An elderly inpatient with schizophrenia and pica developed bowel obstruction after ingesting plastic gloves; laparotomy removed eleven gloves. The case underscores the need to eliminate seemingly harmless plastic items from the environment of patients with pica, especially those with cognitive or communication impairments.
Aim: The current study investigated the superiority of anxiolytic effects of venlafaxine extended release (ER) compared with placebo and its safety and tolerability in Japanese adult outpatients with generalized anxiety disorder (GAD).
Methods: In this placebo-controlled, double-blind study, 357 eligible participants were randomized to receive venlafaxine ER (75-225 mg/day) or placebo for 8 weeks. The primary endpoint was change from baseline to week 8 in Hamilton Anxiety Rating Scale (HAM-A) total score. Secondary endpoints included changes from baseline to week 8 in scores of HAM-A psychic anxiety factors, HAM-A somatic anxiety factors, Clinical Global Impressions-Severity of Illness (CGI-S), Generalized Anxiety Disorder-7 (GAD-7), Zung Self-Rating Anxiety Scale (Z-SAS), Sheehan Disability Scale (SDS), and the absolute score of Clinical Global Impressions-Global Improvement (CGI-I).
Results: Venlafaxine ER showed statistically significant reduction in HAM-A total score at week 8 (difference versus placebo: P = 0.012). The results of all secondary endpoints were consistent with this finding and likewise demonstrated statistical significance in favor of venlafaxine ER in investigator- and patient-rated scales. Venlafaxine ER further showed statistically significant remission in total HAM-A score. These results showed that venlafaxine ER improved patients' functional disabilities along with symptoms more than placebo. Venlafaxine ER was well tolerated, and safety findings were generally consistent with the known safety profile of the drug.
Conclusion: Venlafaxine ER has a favorable benefit-risk profile in adult Japanese patients with GAD, indicating its potential to improve GAD symptoms as well as patients' function and exert superior anxiolytic effects over placebo without any new safety concern.
Trial registration: Japan Registry of Clinical Trials Identifier jRCT2031220156.
Background: Emerging studies link COVID-19 to adverse multi-organ outcomes. To better estimate psychiatric and physical illness after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we analyzed a nationally representative cohort with minimal prior infection (>99% uninfected) and low vaccination coverage (<1%) in Taiwan.
Methods: We conducted a cohort study comprising 11,185 individuals who survived the first 30 days following SARS-CoV-2 infection (alpha variant) between May 1, 2021, and September 30, 2021, confirmed by reverse transcription polymerase chain reaction, along with three age- and sex-matched comparison groups: a contemporary control group (n = 223,700) with no COVID-19 diagnosis, a historical control group (n = 223,700) predating the pandemic, and seasonal influenza group (n = 44,740). We calculated the adjusted incidence rate ratios (aIRRs) of specific psychiatric and physical illnesses to compare their occurrence between the COVID-19 cohort and comparison groups.
Results: During the 6 months after the first COVID-19 diagnosis, aIRRs for psychiatric illnesses in the COVID-19 group were higher across diagnostic categories than those of comparison groups. Moreover, aIRRs of physical illnesses in the COVID-19 group were higher across nearly all major organ systems compared to the comparison ones. The absolute rate difference for overall psychiatric illnesses was 7921.0 (COVID-19 vs contemporary control) and 7226.9 per 100,000 person-years (COVID-19 vs historical control), respectively.
Conclusions: SARS-CoV-2-immunologically naïve individuals have heightened risks of psychiatric illnesses across diagnostic categories and physical illnesses spanning nearly all major organ systems after the infection. Future studies warrant to explore the pathogenesis of these postacute effects.
Aim: Changes in neurometabolites are believed to have a significant impact on the underlying mechanisms of obsessive-compulsive disorder (OCD). However, current findings regarding the neurometabolite levels of OCD patients remain inconsistent. To address this issue, we conducted a comprehensive meta-analysis of proton magnetic resonance spectroscopy studies to investigate the differences in neurometabolite levels in OCD patients relative to healthy controls (HCs).
Methods: A systematic search of PubMed, Web of Science, and Embase included 55 original studies that compared the levels of eight in vivo neurometabolites in OCD patients (n = 1270) and HCs (n = 1186). Hedge's g with random effects model was employed to calculate the effect sizes for the between-group differences in neurometabolite levels. Meta-regression and subgroup analyses were conducted to examine confounding effects.
