Neurobiological Effects Research Articles

Psychosocial interventions for children and adolescents with adverse childhood experiences: A systematic review and meta-analysis.

Exposure to adverse childhood experiences (ACEs) is associated with adverse neurobiological, developmental, cognitive, behavioral, psychological, and social consequences among children and adolescents. Psychosocial interventions hold promise for mitigating the negative impacts of ACEs, but there is a lack of updated and comprehensive evidence summarizing their effects qualitatively and quantitatively. We performed a systematic review and meta-analysis of existing evidence on the effectiveness of psychosocial interventions on children's outcomes, including internalizing and externalizing problems. We searched five database sources from inception to April 2024 for studies on the effectiveness of any psychosocial intervention in any outcome among children and adolescents aged 6-18 who experienced ACEs. We qualitatively synthesized the characteristics of the studies, samples, interventions, and outcomes. We quantitatively estimated the pooled effects of psychosocial interventions on a range of outcomes encompassing internalizing problems, externalizing problems, family relationships, coping, and self-esteem using meta-analysis. Additionally, we conducted a series of subgroup meta-analyses to compare the intervention effects based on sample and intervention characteristics. Forty-four studies were included, with 20 randomized controlled trials, nine controlled trials, and 15 pre-post trials. Significant intervention effects were observed in internalizing problems (standardized mean difference, SMD=-0.36) and externalizing problems (SMD=-0.57), but not in family relationships, coping, or self-esteem. Subgroup analyses have identified various effective interventions for internalizing problems and externalizing problems, respectively. The evidence suggests that psychosocial interventions are effective in preventing internalizing and externalizing problems among children and adolescents who have experienced ACEs. Recommendations are provided for designing and evaluating future psychosocial interventions.

The Effects of Exergaming on the Depressive Symptoms of People With Dementia: A Systematic Review and Meta-Analysis.

Depressive symptoms are common among people with dementia (PWD). Exergaming consisting of combined cognitive and physical training in gaming is increasingly used to alleviate their depressive symptoms in research. With its potential synergistic neurobiological and psychosocial effects on reducing depressive symptoms among PWD, this review aimed to understand its effectiveness and contents. This is a systematic review of the effectiveness of exergames on depressive symptoms among older adults with dementia. A search was conducted on 7 May 2024 of the online databases CINAHL, Embase, PsycINFO, PubMed and the China Academic Journal Network Publishing Database (CNKI). The methodological quality of randomised controlled trials (RCT) and quasi-experimental studies was assessed with RoB2 and ROBINS-I, respectively. A meta-analysis of the included RCTs was conducted. Six studies consisting of four RCTs and two quasi-experimental studies involving 235 participants with various stages of dementia were included. The meta-analysis showed a significant overall improvement in depression with a large effect size (SMD = 1.46, 95% CI = -2.50, -0.43; p = 0.006). Despite high heterogeneity (I2 = 91%), all studies demonstrated a trend of improvement in depression after the intervention. The exergames adopted in the included trials had the following elements: simultaneous motor-cognitive training, a scoring mechanism and a social play. The dose of exergames ranged from 15 to 60 min per session for at least 8 weeks, with a minimum of two sessions weekly. However, the included studies had a moderate-to-serious risk of bias. The certainty of the evidence was very low. Exergames could be effective at improving the depressive symptoms of older adults with dementia. Yet, a moderate-to-severe risk of bias shows a rigorous study should be conducted in the future. This study provides evidence for healthcare professionals and informal caregivers to use exergames to address depressive symptoms in PWD. The review was registered on PROSPERO with the reference CRD42022372762.

Differences in Brain Volume and Thickness between Shammah (Smokeless Tobacco) Users and Non-Users: A Cross-Sectional Study.

