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The term behavioral and psychological symptoms of dementia (BPSD) describes a constellation of symptoms and behaviors that occur in more than 90% of individuals with dementia. (1) BPSD is associated [...]

The impact of plastics on health is an area of increasing concern. Plastics specifically affect brain health and development, which is why psychiatry must pay attention to the growing plastics [...]

Imagine that you and your traveling companion are toming the ruins of the ancient city of Pompeii. Your historically uninformed companion asks you, 'So, what caused the destruction of Pompeii?' [...]

Many individuals with anxiety disorders use alcohol or cannabis for temporary relief of worry, sleeplessness, tension, and other typical anxiety symptoms. For some, this coping response can lead to worsening [...]

Our nation is facing a mental health crisis. This crisis is magnified for perinatal individuals who are pregnant or up to 1 year postpartum. Perinatal mood and anxiety disorders (PMADs) [...]

In this perspective, we highlight the urgent need to study depression in adolescence--a period during which this debilitating disorder often begins to emerge--and propose peripheral molecular indices that may be [...]

Background: Emotional dysregulation affects up to two-thirds of adult patients with attention-deficit/hyperactivity disorder (ADHD) and is increasingly seen as a core ADHD symptom that is clinically associated with greater functional impairment and psychiatric comorbidity. We sought to investigate emotional dysregulation in ADHD and explored its neural underpinnings. Methods: We studied emotion induction and regulation in a clinical cohort of adult patients with ADHD before and after a stimulant challenge. We compared patients with age- and gender-matched healthy controls using behavioural, structural, and functional measures. We hypothesized that patients would demonstrate aberrant emotion processing compared with healthy controls, and sought to find whether this could be normalized by stimulant medication. Results: Behaviourally, the ADHD group showed reduced emotion induction and regulation capacity. Brain imaging revealed abberant activation and deactivation patterns during emotion regulation, lower grey-matter volume in limbic and paralimbic areas, and greater grey-matter volume in visual and cerebellar areas, compared with healthy controls. The behavioural and functional deficits seen in emotion induction and regulation in the ADHD group were not normalized by stimulant medication. Conclusion: Patients with ADHD may have impaired emotion induction and emotion regulation capacity, but these deficits are not reversed by stimulant medication. These results have important clinical implications when assessing which aspects of emotional dysregulation are relevant for patients and if and how traditional ADHD pharmacotherapy affects emotion induction and emotion regulation., Introduction Attention-deficit/hyperactivity disorder (ADHD) is a neuro-developmental disorder that persists later in life and affects around 2.5% of adults. (1,2) The core symptoms of ADHD include inattention and impulsivity or [...]

Background: Schizophrenia is characterized by a complex interplay of genetic and environmental factors, leading to alterations in various molecular pathways that may contribute to its pathogenesis. Recent studies have shown that exosomal microRNAs could play essential roles in various brain disorders; thus, we sought to explore the potential molecular mechanisms through which microRNAs in plasma exosomes are involved in schizophrenia. Methods: We obtained sequencing data sets (SUB12404730, SUB12422862, and SUB12421357) and transcriptome sequencing data sets (GSE111708, GSE108925, and GSE18981) from mouse models of schizophrenia using the Sequence Read Archive and the Gene Expression Omnibus databases, respectively. We performed differential expression analysis on mRNA to identify differentially expressed genes. We conducted Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to determine differentially expressed genes. Subsequently, we determined the intersection of differentially expressed microRNAs in plasma exosomes and in prefrontal cortex tissue. We retrieved downstream target genes of mmu-miR-146a-5p from TargetScan and used Cytoscape to visualize and map the microRNA-target gene regulatory network. We conducted in vivo experiments using MK-801-induced mouse schizophrenia models and in vitro experiments using cultured mouse neurons. The role of plasma exosomal miR-146a-5p in schizophrenia was validated using a cell counting kit, detection of lactate dehydrogenase, dual-luciferase assay, quantitative reverse transcription polymerase chain reaction, and Western blot analysis. Results: Differential genes were mainly enriched in synaptic regulation-related functions and pathways and were associated with neuronal degeneration. We found that mmu-miR-146a-5p was highly expressed in both prefrontal cortical tissue and plasma exosomes, which may be transferred to lobe cortical vertebral neurons, leading to the synergistic dysregulation of gene network functions and, therefore, promoting schizophrenia development. We found that mmu-miR-146a-5p may inhibit the Notch signalling pathwaymediated synaptic activity of mouse pyramidal neurons in the lobe cortex by targeting NOTCH1, which in turn could promote the onset and development of schizophrenia in mice. Limitations: The study's findings are based on animal models and in vitro experiments, which may not fully replicate the complexity of human schizophrenia. Conclusion: Our findings suggest that mmu-miR-146a-5p in plasma-derived exosomes may play an important role in the pathogenesis of schizophrenia. Our results provide new insights into the underlying molecular mechanisms of the disease., Introduction Schizophrenia is a chronic psychiatric disorder that affects early brain development and is characterized by psychotic symptoms, including hallucinations, delusions, unclear thinking, and motivational and cognitive dysfunction. (1) Patients [...]