Results: Compared to HCs, OCD patients exhibited decreased N-acetylaspartate compounds (NAA) in the striatum, as well as elevated choline-containing compounds (Cho) levels in the thalamus. The symptom severity of OCD patients showed positive associations with Cho in the striatum. Subgroup analyses showed that decreased striatal NAA in OCD patients remained evident in both the medicated and 1.5T subgroups. Additionally, significantly increased thalamic Cho in OCD patients was also observed in the unmedicated, adult, 3.0T, and non-comorbid subgroups.
Conclusion: This study reveals neurometabolic dysregulation within the cortico-striatal-thalamo-cortical circuits in OCD, offering integrated insights into its underlying neurobiological mechanisms.
Schizophrenia is a complex psychiatric disorder characterized by positive, negative, and general psychopathological symptoms. While antipsychotic drugs are effective for positive symptoms, they provide limited benefit for negative symptoms, which are often persistent and strongly associated with functional disability. Additionally, up to 30% of patients exhibit resistance to current treatments, including clozapine. These challenges underscore the need for novel adjunctive strategies. This systematic review and meta-analysis, preregistered in PROSPERO (CRD42022359199), evaluated the efficacy and safety of repurposed antihypertensive drugs (AHTs) as adjunctive treatments for schizophrenia. PubMed, Web of Science, and Scopus were searched for double-blind, randomized controlled trials (RCTs) published since 2000. Twelve studies were included (n = 436; sodium nitroprusside = 6; diuretics = 4; telmisartan = 1; clonidine = 1). Meta-analyses were conducted on Positive and Negative Syndrome Scale (PANSS) outcomes and adverse event (AE) rates. Standardized mean differences (SMDs) were calculated as Hedges' g using a restricted maximum likelihood estimator. Incidence rate ratios modeled AE rates. AHTs significantly improved negative symptoms (SMD = -0.37 [-0.59, -0.15]; I2 = 43.8%), positive symptoms (SMD = -0.29 [-0.53, -0.06]; I2 = 25.1%), general psychopathology (SMD = -0.28 [-0.48, -0.08]; I2 = 0.0%), and total symptoms (SMD = -0.44 [-0.66, -0.21]; I2 = 0.0%). No significant increase in AEs was observed. Overall, repurposed AHTs-particularly sodium nitroprusside-may offer adjunctive therapeutic benefits for schizophrenia treatments. Some diuretics also showed preliminary signals of efficacy. However, findings are preliminary and require confirmation in larger, long-term RCTs.
Aim: Adherence to the Mediterranean-dietary approaches to stop hypertension (DASH) intervention for neurodegenerative delay (MIND) diet has been associated with a reduced risk of dementia, yet clinical and mechanistic evidence is limited. This study aims to explore the relationship between MIND diet adherence and cognitive function in Alzheimer's disease (AD), with a specific focus on resting-state EEG to investigate the underlying mechanisms.
Methods: We evaluated 841 memory clinic participants: 119 cognitively normal, 255 with mild cognitive impairment, and 467 with AD. Cognitive, dietary, neuropsychiatric, and functional data were collected. EEG from 204 participants was analyzed for spectral and connectivity features.
Results: MIND scores were significantly lower in the AD group (P < 0.001). Higher MIND adherence was linked to better global cognition, lower dementia severity, fewer mood symptoms, and greater daily functioning (P < 0.05). Individuals in the lowest adherence tertile had 6.78 times higher odds of cognitive impairment compared to those in the highest tertile (OR = 6.78, 95% CI: 4.54-10.13, P < 0.001). EEG analyses revealed that greater MIND adherence was associated with increased alpha power, reduced occipital theta/beta and delta/alpha ratios, and stronger frontoparietal connectivity. Mediation analysis indicated that frontal and global alpha power partially mediated the associations between MIND diet adherence and dementia severity, mood symptoms, and functional status.
Conclusions: High MIND adherence is associated with improved cognitive and functional outcomes in AD. EEG signatures may partially mediate these effects, highlighting the clinical potential of the MIND diet for early intervention and neurophysiological monitoring.
A randomized, double-blinded, placebo-controlled study by Otsubo et al. demonstrated a statistically significant effect of venlafaxine in patients with generalized anxiety disorder. However, the magnitude of improvement may have little clinical value. Methodological factors-including the exclusion of placebo responders, the inclusion of participants with comorbid depressive disorders, and a higher rate of discontinuation due to adverse events-further diminish the clinical significance of the findings. Overall, although venlafaxine achieved statistical efficacy, it may lack a clinically meaningful risk-benefit balance.