Aims/Background Previous research has shown that smoking tobacco is associated with changes or differences in brain volume and cortical thickness, resulting in a smaller brain volume and decreased cortical thickness in smokers compared with non-smokers. However, the effects of smokeless tobacco on brain volume and cortical thickness remain unclear. This study aimed to investigate whether the use of shammah, a nicotine-containing smokeless tobacco popular in Middle Eastern countries, is associated with differences in brain volume and thickness compared with non-users and to assess the influence of shammah quantity and type on these effects. Methods Male shammah users (aged 20 to 47 years, n = 30) and non-users (n = 39) underwent 1.5T magnetic resonance imaging (MRI) scans, and cortical brain volumes and thicknesses were measured using FreeSurfer. Results Significant differences were found in the volume of the right pallidum (p = 0.02), total pallidum (p = 0.02), total ventricle (p = 0.02), middle posterior corpus callosum (p = 0.04), and brainstem (p = 0.02) between shammah users and non-users. Furthermore, yellow shammah users exhibited smaller volumes in the right lateral ventricle (p = 0.02), total lateral ventricle (p = 0.03), and right putamen (p = 0.02) compared with users of other types of shammah. Regarding cortical thickness, significant differences were observed in the right medial orbito-frontal thickness (p = 0.03), left rostral middle frontal thickness (p = 0.03), and right rostral anterior cingulate thickness (p = 0.04). Conclusion These findings shed light on the potential neurobiological effects of shammah use, particularly the yellow shammah, and highlighting the need for further research to fully understand its implications for brain structure and function.

Low emotional contagious behavior induces PTSD susceptibility in observers and is related to the regulation of oxytocin receptor in mice.

Post-traumatic stress disorder (PTSD) is a serious psychiatric disorder that occurs after an individual has witnessed or experienced a major traumatic event. Emotional contagion seems to play an important role in witnessing trauma, highlighting the importance of understanding the neurobiological consequences of psychological or emotional stress and its impact on the individual's mental health. Therefore, understanding the relationship between emotional contagion and PTSD susceptibility and the abnormal neurobiological and behavioral changes behind it could help find effective molecular treatment targets. The formalin pain test was used to distinguish the level of emotional contagion in observer mice, dividing them into quartiles according to their pain response. The upper and lower quartiles were the emotional contagion-prone (ECP) and -resistant (ECR) groups, respectively. The vicarious social defeat stress (VSDS) procedure was used to establish PTSD models in mice with various emotional contagion levels when witnessing stress. Open field, elevated plus maze, social interaction test, and forced swimming test were used to examine PTSD-like symptoms. Changes in the medial prefrontal cortex (mPFC) mRNA expression of brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OTR) were detected by qPCR, and their protein levels were analyzed by Western blot and immunofluorescence staining. The formalin pain test induced emotional contagion behaviors in mice between the ECP and ECR levels. The VSDS procedure resulted in PTSD symptoms in mice; mice in the lowest quartile were characterized by high levels of anxiety, depression, and social avoidance behaviors, such as decreased autonomous activity and residence time in the open field test or open arms position and increased immobility time and social avoidance behavior. These were accompanied by reduced OTR and BDNF protein expression levels and fluorescence intensity, as well as reduced OTR and BDNF mRNA levels in the mPFC. Emotional contagion can induce PTSD-like behavior in mice that witnessed stress. Low emotional contagion behavior increased PTSD susceptibility in the observer mice and might be related to the regulation of their oxytocin receptors.

Psilocybin and hallucinogenic mushrooms.

Psilocybin therapy has recently emerged as a promising new treatment for depression and other mental health disorders. This chapter summarizes the most recent data on its safety and efficacy. The delivery of psilocybin therapy and its subjective effects are also presented. Furthermore, this chapter outlines our current understanding of psilocybin's pharmacology and neurobiological effects. Other similar psychedelic substances with encouraging therapeutic potential are briefly presented.

Neurotransmitter and metabolic effects of interferon-alpha in association with decreased striatal dopamine in a Non-Human primate model of Cytokine-Induced depression.