Background: Childhood trauma plays a crucial role in the dysfunctional reward circuitry in major depressive disorder (MDD). We sought to explore the effect of abnormalities in the globus pallidus (GP)-centric reward circuitry on the relationship between childhood trauma and MDD. Methods: We conducted seed-based dynamic functional connectivity (dFC) analysis among people with or without MDD and with or without childhood trauma. We explored the relationship between abnormal reward circuitry, childhood trauma, and MDD. Results: We included 48 people with MDD and childhood trauma, 30 people with MDD without childhood trauma, 57 controls with childhood trauma, and 46 controls without childhood trauma. We found that GP subregions exhibited abnormal dFC with several regions, including the inferior parietal lobe, thalamus, superior frontal gyrus (SFG), and precuneus. Abnormal dFC in these GP subregions showed a significant correlation with childhood trauma. Moderation analysis revealed that the dFC between the anterior GP and SFG, as well as between the anterior GP and the precentral gyrus, modulated the relationship between childhood abuse and MDD severity. We observed a negative correlation between childhood trauma and MDD severity among patients with lower dFC between the anterior GP and SFG, as well as higher dFC between the anterior GP and precentral gyrus. This suggests that reduced dFC between the anterior GP and SFG, along with increased dFC between the anterior GP and precentral gyrus, may attenuate the effect of childhood trauma on MDD severity. Limitations: Cross-sectional designs cannot be used to infer causality. Conclusion: Our findings underscore the pivotal role of reward circuitry abnormalities in MDD with childhood trauma. These abnormalities involve various brain regions, including the postcentral gyrus, precentral gyrus, inferior parietal lobe, precuneus, superior frontal gyrus, thalamus, and middle frontal gyrus. Clinical trial registration: ChiCTR2300078193, Introduction Childhood trauma refers to distressing experiences that occur during the formative years, typically from 0-16 years of age. (1) Childhood trauma can be classified into 5 distinct categories, namely [...]

Background: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition that often persists into adulthood. Underlying alterations in brain connectivity have been identified but some relevant connections, such as the middle, superior, and inferior cerebellar peduncles (MCP, SCP, and ICP, respectively), have remained largely unexplored; thus, we sought to investigate whether the cerebellar peduncles contribute to ADHD pathophysiology among adults. Methods: We applied diffusion-weighted spherical deconvolution tractography to dissect the cerebellar peduncles of male adults with ADHD (including those who did or did not respond to methylphenidate, based on at least 30% symptom improvement at 2 months) and controls. We investigated differences in tract metrics between controls and the whole ADHD sample and between controls and treatment-response groups using sensitivity analyses. Finally, we analyzed the association between the tract metrics and cliniconeuropsychological profiles. Results: We included 60 participants with ADHD (including 42 treatment responders and 18 nonresponders) and 20 control participants. In the whole ADHD sample, MCP fractional anisotropy (FA; [t.sub.78] = 3.24, p = 0.002) and hindrance modulated orientational anisotropy (HMOA; [t.sub.78] = 3.01, p = 0.004) were reduced, and radial diffusivity (RD) in the right ICP was increased ([t.sub.78] = -2.84, p = 0.006), compared with controls. Although case-control differences in MCP FA and HMOA, which reflect white-matter microstructural organization, were driven by both treatment response groups, only responders significantly differed from controls in right ICP RD, which relates to myelination ([t6.sub.0] = 3.14, p = 0.003). Hindrance modulated orientational anisotropy of the MCP was significantly positively associated with hyperactivity measures. Limitations: This study included only male adults with ADHD. Further research needs to investigate potential sex- and development-related differences. Conclusion: These results support the role of the cerebellar networks, especially of the MCP, in adult ADHD pathophysiology and should encourage further investigation. Clinical trial registration: NCT 03709940, Introduction Attention-deficit/hyperactivity disorder (ADHD) is a neuro-developmental condition characterized by inattentive or hyperactive-impulsive symptoms, (1) and is estimated to affect about 4% of adults. (2) Adult ADHD has been associated [...]

