Clinical Psychopharmacology and Neuroscience最新文献

Intracellular cyclic nucleotides (cyclic adenosine monophosphate and cyclic guanosine monophosphate) and downstream cellular signal transduction are regulated by phosphodiesterases (PDEs). The neuroplasticity, neurotransmitter pathways, and neuroinflammation-controlling functions of PDEs were demonstrated in numerous in vitro and animal model studies. We comprehensively reviewed the literature regarding the expression of PDEs in various brain regions. Subsequently, articles regarding schizophrenia and PDEs were examined. The pathophysiological mechanisms of schizophrenia and PDEs in preclinical and clinical investigations are briefly reviewed. Particularly for those who do not respond to conventional antipsychotics, specific PDE inhibitors may offer innovative therapeutic alternatives. Although the connection between schizophrenia and PDEs is intriguing, additional research is required. Comprehending the brain's PDE isoforms, their therapeutic potential, and any adverse effects of inhibiting them is essential for progress in this field.

Objective: Many studies have explored sense of self in individuals with autism spectrum disorder (ASD); however, few have reported on their experience of "disembodiment." This study aimed to investigate the differences in brain activity between patients with ASD and neurotypicals (NTs) under conditions causing disembodiment and to examine the correlation between their interoceptive abilities and disembodiment-related brain activity.

Methods: 18 Participants with ASD and 21 NTs completed psychological evaluations, interoceptive abilities measurement, and functional magnetic resonance imaging (fMRI). The fMRI images were taken while the participants performed tasks involving ball-throwing animations. The task focused on either self-agency related to ball-throwing (Agency Task) or the spatial location of a ball (Location Task). The animations were presented from constantly changing perspective (Changing View) or fixed perspective (Fixed View). The disembodiment-related condition was the interaction between the Agency Task and Changing View.

Results: Participants with ASD exhibited higher activation than NTs in regions near the left parieto-temporo-occipital junction, left precuneus, left hippocampus, and other brain areas. Furthermore, interoceptive accuracy was negatively correlated with the activity of the left superior parietal and posterior midcingulate areas, whereas interoceptive trait prediction error was positively correlated with the activity of the left hippocampus, mid-temporal area, and left posterior cingulate area in participants with ASD.

Conclusion: These results suggest that disembodiment-related brain activation might be easily manifested by the interaction between perspective-shifting and the experience of agency, and that interoceptive abilities might be related to disembodiment-related brain activation in individuals with ASD.

This case report explores the therapeutic potential of theta burst stimulation (TBS) for cognitive enhancement in individuals with brain injuries. The study presents a 38-year-old male suffering from an organic mental disorder attributed to a traumatic brain injury (TBI), who demonstrated notable cognitive improvements following an intensive TBS protocol targeting the left dorsal lateral prefrontal cortex. The treatment led to significant enhancements in impulse control, irritability, and verbal comprehension without adverse effects. Neuropsychological assessments and brain imaging post-intervention revealed improvements in short-term memory, abstract reasoning, list-generating fluency, and increased cerebral blood flow in the prefrontal cortex. These findings suggest that TBS, by promoting neural plasticity and reconfiguring neural networks, offers a promising avenue for cognitive rehabilitation in TBI patients. Further research is warranted to optimize TBS protocols and understand the mechanisms underlying its cognitive benefits.

Auditory/visual hallucinations and perceptual anomalies are one of the core symptoms experienced by patients with schizophrenia. Studies have implicated lateral occipital cortex (LOC) as one of the areas to be aberrantly functioning in schizophrenia, possibly associated with the auditory/visual symptoms of schizophrenia. Here we report of a case of a 29-year-old female diagnosed with treatment resistant schizophrenia on clozapine with persistent auditory verbal hallucinations (AVH) and visual anomalies. Upon targeting the LOC (-40, -66, -8) in this patient, there was a > 25% reduction in AVH, with reduction in the frequency of most visual anomalies and an overall significant response in terms of reduction of symptoms and improvement in functioning. We further discuss the potential of LOC as a novel target for neuromodulation in patients exhibiting perceptual abnormalities especially in auditory and visual senses.