Inflammatory stimuli administered to humans and laboratory animals affect mesolimbic and nigrostriatal dopaminergic pathways in association with impaired motivation and motor activity. Alterations in dopaminergic corticostriatal reward and motor circuits have also been observed in depressed patients with increased peripheral inflammatory markers. The effects of peripheral inflammation on dopaminergic pathways and associated neurobiologic mechanisms and consequences have been difficult to measure in patients. Postmortem tissue (n=11) from an established, translationally-relevant non-human primate model of cytokine-induced depressive behavior involving chronic interferon-alpha (IFN-a) administration was utilized herein to explore the molecular mechanisms of peripheral cytokine effects on striatal dopamine. Dopamine (but not serotonin or norepinephrine) was decreased in the nucleus accumbens (NAcc) and putamen of IFN-a-treated animals (p<0.05). IFN-a had no effect on number of striatal neurons or dopamine terminal density, suggesting no overt neurodegenerative changes. RNA sequencing examined in the caudate, putamen, substantia nigra, and prefrontal cortical subregions revealed that while IFN-a nominally up-regulated limited numbers of genes enriching inflammatory signaling pathways in all regions, robust, whole genome-significant effects of IFN-a were observed specifically in putamen. Genes upregulated in the putamen primarily enriched synaptic signaling, glutamate receptor signaling, and inflammatory/metabolic pathways downstream of IFN-a, including MAPK and PI3K/AKT cascades. Conversely, gene transcripts reduced by IFN-a enriched oxidative phosphorylation (OXPHOS), protein translation, and pathways regulated by dopamine receptors. Unsupervised clustering identified a gene co-expression module in the putamen that was associated with both IFN-a treatment and low dopamine levels, which enriched similar inflammatory, metabolic, and synaptic signaling pathways. IFN-a-induced reductions in dopamine further correlated with genes related to excitotoxic glutamate, kynurenine, and altered dopamine receptor signaling (r=0.78-97, p<0.05). These findings provide insight into the immunologic mechanisms and neurobiological consequences of peripheral inflammation effects on dopamine, which may inform novel treatment strategies targeting inflammatory, metabolic or neurotransmitter systems in depressed patients with high inflammation.

Individual structural covariance connectome reveals aberrant brain developmental trajectories associated with childhood maltreatment.

The long-term impact of childhood maltreatment (CM) on an individual's physical and mental health is suggested to be mediated by altered neurodevelopment. However, the exact neurobiological consequences of CM remain unclear. The present study aimed to investigate the relationship between CM and brain age based on structural magnetic resonance imaging data from a sample of 214 adults. The participants were divided into CM and non_CM groups according to Childhood Trauma Questionnaire. For each participant, brain connectome age was estimated from a large-scale structural covariance network through relevance vector regression. Brain predicted age difference (brain_PAD) was then calculated for each participant. The brain connectome age matched well with chronological age in young adults (age range: 18-25 years) and adults (age range: 26-44 years) without CM, but not in individuals with CM. Compared with non_CM group, CM group was characterized by higher brain_PAD scores in young adults, whereas lower brain_PAD scores in adults. The finding revealed that brain development in individuals with CM seems to be accelerated in younger adults but retardation with increasing age. Moreover, individuals who suffered child abuse (but not neglect) showed higher brain_PAD scores than non_CM group, suggesting the different influence of abuse and neglect on neurodevelopment. Finally, the brain_PAD was positively correlated with attentional impulsivity in CM group. CM affects different stages of adult brain development differently, and abuse and neglect have different influenced patterns, which may provide new evidence for the impact of CM on structural brain development.

Overlooked consequences of undiagnosed Premenstrual Dysphoric Disorder in Pakistani women.