Background: Psychosis involves a distortion of thought content, which is partly reflected in anomalous ways in which words are semantically connected into utterances in speech. We sought to explore how these linguistic anomalies are realized through putative circuit-level abnormalities in the brain's semantic network. Methods: Using a computational large-language model, Bidirectional Encoder Representations from Transformers (BERT), we quantified the contextual expectedness of a given word sequence (perplexity) across 180 samples obtained from descriptions of 3 pictures by patients with first-episode schizophrenia (FES) and controls matched for age, parental social status, and sex, scanned with 7 T ultra-high field functional magnetic resonance imaging (fMRI). Subsequently, perplexity was used to parametrize a spectral dynamic causal model (DCM) of the effective connectivity within (intrinsic) and between (extrinsic) 4 key regions of the semantic network at rest, namely the anterior temporal lobe, the inferior frontal gyrus (IFG), the posterior middle temporal gyrus (MTG), and the angular gyrus. Results: We included 60 participants, including 30 patients with FES and 30 controls. We observed higher perplexity in the FES group, indicating that speech was less predictable by the preceding context among patients. Results of Bayesian model comparisons showed that a DCM including the group by perplexity interaction best explained the underlying patterns of neural activity. We observed an increase of self-inhibitory effective connectivity within the IFG, as well as reduced self-inhibitory tone within the pMTG, in the FES group. An increase in self-inhibitory tone in the IFG correlated strongly and positively with interregional excitation between the IFG and posterior MTG, while self-inhibition of the posterior MTG was negatively correlated with this interregional excitation. Limitation: Our design did not address connectivity in the semantic network during tasks that selectively activated the semantic network, which could corroborate findings from this resting-state fMRI study. Furthermore, we do not present a replication study, which would ideally use speech in a different language. Conclusion: As an explanation for peculiar speech in psychosis, these results index a shift in the excitatory-inhibitory balance regulating information flow across the semantic network, confined to 2 regions that were previously linked specifically to the executive control of meaning. Based on our approach of combining a large language model with causal connectivity estimates, we propose loss in semantic control as a potential neurocognitive mechanism contributing to disorganization in psychosis., Introduction Psychosis can clinically manifest in forms of speech involving distorted or delusional contents (e.g., 'I was my husband,' 'I am Jesus') and problems of incoherence across the content of [...]

An important concept in managing clozapine's clinical issues and adverse effects is that not all approaches possess the highest levels of evidence from randomized clinical trials (RCTs), leaving clinicians to [...]

I began my career when the major treatments for schizophrenia were haloperidol and chlorpromazine. Since then, treatments for schizophrenia have improved slowly and incrementally, especially when looking back in the [...]

Physician-assisted suicide (PAS)-commonly but misleadingly called 'medical aid in dying' (1)--is now legal in 11 jurisdictions in the US. PAS remains an area of great controversy among physicians, medical ethicists, [...]

Schizophrenia affects only 1% of the population yet it is among the top 20 causes of disability in the US. (1) Schizophrenia is also associated with a 20-year decrease in [...]

CASE 1 On your emergency department (ED) shift, you are psychiatrically evaluating a patient for erratic behavior. She shows signs of psychosis but objects to treatment and to staff corresponding [...]

Caring for psychiatrically healthy individuals at the end of life is typically emotionally taxing and burdensome. Caring for individuals with psychiatric disorders at the end of life is often considerably [...]

In Canada, cannabis was legalized for medical purposes in 2001 and for nonmedical use in 2018, with edibles, concentrates, and topicals following in 2019 under the Canadian Cannabis Act (Bill [...]

