Neuropsychobiology最新文献

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.

Introduction: There has been an increasing focus on sex differences in bipolar disorder in recent years, yet much remains to be understood about their impact on clinical characteristics and treatment approaches. The aim of this study was to identify sex differences that could alter diagnosis and treatment strategies, potentially improving patient compliance and outcomes.

Methods: This retrospective study analysed data from interviews with 340 participants (171 men, 169 women; ages ranging from 18 to 82 years) from the BIPFAT/BIPLONG study at the specialised outpatient centre for bipolar disorder at the Medical University of Graz, Austria. We examined sex differences in clinical characteristics and drug therapy primarily using logistic and linear regression models, with chi-square tests and Mann-Whitney U tests applied as supplementary analyses for subgroup comparisons.

Results: Our findings revealed that the age of onset for bipolar disorder was earlier in women (B = -3.05, 95% confidence interval [CI] = [-5.08, -1.02], p = 0.003), with women reporting their first affective symptoms at an average age of 22.7 (standard deviation [SD] = 9.9) compared to 26.4 (SD = 12.1) in men. Comorbid obsessive-compulsive disorder was significantly more prevalent in women (OR = 2.24, 95% CI = [2.12, 41.33], p = 0.003). In comparison, men were shown to experience manic episodes per year more frequently (B = -0.32, 95% CI = [-0.59, -0.05], p = 0.019). Differences in treatment emerged only within specific age subgroups rather than the overall study sample.

Conclusions: Taken together, we found fewer differences than expected, which suggests that factors other than sex play a greater role in the course of bipolar disorder. Our analysis indicates that more women are suffering from obsessive-compulsive disorder (OCD) as comorbidity than men, a topic that has not yet been extensively researched. While previous studies mostly show that men have an earlier onset of symptoms, we found the opposite in our sample. Another notable difference in illness course was that men experienced more manic episodes per year. Further research in this area is needed to verify our findings, ideally focusing specifically on OCD in bipolar men and women, as sex differences in this comorbidity remain underexplored.

Introduction: Major depressive disorder (MDD) represents a critical public health issue, impacting millions globally and significantly contributing to disability-adjusted life years. Major depressive episode (MDE) is a feature of MDD characterized by severe depressive symptoms. The role of glutamate, a primary excitatory neurotransmitter, in MDD has been extensively studied, and several drugs improving MDE/MDD impact the glutamate cascade; however, findings regarding blood glutamate levels in patients with a current MDE in a context of MDD remain inconsistent. This study aimed to compare blood glutamate levels between MDE/MDD patients and matched controls.

Methods: We conducted a matched case-control study utilizing 185 cases from the METADAP multicentric prospective study (NCT00526383), which was conducted from November 2009 to March 2013, and 185 controls from the VARIETE cohort (NCT01831648), conducted between January 2011 and February 2012. Blood glutamate levels were assessed from plasma samples collected between 8:00 and 10:00 a.m. after an overnight fast. The same method was used for patients and controls.

Results: No significant blood glutamate-level differences were observed between the 185 cases and matched controls of this study (conditional logistic regression: OR = 0.99, 95% CI: 0.98-1.01, p = 0.74).

Conclusion: Further research is warranted to investigate brain glutamate levels and whether glutamate levels of MDE/MDD patients could predict response to conventional antidepressant drugs and anti-glutamatergic drugs such as ketamine.

Introduction: Insomnia is one of the most common symptoms of depression, estimated to occur in approximately 75% of adult patients with depression, and it may persist even after remission from depressive episodes. Our objectives were to evaluate the efficacy of mirtazapine in reducing insomnia and depression symptom severity, assess side effects, and compare quality of life (QoL) before and after intervention in major depressive disorder (MDD) patients with insomnia.

Methods: This was a single-center, prospective, open-label, quasi-experimental pre-post-intervention trial of 6 weeks. The Hamilton Depression Rating Scale (HDRS), Insomnia Severity Index (ISI), Antidepressant Side-Effect Checklist (ASEC), and World Health Organization Quality of Life (WHOQOL-BREF) tools were used during the assessment.

Results: Out of the 135 recruited patients, 109 (80.7%) completed the trial. On day 14, with a mean dose of 18.9 mg/day, 24.8% of patients experienced remission for insomnia, while 7.3% showed remission for depression. By day 42, with a mean dose of 18.7 mg/day, these figures increased to 62.4% for insomnia and 41.3% for depression. The reduction in the ISI score (mean ± SD) from baseline to day 14 and day 42 was 8.74 ± 6.16 and 13.55 ± 5.32, respectively. Similarly, the reduction in the HDRS score from baseline on day 14 and 42 was 10.30 ± 6.89 and 17.78 ± 6.26, respectively. The most commonly reported adverse effects (>10%) included increased appetite, drowsiness, weight gain, dry mouth, headache, and constipation. Regarding QoL, the differences were significant for all four domains with the highest improvement observed in the physical (mean difference 25.67 ± 13.95) and psychological domains (mean difference 26.35 ± 16.42) of QoL.

Conclusion: Mirtazapine treatment was associated with significant improvements in depression, insomnia, and all QoL parameters, with increased appetite and weight gain being the most common adverse effects. Further randomized controlled comparator studies will be beneficial for healthcare providers to improve the clinical care of MDD patients with insomnia.