Madam, Premenstrual Dysphoric Disorder (PMDD) is a depressive disorder which comprises psychological and somatic symptoms brought on by sensitivity to fluctuations in the levels of female sex hormones throughout the menstrual cycle.1 Symptoms of PMDD present at the luteal phase of the menstrual cycle and usually resolve at the end of menstruation.1 These include but are not limited to affective lability and an increase in anxiety, anger and depressive episodes. Women with PMDD may also experience certain physical symptoms that deviate from normal physiological mechanisms such as lethargy, hypersomnia or insomnia and changes in appetite.1 Women worldwide struggle with self-harm and suicidal ideation; however, new studies suggest a possible correlation between these mental health issues and the prevalence of menstrual disorders like PMDD. A 2021 meta-analysis conducted by Divya Prasad et al. indicated that PMDD increases the likelihood of suicide attempt by almost sevenfold and of ideation by fourfold.2 The findings of this study raise grave concerns in countries such as Pakistan where discussions and studies related to both menstrual disorders and mental health are limited. A study on PMDD incidence in Pakistan's general population found no research on the topic. However, a cross-sectional study in three Karachi universities revealed that only 19% of female students were aware of PMDD, highlighting the country's lack of awareness and the taboo associated with menstruation in Pakistan's conservative society.3 Cultural perspectives often overlook PMDD symptoms due to the belief that women experience moodiness and sensitivity during menstruation. This generalization disregards hormonal pathology and views PMDD as a natural physiological phenomenon. This issue affects Pakistani women and physicians, as women may be influenced by this ideology, not considering their symptoms significant enough to warrant treatment. The Pakistani community can benefit from investigating the prevalence of PMDD in rural and urban areas to identify differential factors affecting symptoms and exacerbation. Studies have shown that higher perceived stress is linked to increased perimenstrual symptoms in women with PMDD.4 Future studies should measure the knowledge gap in physicians regarding PMDD's diagnostic criteria to prevent misdiagnosis. Recent findings highlight a single gene polymorphism in the ESR1 gene and contradictory neurobiological effects of Allopregnanolone on GABA-A receptors in women experiencing PMDD.5 This validates the symptoms experienced by women, protecting them from biased dismissals and societal stereotypes. These advancements could reduce healthcare gender disparity and foster confidence in seeking suitable treatment. Continued...

Efficacy of Transcranial Direct Current Stimulation (tDCS) on Neuropsychiatric Symptoms in Multiple Sclerosis (MS)-A Review and Insight into Possible Mechanisms of Action.

Introduction: Neuropsychiatric symptoms such as depression and anxiety are a significant burden on patients with multiple sclerosis (MS). Their pathophysiology is complex and yet to be fully understood. There is an urgent need for non-invasive treatments that directly target the brain and help patients with MS. One such possible treatment is transcranial direct current stimulation (tDCS), a popular and effective non-invasive brain stimulation technique. Methods: This mechanistic review explores the efficacy of tDCS in treating depression and anxiety in MS while focusing on the underlying mechanisms of action. Understanding these mechanisms is crucial, as neuropsychiatric symptoms in MS arise from complex neuroinflammatory and neurodegenerative processes. This review offers insights that may direct more focused and efficient therapeutic approaches by investigating the ways in which tDCS affects inflammation, brain plasticity, and neural connections. Searches were conducted using the PubMed/Medline, ResearchGate, Cochrane, and Google Scholar databases. Results: The literature search yielded 11 studies to be included in this review, with a total of 175 patients participating in the included studies. In most studies, tDCS did not significantly reduce depression or anxiety scores as the studied patients did not have elevated scores indicating depression and anxiety. In the few studies where the patients had scores indicating mild/moderate dysfunction, tDCS was more effective. The risk of bias in the included studies was assessed as moderate. Despite the null or near-null results, tDCS may still prove to be an effective treatment option for depression and anxiety in MS, because tDCS produces a neurobiological effect on the brain and nervous system. To facilitate further work, several possible mechanisms of action of tDCS have been reported, such as the modulation of the frontal-midline theta, reductions in neuroinflammation, the modulation of the HPA axis, and cerebral blood flow regulation. Conclusions: Although tDCS did not overall demonstrate positive effects in reducing depression and anxiety in the studied MS patients, the role of tDCS in this area should not be underestimated. Evidence from other studies indicates the effectiveness of tDCS in reducing depression and anxiety, but the studies included in this review did not include patients with sufficient depression or anxiety. Future studies are needed to confirm the effectiveness of tDCS in neuropsychiatric dysfunctions in MS.

Molecular Positron Emission Tomography and Single-Photon Emission Computed Tomography Imaging for Understanding the Neurobiological Mechanisms of Electroconvulsive Therapy: A Scoping Review.