Background: Critical adolescent neural refinement is controlled by the DCC (deleted in colorectal cancer) protein, a receptor for the netrin-1 guidance cue. We sought to describe the effects of reduced DCC on neuroanatomy in the adolescent and adult mouse brain. Methods: We examined neuronal connectivity, structural covariance, and molecular processes in a DCC-haploinsufficient mouse model, compared with wild-type mice, using new, custom analytical tools designed to leverage publicly available databases from the Allen Institute. Results: We included 11 DCC-haploinsufficient mice and 16 wild-type littermates. Neuroanatomical effects of DCC haploinsufficiency were more severe in adolescence than adulthood and were largely restricted to the mesocorticolimbic dopamine system. The latter finding was consistent whether we identified the regions of the mesocorticolimbic dopamine system a priori or used connectivity data from the Allen Brain Atlas to determine de novo where these dopamine axons terminated. Covariance analyses found that DCC haploinsufficiency disrupted the coordinated development of the brain regions that make up the mesocorticolimbic dopamine system. Gene expression maps pointed to molecular processes involving the expression of DCC, UNC5C (encoding DCC's co- receptor), and NTN1 (encoding its ligand, netrin-1) as underlying our structural findings. Limitations: Our study involved a single sex (males) at only 2 ages. Conclusion: The neuroanatomical phenotype of DCC haploinsufficiency described in mice parallels that observed in DCC- haploinsufficient humans. It is critical to understand the DCChaploinsufficient mouse as a clinically relevant model system., Background Adolescence is a critical period for the maturation of complex cognitive functions like reward, motivation, and behavioural control. (1) This period is also characterized by the maturation of the [...]

Background: Esketamine is a version of ketamine that has been approved for treatment-resistant depression, but our previous studies showed a link between non-medical use of ketamine and brain structural and functional alterations, including dorsal prefrontal grey matter reduction among chronic ketamine users. In this study, we sought to determine cortical thickness abnormalities following long-term, non-medical use of ketamine. Methods: We acquired structural brain images for patients with ketamine use disorder and drug-free healthy controls. We used FreeSurfer software to measure cortical thickness for 68 brain regions. We compared cortical thickness between the 2 groups using analysis of covariance with covariates of age, gender, educational level, smoking, drinking, and whole-brain mean cortical thickness. Results: We included images from 95 patients with ketamine use disorder and 169 controls. Compared with healthy controls, patients with ketamine use disorder had widespread decreased cortical thickness, with the most extensive reductions in the frontal (including the dorsolateral prefrontal cortex) and parietal (including the precuneus) lobes. Increased cortical thickness was not observed among ketamine users relative to comparison participants. Estimated total lifetime ketamine consumption was correlated with reductions in the right inferior parietal and the right rostral middle frontal cortical thickness. Limitations: We conducted a retrospective cross-sectional study, but longitudinal studies are needed to further validate decreased cortical thickness after nonmedical use of ketamine. Conclusion: This study provided evidence that, compared with healthy controls, chronic ketamine users have widespread reductions in cortical thickness. Our study underscores the importance of the long-term effects of ketamine on brain structure and serves as a reference for the antidepressant use of ketamine., Introduction Although ketamine--a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist--is valued for its clinical applications in anesthesia and pain management, and esketamine (the S-enantiomer of ketamine) has begun to be used for [...]

Background: Recent studies have identified empathy deficit as a core impairment and diagnostic criterion for people with autism spectrum disorders; however, the improvement of empathy focuses primarily on behavioural interventions without the target regulation. We sought to compare brain regions associated with empathy-like behaviours of fear and pain, and to explore the role of the oxytocinoxytocin receptor system in fear empathy. Methods: We used C57BL mice to establish 2 models of fear empathy and pain empathy. We employed immunofluorescence histochemical techniques to observe the expression of c-Fos throughout the entire brain and subsequently quantified the number of c-Fos-positive cells in different brain regions. Furthermore, we employed chemogenetic technology to selectively manipulate these neurons in Oxt-[Cre.sup.-/+] mice to identify the role of oxytocin in this process. Results: The regions activated by fear empathy were the anterior cingulate cortex, basolateral amygdala, nucleus accumbens, paraventricular nucleus (PVN), lateral habenula, and ventral and dorsal hippocampus. The regions activated by pain empathy were the anterior cingulate cortex, basolateral amygdala, nucleus accumbens, and lateral habenula. We found that increasing the activity of oxytocin neurons in the PVN region enhanced the response to fear empathy. This enhancement may be mediated through oxytocin receptors. Limitations: This study included only male animals, which restricts the broader interpretation of the findings. Further investigations on circuit function need to be conducted. Conclusion: The brain regions implicated in the regulation of fear and pain empathy exhibit distinctions; the activity of PVN neurons was positively correlated with empathic behaviour in mice. These findings highlight the role of the PVN oxytocin pathway in regulating fear empathy and suggest the importance of oxytocin signalling in mediating empathetic responses., Introduction Empathy refers to an individual's perception and recognition of the internal emotions and feelings of others, including the ability to identify and respond to their voices, expressions, and physical [...]

