Frontiers in Behavioral Neuroscience最新文献

Introduction: Stress-related disorders, such as major depression, anxiety disorders, and post-traumatic stress disorder, lead to considerable disease burden and are notoriously difficult to treat. These disorders are characterized by striking sex differences, but the neurobiological underpinnings of the disparities in mental health between men and women remain largely undefined. With an improved understanding of the biological factors that promote or protect against psychopathology, it may become possible to design interventions that enhance resilience. Preclinical research using rodent models can provide fundamental insight into potential sex differences in the neurobiological consequences of stress, which could have important implications for our understanding of stress-related disorders.

Methods: Towards this end, the current work compared stress-induced alterations in DNA methylation and behavior in male and female c57BL/6 mice. A subchronic stress paradigm consisting of five days of mild stressors was used, and behavioral outcomes were assessed using the elevated plus maze and the light-dark emergence, open field, forced swim and effort-related reward choice tests.

Results: Statistical analyses using two-way ANOVAs revealed that although some of the effects of stress in the light-dark emergence test were specific to females, both sexes were susceptible to several behavioral consequences of this stress paradigm. Stress was also shown to decrease global DNA methylation in the nucleus accumbens one week following the end of stress exposure in both sexes, but no significant effects were observed two hours following stress. In the hippocampus, no global DNA methylation differences were observed at either time point. Targeted evaluations using methylation-specific PCR revealed sex differences in stress-induced changes in DNA methylation at sites in the prodynorphin and inhibitory kappa B kinase beta genes in the nucleus accumbens. In contrast, no significant sex-by-stress interactions were observed for methylation changes in the hippocampus, although stress significantly increased DNA methylation of prodynorphin and inhibitory kappa B kinase beta two hours after the final stress exposure and reduced methylation of the NEMO and D2 dopamine receptor genes one week following stress.

Discussion: Overall, these findings provide further evidence of sex differences in stress susceptibility and suggest that sex differences in epigenetic adaptations to stress could contribute to the partially distinct behavioral outcomes of stress in males and females.

Scents can influence anxiety, including that experienced in clinical environments. This study examined the effects of two distinct aromas: lavender, a fragrance widely recognized for its calming properties, and African stone, a musky and relatively unfamiliar scent. Twenty healthy participants underwent alternating periods of rest and scent inhalation in a dental office environment while anxiety was assessed using the State-Trait Anxiety Inventory (STAI), electroencephalographic (EEG) measures of theta, alpha, and beta power ratios, and electrocardiographic (ECG) measures of heart rate variability (HRV). Lavender inhalation significantly reduced self-reported state anxiety scores but did not produce measurable changes in EEG or HRV indices, possibly due to the short (5 min) exposure duration. African stone, in contrast, did not alter self-reported anxiety but induced significant physiological effects, including reduced theta and, increased alpha power in parieto-occipital regions, and decreased high-frequency (HF) and total HRV power. While the EEG changes are consistent with a more relaxed state, the HRV reductions could indicate a heightened autonomic arousal, suggesting that African stone could have triggered increased attention and physiological activation rather than merely relaxation. These findings demonstrate a divergence between subjective and physiological responses to scent exposure. Lavender appears to primarily reduce perceived anxiety, while African stone influences physiological arousal. We suggest that a multimodal approach be applied in aromatherapy research.

Polyvagal theory (PVT) offers an integrative model of autonomic regulation that accounts for the evolution, neuroanatomy, and functional organization of the vagus nerve in relation to behavioral and emotional processes. This article revisits PVT by synthesizing its scientific foundations with recent advancements in transcriptomics, neurophysiology, and clinical application. Particular emphasis is placed on the theory's hierarchical model of the autonomic nervous system, the role of the ventral vagal complex in social behavior, and the construct of neuroception-the neural process by which safety and threat are detected without conscious awareness. The discussion incorporates both theoretical refinement and empirical validation while addressing common misconceptions and critiques of the model. In addition to the scientific narrative, the author offers a personal perspective on the intellectual and experiential origins of PVT, illustrating its translational value in clinical and therapeutic settings. By combining rigorous science with experiential insight, this article seeks to advance understanding of the autonomic foundations of social behavior and mental health.

