Xiao Huang

Innate escape behaviors, while not requiring prior learning, are shaped by an animal’s learned experiences, such as previous exposure. Here, we found that learned threat experience in mice enhances flight behaviors, which is linked to increased activation of cholecystokinin-expressing neurons in the dorsal premammillary nucleus (PMd^CCK neurons), a population that controls circa-strike escape responses. This heightened activity coincides with reduced inhibition from parvalbumin-expressing GABAergic neurons in the ventral tegmental nucleus of Gudden (VTg^PV), which typically suppress PMd^CCK activity and escape behaviors. Furthermore, threat memory prompts a prefrontal projection to stimulate the release of endocannabinoids, inhibiting the axon terminals of VTg^PV neurons. The necessity of this endocannabinoid-mediated disinhibition for the observed enhancement in flight behaviors is confirmed through genetic deletion or pharmacological blockade of endocannabinoid receptors on VTg^PV neurons. Thus, our study uncovers a neural mechanism by which experience amplifies innate escape behaviors, highlighting the crucial role of endocannabinoids.

Summary Active avoidance is a type of instrumental behavior that requires an organism actively to engage in specific actions to avoid or escape from a potentially aversive stimulus and is crucial for the survival and well-being of organisms. It requires a widely distributed, hard-wired neural circuits spanning multiple brain regions, including the amygdala and thalamus. However, less is known about whether and how the hypothalamus encodes and controls active avoidance learning. Here we identify a previously unknown role for the parasubthalamic nucleus (PSTN), located in the lateral subdivision of the posterior hypothalamus, in the encoding and control of active avoidance learning. Fiber photometry calcium imaging shows that the activity of tachykinin1-expressing PSTN (PSTNTac1) neurons progressively increases during this learning. Cell-type specific ablation and optogenetic inhibition of PSTNTac1 neurons attenuates active avoidance learning, whereas optogenetic activation of these cells promotes this learning via a negative motivational drive. Moreover, the PSTN mediates this learning differentially through its downstream targets. Together, this study identifies the PSTN as a new member of the neural networks involved in active avoidance learning and offers us potential implications for therapeutic interventions targeting anxiety disorders and other conditions involving maladaptive avoidance learning.

The Weight-Adjusted Waist Index (WWI) is a novel indicator of obesity that accurately reflects body composition. However, the association between WWI and depression in patients with non-alcoholic fatty liver disease (NAFLD) remains unclear. This study aims to explore this relationship through a nationally representative cross-sectional analysis. This study included adult participants diagnosed with NAFLD from NHANES 2017–2020. WWI was calculated as the waist circumference (cm) divided by the square root of body weight (kg). NAFLD diagnosis relied on vibration-controlled transient elastography (VCTE) with a controlled attenuation parameter (CAP) exceeding 248 dB/m to indicate hepatic steatosis. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), with scores ≥ 10 indicating the presence of major depression. After adjusting for all covariates, a significant positive association was found between WWI and depression in NAFLD (OR = 1.725, 95% CI: 1.442–2.063, p < 0.00001), with a dose-response relationship indicated by restricted cubic spline analysis. The association was stronger in men and lean/normal weight NAFLD patients. Adjusting further for BMI did not alter these findings (OR = 1.643, 95% CI: 1.357–1.989, p < 0.00001). BMI’s association with depression was negated after adjusting for WWI. WWI had a positive association with depression in NAFLD, independent of BMI. This association was more pronounced in men and lean/normal weight NAFLD. These findings suggest that WWI may be a novel indicator of depression in NAFLD and potentially valuable in depression prevention.

Active avoidance is a type of instrumental behavior that requires an organism actively to engage in specific actions to avoid or escape from a potentially aversive stimulus and is crucial for the survival and well-being of organisms. It requires a widely distributed, hard-wired neural circuits spanning multiple brain regions, including the amygdala and thalamus. However, less is known about whether and how the hypothalamus encodes and controls active avoidance learning. Here we identify a previously unknown role for the parasubthalamic nucleus (PSTN), located in the lateral subdivision of the posterior hypothalamus, in the encoding and control of active avoidance learning. Fiber photometry calcium imaging shows that the activity of tachykinin1-expressing PSTN (PSTN ^Tac1 ) neurons progressively increases during this learning. Cell-type specific ablation and optogenetic inhibition of PSTN ^Tac1 neurons attenuates active avoidance learning, whereas optogenetic activation of these cells promotes this learning via a negative motivational drive. Moreover, the PSTN mediates this learning differentially through its downstream targets. Together, this study identifies the PSTN as a new member of the neural networks involved in active avoidance learning and offers us potential implications for therapeutic interventions targeting anxiety disorders and other conditions involving maladaptive avoidance learning.