Electroconvulsive therapy (ECT) effectively treats severe psychiatric disorders such as depression, mania, catatonia, and schizophrenia. Although its exact mechanism remains unclear, ECT is thought to induce neurochemical and neuroendocrine changes. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) have provided vital insights into ECT's neurobiological effects. This scoping review investigates the role of molecular imaging in understanding these effects. A systematic search across PubMed, EMBASE, Web of Science, Cochrane, and Scopus databases yielded 857 unique records, from which 45 peer-reviewed articles in English with longitudinal PET or SPECT measures in ECT patients were included. The review identifies 2 main research directions: ECT's impact on brain activity and neurotransmitters. Initial research assessed regional cerebral blood flow and regional glucose metabolism during ictal (during ECT), postictal (within 24 hours), short-term (within a week), and long-term (beyond a week) follow-up as markers of brain activity. Initial findings showed an anterior-posterior regional cerebral blood flow gradient during the ictal phase, with subsequent normalization of hypoperfusion in frontal and parietal regions, and persistent long-term effects. Later, research shifted to the monoamine hypothesis of depression, examining ECT's impact on serotonin and dopamine systems via PET imaging. Results on receptor availability post-ECT were mixed, showing both reductions and no significant changes, indicating variable effects. This scoping review further highlights the need to explore new targets, tailor methodologies for patient populations, and foster multicenter studies. Although SPECT has been valuable, advances in PET imaging now make it preferable, offering unparalleled insights into ECT's molecular and neurobiological mechanisms.

Triangulating the associations of different types of childhood adversity and first-episode psychosis with cortical thickness across brain regions.

Both childhood adversity (CA) and first-episode psychosis (FEP) have been linked to alterations in cortical thickness (CT). The interactive effects between different types of CAs and FEP on CT remain understudied. One-hundred sixteen individuals with FEP (mean age = 23.8 ± 6.9 years, 34% females, 80.2% non-affective FEP) and 98 healthy controls (HCs) (mean age = 24.4 ± 6.2 years, 43% females) reported the presence/absence of CA <17 years using an adapted version of the Childhood Experience of Care and Abuse (CECA.Q) and the Retrospective Bullying Questionnaire (RBQ) and underwent magnetic resonance imaging (MRI) scans. Correlation analyses were used to assess associations between brain maps of CA and FEP effects. General linear models (GLMs) were performed to assess the interaction effects of CA and FEP on CT. Eighty-three individuals with FEP and 83 HCs reported exposure to at least one CA. CT alterations in FEP were similar to those found in participants exposed to separation from parents, bullying, parental discord, household poverty, and sexual abuse (r = 0.50 to 0.25). Exposure to neglect (β = -0.24, 95% CI [-0.37 to -0.12], p = 0.016) and overall maltreatment (β = -0.13, 95% CI [-0.20 to -0.06], p = 0.043) were associated with cortical thinning in the right medial orbitofrontal region. Cortical alterations in individuals with FEP are similar to those observed in the context of socio-environmental adversity. Neglect and maltreatment may contribute to CT reductions in FEP. Our findings provide new insights into the specific neurobiological effects of CA in early psychosis.

Combination of Haloperidol With UNC9994, β-arrestin-Biased Analog of Aripiprazole, Ameliorates Schizophrenia-Related Phenotypes Induced by NMDAR Deficit in Mice.

