Neuropsychobiology最新文献

Background: The role of chemokines in motor abnormalities (MAs) in first-episode psychosis (FEP) is underexplored. Investigating both immune biomarker levels in FEP, their association with MAs, and their differences with individuals without FEP may reveal therapeutic targets.

Methods: Thirty-eight patients and thirty-four controls were included. Primary outcomes assessed group differences in chemokines related immune whole blood biomarkers, including innate (CCL2, CCL3, and CCL11), compensatory (PPARα, CXCL1, and CB2), natural immune chemotaxis biomarkers (CXCL2 and CXCR4), and growth factors (LPAR2, BDNF, and VEGF). Our secondary aim was to examine their association with the total score of five motor scales: the Neurological Evaluation Scale (NES), Simpson Angus Scale (SAS), catatonia symptom of the Comprehensive Assessment of Symptoms and History (CASH), Barnes Akathisia Rating Scale, and Unified Parkinson's Disease Rating Scale (UPDRS).

Results: We found significantly higher levels of protein markers (CCL2, VEGF, and CXCL12) and mRNA expression (CXCR4, PPARα, CB2, and LPAR2) in FEP patients compared to the control group. We only observed positive and significant results for CCL2-UDPRS total and CXCR4-SAS associations in post-hoc multivariate analyses (β = 0.401, p = 0.036 and β = 0.58, p = 0.001, respectively).

Conclusions: Elevated levels of potential neurotoxic (CCL2) or neuroprotective (PPARα and CB2) biomarkers were seen in FEP patients when compared to controls. Moreover, CCL2 levels seem to be directly associated with parkinsonism in FEP patients, while CXR4 may be protective against extrapyramidal symptoms. Further research should clarify immune differences between FEP and non-FEP groups, especially in chemotaxis and endocannabinoid pathways.

Introduction: Intrusive memories are a central identifying symptom of post-traumatic stress disorder (PTSD), and their development can be modelled in experimental settings with the trauma film paradigm. Neurosteroids and sex hormones such as allopregnanolone and testosterone, respectively, have recently become potential targets for PTSD pharmacological treatment due to their influence on the stress response.

Methods: In the current study 49 healthy female participants underwent stress induction and viewed a trauma film. Plasma allopregnanolone, testosterone, and cortisol responses to stress induction and the trauma film were recorded and stress-induced responses were modelled as predictors of intrusive memory frequency using negative binomial regression models.

Results: Compared to baseline, plasma allopregnanolone and cortisol levels, along with subjective stress, were significantly higher after the stress induction. Plasma cortisol and subjective stress responses to the stress induction task significantly predicted intrusive memories. Allopregnanolone and testosterone did not predict intrusive memories, though allopregnanolone and cortisol stress responses were significantly correlated.

Discussion: These findings expand our current understanding of the biochemical processes of intrusive memory formation under stress. Additionally, changes in allopregnanolone were observed in response to stress, which contributes towards the discussion of neurosteroids and sex hormones as potential pharmacological targets for the treatment of PTSD.

Introduction: Throughout time, there has always been a trend connecting stress and tangible damage to one's physical well-being. However, there's a lack of research that elucidates the physical and molecular traits of this stress on organ integrity. Chronic stress disrupts homeostasis, causing oxidative stress, mitochondrial dysfunction, inflammatory markers, and histological damage.

Methods: In this study, a repeated forced swim stress (FSS) was used to induce stress in the C57BL/6 mice model and analyzed its effects on the brain and liver at behavioral, biochemical, histology, and genetic marker levels.

Results: Behavioral analysis showed reduced mobility duration in experimental mice. This was further supplemented by histopathological data, which revealed mild brain deterioration and moderate liver damage. Biochemical analysis revealed upregulated levels of aminotransferase (ALT) and alkaline phosphatase (ALP) and decreased levels of mean corpuscular haemoglobin (MCH), pointing towards the existence of liver dysfunctionality due to stress. Moreover, we reported the gene expression analysis of stress biomarkers (Bdnf, Fkbp5, Npy, Comt, Ppm1f, Adra2b, and Slc6a4), with a particular focus on Fkbp5, which is associated with depression and cognitive impairment. Similarly, we also studied the expressions of Crp, Cyp2e1, and Irs-2 to gauge liver damage. Results revealed significantly upregulated expression of Npy, Fkbp5, and Ppm1f in stressed mice.

Conclusion: Our study identifies that chronic stress shows physical and molecular realizations. Additionally, this offers further incentive to look closely at Fkbp5, Npy, and Ppm1f under similar conditions and highlights their possible roles as markers of stress-induced damage.