Most neuropsychiatric conditions, including neurodevelopmental disorders, can have different etiology depending on genetic influences, environmental factors, and gene-environment interactions. Consistent evidence points to low birth weight, commonly associated with prenatal exposure to excess glucocorticoids (GC), as risk factor for neuropsychiatric disorders including depression, ADHD and schizophrenia. In this review we give an overview of our behavioral and mechanistic studies linking prenatal exposure to GC to depression. The behavioral analyses in our mouse model revealed that prenatal exposure to synthetic GC dexamethasone (DEX) alters hippocampal neurogenesis and induces depression-like behavior that responds differently to antidepressive therapies. Using neural progenitor cells as an in vitro experimental model, we could show changes in the methylation state of genes regulating proliferation, differentiation, and migration suggesting that epigenetic modifications are involved in neurogenesis alterations induced by GC. A particularly interesting observation was the alteration in circadian patterns of activity accompanied by weaker coupling between the central clock and peripheral oscillators preceding the late onset of depression in mice exposed to DEX in utero. The results suggest that alterations in patterns of circadian spontaneous activity may predict the onset of depression and the response to therapy in depressed patients. Our collaborative clinical investigations provide evidence for the prognostic value of circadian activity analysis in predicting the response to antidepressant treatments in patients affected by major depressive disorder.

Introduction: A key skill useful in everyday life is learning from our past choices to overcome cognitive biases and cope with our environment. In this regard, we are often responsible not only for ourselves but also for others.

Methods: As our previous results showed that after excitatory stimulation of the ventromedial prefrontal cortex (vmPFC) people improved risk weighing and reduced their cognitive biases via improved affective learning, here we examined whether the above results differ when participants are playing for themselves versus for someone else. Therefore, we added this experimental manipulation to our previously well-validated gambling paradigm.

Results: We found that participants showed improved learning after excitatory stimulation when playing for themselves but not when playing for someone else. At the neural level, we observed interaction effects involving the stimulation (inhibitory vs. excitatory), the frame (gain vs. loss) and the recipient (self vs. other) in prefrontal, temporal and parietal areas during the decision-making and feedback phase.

Discussion: Our results suggest that excitatory vmPFC-tDCS can facilitate gambling and enhance the neural processing of gambling-related stimuli when playing for oneself.

Motivated behaviors, such as reproduction and feeding, are essential for mammalian survival. Although these behaviors serve distinct evolutionary purposes, they share a common function: fulfilling specific biological needs. Their regulation involves distinct brain regions and is influenced by a complex interplay of neural circuits, with significant sex-based differences. Alterations in motivation represent critical components of effort-based decision-making processes in eating disorders (EDs). Importantly, the impairments in motivated behavior observed in EDs arise not from structural changes within the relevant brain regions but rather from functional alterations influenced primarily by gonadal hormones. These hormones play a pivotal role in the pathophysiology of EDs, driving sex-based differences in both the qualitative aspects of symptom presentation and developmental trajectories through intracellular genomic signaling pathways. The current review examines sex differences in motivated behavior within the context of EDs.

Background: Early intervention services (EIS) for first-episode psychosis (FEP) play a key role in shaping a better disease trajectory for both affective and non-affective psychosis. Psychotic disorders tend to present sex differences both from an epidemiological and clinical perspective.

Aims: The primary aim of this study is to investigate sex-based differences in outcome of patients admitted to EIS for FEP, analysing clinical differences and recovery rates during a 24 months long follow-up.

Methods: A longitudinal cohort study was conducted. Patients were those admitted to the EIS in Ferrara between 2012 and February 27th, 2025 who met the following enrolment criteria: (a) diagnosed with affective or non-affective FEP; (b) not being treated for more than 24 months; (c) absence of intellectual disability; (d) aged between 18 and 35 years; (e) absence of organic psychosis. Socio-demographic and clinical characteristics were collected at program admission. The HoNOS (Health of the Nation Outcome Scale) was administered at baseline and every 6 months for the 24 months follow-up to compare sex differences in terms of symptoms severity and clinical recovery (HoNOS total score <8). Outcomes over time were compared between groups using mixed effects models repeated measures analysis of variance (MMRM).

Results: A total of 174 patients were included in the study, most were males (74.1%), and most men vs. women were born in Italy (81.4% vs. 66.7%, p = 0.04). At admission, men had significantly higher rates of cannabis use (56.6% vs. 22.2%), tobacco use (62% vs. 28.9%), and alcohol misuse (51.2% vs. 15.5%) (p < 0.001). Men, compared to women, at 6 and 12 months showed significantly lower clinical severity than women (11.9 vs. 14.5, p = 0.03; 9.4 vs. 11.9, p = 0.05 respectively), and higher probability of being in recovery at 12 months (p = 0.04), indicating a faster clinical improvement. At 24-month, more men than women were NEET (Not in Education, Employment or Training) (26.3% vs. 8%, p = 0.04).