Glutamatergic system dysfunction contributes to a full spectrum of schizophrenia-like symptoms, including the cognitive and negative symptoms that are resistant to treatment with antipsychotic drugs (APDs). Aripiprazole, an atypical APD, acts as a dopamine partial agonist, and its combination with haloperidol (a typical APD) has been suggested as a potential strategy to improve schizophrenia. Recently, an analog of aripiprazole, UNC9994, was developed. UNC9994 does not affect dopamine 2 receptor (D2R)-mediated Gi/o protein signaling but acts as a partial agonist for D2R/β-arrestin interactions. Hence, one of our objectives was to probe the behavioral effects of co-administrating haloperidol with UNC9994 in the N-methyl-D-aspartate receptor (NMDAR) mouse models of schizophrenia. The biochemical mechanisms underlying the neurobiological effects of dual haloperidol × UNC9994 action are currently missing. Hence, we aimed to explore D2R- and NMDAR-dependent signaling mechanisms that could underlie the effects of dual drug treatments. NMDAR hypofunction was induced pharmacologically by acute injection of MK-801 (NMDAR pore blocker; 0.15mg/kg) and genetically by knockdown of Grin1 gene expression in mice, which have a 90% reduction in NMDAR levels (Grin1 knockdown [Grin1-KD]). After intraperitoneal injections of vehicle, haloperidol (0.15mg/kg), UNC9994 (0.25mg/kg), or their combination, mice were tested in open field, prepulse inhibition (PPI), Y-maze, and Puzzle box. Biochemical effects on the phosphorylation of Akt, glycogen synthase kinase-3 (GSK-3), and CaMKII in the prefrontal cortex (PFC) and striatum of MK-801-treated mice were assessed by western blotting. Our findings indicate that low dose co-administration of UNC9994 and haloperidol reduces hyperactivity in MK-801-treated animals and in Grin1-KD mice. Furthermore, this dual administration effectively reverses PPI deficits, repetitive/rigid behavior in the Y-maze, and deficient executive function in the Puzzle box in both animal models. Pharmacological inhibition of NMDAR by MK-801 induced the opposite effects in the PFC and striatum on pAkt-S473 and pGSK3β-Ser9. Dual injection of haloperidol with UNC9994 reversed MK-801-induced effects on pAkt-S473 but not on pGSK3β-Ser9 in both brain structures. The dual administration of haloperidol with UNC9994 at low doses represents a promising approach to ameliorate symptoms of schizophrenia. The combined drug regimen elicits synergistic effects specifically on pAkt-S473, suggesting it as a potential biomarker for antipsychotic actions.

Harmonization for Parkinson's Disease Multi-Dataset T1 MRI Morphometry Classification.

Classification of disease and healthy volunteer cohorts provides a useful clinical alternative to traditional group statistics due to individualized, personalized predictions. Classifiers for neurodegenerative disease can be trained on structural MRI morphometry, but require large multi-scanner datasets, introducing confounding batch effects. We test ComBat, a common harmonization model, in an example application to classify subjects with Parkinson's disease from healthy volunteers and identify common pitfalls, including data leakage. We used a multi-dataset cohort of 372 subjects (216 with Parkinson's disease, 156 healthy volunteers) from 11 identified scanners. We extracted both FreeSurfer and the determinant of Jacobian morphometry to compare single-scanner and multi-scanner classification pipelines. We confirm the presence of batch effects by running single scanner classifiers which could achieve wildly divergent AUCs on scanner-specific datasets (mean:0.651 ± 0.144). Multi-scanner classifiers that considered neurobiological batch effects between sites could easily achieve a test AUC of 0.902, though pipelines that prevented data leakage could only achieve a test AUC of 0.550. We conclude that batch effects remain a major issue for classification problems, such that even impressive single-scanner classifiers are unlikely to generalize to multiple scanners, and that solving for batch effects in a classifier problem must avoid circularity and reporting overly optimistic results.

Neural modulation by nicotine aerosols and the role of flavor additives: insights from local field potentials in mice

Research on nicotine's neurobiological effects has rarely focused on aerosols, despite their primary role in tobacco product consumption. Here, we utilized in vivo electrophysiology to examine brain activity in mice exposed to nicotine aerosols, both alone and with flavor additives (citric acid and menthol). Local field potential (LFP) recordings from the nucleus accumbens (NAc), basolateral amygdala (BLA), ventral tegmental area (VTA), and ventral posteromedial nucleus (VPM) were analyzed under saline, nicotine, nicotine with citric acid(CA + NIC), and nicotine with menthol(MENT + NIC) conditions. Nicotine exposure significantly reduced power spectral density (PSD) in the NAc-Alpha, NAc-Beta, and BLA-Beta bands, unaffected by flavor additives. Coherence between key brain regions (e.g., VPM-VTA in Beta, VPM-BLA in Alpha) also decreased with nicotine but was restored with citric acid or menthol, suggesting their role in mitigating nicotine's disruptive effects on neural synchronization. Our findings show that LFPs can effectively capture nicotine's neural effects and highlight the modulatory role of flavor additives, offering new insights into nicotine exposure management and tobacco product design.

Changes in IL-6, IL-12, IL-5, IL-10 and TGF-β1 Concentration in Patients with Treatment-Resistant Schizophrenia (TRS) Following Electroconvulsive Therapy (ECT)-A Pilot Study.