Bipolar disorder (BD) is a severe, recurrent mood disorder associated with mitochondrial and bioenergetic dysfunction, which may contribute to both symptom expression and variability in treatment response. Although lithium remains the gold standard treatment, a significant proportion of patients fail to achieve full benefit, and reliable predictive biomarkers are still lacking. Increasing evidence suggests that lithium exerts part of its therapeutic effects through modulation of mitochondrial function, including enhanced oxidative phosphorylation, regulation of mitochondrial dynamics, and reduction of oxidative stress. In this state-of-the-art review, we synthesize the current literature on the relationship between lithium and mitochondrial function, with the aim of evaluating how this relationship may inform our understanding of lithium response in BD. We reviewed findings on mitochondrial bioenergetics, oxidative stress, and mitochondrial DNA alterations, and discussed the roles of key regulatory proteins such as Drp1, Opa1, Mfn2, and Nrf2. In addition, we explore peripheral and epigenetic biomarkers, including mitochondrial DNA D-loop methylation, microRNAs and a potential therapeutic target ⎻ mitochondrial transfer mechanism. In addition to synthesizing the existing literature, we identify key gaps that hinder progress, such as clinical studies being predominantly cross-sectional, lacking standardized mitochondrial assessments, and rarely employing longitudinal or genetically informed designs like mitochondrial twin studies. We highlight the need for unified protocols, integration of omics technologies, extracellular vesicle-based sampling strategies, and improved in vitro and in vivo models. A better understanding of mitochondrial signatures related to lithium may enable biomarker discovery and advance personalized treatment in BD.

Introduction: Obsessive-compulsive disorder (OCD) and related disorders (OCRDs) represent a group of conditions in which lack of response to first-line treatments, such as serotonin reuptake inhibitors (SRIs), is common. Therefore, exploring alternative strategies is necessary. We conducted a systematic review of the use of lithium in OCRDs.

Methods: This systematic review was conducted in accordance with PRISMA guidelines. We included studies evaluating the use of lithium for OCRDs in adults. Eligible designs included case reports, case series, observational studies, and clinical trials. Four databases (PubMed, PsycInfo, Web of Science, and ClinicalTrials.gov) were searched on January 21, 2025. Response to lithium was defined by improvement on validated scales or, when unavailable, based on clinical descriptions.

Results: Twenty-nine studies met inclusion criteria, including 25 case reports or case series and four clinical trials. Most studies focused on OCD (n = 20), followed by trichotillomania (n = 5), tic disorders (n = 3), and body dysmorphic disorder (n = 1). Across the full sample (n = 97), 38.1% of the subjects showed "clinical improvement," although only 54.6% were assessed using validated instruments. Among case reports and case series (n = 37), 89.2% reported "improvement." However, three crossover RCTs found no consistent benefit of lithium, and the only placebo-controlled trial did not detect significant differences between groups in the final pooled analysis. Analysis of individual data showed response to lithium to be more common among younger individuals (p = 0.02), those with comorbid bipolar disorder (p = 0.005), individuals receiving lithium as monotherapy (p < 0.018), and those without prior exposure to SRIs (p < 0.001). Additionally, responders were less likely to have been assessed using standardized instruments (p < 0.001).

Conclusion: This is the first systematic review to evaluate lithium as a treatment strategy for OCRDs. While some reports suggest potential benefits, current evidence - largely based on low-quality studies without standardized assessments - does not support its use. Findings from randomized trials remain inconclusive, and further high-quality research is needed.

Introduction: Emotion regulation (ER) is essential for psychological functioning and daily life. Deficits in ER are associated with various psychiatric disorders and are important targets for therapeutic interventions. Self-compassion, the practice of responding to one's own suffering with kindness, has been proposed to support adaptive ER. This study examined changes during a 6-week psychiatric inpatient rehabilitation program to evaluate the effects of a mindfulness- and self-compassion-based intervention on ER.

Methods: In a randomized controlled trial, 168 psychiatric inpatients were allocated to either a Mindful Self-Compassion (MSC) intervention group (n = 95) or an active control group receiving Progressive Muscle Relaxation (PMR; n = 73). Participants completed assessments at baseline and post-treatment, including the Self-Compassion Scale (SCS), the Emotion Regulation Questionnaire (ERQ), and the Positive and Negative Affect Schedule (PANAS). At post-treatment, the Reappraisal Inventiveness Test (RIT) was additionally administered. Data were analyzed using mixed-design ANOVAs and independent t tests.

