CNS Spectrums最新文献

Parkinson's disease (PD) is a severe neurodegenerative disorder characterized by prominent motor and non-motor (e.g., cognitive) abnormalities. Notwithstanding Food and Drug Administration (FDA)-approved treatments (e.g., L-dopa), most persons with PD do not adequately benefit from the FDA-approved treatments and treatment emergent adverse events are often reasons for discontinuation. To date, no current therapy for PD is disease modifying or curative. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are central nervous system (CNS) penetrant and have shown to be neuroprotective against oxidative stress, neuroinflammation, and insulin resistance, as well as promoting neuroplasticity. Preclinical evidence suggests that GLP-1RAs also attenuate the accumulation of α-synuclein. The cellular and molecular effects of GLP-1RAs provide a basis to hypothesize putative therapeutic benefit in individuals with PD. Extant preclinical and clinical trial evidence in PD provide preliminary evidence of clinically meaningful benefit in the cardinal features of PD. Herein, we synthesize extant preclinical and early-phase clinical evidence, suggesting that GLP-1RAs may be beneficial as a treatment and/or illness progression modification therapeutic in PD.

Suicide accounts for over 700,000 deaths per year globally and remains a public health priority. Evidence suggests that sleep-related interventions may be effective in reducing depressive symptom severity and suicidal thoughts in patients diagnosed with depression and comorbid insomnia. This study aims to systematically review the efficacy of sedative-hypnotics and/or cognitive behavioral therapy for insomnia (CBT-I) on measures of suicidality.In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, PubMed, Medline, Cochrane Library, Embase, Scopus, and Web of Science were searched from inception to July 30, 2024. Studies were included if they (1) were randomized controlled trials (RCTs) and (2) reported on suicide-related measures associated with sleep interventions as a primary outcome, secondary outcome, or a safety measure. We endeavored to define and operationalize suicidality as suicidal ideation (SI), suicide attempts (SA), and suicide completion (SC). In cases where study authors failed to separate these three dimensions, the term "suicidality" was applied.Eighteen studies were identified meeting inclusion criteria, comprised of studies investigating benzodiazepines (n = 2), Z-drugs (n=4), orexin receptor antagonists (ORAs) (n=8), and CBT-I (n=4). Zolpidem reduces SI as well as insomnia (linear association = 0.12, p<0.05) as evidenced by improvement on both the Columbia-Suicide Severity Rating Scale (C-SSRS) and the Scale for Suicide Ideation (SSI). ORAs were not associated with either an increase or decrease in suicidality. CBT-I alleviates SI in patients with insomnia (t = -3.35, p<0.05).Effectively treating insomnia is associated with reduced SI. Available evidence suggests that Food and Drug Administration (FDA)-approved sedative-hypnotics do not increase the risk of suicidality.

Major depressive disorder (MDD) is a chronic, highly prevalent, and debilitating mental disorder associated with significant illness and economic burden globally. Exposure to trauma (eg, physical, sexual, emotional abuse, and/or physical, and emotional neglect) is common among individuals with MDD. Persons with MDD and a history of trauma often exhibit an attenuated response to conventional serotonergic antidepressants compared to those with non-traumatized depression. Emerging evidence indicates that exposure to trauma is associated with increased inflammatory markers [eg, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)] as well as glutamatergic dysregulation in the central nervous system (CNS). It is hypothesized that individuals with MDD and a history of trauma may be conceptualized as a distinct bio-phenotype compared to non-traumatized depression. Furthermore, preliminary evidence positions select glutamatergic modulators as potential, novel, mechanistically-informed therapeutic strategies that may provide benefit to persons with elevated inflammation and glutamatergic dysregulation.

Anxiety disorders, characterized by excessive fear and behavioral disturbances, are among the most prevalent psychiatric conditions, yet treatment options remain suboptimal for many patients. Clonidine, an alpha-2 adrenergic receptor agonist, has shown potential anxiolytic effects and may address treatment-resistant cases. This review explores the efficacy, safety, and mechanism of clonidine as a pharmacological option for anxiety disorders, with emphasis on its role in modulating noradrenergic dysfunction and its potential synergistic effects with existing therapies. A literature review was conducted to evaluate clinical studies, case reports, and comparative trials on clonidine's use in anxiety disorders, focusing on its pharmacological profile, efficacy, and tolerability. Evidence suggests clonidine may reduce anxiety symptoms, particularly in treatment-resistant cases and specific populations, such as pediatric patients and those with comorbid psychiatric disorders. Its mechanism involves modulating norepinephrine release and glutamatergic pathways. Case studies and small trials highlight its potential in reducing cognitive symptoms of anxiety, but inconsistencies in efficacy and side effects, including sedation and hypotension, were noted. Comparative studies suggest clonidine may have similar efficacy to SSRIs in some cases but lack large-scale validation. Clonidine presents as a promising pharmacotherapeutic option for anxiety disorders, particularly in cases resistant to conventional treatments or in patients with contraindications to other typical medications. Its mechanism of action, tolerability, and potential synergistic effects with existing therapies underscore the need for continued exploration and clinical trials to establish its optimal role in anxiety disorder management.

