Journal of Neural Transmission最新文献

Background: Miscarriage (MC) and stillbirth (SB) can be considered as potentially traumatic events (PTE) and affect approximately 10-20% of all pregnancies. PTEs can lead to the development of post-traumatic stress disorder (PTSD). While the psychobiology of PTSD is well-understood, our knowledge on psychobiological adaptations shortly after a PTE is limited. This study aimed to shed light on early psychobiological changes associated with MC and SB.

Methods: We included 25 women who had experienced a MC/SB within the previous three months and compared them with 28 healthy control women. All participants were asked to attend a study appointment, during which they participated in a socially evaluated cold-pressor test (SECPT) to induce psychosocial stress. Saliva and blood samples were collected at rest, immediately and at 20, 45 and 90 min after the SECPT. We determined salivary cortisol levels and α-amylase (sAA) activity, and plasma interleukin-6 (IL-6) concentrations. We assessed symptoms of PTSD, anxiety and depression using self-report questionnaires.

Results: Women who had experienced MC or SB reported significantly more symptoms of PTSD (p < 0.001) and anxiety (p < 0.001), when compared to the control group. Despite elevated psychological distress in the MC/SB group, there were no significant differences of salivary cortisol, sAA and IL-6 levels between the two groups at rest or after SECPT induced stress.

Conclusions: Despite the high psychological strain on women after MC/SB, the stress is not yet reflected at a biological level. These results highlight the complex relationship between early trauma, PTSD symptoms, and biological responses. Further research is needed to understand the long-term effects of trauma related to MC/SB, and the development of PTSD, as well as the underlying mechanisms contributing to the observed psychological and biological changes.

Progressive supranuclear palsy (PSP) is a rare, debilitating neurodegenerative disorder that significantly impairs both motor and cognitive functions. Current pharmacological treatments offer only transient symptomatic relief, driving interest in the past in alternative therapeutic strategies such as deep brain stimulation. Deep brain stimulation (DBS), known for its success in treating motor symptoms of Parkinson's disease, has been explored as a possible symptomatic treatment for PSP, considering the pedunculopontine nucleus (PPN), involved in motor control and postural stability, as a promising target for deep brain stimulation in PSP. However, its complex anatomy and the clinical variability of PSP complicate the prediction and generalization of the effectiveness of DBS. The present review examines the existing studies in the literature about DBS in PSP patients. Some studies highlighted modest benefits in motor symptoms, while others reported variable outcomes and inherent risks of the procedure. Generally, patients with a parkinsonism predominant phenotype have shown some subjective or clinical improvements in gait and balance when subjected to low-frequency stimulation. While DBS of the PPN holds promise for ameliorating gait and balance of PSP, current evidence does not yet establish clear criteria for ideal candidates, nor does it provide overwhelmingly supportive results in favor of PPN-DBS in PSP patients. Without any further systematic study is not possible to define accurate candidate selection parameters and understand long-term outcomes and safety profiles.

Anxiety disorders are mental health disorders characterized by long-lasting fear, worry, nervousness, and alterations in gut microbiota (GM). The GM is a vital modulator of brain function through the gut-brain axis, which acts as the neural pathway between the central and peripheral nervous systems. Dysbiosis of GM plays an essential role in anxiety development because of alterations in the vagus nerve, increased intestinal permeability, and altered breakdown of tryptophan (TRP). The Kynurenine (KYN) pathway plays a crucial role in the pathogenesis of anxiety disorders, primarily through its neuroprotective (KYNA) and neurotoxic (QUIN) metabolites. Higher ratios of KYNA/QUIN result in neuroprotection, whereas higher KYN/TRP ratios indicate increased QUIN production causing neuroinflammation. Studies on germ-free models exhibit higher plasma TRP levels, which interrupt the metabolic balance of TRP-derived compounds, thus causing brain impairment. A key issue in anxiety disorders is the dysregulation of GM, which disrupts TRP metabolism and neuroinflammatory pathways, however, remains poorly understood. Hence, the proper understanding of these mechanisms is crucial for future therapeutic advancements. Here, we highlight the significance of the TRP-KYN pathway and the potential of modulating KYN pathway enzymes, such as kynurenine aminotransferases (KATs), to adjust KYNA levels and restore neurotransmitter balance. It further discusses new therapeutic methods with a particular focus on probiotics that may restore GM and modulate TRP metabolism. Advancing our understanding of the intricate relationship between GM and anxiety disorders may facilitate novel, microbiota-targeted interventions. This ultimately contributes to precision medicine approaches in mental health care, thereby enhancing treatment efficacy and patient outcomes.

