CNS Spectrums最新文献

Incretin-based treatments, such as glucagon-like peptide-1 receptor (GLP-1R) agonists (eg liraglutide and semaglutide), have rapidly transformed obesity treatment. The well-documented weight loss effect from these agents is considered to be primarily a result of their actions on food intake, but frequent anecdotal reports from varied sources have suggested that they might also broadly affect consummatory behavior, including alcohol and drugs of abuse, suggesting a potential modulatory effect on reward behavior. Herein, we critically review the extant literature on the behavioral effects of GLP-1R agonists in humans, including their impact on feeding behavior, alcohol/drug intake, and overall reward response. We also consider the physiological and neurobiological underpinnings of GLP-1 actions, with a focus on its distinct central and peripheral roles, as well as its relationships with the broader energy homeostasis network. We conclude with a discussion on the implications of this line of research on how behavior is conceptualized, and the potential future directions for research.

Background: Antidepressants are commonly prescribed for mood disorders. Epidemiological studies suggest antidepressant use may be associated with cataracts and glaucoma. We aim to investigate the association between antidepressants and cataracts and glaucoma.

Methods: Data was collected from the United States Food and Drug Administration Adverse Event Reporting System. Reporting odds ratio (ROR) and Bayesian information components (IC₀₂₅) were calculated for antidepressants (ie, selective serotonin reuptake inhibitors [SSRIs], selective norepinephrine reuptake inhibitors [SNRIs], serotonin-norepinephrine-dopamine reuptake inhibitors, serotonin modulators and stimulators, serotonin antagonists and reuptake inhibitors [SARIs], norepinephrine reuptake inhibitors, norepinephrine-dopamine reuptake inhibitors, tricyclic antidepressants [TCAs], tetracyclic antidepressants [TeCAs], and monoamine oxidase inhibitors [MAOIs]). The reference agent was acetaminophen.

Results: TeCAs and MAOIs were significantly associated with a decreased risk of cataracts (ROR = 0.11-0.65 and 0.16-0.69, respectively). TCAs, brexanolone, esketamine, and opipramol reported an increased cataract risk (ROR = 1.31-12.81). For glaucoma, SSRIs, SNRIs, SARIs, TCAs, MAOIs, and other investigated antidepressants reported significant RORs ranging from 1.034 to 21.17. There was a nonsignificant association of angle closure glaucoma (ACG) and open angle glaucoma (OAG) with the investigated antidepressants.

Limitations: For adverse event cases, multiple suspected product names are listed, and as cases are not routinely verified, there may be a possibility of duplicate reports and causality cannot be established.

Conclusion: Most of the investigated antidepressants were associated with a lower risk of cataract reporting. TCAs, brexanolone, esketamine, and opipramol were associated with greater odds of cataract. For most antidepressants, there was an insignificant increase in reports of ACG and OAG.

Background: A double-blind, randomized, active-controlled, parallel-group, noninferiority trial (NCT03345342) demonstrated that paliperidone palmitate once-every-6-months (PP6M) was noninferior to paliperidone palmitate once-every-3-months (PP3M) in preventing relapse in clinically stable adults with schizophrenia. This post hoc analysis assessed efficacy and safety following transition to PP6M from paliperidone once-monthly (PP1M) versus PP3M.

Methods: Adults with schizophrenia who were clinically stable on moderate/high doses of PP1M or PP3M were randomly assigned 1:2 to dorsogluteal PP3M or PP6M treatment for 12 months. The primary efficacy measure was time to relapse during the 12-month DB phase. Secondary endpoints included change from DB baseline to endpoint in Positive and Negative Syndrome Scale (PANSS) total and subscale scores, Clinical Global Impression-Severity (CGI-S) scale score, and Personal and Social Performance (PSP) scale score. Safety was assessed by treatment-emergent adverse events (TEAEs), vital signs, and clinical laboratory tests.

Results: Of 702 patients in the study, 231 transitioned from PP1M to PP6M and 247 transitioned from PP3M to PP6M. Low relapse rates for PP6M were observed regardless of transition pathway (PP1M/PP6M: 7.8%; PP3M/PP6M: 7.3%). Changes from DB baseline to endpoint in PANSS total, PSP, and CGI-S scores were similar between transition groups. In the DB phase, ≥1 TEAE was observed in 61.0% and 63.2% of patients in the PP1M/PP6M and PP3M/PP6M, groups, respectively.