Background: Advances in medicine have led to an improvement in life expectancy, thus increasing the population of older individuals within the criminal justice system. This study investigates the determinants of risk formulation, care plan, and disposition among older adult forensic patients (OAFP) in Ontario, Canada.

Methods: This retrospective analysis utilized the Ontario Review Board database, focusing on 161 OAFP, aged 55 years and older. Hierarchical regression was used to analyze the relationship between changes in risk and six blocks of variables: sociodemographic characteristics (Block 1), circumstances during the index offense (Block 2), current clinical profile (Block 3), past psychiatric history and behavioral patterns (Block 4), criminal history and legal status (Block 5), and recent violent events (Block 6).

Results: The median age of patients was 61 years (IQR 58-67), with 83.4% being male. Schizophrenia was the most common diagnosis (68.3%), and 9.3% had neurocognitive disorders. The model with six blocks of factors explained 92% of the variability in risk change. Models 2 (blocks 1 and 2) and 4 (blocks 1-4) were statistically significant, explaining 34% (p = 0.010) and 22% (p = 0.018) of the variance in the change in risk of threat to public safety, respectively. OAFP with a significant risk to public safety were more likely to be inpatients and less likely intoxicated during their index offense.

Conclusion: Resources, policies, and a supervised model of care to curtail behavioral risks are relevant to the care of OAFP. Innovative risk management models for OAFP are indicated.

Cannabis has a long history as a medicine and was a part of medical practice until the late 19th century. The discovery of cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC) in the mid-20th century, and then the various components of the endocannabinoid system (ECS) over the following decades has again brought cannabis back into the public eye as a potential therapeutic agent. At present, cannabis is being used in the community across the world for both recreational and medical purposes. In the case of medical usage, it may be prescribed by a medical doctor or purchased either legally or illicitly for medical purposes such as symptom relief. Evidence for cannabis as a medicine is still an emerging field, and while potential mechanisms of action for a variety of conditions have been elucidated, including cancer, epilepsy, and chronic pain, high-quality randomized controlled trials in humans are still lacking. Despite popular beliefs, cannabis, like all other medicines, has potential benefits and harms, and long-term consumption of cannabis, even for medical reasons, may not be risk-free. In addition, consumption via modes of administration such as smoking or using a bong may increase the risk of negative health outcomes.

Major depressive disorder (MDD) is a serious and often chronic illness that requires early and urgent treatment. Failing to provide effective treatment of MDD can worsen the illness trajectory, negatively impact physical health, and even alter brain structure. Early optimized treatment (EOT) of MDD, with a measurement-based approach to diagnosis, rapid treatment initiation with medication dosage optimization, frequent monitoring, and prompt adjustments in treatment planning when indicated, should proceed with a sense of urgency. In this article, we describe common barriers to providing an EOT approach to treating MDD at each phase of care, along with strategies for navigating these obstacles. Approaching the treatment of MDD with a greater sense of urgency increases the likelihood of symptom reduction in MDD, facilitating full functional recovery and a return to life engagement.

Background: Sleep disturbances are prevalent in major depressive disorder (MDD). Emerging evidence suggests a bidirectional relationship between inflammation and sleep disturbances, but the role of peripheral inflammatory markers in subjective sleep quality in treatment-resistant depression (TRD) remains unclear.

Methods: 34 MDD patients (20 TRD and 14 non-TRD) and 34 healthy controls were enrolled. Participants underwent clinical assessments, including the Hamilton Rating Scale for Depression and Pittsburgh Sleep Quality Index (PSQI). Serum levels of inflammatory markers, including soluble interleukin-2 receptor (sIL-2R), soluble interleukin-6 receptor, soluble tumor necrosis factor-α receptor type 1 (sTNF-αR1), monocyte chemoattractant protein-1, and C-reactive protein, were measured. General linear models were used to assess associations between inflammatory markers and subjective sleep quality, adjusting for relevant covariates.

Results: Patients with MDD scored higher in PSQI than healthy subjects. Higher serum levels of sTNF-αR1 were associated with longer sleep latency across the TRD and non-TRD groups. Elevated serum sIL-2R levels correlated with poorer overall sleep quality among patients with MDD.

Conclusions: These findings underscored the importance of considering inflammatory pathways in understanding sleep disturbances in depression. Longitudinal studies are needed to elucidate causal relationships and inform potential therapeutic interventions targeting both inflammation and sleep in MDD.