Background/Objectives: Treatment-resistant schizophrenia (TRS) may be considered as a neuro-immune disorder. Electroconvulsive therapy (ECT) remains an important therapeutic option for patients with TRS, however, its impact on cytokine profile is barely investigated. Therefore, this study attempts to establish associations between serum cytokines IL-6, IL-12, IL-5, IL-10 and TGF-β1 changes (pre- and post-ECT) and the effectiveness of ECT in TRS patients. The second aim is to search for correlations between serum concentrations of the above specified cytokines and psychometric assessments of clinical schizophrenia symptoms. Methods: The cytokine concentrations were measured in eight TRS patients on psychopharmacological treatment prior to and following ECT and in 13 control subjects. Psychopathology assessment was based on the Positive and Negative Syndrome Scale (PANSS). Results: Prior to ECT, IL-10 concentration was significantly higher in TRS patients, while IL-5 was decreased in comparison to the controls. A significant concentration decrease in the pro-inflammatory cytokines IL-6 (p = 0.012), IL-12 (p = 0.049) and anti-inflammatory IL-10 (p = 0.012) post-ECT vs. pre-ECT was observed, whereas concentrations of IL-5 and TGF-β1 did not significantly change. Also, a significant decrease in schizophrenia symptoms measured by the PANSS post-ECT was found. Furthermore, the pattern of correlations between PANSS scores and cytokine concentrations was different when comparing levels pre- and post-ECT. Additionally, correlations between changes in PANSS scores and cytokine concentrations were found. Conclusions: These results may indicate the probable impact of electroconvulsive therapy on the balance between pro- and anti-inflammatory cytokines, which may correspond to a neurobiological therapeutic effect of ECT in TRS patients.

Neurobiological and Anti-Inflammatory Effects of a DeepDiaphragmatic Breathing Technique Based on Neofunctional Psychotherapy: A Pilot RCT.

We examined the feasibility of using the neofunctional deep breathing (NDB) technique to reduce the allostatic load following the Trier Social Stress Test (TSST). Forty-four healthy subjects were randomised into experimental and control groups. Following the TSST procedure, participants underwent either a single session of NDB or an attention control intervention. The Procomp Infinity Biofeedback system measured breath per minute (BPM), respiratory amplitude, HRV linear domains, skin conductance, and trapezius muscle electromyographic activity. Cortisol and cytokine salivary concentrations, perceived stress, and anxiety levels were also assessed. These parameters were combined into an allostatic load index (ALI) to measure the intervention's effect. This pilot RCT demonstrated the feasibility of the study design and practicality of the intervention. The NDB group showed reduced ALI, increased respiratory abdominal amplitude, decreased BPM, increased HRV indicating parasympathetic activation, and decreased cortisol and inflammatory cytokines. This study highlighted the feasibility of testing the NDB technique in reducing allostatic load through a neurobiological and anti-inflammatory response after exposure to psychosocial stress. This protocol can represent a non-invasive therapeutic adjutant in disorders related to a dysregulation of the HPA axis or to an inflammatory state. Trial Registration: NCT04102813.

Depression and metabolic connectivity: insights into the locus coeruleus, HF-rTMS, and anxiety

The use of repetitive Transcranial Magnetic Stimulation (rTMS) in treating major depressive disorder (MDD) is increasingly being explored in precision medicine. However, there’s a notable lack of understanding of the underlying neurobiological effects, which limits our ability to correlate specific imaging features with treatment efficacy. As one possible neurobiological mechanism, clinical research has already shown that in MDD, lower norepinephrine release in the locus coeruleus (LC) triggers depressive symptoms, and pharmacological approaches that block norepinephrine reuptake boost its levels, easing depression. Surprisingly, the LC has not received a more pronounced focus in contemporary rTMS research. This study investigates the role of the LC in MDD and its response to high-frequency (HF)-rTMS using 18FDG-PET imaging. We compared LC metabolic connectivity between MDD patients (n = 43) and healthy controls (n = 32). Additionally, we evaluated the predictive value of LC connectivity for HF-rTMS treatment outcomes and examined post-treatment changes in LC metabolic connectivity. Our findings revealed significant differences in LC metabolic connectivity between MDD patients and controls. Baseline LC metabolic connectivity did not predict HF-rTMS treatment outcomes. However, post-treatment analyses showed a significant correlation between improved clinical outcomes and attenuation of LC metabolic connectivity in regions associated with cognitive control and the default mode network. Notably, a reduction in state anxiety moderated this relationship, highlighting the role of anxiety in HF-rTMS efficacy for MDD treatment. Our findings suggest that LC metabolic connectivity, influenced by state anxiety levels, may be crucial in HF-rTMS efficacy, offering further insights for personalized MDD treatment strategies.