Conclusion: Adults with schizophrenia who transitioned to PP6M from either PP1M or PP3M experienced similarly low relapse rates. Additionally, symptom and functionality scores supported the primary analysis and, along with TEAE incidences, were comparable between transition groups.

Objective: Cognitive and psychiatric symptoms have been increasingly reported after severe acute respiratory syndrome coronavirus 2 infection, developing soon after infection and possibly persisting for several months. We aimed to study this syndrome and start implementing strategies for its assessment.

Methods: Consecutive patients, referred by the infectious disease specialist because of cognitive complaints after COVID-19, were neurologically evaluated. Neurological evaluation included a cognitive screening test (Montreal Cognitive Assessment, MoCA). Moreover, patients were invited to fill out a general symptom questionnaire and a self-administered multidimensional assessment of psychiatric symptoms, followed by a full psychiatric assessment if scores were above validated cutoffs.

Results: Of 144 referred patients, 101 (mean age 55.2±13.1, 63.4% females) completed the cognitive screening and the self-administered psychiatric questionnaire. Acute infection severity was low for most patients and the most common persisting symptoms were fatigue (92%), sleep problems (69.5%), and headache (52.4%). MoCA outlined cognitive deficits in ≥1 cognitive domain in 34% of patients, mainly in memory and attention. About 60% of patients presented depressive, anxiety, or stress-related symptoms. Psychiatric scale scores significantly correlated with overall symptom burden and MoCA score. No significant correlation was found between MoCA scores and overall symptom burden.

Conclusion: We hypothesize that persistent cognitive complaints after COVID-19 might reflect a concomitant or reactive psychopathological condition, possibly coupled with an infection-related impact on cognitive functions. The application of a combined neurological and psychiatric assessment seems crucial to appraise the nature of post-COVID-19 condition.

Objective: Orthorexia nervosa (ON) is characterized by the pursuit of extreme dietary purity due to an exaggerated focus on food quality that could ultimately lead to a new kind of eating disorder. Even though researchers have tried to reach a univocal description of ON, to this date, there is no consensus on its diagnostic criteria, making it considerably more difficult to develop a valid questionnaire for assessing the symptoms of ON and to assess its actual prevalence. The aim of this review was to evaluate and gather scientific evidence about the prevalence of ON in both clinical and non-clinical adult populations, using the main validated scale for ON evaluation.

Methods: Electronic databases (PubMed, Scopus, and Web of Science) were reviewed to identify studies in accordance with PRISMA guidelines; at the end of the selection process, 62 studies were included.

Results: Prevalence rates of ON vary greatly due to the differences in psychometric qualities of the tools used and the socio-cultural norms of the countries, with the lowest being obtained with the Dusseldorf orthorexic scale (DOS) (2.6% up to 36.7% in cancer survivor women) and the BOS-T (12.8% up to 34.7%), the greatest variability concerning the two thresholds of the ORTO-15 (14.6% with the >35 threshold and up to 86% with the >40 threshold) and the higher score being reported with the ORTO-11 in post-partum women (87.7%).

Conclusions: Additional research is necessary to support the development of a thorough, sensitive, and valid questionnaire for assessing the symptoms of ON.

Introduction and objectives: Clozapine is the antipsychotic medication with the greatest efficacy in treatment-resistant schizophrenia (TRS). Unfortunately, clozapine is ceased in approximately 0.2% to 8.5% of people due to concerns about clozapine-associated myocarditis (CAM). The opportunity for clozapine rechallenge is important for people with TRS and CAM, due to limited alternative treatments. However, there is a lack of consensus regarding the optimal process, monitoring, and dose titration to achieve successful clozapine rechallenge. The study aimed to review the process, monitoring, and dose titration within cases of clozapine rechallenge after CAM, to identify features associated with successful rechallenge.

Methods: A systematic review of clozapine rechallenge cases following CAM was conducted. PubMed, EMBASE, Cinahl, and PsycINFO were searched for cases. Reference lists of retrieved articles and field experts were consulted to identify additional studies.