Background The presence of mental health conditions is pervasive in patients who experienced acute myocardial infarction (AMI), significantly disrupting their recovery. Providing timely and easily accessible psychological interventions using virtual reality-based cognitive–behavioural therapy (VR-CBT) could potentially improve both acute and long-term symptoms affecting their mental health. Aims We aim to examine the effectiveness of VR-CBT on anxiety symptoms in patients with AMI who were admitted to the intensive care unit (ICU) during the acute stage of their illness. Methods In this single-blind randomised clinical trial, participants with anxiety symptoms who were admitted to the ICU due to AMI were continuously recruited from December 2022 to February 2023. Patients who were Han Chinese aged 18–75 years were randomly assigned (1:1) via block randomisation to either the VR-CBT group to receive VR-CBT in addition to standard mental health support, or the control group to receive standard mental health support only. VR-CBT consisted of four modules and was delivered at the bedside over a 1-week period. Assessments were done at baseline, immediately after treatment and at 3-month follow-up. The intention-to-treat analysis began in June 2023. The primary outcome measure was the changes in anxiety symptoms as assessed by the Hamilton Anxiety Rating Scale (HAM-A). Results Among 148 randomised participants, 70 were assigned to the VR-CBT group and 78 to the control group. The 1-week VR-CBT intervention plus standard mental health support significantly reduced the anxiety symptoms compared with standard mental health support alone in terms of HAM-A scores at both post intervention (Cohen’s d=−1.27 (95% confidence interval (CI): −1.64 to −0.90, pConclusions Our results indicate that VR-CBT can significantly reduce post-AMI anxiety at the acute stage of the illness; the improvement was maintained at the 3-month follow-up. Trial registration number The trial was registered at www.chictr.org.cn with the identifier: ChiCTR2200066435.

Background: This study was designed to investigate incidences of surgeons’ mental distress following severe complications after radical gastrectomy. Methods: A cross-sectional survey was conducted between 1 June 2021 and 30 September 2021 among Chinese general and/or gastrointestinal surgeons who experienced severe complications after radical gastrectomy. The clinical features collected in the questionnaire included: (i) feeling burnout, anxiety, or depression; (ii) avoiding radical gastrectomy or feeling stress, slowing down the process during radical gastrectomy operations; (iii) having physical reactions, including heart pounding, trouble breathing, or sweating while recalling; (iv) having urges to quit being a surgeon; (v) taking psychiatric medications; and (vi) seeking psychological counselling. Analyses were performed to identify risk factors of severe mental distress, which was defined as meeting three or more of the above-mentioned clinical features. Results: A total of 1062 valid questionnaires were received. The survey showed that most of the participating surgeons (69.02%) had at least one clinical feature of mental distress following severe complications after radical gastrectomy, and more than 25% of the surgeons suffered from severe mental distress. Surgeons from non-university affiliated hospitals, the junior surgeons, and existing violent doctor–patient conflicts were recognized as independent risk factors for surgeons’ severe mental distress related to the severe complications after radical gastrectomy. Conclusions: About 70% of surgeons had mental health problems following severe complications after radical gastrectomy, and more than 25% of the surgeons suffered from severe mental distress. More strategies and policies are needed to improve the mental well-being of these surgeons after such incidences.

Background: Increasing evidence indicates that dysregulated TNF-α and oxidative stress (OxS) contribute to the pathophysiology of schizophrenia. Additionally, previous evidence has demonstrated sex differences in many aspects of schizophrenia including clinical characteristics, cytokines, and OxS markers. However, to the best of our knowledge, there is no study investigating sex differences in the association between TNF-α, the OxS system, and their interaction with clinical symptoms in schizophrenia patients, especially in first-episode drug-naïve (FEDN) patients. Methods: A total of 119 FEDN schizophrenia patients and 135 healthy controls were recruited for this study. Serum TNF-α, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) were measured. The Positive and Negative Syndrome Scale (PANSS) was applied to evaluate psychotic symptoms. Two-way ANOVA, partial correlation analysis, and multivariate regression analysis were performed. Results: A sex difference in MDA levels was demonstrated only in healthy controls (F = 7.06, p_Bonferroni = 0.045) and not seen in patients. Furthermore, only male patients had higher MDA levels than male controls (F = 8.19, p_Bonferroni = 0.03). Additionally, sex differences were observed in the association of TNF-α and MDA levels with psychotic symptoms (all p_Bonferroni < 0.05). The interaction of TNF-α and MDA was only associated with general psychopathology symptom in male patients (B = − 0.07, p = 0.02). Conclusion: Our results demonstrate the sex difference in the relationship between TNF-α, MDA, and their interaction with psychopathological symptoms of patients with schizophrenia.

Objective: This study aimed to explore the mechanism of venlafaxine in regulating the apoptosis of SHSY-5Y cells induced by hypoxia. Methods: The CoCl2-induced neuronal hypoxia model was established based on SHSY-5Y cells. The morphology and related protein expression of SHSY-5Y cells were detected by qPCR, ELISA and Western blot. Results: Under the condition of hypoxia-induced by CoCl2, the expression of HIF-1α in SHSY-5Y cells was up-regulated and the expression of β-catenin was down-regulated. After adding siRNA targeting HIF-1 α to the culture cell system, down-regulation of β -catenin expression in SHSY-5Y cells was restored. This confirmed the existence of the “hypoxia-HIF-1α-Wnt/β-catenin-depression” axis. Further studies have shown that venlafaxine can alleviate neuronal apoptosis induced by hypoxia by upregulating the Wnt/β-catenin signaling pathway. Conclusion: Venlafaxine regulates apoptosis induced by hypoxia through the Wnt/β-catenin signaling pathway, which provides a new theoretical basis for the treatment of depression.