Background: The mechanism of memory impairment in patients with major depressive disorder (MDD) after modified electroconvulsive therapy (MECT) is still unclear. This study explored the role of the circular RNA-miRNA interaction network in MECT treatment of MDD to provide new evidence on the possible mechanism of memory impairment caused by MECT.
Methods: Differentially expressed miRNAs in peripheral blood of patients with MDD before and after MECT were screened, and a prediction model for the circular RNA-miRNA interaction network was constructed based on this. Then, the relationship between MECT and the expression of circular RNA (circRNA) and miRNA was analyzed. Finally, the correlations among circRNA, miRNA and clinical symptoms and memory function in patients with MDD were analyzed.
Results: After MECT, 26 significantly differentially expressed miRNAs were found in peripheral blood of patients with MDD. According to the prediction model, three miRNAs were significantly downregulated and two circRNAs were significantly upregulated after MECT. In addition, the expression of miRNA was significantly correlated with that of circRNA. The circRNA-miRNA regulatory network was associated with multiple clinical symptoms and memory scores in patients with MDD treated with MECT.
Conclusion: The circRNA-miRNA interaction network may be involved in the neuropsychiatric mechanism of MECT in the treatment of MDD. The expression levels of multiple regulatory factors in this network can be used as biomarkers to reflect the improvement of some symptoms and the risk of memory impairment in patients with MDD after MECT.
Aim: To determine whether catatonia is associated with increased long-term all-cause and cause-specific mortality.
Methods: Using Taiwan's National Health Insurance Database (2000-2022), we assembled a population-based cohort of all adults (≥18 years) with catatonia and matched each to four controls without catatonia on sex and birthdate. Mortality was compared between (1) individuals with catatonia and their unaffected siblings and (2) individuals with schizophrenia spectrum disorders with catatonia and those with schizophrenia spectrum disorders without catatonia. The primary outcome was all-cause mortality; secondary outcomes were natural- and unnatural-cause deaths. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated with Cox models controlling for age, sex, socioeconomic status, urbanization level, and comorbidities.
Results: We included 6642 individuals with catatonia and 26,568 matched controls. Over mean follow-ups of 11.4 and 13.1 years, respectively, 2150 versus 3459 deaths occurred (adjusted HR 2.60, 95% CI 2.46-2.75). Risks were higher for natural causes (2.42, 2.28-2.57) and unnatural causes (5.57, 4.59-6.77). Compared with unaffected siblings, catatonia remained associated with excess all-cause (1.82, 1.34-2.49), natural (1.57, 1.07-2.30), and unnatural mortality (2.73, 1.56-4.77). Within schizophrenia spectrum disorders, catatonia conferred higher all-cause (1.20, 1.12-1.28) and natural mortality (1.27, 1.18-1.36), whereas unnatural mortality was similar (1.01, 0.87-1.17).
Conclusions: Catatonia conferred a substantial, independent risk of premature mortality across multiple causes. Clinicians should recognize that catatonia is a serious disorder with long-term consequences and should remain vigilant to prevent and manage complications beyond the acute episode.
Aim: Noninvasive neuromodulation techniques, including transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and transcranial focused ultrasound stimulation (tFUS), are promising interventions for acute treatment of depressive episodes. However, the comparative efficacy and acceptability of stimulation protocols remain unclear. This network meta-analysis (NMA) aimed to compare the efficacy and tolerability of various noninvasive neuromodulation strategies.
Methods: We conducted a systematic review and NMA of randomized controlled trials (RCTs) enrolling patients with major depressive disorder or bipolar depression, including nine repetitive TMS (rTMS) protocols, three theta burst stimulation (TBS) protocols, as well as tDCS and tFUS. Primary outcomes were response and all-cause discontinuation rates. Subgroup analyses examined treatment-resistant depression (TRD) and monotherapy versus add-on therapy.
Results: A total of 129 RCTs (7667 patients; 272 treatment arms) were included. All protocols except low-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC) showed higher response rates than sham. tFUS demonstrated the highest response rate (OR: 7.24, 95% CI: 1.35-38.47), followed by bilateral rTMS (OR: 5.75, 95% CI: 3.29-10.07) and bilateral TBS (OR: 5.37, 95% CI: 2.51-11.36), both effective for general depression and TRD. Bilateral TBS showed the highest response rate when administered as monotherapy, whereas bilateral rTMS was most effective as add-on therapy. Most studies (87.6%) were rated as having low or unclear risk of bias.
Conclusions: Our findings provide preliminary evidence that bilateral stimulation over DLPFC is more beneficial than unilateral stimulation for treating depressive episodes. Nonetheless, tFUS may represent a highly promising novel intervention warranting further investigation.
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