological findings in PTSD is alterations in the hypothalamic–pituitary–adrenal (HPA) axis, including enhanced negative feedback sensitivity and attenuated peripheral cortisol. Given the role of the HPA axis in cognition, this pattern may contribute to PTSD symptoms and interfere with key processes of standard first-line treatments, such as trauma-focused cognitive behavioural therapy (TF-CBT). Methods This review provides a comprehensive summary of the current state of research regarding the role of HPA axis functioning in PTSD symptoms and treatment. Results Overall, there is preliminary evidence that hypocortisolaemia contributes to symptom manifestation in PTSD; that it predicts non-responses to TF-CBT; and that it is subject to change in parallel with positive treatment trajectories. Moreover, there is evidence that genetic and epigenetic alterations within the genes NR3C1 and FKBP5 are associated with this hypocortisolaemic pattern and that some of these alterations change as symptoms improve over the course of treatment. Conclusions Future research priorities include investigations into the role of the HPA axis in day-to-day symptom variation, the time scale in which biological changes in response to treatment occur, and the effects of sex. Furthermore, before conceiving augmentative or alternative treatments that target the described mechanisms, multilevel studies are warranted.

scholarly journals Reduced Energy Per Cycle, a Marker of Glutamatergic Synaptic Strength, in Individuals Diagnosed with PTSD and Depression

2021 ◽  
Author(s):  
Lynnette Averill ◽  
Lihong Jiang ◽  
Prerana Purohit ◽  
Anastasia Coppoli ◽  
Christopher Averill ◽  
...  
Keyword(s):  
Depressive Disorders ◽  
Antidepressant Treatment ◽  
Synaptic Strength ◽  
Resonance Spectroscopy ◽  
Major Depressive ◽  
Novel Treatments ◽  
Study Results ◽  
Healthy Control ◽  
Major Depressive Disorders

Trauma and chronic stress are believed to induce and exacerbate psychopathology by disrupting glutamate synaptic connectivity. In this pilot study, we utilized energy-per-cycle (EPC), a novel putative biomarker of glutamatergic synaptic strength, to investigate the role of prefrontal neurotransmission in trauma psychopathology. Healthy control (n=18) and patients with comorbid posttraumatic stress and major depressive disorders (PTSD+MDD; n=16) completed 13C-acetate magnetic resonance spectroscopy scans to estimate prefrontal EPC, which is the ratio of neuronal energetic needs per glutamate neurotransmission cycle (VTCA/VCycle). Patients with PTSD+MDD were found to have 28% reduction in prefrontal EPC (t=3.0; df=32, p=0.005). There was no effect of sex on EPC, but age was negatively associated with prefrontal EPC across groups (r=-0.46, n=34, p=0.006). Controlling for age did not affect the study results. Exploratory analyses found antidepressants to have statistically significant effects (F(2,30)=5.3, p=0.01), with the lowest EPC in the unmedicated PTSD+MDD participants (p=0.003). Patients with comorbid PTSD and MDD have reduced prefrontal glutamatergic synaptic strength, as estimated by EPC. Antidepressant treatment appears to partially normalize the prefrontal EPC deficits. These findings suggest that reduced glutamatergic synaptic strength may contribute to the pathophysiology of comorbid PTSD and MDD and might be targeted by novel treatments.

scholarly journals Plasma concentrations of Granulocyte Colony-Stimulating Factor (G-CSF) in Patients with Substance Use Disorders and Comorbid Major Depressive Disorders

2021 ◽  
Author(s):  
Sandra Torres Galván ◽  
María Flóres López ◽  
Pablo Romero Sanchíz ◽  
Nerea Requena Ocaña ◽  
Oscar Porras Perales ◽  
...  
Keyword(s):  
Substance Use ◽  
Substance Use Disorders ◽  
Depressive Disorders ◽  
Plasma Concentrations ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Major Depressive ◽  
Major Depressive Disorders ◽  
Stimulating Factor

Abstract Aims: Granulocyte colony–stimulating factor (G-CSF) has raised much interest due to its role to cocaine addiction in preclinical models. We analyzed the circulating expression of G-CSF in abstinent chronic users of alcohol and/or cocaine with or without comorbid major depressive disorders to investigate the role of this trophic factor with complicated substance use disorders.Methods: We recruited 176 patients and 136 controls. Patients were divided in 50 patients with major depressive disorder (MDD) and 126 abstinent substance use disorders (SUD) patients undergoing treatments for alcohol (N=66) or cocaine (N=60) addiction according to DSM-IV-TR criteria. A blood sample was collected to examine plasma concentrations of G-CSF.Results: The plasma concentrations of G-CSF were significantly decreased in the cocaine group compared with the SUD control group. There was a sex dimorphism in the alcohol group, with lower G-CSF concentrations in women compared with men. Plasma concentrations of G-CSF were associated with abstinence and with the length of alcohol problems. The decrease in G-CSF was associated with comorbid MDD, a finding specific for SUD patients since there were no alterations of G-CSF primary settings MDD outpatients.Conclusions: Circulating G-CSF is reduced in SUD patients, being associated to comorbid MDD. A sex-dependent effect was observed in female AUD. Plasma G-CSF concentrations might be used as a predictor of length of chronic alcohol use and as a stratification role in the dual diagnosis in SUD. Further investigation is needed to explore the role of G-CSF as potential biomarker of pathogenic/prognosis in SUD population.