Objective: Cerebral ischemia is a medical condition that occurs due to poor supply of blood in the brain. Reperfusion being savage further exaggerates the tissue injury causing cerebral ischemia/reperfusion injury (CI/R). CI/R is marked by an impairment in release of neurotransmitter, excitotoxicity, oxidative stress, inflammation, and neuronal apoptosis. The current study has utilized brivaracetam (BRV), a synaptic vesicle protein 2A modulator in experimental model of CI/R injury.

Methods: CI/R injury was induced in Swiss Albino mice by occlusion of common carotid arteries followed by reperfusion. Animals were assessed for learning and memory, motor coordination (Rota rod, lateral push, and inclined beam walking test), cerebral infarction, and histopathological alterations. Biochemical assessments were made for oxidative stress (thiobarbituric acid reactive species, reduced glutathione, catalase, superoxide dismutase), inflammation (tumor necrosis factor-α and interleukin-10), and acetylcholinesterase activity (AChE) in brain supernatants.

Results: CI/R animals showed impairment in learning, memory, and motor coordination, along with increase in cerebral infarction, and histopathological alterations. Furthermore, increase in brain oxidative stress, inflammation, and AChE activity were recorded in CI/R animals. Administration of BRV (10 mg/kg and 20 mg/kg; p.o.) was observed to recuperate CI/R induced impairments in behavioral, biochemical, and histopathological analysis.

Conclusion: It may be concluded that BRV mediates neuroprotection during CI/R via decreasing brain oxidative stress, inflammation, and AChE activity.

Objective: Bipolar disorder (BD), schizoaffective disorder (SAD), and schizophrenia (SCH) are psychiatric disorders characterized by persistent cognitive impairments, even during periods of remission. Psychotropic medications commonly used to manage these conditions have anticholinergic properties, which may contribute to cognitive impairment.

Methods: This study examined the relationship between anticholinergic medication burden and cognitive function in individuals diagnosed with BD, SAD, and SCH. Anticholinergic burden was assessed using two validated scales, the Anticholinergic Cognitive Burden Scale (ACB) and the CRIDECO Anticholinergic Load Scale (CALS). Cognitive function was evaluated using the Digit Span and the Öktem Verbal Memory Process Test. Retrospective data analysis was conducted to examine the association between anticholinergic medication burden and cognitive performance.

Results: The study included 132 participants including individuals with BD (n = 45), SAD (n = 29), and SCH (n = 58). Higher scores on the ACB and CALS scales were associated with impairments in working memory and immediate memory in the BD group. Similarly, increased anticholinergic burden was associated with immediate memory deficits in the SCH group. However, no significant association was found in the SAD group despite a higher anticholinergic burden.

Conclusion: Our findings highlight the impact of anticholinergic burden on neurocognitive function in individuals with severe psychiatric disorders. The association between anticholinergic burden and cognitive impairment extends beyond SCH spectrum disorders to include BD. These findings underscore the importance of considering anticholinergic burden in psychiatric treatment strategies and call for further research with larger samples to better understand cognitive consequences and refine prescribing practices.

Objective: We aimed to investigate the effectiveness of buspirone as an adjunctive therapy for alleviating anxiety symptoms in patients with depressive disorders who are already taking antidepressants.

Methods: This was an open-label prospective multicenter non-interventional observational study conducted over 12 weeks. We enrolled 180 patients diagnosed with depressive disorders according to DSM-5 criteria and Hamilton Anxiety Rating Scale (HAMA) scores ≥ 18. Participants were already taking selective serotonin reuptake inhibitors or serotoninnorepinephrine reuptake inhibitors and were prescribed adjunctive buspirone. Efficacy was assessed using HAMA, Hamilton Depression Rating Scale (HAMD), Clinical Global Impression Scale-Improvement, Clinical Global Impression Scale-Severity, Sheehan Disability Scale (SDS), and WHO-5 Well-Being Index.

