CNS Spectrums最新文献

Glutamatergic neurons represent 40% of neurons in the human central nervous system. Glutamate accounts for approximately 90% of all excitatory neurotransmitters. Previous research reports the presence of glucagon-like peptide-1 (GLP-1) receptors on neurons that produce glutamate. Herein, we aim to evaluate whether GLP-1 receptor agonists' (GLP-1 RAs) modulate glutamatergic signaling and whether GLP-1 RAs' anti-obesity effects are mediated through the glutamatergic system. We conducted a systematic review of extant literature published on PubMed, Ovid and Scopus databases from inception to March, 2025. Identified studies were screened independently by two reviewers (S.W. and G.H.L.) using the Covidence platform. We sought to include in vitro, in vivo, and human clinical studies. A total of 31 studies were identified as meeting eligibility for an inclusion in this review. No human studies were identified. Across the included preclinical and pharmacologic studies, GLP-1 RAs were associated with increased glutamate release, NMDA/AMPA receptor activation and increased release of neurotrophic factors associated with neurogenesis, neurodifferentiation, and synaptic plasticity. In addition, GLP-1 RA-induced suppression of food intake was reported to be dependent on AMPA, but not NMDA, receptor signaling. The effect of GLP-1 RAs on feeding behavior is mediated via central glutamatergic signaling. A comprehensive mechanistic framework mediating GLP-1 RA activity implicates crosstalk between GLP-1 and ionotropic glutamate receptors. The aforementioned trends instantiate a need to evaluate the therapeutic efficacy of GLP-1 RAs for disparate neuropsychiatric disorders. Conducting target engagement studies of GLP-1 RAs with the glutamatergic system in humans is a future research vista.

Objective: Adult major depression (MDD) studies implicate reward- and control-network dysconnectivity in suicidality, but it is unclear whether analogous alterations characterize adolescents, whose neural systems are still maturing.

Methods: Resting-state fMRI was obtained from 102 adolescents (12-17 years): 21 MDD with suicidal ideation (SI), 33 MDD without SI, and 48 matched healthy controls. Seed-based analyses targeted bilateral nucleus accumbens (NAc), ventral tegmental area (VTA), and bilateral dorsolateral prefrontal cortex (DLPFC).

Results: Between-group effects were specific to NAc circuitry. Adolescents with SI showed reduced coupling of the left NAc with the left superior parietal lobule (BA7) versus controls, and diminished connectivity between the right NAc and right frontal pole (BA47) versus depressed peers without SI. No significant differences emerged for DLPFC- or VTA-seeded connectivity.

Conclusions: The identified functional dysconnectivities in reward-related circuits, particularly the FCs between the NAc and both the frontal pole and superior parietal lobule, may be implicated in the manifestation of suicidality among adolescents with MD. However, the lack of significant associations for DLPFC- and VTA-seeded FC in adolescent MDSI requires further elucidation.

Objective: A longer duration of untreated illness (DUI) has been associated with poorer outcomes across several mental disorders; however, few studies have investigated DUI in anxiety disorders, particularly in generalized anxiety disorder (GAD). This study aimed to identify sociodemographic and clinical factors associated with a longer DUI in GAD.

Methods: We conducted a cross-sectional, multicenter study, retrospectively reviewing the medical records of GAD patients from three mental health services. Sociodemographic and clinical variables were extracted for analysis. One-way analyses of variance and Pearson's correlations were used to examine the relationship between DUI and categorical and quantitative variables, respectively. A multivariate linear regression model was then conducted to identify variables independently associated with DUI.

Results: The total sample included 243 patients; the mean DUI was 30.92 (±65.25) months. In the final model, a longer DUI was associated with an earlier age at onset (B = -0.428; p = 0.023), a longer duration of illness (B = -0.431; p < 0.001), and the presence of multiple side effects (B = 55.778; p < 0.001). There was a trend toward statistical significance for the association between a longer DUI and multiple medical comorbidities (B = 13.122; p = 0.076).

Conclusions: Our findings suggest that reducing the time between the onset of GAD and the initiation of appropriate pharmacological treatment may improve clinical outcomes, mitigating the risk of a chronic course of illness. Further studies are needed to elucidate the role of DUI as a prognostic factor in GAD.

Long-acting injectable (LAI) antipsychotics are not routinely offered and, thus, are underutilized despite their many advantages over oral formulations. In this special collection of articles, the reader will find overviews of the art and science of prescribing this important treatment option. Guidance is offered regarding incorporating LAIs in treatment planning, including inpatient, outpatient, and jail settings. Reviewed is the evidence surrounding the use of LAIs for patients in their first episode of schizophrenia, as well as switching from oral agents and other common issues that come up in day-to-day practice. Also provided is a comprehensive summary of each of the currently available formulations of LAIs, and some pragmatic reasons why one would be considered over another. In the end, the reader will come away with the notion that LAIs are not a "last resort" but an important and useful treatment modality that ought to be considered more often.

Long-acting injectable (LAI) antipsychotics are highly effective tools for managing serious mental illness, yet their clinical utility is often compromised by logistical and pharmacological complexities. This review serves as a practical guide to optimizing LAI therapy by addressing common clinical hurdles. Maintaining a consistent injection schedule is essential to successful treatment. To improve adherence, clinicians should implement proactive reminder systems-such as phone calls or text messages-and involve family or caregivers in the care plan. When injections are delayed, management strategies must be tailored to the specific medication and the length of the "dosing window". For example, aripiprazole monohydrate (Abilify Maintena) allows a ±7 day window, whereas paliperidone palmitate (Invega Sustenna) provides a +14 day window. If these windows are exceeded, catch-up protocols may involve administering the next dose as soon as possible, utilizing supplemental oral antipsychotics for a bridge period (e.g., 14 days for aripiprazole or 21 days for risperidone), or restarting initiation loading regimens entirely. Clinically significant drug interactions, such as the reduction of aripiprazole or risperidone levels by carbamazepine, can lead to symptom breakthrough. Conversely, CYP450 inhibitors like fluvoxamine or fluoxetine may increase antipsychotic concentrations, necessitating dose reductions. Adverse effects, including drug-induced Parkinsonism and akathisia, should be managed by reducing the LAI dose or switching to agents with lower risk profiles, such as aripiprazole-based products. For akathisia, short-term adjunctive treatments like vitamin B6 or mirtazapine may be utilized until dose adjustments reach steady state. Patient-centered care requires a collaborative approach to substance use, which can exacerbate symptoms or interfere with LAI effectiveness. Clinicians must also engage in nonjudgmental discussions when patients request a return to oral therapy, carefully considering the pharmacokinetic properties of the LAI to time the transition safely. Ultimately, a proactive management plan that addresses these clinical variables is essential for reducing relapse risk and improving long-term quality of life.