Results: Forty-five cases were identified that described clozapine rechallenge, 31 of which were successful. Successful rechallenge cases generally used a slower dose titration regime with more frequent monitoring than standard clozapine initiation protocols; however, this data was not always completely recorded within cases. Six cases referred to published rechallenge protocols to guide their rechallenge.

Conclusions: The process, monitoring, and dose titration of clozapine rechallenge are inconsistently reported in the literature. Despite this, 69% of case reports detailed a successful rechallenge post CAM; noting limitations associated with reliance on case data. Ensuring published clozapine rechallenge cases report standardised data, including titration speed and monitoring frequencies, is required to guide the development and validation of guidelines for clozapine rechallenge.

Background: Recent guidance from UK health authorities strongly cautions against the use of valproic acid (VPA) in persons under 55 because of reevaluated risk of teratogenicity.

Objective: To summarize the extant literature documenting VPA-associated anatomical, behavioral, and cognitive teratogenicity.

Method: Pubmed, Medline, Cochrane Library, PsychInfo, Embase, Scopus, Web of Science, and Google Scholar were searched in accordance with PRISMA guidelines. Collected data covered study design, participant characteristics, anatomical, behavioral, or cognitive effects, and folic acid outcomes.

Results: 122 studies were identified meeting inclusion comprised of studies evaluating anatomical (n = 67), behavioral (n = 28), and cognitive (n = 47) teratogenicity. Twenty studies were identified reporting on the risk mitigation effects of folic acid supplementation. Prenatal VPA exposure is associated with anatomical teratogenicity including major congenital malformations (odds ratio [OR] 2.47-9.30; p < 0.005). Behavioral teratogenicity including autism (OR 1.70-4.38), impaired motor development (OR 7.0), and ADHD (OR 1.39) are also significantly associated with VPA exposure. VPA was associated with intellectual disability and low IQ (hazard ratio [HR] 2.4-4.48, verbal intelligence: Spearman's ρ = -0.436, respectively). Teratogenic effects were dose-dependent across all domains and were significant when compared with controls and other antiepileptic drugs (eg, carbamazepine, lamotrigine, and levetiracetam). Folic acid supplementation does not significantly reduce the hazard associated with VPA.

Conclusions: VPA is significantly associated with anatomical, behavioral, and cognitive teratogenicity. Folic acid supplementation does not abrogate the risk of teratogenicity associated with VPA exposure. Available evidence supports recommendations to reduce VPA exposure in women of reproductive age.

Objective: The World Health Organization (WHO) has defined Post-COVID-19 Condition (PCC) as the onset of symptoms within three months after resolution of an acute SARS-CoV-2 infection, wherein symptoms persist for at least two months and cannot be explained by another medical/psychiatric condition. Persons living with PCC report debilitating symptoms including, but not limited to, depressive symptoms and motivational deficits. The aim of this post-hoc analysis was to evaluate the association between depressive symptoms and motivation in adults with PCC.

Methods: We conducted a post-hoc analysis of an 8-week, double-blind, randomized, placebo-controlled trial evaluating adults (18 years or older) in Canada with WHO-defined PCC and cognitive symptoms. This post-hoc analysis is comprised of baseline data that evaluates the association between depressive symptom severity measured by the 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR-16) and motivational systems measured by the Behavioral Inhibition System/Behavioral Activation System Questionnaire (BIS/BAS).

Results: There was a statistically significant association between depressive symptoms and BIS (β = -0.041 95% CI [-0.066, -0.016], p<0.05), BAS reward responsiveness (β = 0.043 95% CI [0.012, 0.074], p<0.05), sex (β = -0.137 95% CI [-0.266, -0.008], p<0.05), and confirmed COVID-19 infection (β = 0.196 95% CI [0.061, 0.332], p<0.05).

Conclusions: Depressive symptoms were associated with motivational deficits in persons living with PCC. Optimizing treatment for depressive symptoms may potentially improve aspects of motivational impairment amongst persons with PCC. All patients presenting with MDD and a history of COVID-19 infection should be assessed for the presence of PCC.