Results: The efficacy analysis included 161 patients. HAMA scores decreased significantly from 25.2 ± 6.7 at baseline to 15.4 ± 8.6 at 12 weeks (p < 0.001), whereas HAMD scores decreased from 19.4 ± 4.6 to 12.7 ± 5.7 (p < 0.001). WHO-5 and SDS scores showed significant improvements. The HAMA response rate was 39.1% and the remission rate was 13.7% at 12 weeks. Adverse drug reactions were reported in 3.7% of participants. Subgroup analyses showed no significant differences in treatment response based on buspirone dosage, baseline anxiety/depression severity, or benzodiazepine use.

Conclusion: Adjunctive buspirone therapy effectively improved anxiety symptoms in depressed patients taking antidepressants, regardless of baseline symptom severity or buspirone dosage. The treatment was well-tolerated with few adverse events. Future studies using a control group are needed.

Objective: This study investigated how educational levels modify the relationship between the standard deviation of NN intervals (SDNN) of heart rate variability and the development of post-traumatic stress disorder (PTSD).

Methods: Participants with physical injuries were enrolled from a trauma center and monitored over two years. Initial assessments included SDNN and educational attainment, along with socio-demographic and clinical variables. PTSD diagnoses were made at 3, 6, 12, and 24 months post-injury using the Clinician-Administered PTSD Scale for DSM-5. Logistic regression analyses were conducted.

Results: Of the 538 participants, 58 (10.8%) developed PTSD during the follow-up period. A significant interaction effect was observed: lower SDNN was significantly linked to PTSD in individuals with higher education, but not in those with lower education.

Conclusion: The study identified education-dependent associations between SDNN and PTSD development, emphasizing the importance of tailored PTSD prevention strategies that consider both SDNN and educational levels.

Psychiatric disorders are common in patients on hemodialysis. To the best of our knowledge there are no reported cases of psychosis developing in hemodialysis patients in the context of nephrectomy, and there is limited data on the use of long-acting antipsychotics in hemodialysis, which are generally not recommended in chronic kidney disease. We present the case of a 40-year-old lady with bilateral nephrectomy receiving hemodialysis who developed psychosis that resulted in her refusing to continue hemodialysis and was irregularly compliant with oral antipsychotics, necessitating the use of a long-acting injection. We report on the approach to clinical reasoning in the choice of aripiprazole and the need for a long-acting injection. Based on its pharmacological and pharmacokinetic properties oral aripiprazole 20 mg was commenced and after establishing tolerability and response, the patient was switched to long-acting aripiprazole 400 mg monthly achieving full remission of psychotic symptoms after 6 months with maintained improvement after 12 months. Based on its properties, aripiprazole may be a reasonable option in the treatment of psychosis in patients on hemodialysis with nephrectomy and can be considered even as a long-acting injection in these patients.

Objective: Variants within genes encoding microRNAs (miRNAs) may alter the expression of both miRNAs and their target genes, thus contributing to the etiology of psychiatric disorders. The involvement of miRNAs in neuronal differentiation and synaptic plasticity supported this hypothesis. We aimed to investigate the links between miR-155 rs767649/miR-22 rs8076112 and the risk of panic disorder (PD) in a sample of Turkish population.

Methods: In this experimental study, 134 PD patients and 140 healthy controls were recruited. Genotyping was carried out using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. To evaluate PD phenotypes, Panic Disorder Severity Scale (PDSS) was also administered to patients to clarify possible associations between the scale and risk variants analyzed.

Results: The genotype analysis of miR-155 rs767649 did not show an association with PD risk and it was not related to the disease severity. For miR-22 rs8076112 variant, a statistically significant association was determined; CC genotypes were lower in patients compared to controls. Logistic regression analysis proved the highly protective effect (80.4%) of CC genotype against PD (p = 0.041; OR = 0.196, 95% CI = 0.041-0.934). Though its significance in disease liability, miR-22 rs8076112 was not associated with the disease severity.

Conclusion: Our findings firstly report the combined analysis of miR-155 rs767649 and miR-22 rs8076112 in PD in terms of both disease susceptibility and severity. These findings await replication in independent cohorts with enrichment of other miRNA gene variants. Thus, certain miRNAs and their target genes involved in the etiology and phenotypes of PD could be enlightened.