A recent meta-analysis of functional neuroimaging contrasts between emotional and neutral face processing has shown that the processing of facial emotions can be better classified according to threat detection than emotional valence, with the authors suggesting that their data are inconsistent with both the right-hemisphere and valence models of emotional laterality. I report empirical and theoretical data indicating that facial expressions are better classified according to threat detection than to the distinction between positive and negative emotions. I challenge, however, the claim that laterality effects provide little support to the right-hemisphere model of emotional laterality. This claim contrasts with neuropsychological and psychophysiological investigations that have shown that the right hemisphere has a graded prevalence for emotions provoked by threatening events. A reanalysis of data obtained in the target study suggests that the reported data are not necessarily inconsistent with a model assuming a graded, right-hemisphere dominance for emotions. I present a model of hemispheric asymmetries that could be consistent with the assumption that the right hemisphere's dominance for emotions may mainly be concerned with threatening events., Introduction In a recent article, Lukito and collleagues (1) published an updated meta-analysis of functional neuroimaging contrasts between emotional (e.g., angry, happy) and neutral face processing, taking into account the [...]

Background: Neuroimaging studies have revealed abnormal functional interaction during the processing of emotional faces in patients with major depressive disorder (MDD), thereby enhancing our comprehension of the pathophysiology of MDD. However, it is unclear whether there is abnormal directional interaction among face-processing systems in patients with MDD. Methods: A group of patients with MDD and a healthy control group underwent a face-matching task during functional magnetic resonance imaging. Dynamic causal modelling (DCM) analysis was used to investigate effective connectivity between 7 regions in the face- processing systems. We used a Parametric Empirical Bayes model to compare effective connectivity between patients with MDD and controls. Results: We included 48 patients and 44 healthy controls in our analyses. Both groups showed higher accuracy and faster reaction time in the shape-matching condition than in the face-matching condition. However, no significant behavioural or brain activation differences were found between the groups. Using DCM, we found that, compared with controls, patients with MDD showed decreased selfconnection in the right dorsolateral prefrontal cortex (DLPFC), amygdala, and fusiform face area (FFA) across task conditions; increased intrinsic connectivity from the right amygdala to the bilateral DLPFC, right FFA, and left amygdala, suggesting an increased intrinsic connectivity centred in the amygdala in the right side of the face-processing systems; both increased and decreased positive intrinsic connectivity in the left side of the face-processing systems; and comparable task modulation effect on connectivity. Limitations: Our study did not include longitudinal neuroimaging data, and there was limited region of interest selection in the DCM analysis. Conclusion: Our findings provide evidence for a complex pattern of alterations in the face-processing systems in patients with MDD, potentially involving the right amygdala to a greater extent. The results confirm some previous findings and highlight the crucial role of the regions on both sides of face-processing systems in the pathophysiology of MDD., Introduction Major depressive disorder (MDD) is one of the most severe and prevalent mental illnesses, with significantly impaired social functioning. (1-3) The processing of emotional human faces plays a vital [...]