Positive reinforcement-based magnet training permits social housing in catheterized squirrel monkeys

BackgroundNon-human primates play a critical role in neuroscience research. Though they are social animals, laboratory study requirements can sometimes require single housing and thereby prevent social housing. New MethodTo eliminate single housing and promote well-being within our squirrel monkey colony, we used positive reinforcement training in combination with magnetic/mechanical clasps and custom jackets to permit pair housing of catheterized squirrel monkeys used in behavioral studies. ResultsAdult Saimiri boliviensis boliviensis monkeys (n = 7) readily progressed through a six-stage training procedure for cooperative handling and transport from the home cage to the experimental testing rooms.Comparison with existing methods and conclusions: Given the evidence of isolation induced stress and neurobiological consequences in multiple species, and consistent with an increased regulatory emphasis on social housing of non-human primates, the methods presented herein provide a method for handling squirrel monkeys in behavioral studies that is compatible with social housing.

Effects of repeated voluntary oral consumption of synthetic delta-9-tetrahydrocannabinol on locomotor activity and cannabinoid receptor 1 expression

As cannabis legalization expands, preclinical studies continue to investigate the impact of repeated exposure to delta-9-tetrahydrocannabinol (THC), the primary psychoactive compound in the plant. With the increasing popularity of cannabis infused foods, the rise of THC in medicinal applications have also expanded. The present study addresses a critical gap in existing literature by investigating the behavioral and neurobiological effects of low-dose edible THC in a preclinical rodent model. Adult male rats were administered synthetic-THC (Dronabinol) (0.0625 mg/kg, 0.125 mg/kg, and 0.25 mg/kg) or vehicle (sesame oil) through edible cookies, 90 min prior to eight locomotor sessions. Locomotor activity significantly increased in both 0.0625 mg/kg and 0.25 mg/kg THC groups, indicating a dose-dependent relationship. Repeated 0.25 mg/kg THC administration dose-dependently reduced cannabinoid receptor 1 expression in the hippocampus. The observed neurobiological change from low dose oral THC advances our understanding of repeated cannabis use. These findings also emphasize the importance of refining rodent models for translational relevance.

Is There such a Thing as Post-Viral Depression?: Implications for Precision Medicine.

Viral infections are increasingly recognized as triggers for depressive disorders, particularly following the SARS-CoV-2 pandemic and the rise of long COVID. Viruses such as Herpes Simplex Virus (HSV), Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), and Human Immunodeficiency Virus (HIV) are linked to depression through complex neurobiological mechanisms. These include immune system dysregulation, chronic inflammation, and neurotransmitter imbalances that affect brain function and mood regulation. Viral activation of the immune system leads to the release of pro-inflammatory cytokines, resulting in neuroinflammation and associated depressive symptoms. Furthermore, specific viruses can disrupt neurotransmitter systems, including serotonin, dopamine, and glutamate, all of which are essential for mood stabilization. The unique interactions of different viruses with these systems underscore the need for virus-specific therapeutic approaches. Current broad-spectrum treatments often overlook the precise neurobiological pathways involved in post-viral depression, reducing their efficacy. This review emphasizes the need to understand these virus-specific interactions to create tailored interventions that directly address the neurobiological effects induced by each type of virus. These interventions may include immunomodulatory treatments that target persistent inflammation, antiviral therapies to reduce the viral load, or neuroprotective strategies that restore neurotransmitter balance. Precision medicine offers promising avenues for the effective management of virus-induced depression, providing patient-specific approaches that address the specific biological mechanisms involved. By focusing on the development of these targeted treatments, this review aims to pave the way for a new era in psychiatric care that fully addresses the root causes of depression induced by viral infections.