scholarly journals Anticonvulsant effects of desvenlafaxine on modulating brain monoamine and oxidative stress in mice

2023 ◽  
Vol 83 ◽  
Author(s):  
Khalid Saad Alharbi
Keyword(s):  
Oxidative Stress ◽  
Depressive Disorders ◽  
Motor Coordination ◽  
Maximal Electroshock ◽  
Gamma Aminobutyric Acid ◽  
Major Depressive ◽  
Major Depressive Disorders ◽  
Brain Monoamine ◽  
And Oxidative Stress

Abstract Desvenlafaxine succinate (DVS) inhibits serotonin reuptake selectively and is approved for major depressive disorders. This research investigated influence of DVS on modulating brain monoamine and oxidative stress in mice. The antiepileptic potential of DVS (10, 20, or 30 mg/kg/i.p.) in pentylenetetrazole (PTZ; 85 mg/kg) with i.p. route of administration, strychnine (STR; 75 mg/kg) with i.p. route, pilocarpine (400 mg/kg) with s.c. route and maximal electroshock MES-induced convulsion in mouse models. The activities of oxidative stress, i.e. superoxide dismutase (SOD), glutathione (GSH) and lipid peroxidation (LPO) as well as gamma-aminobutyric acid (GABA) in the brains of PTZ-induced convulsive mice. Treatment with DVS increased the latency to develop siezures and declined mortalities in rodents against PTZ, STR and pilocarpine-induced convulsions. Results of MES-leaded siezures revealed that DVS reduced tonic hind limb extension duration and mortalities significantly. Brain, SOD, GSH and GABA level were significantly (P<0.01) increased and LPO reduced significantly (P<0.01) after DVS treatment. Furthermore, the DVS did not show any motor coordination signs in the rotarod test. We demonstrated that the role of DVS in convulsion genesis in mice under control condition and attenuate the PTZ-induced oxidative damage.

scholarly journals The Role of Intelligence Quotient as a Risk Factor for Depression: a Literature Review

2021 ◽  
Vol 2 (1) ◽  
pp. 51-54
Author(s):  
Bella Sagita Pratiwi
Keyword(s):  
Risk Factor ◽  
Literature Review ◽  
Intelligence Quotient ◽  
Depressive Disorders ◽  
Cure Rate ◽  
Major Depressive ◽  
Psychomotor Disorders ◽  
Long Time ◽  
Major Depressive Disorders

A B S T R A C TDepression is a mood disorder with general characteristics in the form of changes insleep patterns and appetite, psychomotor disorders, concentration problems,anhedonia, fatigue, hopelessness and helplessness, and suicidal ideation. If thedepressive disorder goes on for a long time (dysthymia), the person is suggested to bemoody, lazy, or withdrawn from relationships because he loses interest in almost allaspects of his life. Depression is a psychiatric disorder that is often found with aprevalence of around 15%. In general, the onset of major depressive disorders is atthe age of 20 to 50 years, but the most often is at the age of 40 years. Cognitive playsa role in the aetiology and prognosis of someone with depression. The higher thecognitive level of a person, the more it will affect the cure rate and prevent recurrencein someone experiencing psychiatric disorders. This literature review will explain therole of intelligence quotient in depressive disorders.

scholarly journals Decoding shared versus divergent transcriptomic signatures across cortico-amygdala circuitry in PTSD and depressive disorders

2021 ◽  
Author(s):  
Andrew E. Jaffe ◽  
Brianna K. Barry ◽  
Ran Tao ◽  
Matthew N. Tran ◽  
Stephanie C. Page ◽  
...  
Keyword(s):  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Depressive Disorders ◽  
Postmortem Brain ◽  
Supporting Evidence ◽  
Rna Seq ◽  
Post Traumatic Stress ◽  
Major Depressive ◽  
Gene Sets ◽  
Post Traumatic

AbstractPost-traumatic stress disorder (PTSD) is a debilitating neuropsychiatric disease with a projected lifetime risk of 8.7%. PTSD is highly comorbid with depressive disorders including major depressive disorder (MDD) and bipolar disorder (BD). It is hypothesized that the overlap in symptoms stems from partially shared underlying neurobiological mechanisms. To better understand shared and unique transcriptional patterns of PTSD and MDD we performed RNA-sequencing in the postmortem brain of two prefrontal cortex (PFC) regions and two amygdala (AMY) regions, from neurotypical donors (N=109) as well as donors with diagnoses of PTSD (N=107) or MDD (N=109) across 1285 RNA-seq samples. We identified a small number of differentially expressed genes (DEGs) specific to PTSD, mostly in the cortex compared to amygdala. PTSD-specific DEGs were preferentially enriched in cortistatin-expressing cells, a subpopulation of somatostatin interneurons. These PTSD DEGs also showed strong enrichment for gene sets associated with immune-related pathways and microglia, largely driven by decreased expression of these genes in PTSD donors. While we identified a greater number of DEGs for MDD, there were only a few that were specific to MDD as they showed high overlap with PTSD DEGs. Finally, we used weighted gene co-expression network analysis (WGCNA) as an orthogonal approach to confirm the observed cellular and molecular associations. These findings highlight the sub-population of cortistatin-expressing interneurons as having potential functional significance in PTSD and provide supporting evidence for dysregulated neuroinflammation and immune signaling in MDD and PTSD pathophysiology.

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