Background: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD), but substantial heterogeneity in outcomes remains. We examined a potential mechanism of action of rTMS to normalize individual variability in resting-state functional connectivity (rs-fc) before and after a course of treatment. Methods: Variability in rs-fc was examined in healthy controls (baseline) and individuals with MDD (baseline and after 4-6 weeks of rTMS). Seed-based connectivity was calculated to 4 regions associated with MDD: left dorsolateral prefrontal cortex (DLPFC), right subgenual anterior cingulate cortex (sgACC), bilateral insula, and bilateral precuneus. Individual variability was quantified for each region by calculating the mean correlational distance of connectivity maps relative to the healthy controls; a higher variability score indicated a more atypical/idiosyncratic connectivity pattern. Results: We included data from 66 healthy controls and 252 individuals with MDD in our analyses. Patients with MDD did not show significant differences in baseline variability of rs-fc compared with controls. Treatment with rTMS increased rs-fc variability from the right sgACC and precuneus, but the increased variability was not associated with clinical outcomes. Interestingly, higher baseline variability of the right sgACC was significantly associated with less clinical improvement (p = 0.037, uncorrected; did not survive false discovery rate correction). Limitations: The linear model was constructed separately for each region of interest. Conclusion: This was, to our knowledge, the first study to examine individual variability of rs-fc related to rTMS in individuals with MDD. In contrast to our hypotheses, we found that rTMS increased the individual variability of rs-fc. Our results suggest that individual variability of the right sgACC and bilateral precuneus connectivity may be a potential mechanism of rTMS., Introduction Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (DLPFC) is an effective treatment for major depressive disorder (MDD). (1,2) It can alter connectivity of networks, including the [...]

In the modern history of medicine, some of the most lifesaving advances have come from the field of critical care medicine. Current medical knowledge and technology have transformed it into [...]

Despite advances in psychotropic agents, treatment-resistant psychotic symptoms remain surprisingly prevalent in schizophrenia spectrum disorders. Deep brain stimulation (DBS) could be an attractive option in terms of effectiveness, although more [...]

In humans, sleep is divided into nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. (1) The non-REM sleep consists of 3 stages (N1-N3), with N1 and N2 [...]

Suicidal thoughts and behaviors (STBs) are among the most dreaded complications of treatment-resistant depression (TRD), which is associated with elevated risk of death from suicide as well as from other [...]

In February 2023, I gave my presidential address for the Association for Academic Surgery. (1) I did something scary. I told the truth. I began my speech like this: 'Yes, [...]

According to new data from the US Centers for Disease Control and Prevention, the suicide rate in the United States recently reached its highest peak since 1941. The Provisional number [...]

The pathophysiology of schizophrenia and bipolar disorder involves a complex interaction between genetic and environmental factors that begins in the early stages of neurodevelopment. Recent advancements in the field of induced pluripotent stem cells (iPSCs) offer a promising tool for understanding the neurobiological alterations involved in these disorders and, potentially, for developing new treatment options. In this review, we summarize the results of iPSC-based research on schizophrenia and bipolar disorder, showing disturbances in neurodevelopmental processes, imbalance in glutamatergic-GABAergic transmission and neuromorphological alterations. The limitations of the reviewed literature are also highlighted, particularly the methodological heterogeneity of the studies, the limited number of studies developing iPSC models of both diseases simultaneously, and the lack of in-depth clinical characterization of the included samples. Further studies are needed to advance knowledge on the common and disease-specific pathophysiological features of schizophrenia and bipolar disorder and to promote the development of new treatment options., Introduction Schizophrenia and bipolar disorder are complex and challenging mental disorders, whose etiopathogenesis can be traced back to a complex interaction between genetic and environmental factors that begins at the [...]

Background: Recent reports have indicated that symptom exacerbation after a period of improvement, referred to as relapse, in early-stage psychosis could result in brain changes and poor disease outcomes. We hypothesized that substantial neuroimaging alterations may exist among patients who experience relapse in early-stage psychosis. Methods: We studied patients with psychosis within 2 years after the first psychotic event and healthy controls. We divided patients into 2 groups, namely those who did not experience relapse between disease onset and the magnetic resonance imaging (MRI) scan (no-relapse group) and those who did experience relapse between these 2 timings (relapse group). We analyzed 3003 functional connectivity estimates between 78 regions of interest (ROIs) derived from resting-state functional MRI data by adjusting for demographic and clinical confounding factors. Results: We studied 85 patients, including 54 in the relapse group and 31 in the no-relapse group, along with 94 healthy controls. We observed significant differences in 47 functional connectivity estimates between the relapse and control groups after multiple comparison corrections, whereas no differences were found between the no-relapse and control groups. Most of these pathological signatures (64%) involved the thalamus. The Jonckheere-Terpstra test indicated that all 47 functional connectivity changes had a significant cross-group progression from controls to patients in the no-relapse group to patients in the relapse group. Limitations: Longitudinal studies are needed to further validate the involvement and pathological importance of the thalamus in relapse. Conclusion: We observed pathological differences in neuronal connectivity associated with relapse in early-stage psychosis, which are more specifically associated with the thalamus. Our study implies the importance of considering neurobiological mechanisms associated with relapse in the trajectory of psychotic disorders., Introduction The trajectory of psychotic disorders after onset is heterogeneous and many patients show deteriorating courses. (1,2) One of the major determinants of poor prognosis is the occurrence of relapse, [...]