A history of viral infection has been associated with a higher risk for psychiatric disorders. One potential underlying mechanism is that antiviral immunological responses could trigger cross-reactivity between viral and neural antigens, which would raise the co-occurrence of antiviral antibodies and anti-neural autoantibodies. We studied 619 patients' psychiatric diagnoses from the Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Germany. Anti-neural autoantibodies and antiviral antibody specific indices were measured in serum and/or cerebrospinal fluid (CSF) from all patients. Among these 619 patients, 115 tested positive for serum and/or CSF neural autoantibodies (18.6%), with the most often identified autoantibodies being anti-GAD65 in serum (2.2%) and CSF (1.6%), and anti-NMDA in serum (0.6%) and CSF (1.3%). The three main diagnostic groups presenting neural autoantibodies were patients with organic psychiatric disorders including dementia (81 of 377; 21.7%), those with psychotic disorders (9 of 66; 13.6%), and patients with affective disorders (19 of 138; 13.9%). Logistic regression analysis revealed a significant association between the varicella zoster virus (VZV) antibody-specific index and autoantibody positivity in patients with all diagnoses (F00-F79) (p < 0.005). Furthermore, the rubella antibody-specific index proved to be significantly associated with neural autoantibody positivity (p < 0.001) across all patients (F00-F79), and in those with affective disorders (p < 0.01). Our results show that VZV and rubella antiviral antibodies are associated with a higher propensity to develop anti-neural autoantibodies, suggesting that the known association between viral infection and later developing psychiatric disorders may be partly attributable to the development of anti-neural autoimmunity.

Neuropsychiatric disorders such as bipolar disorder, migraine, major depressive disorder, epilepsy, attention-deficit/hyperactivity disorder, autism spectrum disorder and schizophrenia, are a huge burden on global health, impacting millions of individuals worldwide and posing significant barriers to effective treatment. Despite advancements in medication and psychotherapy, many patients continue to suffer from severe symptoms and receive little alleviation. All of these conditions are quite frequent, yet they affect people in a way that is exceedingly detrimental. The increasing evidence suggests the connection between these disorders and inflammation. Therefore, the use of anti-inflammatory agents, namely cyclooxygenase-2 (COX-2) inhibitors, offers a new approach to prevent and treat neuropsychiatric disorders. This review discusses about the COX pathway and the role of COX-2 in the neuroinflammation. Furthermore, this review highlights the COX-2 inhibitors as a promising therapeutic agent in these neuropsychiatric disorders, however, further studies are required to assess appropriate illness stage-related indication.

The complexity of α-synucleinopathies, namely Parkinson's disease (PD) and multiple system atrophy (MSA), calls for the adoption a multimodal approach integrating biological, morphological, and functional data. Phosphorylated α-synuclein (α-syn) detection in bodily fluids and tissues such as the skin helps provide biological characterization of the disease, but specific and accessible biomarkers are not available yet. The aim of this study was to define the role of Optical Coherence Tomography (OCT, a minimally invasive retinal imaging technique) patterns as possible biomarkers in the early stages of α-synucleinopathies, also supporting the differential diagnosis. Thirty-five (23 PD, 12 MSA), clinically, biologically and genetically characterized patients included in the PADUA-CESNE (Centro Studi per la Neurodegenerazione) cohort underwent OCT. A significant atrophy in the inferior, superior and temporal regions of the Retinal Nerve Fiber Layer (RNFL) and in the inner nuclear layer (INL) were observed in PD compared to controls, differently from MSA. Hyperreflective foci (HRF) counts were elevated across all retinal layers in all patients with PD exhibiting significantly higher numbers, suggesting microglial activation and greater retinal damage. Further research regarding OCT patterns in PD and MSA may consolidate the role of specific features, such as INL abnormalities and different HRF counts, in supporting the diagnosis and differential diagnosis in α-synucleinopathies. In light of the availability of potentially disease-modifying therapies, studies should focus on newly diagnosed patients, also undergoing thorough clinical, biological and genetic characterization.

