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Behavioural Brain Research Jun 2024Stressful life event is closely associated with depression, thus strategies that blunt or prevent the negative effect stress on the brain might benefits for the...
Stressful life event is closely associated with depression, thus strategies that blunt or prevent the negative effect stress on the brain might benefits for the treatment of depression. Although previous study showed the role of protein kinase R (PKR)-like ER kinase (PERK) in inflammation related depression, its involvement in the neuropathology of chronic stress induced depression is still unknown. We tried to explore whether block the PERK pathway would alleviate the animals' depression-like behavior induced by chronic restraint stress (CRS) and investigate the underlying mechanism. The CRS-exposed mice exhibited depression-like behavior, including anhedonia in the sucrose preference test (SPT), and increased immobility time in tail suspension test (TST) and forced swim test (FST). ISRIB administration for 2 weeks significantly improved the depression-like behavior in male mice exposed to CRS,which was manifested by markedly increasing the sucrose preference and reducing the immobility time in the FST and TST. However, we observed that exposure to the same dose of ISRIB in CRS female mice only showed improved anhedonia-like deficits,leaving un-altered improvement in the FST and TST. Mechanically, we found thatISRIB reversed the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, indicatingby decreased levels of serum corticosterone, reduced hippocampal glucocorticoidreceptor (GR) expression and expression of FosB in hypothalamic paraventricularnucleus (PVN), which was accompanied by preserved hippocampal neurogenesis. Thepresent findings further expand the potential role of ER stress in depression andprovide important details for a therapeutic path forward for PERK inhibitors in mood disorders.
PubMed: 38942086
DOI: 10.1016/j.bbr.2024.115122 -
Clinical Psychology & Psychotherapy 2024Previous research has indicated that various factors, such as psychological distress, distress intolerance, anhedonia, impulsivity and smoking metacognitions, have been...
Previous research has indicated that various factors, such as psychological distress, distress intolerance, anhedonia, impulsivity and smoking metacognitions, have been individually linked to the urge to smoke, withdrawal symptoms and dependence. However, these factors have not been collectively examined to determine whether smoking metacognitions independently and significantly contribute to these outcomes. Therefore, the aim of this study was to investigate the impact of distress intolerance, anhedonia, impulsivity and smoking metacognitions on the urge to smoke, withdrawal symptoms and dependency in men who are dependent on smoking. A total of 300 smoking-dependent men completed psychological scales and smoking-related measures. The findings of the study indicated that positive metacognitions about emotion regulation significantly predicted the urge to smoke, even when accounting for other significant predictors such as the number of daily cigarettes smoked, psychological distress, anhedonia and impulsivity. Furthermore, positive metacognitions about cognitive regulation were found to be a significant predictor of withdrawal symptoms, independent of other significant predictors such as psychological distress and the urge to smoke. Smoking dependence was predicted by negative metacognitions about uncontrollability beyond other significant predictors, including the number of daily cigarettes smoked and distress intolerance. These results highlight the role of metacognitions about smoking in both short- and long-term clinical outcomes related to smoking. Consequently, addressing such beliefs during treatment for smoking dependence should be an important therapeutic goal.
Topics: Humans; Male; Substance Withdrawal Syndrome; Adult; Metacognition; Tobacco Use Disorder; Impulsive Behavior; Smoking; Middle Aged; Young Adult; Anhedonia
PubMed: 38940697
DOI: 10.1002/cpp.3024 -
Behavior Therapy Jul 2024Many people with schizophrenia spectrum disorders (SSDs) experience profound amotivation, which is strongly related to anticipatory anhedonia. Yet, the...