Results: Both MSC and PMR groups showed significant increases in self-compassion, positive affect, and self-reported cognitive reappraisal. No significant changes were observed in expressive suppression, and no between-group differences were found for reappraisal inventiveness as measured by the RIT.

Conclusions: Participation in either intervention was associated with enhanced use of cognitive reappraisal, suggesting that both MSC and PMR may foster adaptive ER in psychiatric rehabilitation. Further research is warranted to clarify the specific mechanisms and potential long-term benefits of mindful self-compassion interventions in clinical populations.

Introduction: Among the possible risk factors for dyslexia and specific learning disabilities (SLD) in children, being exposed to heavy metals in the environment has been considered a significant one, serving as a biological marker. The precise mechanisms by which heavy metals affect cognitive functions were discussed. However, their shared affinity for NMDA receptors or the Na+/K+ ATPase pump can disrupt the balance between reactive oxygen species and antioxidants. Several studies have scrutinized the effect of heavy and toxic metals on dyslexia. Consequently, this research aimed to systematically assess the most recent evidence of the effects of heavy metals on SLD and dyslexia.

Methods: Four databases (i.e., Scopus, Web of Science, Google Scholar, and PubMed/Medline) were searched; 450 studies published up to 2024 were found. After applying inclusion/exclusion criteria, five studies were selected, and data regarding the participants' age, measurement instruments, the year of the studies, and the outcomes were extracted and analyzed.

Results: Generally, the total sample size in the five studies was 1,909 individuals. These studies examined 25 heavy metals, with selenium (Se), copper (Cu), lead (Pb), zinc (Zn), and nickel (Ni) showing consistent associations with dyslexia and SLD. Metals such as aluminum (Al), arsenic (As), antimony (Sb), cadmium (Cd), cobalt (Co), mercury (Hg), iron (Fe), and manganese (Mn) were cited only once. Notably, heavy metals such as Pb, Al, Sb, and Cd had a definitive role in the neuropathogenesis of SLD.

Conclusion: These findings highlighted the importance of implementing environmental control measures to minimize children's exposure to toxic heavy metals.

Introduction: Depression severely affects the psychosocial functioning and quality of life of patients. Among first-line selective serotonin reuptake inhibitors (SSRIs), the incidence of neuropsychiatric side effects caused by paroxetine is 4-6 times higher than that caused by citalopram.

Methods: In this study, a depression model was established using Wistar rats to examine the effects of paroxetine and citalopram on neuronal nitric oxide synthase (nNOS) mRNA expression in the prefrontal cortex and hippocampus and to clarify the possible mechanisms of SSRI-induced neuropsychiatric side effects.

Results: In the hippocampus, nNOS expression was significantly higher in the depression group than in the control group. However, in the prefrontal cortex, nNOS expression was significantly lower in the depression group than in the control group. Following the administration of postsynaptic density protein 95 (PSD-95)/nNOS inhibitor ZL006, nNOS levels decreased significantly in the paroxetine group but showed no significant change in the citalopram group.

Conclusion: The mechanisms regulating nNOS expression differed between the paroxetine and citalopram groups. Paroxetine-induced nNOS expression may be associated with PSD-95/nNOS.

Introduction: Anxiety has been described in the initial stages of schizophrenia and affective flattening in the chronic illness. The aetiology remains unknown. Ketamine, a non-competitive n-methyl-d-amino-aspartate acid receptor antagonist, is used in rats as a translational model of schizophrenia. A glutamate deficit within nucleus accumbens septi (NAS) afferent projections has been proposed to be involved in schizophrenia. The amygdala is related to memory, fear, and anxiety and is closely linked to the NAS. Here, we studied anxiety in male rats using the elevated plus maze (EPM) after receiving acute administration of different subanaesthetic doses of ketamine. The metabolic state of the amygdala was measured after ketamine treatment. The main aim of the present study was to compare the effect of different doses as emulating progressive stages of schizophrenia.

Methods: Classical anxiety parameters were observed during EPM experiments in rats with the low doses of ketamine. After this, amygdalas were randomly extracted and submitted to a test of redox cellular metabolic activity with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT).

Results: Low doses (1.25 and 2.5 mg/kg) significantly decreased time spent in the open arm, time per entry, and open arm entries and increased time in the closed arms and grooming. These doses also decreased metabolic activity.

Conclusion: We conclude that the administration of subanaesthetic doses of ketamine exerts an acute anxiogenic effect in the plus maze test at the lower doses, accompanied by a decrease in amygdala metabolic activity, suggesting metabolic exhaustion. The higher doses reversed the anxiety parameters, suggesting an explanation of the opposite symptoms in schizophrenia progression.