Conclusion: Overall, our study highlighted significant sex differences both at admission as well as in outcomes. Men tend to improve more rapidly than women, then reaching a plateau with no substantial differences between sexes at 24 months. Further studies should identify sex-specific outcome predictors that could help in early patients' identification, thus leading to improve clinical trajectories and long-term prognosis.

Background: Preclinical studies have shown that exposure to a multisensory, stimulating environment (environmental enrichment, EE) can prevent the development of addictive behaviors and reduce the risk of relapse in animal models. However, the extent to which these preclinical findings apply to human addiction remains largely unknown. In this research, we investigated the role of EE in human substance use disorders (SUDs).

Methods: A new self-report measure of perceived EE was developed to test, in human participants, whether EE is associated with lower levels of SUD. This scale was administered to two distinct groups: regular smokers (N = 286) and patients diagnosed with severe alcohol use disorder (N = 52). Smokers also provided demographic information and data on nicotine use, while patients with alcohol use disorder reported pre-hospitalization drug intake, detoxification history, and levels of depression and anxiety.

Results: The EE scale demonstrated adequate psychometric properties, including a stable factorial structure and high test-retest reliability over 1 month. Among smokers, higher scores were significantly associated with lower nicotine consumption, dependence and craving. In patients with alcohol use disorder, lower scores were linked to a history of more frequent relapse. These effects were independent from depression and anxiety.

Conclusion: Environmental enrichment, as perceived and self-reported by individuals, appears to be a promising construct for understanding vulnerability and resilience in human addiction. The scale may serve as a valuable translational tool between preclinical and clinical models, with potential implications for the development of new intervention strategies for SUD.

The development of metacognition and executive functions supports adaptive and goal-oriented behavior in adulthood. Therefore, effective screening of these skills is essential for implementing early interventions in educational and clinical settings. While neuropsychological tests usually focus on a single skill and require clinicians to use lengthy batteries, the Metacognitive Wisconsin Card Sorting Test (Meta-WCST) assesses metacognition, executive functions, and their interaction. However, this test has not yet been scientifically validated for children with either typical or atypical development. This gap highlights both a methodological shortcoming and a missed opportunity for developmental neuropsychology. In this review, we provide a comprehensive analysis of studies involving the Meta-WCST, aiming to evaluate its translational potential for developmental applications. Despite several methodological limitations in the current literature, our evaluation indicates that the Meta-WCST can be adapted to developmental contexts through targeted improvements to theoretical and computational frameworks, data analysis methods, and protocol procedures. These considerations have meaningful implications for multiple areas of developmental neuropsychology, including scientific research, educational practices, and clinical assessments.

Introduction: Parkinson's disease (PD) is characterized by non-motor impairments including symptoms anxiety. These disturbances manifest in up to 40% of patients, most often early in the course of disease. While disruptive to all patients' lives, signs of anxiety are also more prevalent and/or more severe in female PD patients. Unfortunately, anxiolytic drugs are rarely used to manage these signs, as these medications can increase PD patients' risks for worsening of cognitive deficits and falls. The treatments commonly used in PD to improve patients' motor function or lessen signs of depression are often without positive effect on measures of anxiety. Thus, clinical needs for successful treatment of anxiety symptoms in PD are frequently unmet.

Methods: The work presented here used longitudinal Elevated Plus Maze (EPM) testing in male and female wild type rats and in male and female rats with knockout of the PTEN-induced putative kinase 1 gene (Pink1^-/- ) to determine whether these are suitable models for translational studies examining the neural substrates that underpin the sex-specific expression of anxiety symptoms in PD.

Results: Behavioral testing in male and female wild type and Pink1^-/- rats showed that Pink1^-/- rats of both biological sex initially displayed hyperlocomotion and broad, possibly impulsive exploration of all portions of the elevated plus maze, including its open, unprotected spaces. While these behaviors persisted in Pink1^-/- males, by 7 months of age, EPM performance in female Pink1^-/- rats changed dramatically and included convergent behavioral measures indicative of significantly heightened anxiety, e.g., reduced open arm entries, slower speeds of ambulation in open arms, avoidance of distal ends of open arms. These and other signs of an anxiety remained through final testing of the female Pink1^-/- cohort at 12 months of age.

Discussion: Unlike a surprising number of other rodent models of PD that fail to emulate clinically observed anxiety and/or male/female differences in these signs, the data presented here identify Pink1^-/- rats as strongly suited to lead translational efforts to better understand the neurobiological and neuroendocrine bases for anxiety symptoms in PD, their sex differences and their sex-specific sensitivities to therapeutic interventions.