Many people with schizophrenia spectrum disorders (SSDs) experience profound amotivation, which is strongly related to anticipatory anhedonia. Yet, the neuropsychological fundamentals of anticipatory anhedonia and amotivation are barely understood, resulting in a lack of effective treatments for these patients. Aberrancies in positive mental imagery may interfere with the anticipation of pleasure and could thus explain anticipatory anhedonia and amotivation. However, the nature of mental imagery and its relationship with amotivational psychopathology in SSD is largely unknown. In this preregistered study, we therefore examined mental imagery characteristics and their relation to anticipatory anhedonia, amotivation, and daily life activity in SSD. TheN = 86 participants included individuals with SSD (n = 43) and demographically matched healthy controls (n = 43). Mental imagery, anticipatory pleasure, amotivation, and activity engagement were assessed with structured interviews and self-report questionnaires. Ecological momentary assessment was used to measure state anticipatory pleasure and activity engagement in daily life (n = 81). Compared to the control group, the SSD group showed comparable quantity, but less vividness of mental imagery. Reduced vividness of mental imagery in SSD was significantly associated with higher anticipatory anhedonia, amotivation, and low activity engagement in cross-sectional and prospective analyses. Reduced mental imagery vividness may cause a lack of internal incentive to seek pleasurable experiences and could explain amotivation. Interventions aiming to improve mental imagery vividness and related anticipatory pleasure responses in SSD may be effective in targeting amotivation.
Topics: Humans; Female; Male; Adult; Anhedonia; Imagination; Motivation; Schizophrenia; Middle Aged; Schizophrenic Psychology; Pleasure; Ecological Momentary Assessment; Case-Control Studies; Young Adult; Anticipation, Psychological
PubMed: 38937057
DOI: 10.1016/j.beth.2024.01.009 -
Brain Sciences Jun 2024Correct classification of irritability is extremely important to assess prognosis and treatment indications of juvenile mood disorders. We assessed factors associated...
Correct classification of irritability is extremely important to assess prognosis and treatment indications of juvenile mood disorders. We assessed factors associated with low versus high parent- and self-rated irritability using the affective reactivity index (ARI) in a sample of 289 adolescents diagnosed with a bipolar or a major depressive disorder. Bivariate analyses were followed by multilinear logistic regression model. Factors significantly and independently associated with high versus low parent-rated ARI score were: more severe emotional dysregulation and bipolar disorders diagnosis. Factors significantly and independently associated with high versus low self-rated ARI score were: lower children depression rating scale (CDRS-R) difficulty of having fun item score, greater children depression inventory (CDI-2) self-report score, more severe emotional dysregulation, and greater CDRS-R appetite disturbance item score. High parent-rated irritability was strictly related with a bipolar disorder diagnosis, whereas high youth-rated irritability was related to depressive phenotype characterized by appetite/food-intake dysregulation, mood lability, and less anhedonia and apathy.
PubMed: 38928611
DOI: 10.3390/brainsci14060611 -
International Journal of Molecular... Jun 2024Astrocyte dysfunctions have been consistently observed in patients affected with depression and other psychiatric illnesses. Although over the years our understanding of... (Review)
Review
Astrocyte dysfunctions have been consistently observed in patients affected with depression and other psychiatric illnesses. Although over the years our understanding of these changes, their origin, and their consequences on behavior and neuronal function has deepened, many aspects of the role of astroglial dysfunction in major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) remain unknown. In this review, we summarize the known astroglial dysfunctions associated with MDD and PTSD, highlight the impact of chronic stress on specific astroglial functions, and how astroglial dysfunctions are implicated in the expression of depressive- and anxiety-like behaviors, focusing on behavioral consequences of astroglial manipulation on emotion-related and fear-learning behaviors. We also offer a glance at potential astroglial functions that can be targeted for potential antidepressant treatment.
Topics: Animals; Astrocytes; Humans; Stress Disorders, Post-Traumatic; Mood Disorders; Disease Models, Animal; Depressive Disorder, Major; Stress, Psychological; Rodentia
PubMed: 38928062
DOI: 10.3390/ijms25126357 -
Journal of Neurochemistry Jun 2024Stagnation in the development of novel therapeutic strategies for treatment-resistant depression has encouraged continued interest in improving preclinical methods. One...
Chronic ecologically relevant stress effects on reverse-translated touchscreen assays of reward responsivity and attentional processes in male rats: Implications for depression.