Hereditary factors play a significant role in the development of Parkinson's disease and the identification of causative genes is ongoing. Biallelic variants in Diacylglycerol lipase β (DAGLB) are related to early-onset Parkinson's disease (EOPD) in the Chinese population, and have also been identified in an Algerian case. To date, no EOPD cases with DAGLB variants have been reported among Japanese patients. This study was conducted to clarify the occurrence of DAGLB variants among Japanese EOPD patients. We screened 270 patients with sporadic EOPD (male: female ratio, 1.37:1; mean age at onset ± standard deviation, 37.32 ± 7.91 years), and 276 patients with suspected autosomal recessive Parkinson's disease (ARPD, male: female ratio, 0.75:1; mean age at onset ± standard deviation, 58.86 ± 14.67 years). Genetic screening of all coding exons and flanking splicing regions was performed by Sanger sequencing. We identified two rare biallelic variants in two patients, both from consanguineous families. One variant was a homozygous frameshift variant (c.1770_1771del, p.Tyr591ProfsTer26), which was predicted to be pathogenic. The other was a missense variant (c.1444T > C, p.Tyr482His) and was predicted to be benign, with co-segregation ruled out for this variant. We identified a pathogenic variant in the DAGLB gene. Together with previous reports, these findings provide further evidence that loss-of-function variants in DAGLB are involved in EOPD in the Japanese population.

Depression, a significant mental health issue, is one of the diseases with the highest disability rates worldwide. The exact etiology of depression remains undetermined, complicating the development of treatment strategies targeting specific mechanisms, and there is currently no effective cure. In this context, ferroptosis may represent a breakthrough in the understanding of depression. Ferroptosis is primarily associated with iron accumulation and lipid peroxidation, and recent studies have revealed its potential association with depression. Clinical evidence suggests that ferroptosis may influence the development and function of the hippocampus through interactions with neuroinflammation. Activated microglia, astrocytes, and neurons are involved in ferroptosis. This review summarizes recent findings on how ferroptosis contributes to depression, including glutathione peroxidase 4 (GPX4), nuclear factor-erythroid 2-related factor 2 (Nrf2), phase separation, and neuroinflammatory pathways, allowing the proposal of some new hypotheses. We hope that exploring the role of ferroptosis in the mechanism of depression will offer a new perspective on the complex biological basis of depression and provide theoretical support for the development of new therapeutic methods.

Subthalamic nucleus (STN) deep brain stimulation (DBS) is well-established for improving appendicular motor signs but its effect on axial motor signs is less clear. Additionally, the location of active electrode contact within the STN has been shown to differentially affect motor outcomes. We investigate the effect of STN DBS and the role of active electrode contact location on axial motor outcomes. Axial scores were assessed in 70 patients with advanced PD between 6 and 12 months after bilateral STN DBS. Repeated measures one-way ANOVA was performed to compare the mean axial motor scores between different medication and stimulation treatment conditions. Multiple linear regression was performed to determine the association between electrode contact location and axial motor score. The mean duration of follow-up was 7.37 ± 2.49 months. The mean total axial score was improved with STN DBS compared to the OFF MED-OFF STIM condition (6.36 ± 4.50 vs. 8.91 ± 5.49, p < 0.0001). A more dorsal electrode contact location on the right was associated with increased (worsened) total axial score (slope = 0.407, p = 0.0047). Total axial score was also lower (improved) in the anterior ventral STN region but not the posterior ventral STN region on the right. STN DBS improves total axial score and several axial subscores in patients with PD 6-12 months postoperatively. A more ventral electrode contact location on the right was associated with improved axial score. Additional research is warranted to determine if this is the optimal stimulation location to improve axial signs in other DBS cohorts.

Executive functioning (EF) deficits are common in both schizophrenia (SZ) and major depressive disorder (MDD). However, it remains unclear whether specific EF subdomains are differently affected in SZ and MDD, particularly in relation to depressive symptoms. This study aims to investigate EF subdomains in MDD, SZ with depressive symptoms (SZ-D), SZ without depressive symptoms (SZ-ND) and healthy controls (HC), and to explore the relationships between psychopathological symptoms and EF performance. A total of 213 participants were recruited, including 76 MDD, 81 SZ patients and 56 HC. EF was assessed using the n-back, Stroop color-word and more-odd shifting tasks. The 17-item Hamilton Depression Scale, Hamilton Anxiety Scale and Positive and Negative Syndrome Scale were used to assess depression, anxiety and psychopathological symptoms. In the 2-back task, SZ-D patients had longer response time (RT) (p < 0.01), while SZ-ND patients had lower accuracy rates (AR) (p < 0.01) compared to MDD patients and HC. In more-odd shifting task, SZ-D patients showed longer RT for shift cost (p < 0.01), and SZ-ND patients had lower AR for shift cost (p < 0.01) compared to MDD and HC. Multiple regression analysis revealed that negative symptoms were associated with AR in the 2-back condition in SZ-D, while in SZ-ND, negative symptoms was related to AR in the 1-back condition. SZ patients showed more severe EF dysfunction, with depressive symptoms in SZ primarily affecting response speed rather than accuracy. Negative symptoms were associated with EF dysfunction in both MDD and SZ patients.