Background: The assessment of deep brain stimulation (DBS) as a therapeutic alternative for treating Alzheimer disease (AD) is ongoing. We aimed to determine the effects of intracranial self-stimulation at the medial forebrain bundle (MFB-ICSS) on spatial memory, neurodegeneration, and serum expression of microRNAs (miRNAs) in a rat model of sporadic AD created by injection of streptozotocin. We hypothesized that MFB-ICSS would reverse the behavioural effects of streptozotocin and modulate hippocampal neuronal density and serum levels of the miRNAs. Methods: We performed Morris water maze and light-dark transition tests. Levels of various proteins, specifically amyloid-[beta] precurser protein (APP), phosphorylated tau protein (pTAU), and sirtuin 1 (SIRT1), and neurodegeneration were analyzed by Western blot and Nissl staining, respectively. Serum miRNA expression was measured by reverse transcription polymerase chain reaction. Results: Male rats that received streptozotocin had increased hippocampal levels of pTAU S202/T205, APP, and SIRT1 proteins; increased neurodegeneration in the CA1, dentate gyrus (DG), and dorsal tenia tecta; and worse performance in the Morris water maze task. No differences were observed in miRNAs, except for miR-181c and miR-let-7b. After MFB-ICSS, neuronal density in the CA1 and DG regions and levels of miR-181c in streptozotocin-treated and control rats were similar. Rats that received streptozotocin and underwent MFB-ICSS also showed lower levels of miR-let-7b and better spatial learning than rats that received streptozotocin without MFB-ICSS. Limitations: The reversal by MFB-ICSS of deficits induced by streptozotocin was fairly modest. Conclusion: Spatial memory performance, hippocampal neurodegeneration, and serum levels of miR-let-7b and miR-181c were affected by MFB-ICSS under AD-like conditions. Our results validate the MFB as a potential target for DBS and lend support to the use of specific miRNAs as promising biomarkers of the effectiveness of DBS in combatting AD-associated cognitive deficits., Introduction Alzheimer disease (AD), the most prevalent aging-related neurodegenerative disease, is characterized by progressive memory loss and cognitive dysfunction in older adults. (1) Although the underlying molecular mechanisms for AD [...]

The views expressed in this editorial are those of the authors and do not necessarily reflect the position of the Canadian Medical Association or its subsidiaries, the journal's editorial board [...]

Background: Previous electroencephalography (EEG) studies have indicated altered brain oscillatory [alpha]-band activity in schizophrenia, and treatment with repetitive transcranial magnetic stimulation (rTMS) using individualized [alpha]-frequency has shown therapeutic effects. Magnetic resonance imaging-based neuronavigation methods allow stimulation of a specific cortical region and improve targeting of rTMS; therefore, we sought to study the efficacy of navigated, individual [alpha]-peak-frequency-guided rTMS ([alpha]TMS) on treatment-refractory schizophrenia. Methods: We recruited medication-refractory male patients with schizophrenia or schizoaffective disorder in this double-blind, sham-controlled study. We randomized patients to a 3-week course of either active [alpha]TMS or sham stimulation applied to the left dorsolateral prefrontal cortex (DLPFC). We assessed participants with the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Scale (CGI) at baseline and after treatment. We conducted a follow-up assessment with the PANSS 3 months after intervention. Results: We included 44 patients. After treatment, we observed a significantly lower PANSS total score (p = 0.029), PANSS general psychopathology score (p = 0.027) and PANSS 5-factor model cognitive-disorganized factor score (p = 0.011) in the [alpha]TMS group than the sham group. In addition, the CGI-Improvement score was significantly higher among those who received [alpha]TMS compared with sham stimulation (p = 0.048). Limitations: The limited number of study participants included only male patients. Depression was not formally evaluated. Conclusion: Navigated [alpha]TMS to the left DLPFC reduced total, general psychopathological, and cognitive-disorganized symptoms of schizophrenia. These results provide evidence for the therapeutic efficacy of individual [alpha]-peak-frequency-guided rTMS in treatment-refractory schizophrenia. Clinical trial registration: NCT01941251; ClinicalTrials.gov, Introduction Around 30% of patients with schizophrenia are mostly unresponsive to antipsychotic medication. (1) Treatment resistance usually refers to persistent positive symptoms, although negative and cognitive symptoms may be the [...]