Stagnation in the development of novel therapeutic strategies for treatment-resistant depression has encouraged continued interest in improving preclinical methods. One tactic prioritizes the reverse translation of behavioral tasks developed to objectively quantify depressive phenotypes in patient populations for their use in laboratory animals via touchscreen technology. After cross-species concordance in task outcomes under healthy conditions is confirmed, construct validity can be further enhanced by identifying environmental stressors that reliably produce deficits in task performance that resemble those in depressive participants. The present studies characterized in male rats the ability of two chronic ecologically relevant stressors, inescapable ice water or isolated restraint, to produce depressive-like behavioral phenotypes in the Probabilistic Reward Task (PRT) and Psychomotor Vigilance Task (PVT). These tasks previously have been reverse-translated using touchscreen technology for rodents and nonhuman primates to objectively quantify, respectively, reward responsivity (anhedonia) and attentional processes (impaired cognitive function), each of which are core features of major depressive disorder. In the PRT, both inescapable ice water and isolated restraint produced persistent anhedonic phenotypes compared to non-stressed control performance (i.e., significantly blunted response bias for the richly rewarded stimulus). In the PVT, both chronic stressors impaired attentional processing, revealed by increases in titrated reaction times; however, these deficits largely subsided by the end of the chronic condition. Taken together, these findings confirm the ability of reverse-translated touchscreen tasks to effectively generate behavioral phenotypes that exhibit expected deficits in performance outcomes following exposure to chronic ecologically relevant stress. In turn, this approach is well positioned to appraise the ability of candidate therapeutics to attenuate or reverse such behavioral deficits and, thereby, contribute to preclinical medications development for treatment-resistant depression.
PubMed: 38922872
DOI: 10.1111/jnc.16157 -
Cells Jun 2024Chronic pain is a pathological state defined as daily pain sensation over three consecutive months. It affects up to 30% of the general population. Although significant... (Review)
Review
Chronic pain is a pathological state defined as daily pain sensation over three consecutive months. It affects up to 30% of the general population. Although significant research efforts have been made in the past 30 years, only a few and relatively low effective molecules have emerged to treat chronic pain, with a considerable translational failure rate. Most preclinical models have focused on sensory neurotransmission, with particular emphasis on the dorsal horn of the spinal cord as the first relay of nociceptive information. Beyond impaired nociceptive transmission, chronic pain is also accompanied by numerous comorbidities, such as anxiety-depressive disorders, anhedonia and motor and cognitive deficits gathered under the term "pain matrix". The emergence of cutting-edge techniques assessing specific neuronal circuits allow in-depth studies of the connections between "pain matrix" circuits and behavioural outputs. Pain behaviours are assessed not only by reflex-induced responses but also by various or more complex behaviours in order to obtain the most complete picture of an animal's pain state. This review summarises the latest findings on pain modulation by brain component of the pain matrix and proposes new opportunities to unravel the mechanisms of chronic pain.
Topics: Animals; Humans; Chronic Pain; Disease Models, Animal; Pain; Nerve Net
PubMed: 38920628
DOI: 10.3390/cells13120997 -
European Neuropsychopharmacology : the... Jun 2024Ketamine, an N-methyl-D-aspartate receptor antagonist, is a racemic mixture of esketamine and arketamine used to treat unipolar and bipolar depression. Preliminary... (Review)
Review
Ketamine, an N-methyl-D-aspartate receptor antagonist, is a racemic mixture of esketamine and arketamine used to treat unipolar and bipolar depression. Preliminary reports indicate that it may be beneficial for depressed patients reporting symptoms of anhedonia. In this systematic review we aim to assess and analyze the existing body of evidence regarding the therapeutic effects of ketamine on the domain of anhedonia. Electronic databases (PubMed, APA Psycinfo and Web of Science) were searched from inception to November 2023. Protocol was registered in PROSPERO under the identifier CRD42023476603. A total of twenty-two studies, including four randomized-controlled trials and eighteen open-label trials were included. All studies reported alleviation of anhedonia symptoms following ketamine or esketamine administration, regardless of the number of infusions. Several important limitations were included, first and foremost low number of placebo-controlled randomized-controlled trials. This review indicates a potential anti-anhedonic effect of ketamine in patients with depression. Several trials used neuroimaging techniques which confirm ketamine's effect on functional connectivity correlating with the improvement in anhedonia. Despite considerable variations in methodology and the specific brain regions investigated, these studies collectively point towards ketamine's neuroplastic effects in mitigating anhedonia.