All research needs ethical regulation, which is institutionalized in research ethics committees. The patient information sheet, approved by a research ethics committee, sets out what patients need to know to make an informed choice about research participation. However, guidance from research ethics committees is much less explicit about risk communication. In this commentary, the balance of risk in the patient information sheets from protocols of 2 randomized controlled trials (RCTs) of medication reduction in psychosis was compared with numbers needed to treat and harm from the literature. The patient information sheet omitted risk of excess death and incomplete recovery following relapse, and overestimated the anticipated benefits. All of these risks were demonstrated in the published results of 1 of the 2 RCTs. Quantifying and tabulating risk might improve patient information sheets., Introduction All research must be conducted within a regulatory framework. Research ethics committees (RECs) are regulatory gatekeepers that seek to ensure that research is conducted according to agreed-upon, accepted ethical [...]

Since the introduction of the first antidepressant in the 1950s, biological treatments for unipolar depressive disorders have largely focused on altering monoaminergic neurotransmission, with varying degrees of success. In the [...]

At the heart of this matter is the eye-popping and contentious difference in the results of 2 teams analyzing ostensibly the same data set, with one team reporting an estimated [...]

Outpatient civil commitment is one of those polarizing topics where many individuals are adamantly for or against legislation and where emotions are high on both sides. Advocates are often the [...]

At the 2024 American Psychiatric Association (APA) Annual Meeting, the American Association for Social Psychiatry (AASP) bestowed H. Steven Moffi c, MD, with the Abraham L. Halpern Humanitarian Award for [...]

Clozapine remains the only effective medication for treatment-resistant schizophrenia (TRS), with response rates [greater than or equal to] 40% in controlled trials, compared with < 5% for other antipsychotics, and [...]

The Wall Street Journal recently published an essay entitled, 'The Danger of Relying on Anti-Anxiety Drugs,' by Jenny Taitz, PsyD. (1) The article is gracefully written and reasonably well-informed. Taitz [...]

Aims: Aggression on psychiatric wards is a complex issue with significant consequences for both patients and healthcare providers. This study aimed to investigate the behavioural and emotional consequences of aggressive experiences on nurses working in psychiatric wards both at work and at home as well as the contribution of nurses' behaviour to the development of aggression. Methods: This research utilised the experience sampling method (ESM) to collect real-time data from nurses working in a high intensive care (HIC) unit within a mental health institution in the Netherlands. Results: The findings revealed that most nurses reported good sleep quality, feeling fit for the day and looking forward to starting their day. These reports were not significantly associated with having a workday ahead or the number of patients admitted. There was a negative association with the number of admitted patients being on or over the maximum bed capacity, although not significant. There were no statistically significant associations between the answers to the morning questionnaire and the behaviour and emotions of nurses and patients later that day nor the appearance of aggressive incidents. Experiencing an aggressive incident had no influence on the sleep of the nurse later that day, nor on their social behaviour. Conclusion: This study offers valuable insights into the daily experiences of nurses in psychiatric wards, particularly in relation to aggression. The real-time data collection by ESM allowed for a nuanced understanding of nurses' behaviours and emotions. No significant associations were found between nurses' functioning and aggressive incidents happening on the ward, but this study might have been contextually influenced so that this study mainly highlights the need for further research with larger samples and across multiple wards to draw definitive conclusions., Author(s): Irene Weltens (corresponding author) [1]; Marjan Drukker [1]; Thérèse van Amelsvoort [1]; Patrick Domen [1]; Maarten Bak [1] 1. Introduction Aggression on the psychiatric ward is a highly prevalent [...]