PubMed: 38917771
DOI: 10.1016/j.euroneuro.2024.04.014 -
Schizophrenia (Heidelberg, Germany) Jun 2024Functional impairments contribute to poor quality of life in schizophrenia spectrum disorders (SSD). We sought to (Objective I) define the main functional phenotypes in...
Functional impairments contribute to poor quality of life in schizophrenia spectrum disorders (SSD). We sought to (Objective I) define the main functional phenotypes in SSD, then (Objective II) identify key biopsychosocial correlates, emphasizing interpretable data-driven methods. Objective I was tested on independent samples: Dataset I (N = 282) and Dataset II (N = 317), with SSD participants who underwent assessment of multiple functioning areas. Participants were clustered based on functioning. Objective II was evaluated in Dataset I by identifying key features for classifying functional phenotype clusters from among 65 sociodemographic, psychological, clinical, cognitive, and brain volume measures. Findings were replicated across latent discriminant analyses (LDA) and one-vs.-rest binomial regularized regressions to identify key predictors. We identified three clusters of participants in each dataset, demonstrating replicable functional phenotypes: Cluster 1-poor functioning across domains; Cluster 2-impaired Role Functioning, but partially preserved Independent and Social Functioning; Cluster 3-good functioning across domains. Key correlates were Avolition, anhedonia, left hippocampal volume, and measures of emotional intelligence and subjective social experience. Avolition appeared more closely tied to role functioning, and anhedonia to independent and social functioning. Thus, we found three replicable functional phenotypes with evidence that recovery may not be uniform across domains. Avolition and anhedonia were both critical but played different roles for different functional domains. It may be important to identify critical functional areas for individual patients and target interventions accordingly.
PubMed: 38914577
DOI: 10.1038/s41537-024-00479-9 -
Neurobiology of Stress Jul 2024Depression is increasingly diagnosed in adolescence, necessitating specific prevention and treatment methods. However, there is a lack of animal models mimicking...
INTRODUCTION
Depression is increasingly diagnosed in adolescence, necessitating specific prevention and treatment methods. However, there is a lack of animal models mimicking juvenile depression. This study explores a novel model using ultrasound (US) stress in juvenile mice.
METHODS
We employed the US stress model in one-month-old C57/BL6 mice, exposing them to alternating ultrasound frequencies (20-25 kHz and 25-45 kHz) for three weeks. These frequencies correspond to negative and neutral emotional states in rodents and can induce a depressive-like syndrome. Concurrently, mice received either an omega-3 food supplement (FS) containing eicosapentaenoic acid (EPA; 0.55 mg/kg/day) and docosahexaenoic acid (DHA; 0.55 mg/kg/day) or a vehicle. Post-stress, we evaluated anxiety- and depressive-like behaviors, blood corticosterone levels, brain expression of pro-inflammatory cytokines, and conducted metabolome analysis of brain, liver and blood plasma.
RESULTS
US-exposed mice treated with vehicle exhibited decreased sucrose preference, a sign of anhedonia, a key feature of depression, increased anxiety-like behavior, elevated corticosterone levels, and enhanced TNF and IL-1β gene expression in the brain. In contrast, US-FS mice did not display these changes. Omega-3 supplementation also reduced anxiety-like behavior in non-stressed mice. Metabolomic analysis revealed US-induced changes in brain energy metabolism, with FS increasing brain sphingomyelin. Liver metabolism was affected by both US and FS, while plasma metabolome changes were exclusive to FS. Brain glucose levels correlated positively with activity in anxiety tests.
CONCLUSION
Chronic omega-3 intake counteracted depressive- and anxiety-like behaviors in a US model of juvenile depression in mice. These effects likely stem from the anti-inflammatory properties of the supplement, suggesting potential therapeutic applications in juvenile depression.
PubMed: 38912378
DOI: 10.1016/j.ynstr.2024.100646