The Danish high-risk and resilience study—VIA 15–a study protocol for the third clinical assessment of a cohort of 522 children born to parents diagnosed with schizophrenia or …

Schizophrenia Research

BackgroundChildren of parents with severe mental illness report bullying more often compared with controls. We hypothesized that deviations in attributional styles may explain the increased prevalence of bullying experiences. We aimed to assess real-time responses to standardized ambiguous social situations, bullying experiences by children, their primary caregivers, and teachers, and to investigate potential associations between attributional styles and bullying.MethodThe study included 465 children aged 11–12, born to parents with schizophrenia, N =179, bipolar disorder, N = 105, or population-based controls, N = 181. Attributional style was evaluated using virtual reality environments depicting ambiguous social everyday situations. We created a tailored assessment since no suitable assessments were found. Bullying was assessed through self-reports and reports from primary caregivers and teachers …

Proc Int Soc Magn Reson Med

Dynamic bolus tracking MRI has been used to calculate maps of cerebral blood volume (1, 2) and, more recently, cerebral blood flow (3, 4). It has been predicted that a shorter contrast agent bolus may be advantageous for the quality of the perfusion maps (3-5). Gadobutrol, a neutral macrocyclic contrast agent, allows concentrations of 0.5 mol/l and 1.0 mol/l and therefore allows halved injection volumes at the same dose. Animal experiments showed that the arterial concentration following intravenous bolus injection of gadobutrol at the same dose was about 30% higher for the 1.0 molar concentration than for the 0.5 molar concentration (6). This supported further animal experiments which showed improved contrast between ischemic and non-ischemic brain tissue at the same dose for the 1.0 molar concentration (7).

BMC neurology

Post-stroke cognitive impairment (PSCI) is common. However, the underlying pathophysiology remains largely unknown. Understanding the role of microvascular changes and finding markers that can predict PSCI, could be a first step towards better screening and management of PSCI. Capillary dysfunction is a pathological feature of cerebral small vessel disease and may play a role in the mechanisms underlying PSCI. Extracellular vesicles (EVs) are secreted from cells and may act as disease biomarkers. We aim to investigate the role of capillary dysfunction in PSCI and the associations between EV characteristics and cognitive function one year after acute ischemic stroke (AIS) and transient ischemic attack (TIA). The ENIGMA study is a single-centre prospective clinical observational study conducted at Aarhus University Hospital, Denmark. Consecutive patients with AIS and TIA are included and followed for …

European Child & Adolescent Psychiatry

Executive functions (EF) deficits are well documented in children at familial high risk of schizophrenia (FHR-SZ), and to a lesser degree in children at familial high risk of bipolar disorder (FHR-BP). The aim of this study was to assess EF development in preadolescent children at FHR-SZ, FHR-BP and population-based controls (PBC) using a multi-informant rating scale. A total of 519 children (FHR-SZ, n = 201; FHR-BP, n = 119; PBC, n = 199) participated at age 7, at age 11 or at both time points. Caregivers and teachers completed the Behavior Rating Inventory of Executive Functions (BRIEF). The developmental pattern from age 7 to age 11, did not differ between groups. At age 11, caregivers and teachers rated children at FHR-SZ as having widespread EF deficits. A higher proportion of children at FHR-SZ had clinically significant scores on the General executive composite (GEC) and all BRIEF indices …

Journal of Bone and Mineral Research

Hypoparathyroidism (HypoPT) is a disease with no/or inadequate production/secretion of parathyroid hormone (PTH) from the parathyroid glands. Low levels of PTH result in hypocalcemia, which is often treated with calcium supplementation and active vitamin-D analogs. However, increasing evidence suggests that HypoPT has a profound impact on several organ systems. Quality of life (QOL) is reduced in patients with HypoPT, partly due to symptoms related to the central nervous system—including subjective feelings of confusion, a reduced ability to focus and think clearly(i.e., “brain fog”). However, the extent to which these complex symptoms relate to quantifiable changes in patients’ cognitive performance as determined by neuropsychological tests remains unclear. The brains of HypoPT patients may reveal tissue calcifications, but the extent to which long-term brain exposure to low PTH levels and/or …

Cognitive Modelling of the Intra-Extra Dimensional Set Shift Task in Children at Familial High Risk of Schizophrenia or Bipolar Disorder — Aarhus University Skip to main navigation Skip to search Skip to main content Aarhus University Home Aarhus University Logo Help & FAQ English Dansk Home Profiles Research units Projects Research output Prizes Activities Courses Press/Media Search by expertise, name or affiliation Cognitive Modelling of the Intra-Extra Dimensional Set Shift Task in Children at Familial High Risk of Schizophrenia or Bipolar Disorder Arndis Simonsen * , Oskar Hougaard Jefsen, Nicoline Hemager, Ditte Lou Langhoff Gantriis, Birgitte Klee Burton, Ditte Ellersgaard, Kerstin Jessica Plessen, Anne AE Thorup, Jens Richardt Møllegaard Jepsen, Merete Nordentoft, Ole Mors, Aja Neergaard Greve, Riccardo Fusaroli * Corresponding author for this work Department of Clinical Medicine - Psychosis …

Communications Biology

Mitochondria are the main suppliers of energy for cells and their bioenergetic function is regulated by mitochondrial dynamics: the constant changes in mitochondria size, shape, and cristae morphology to secure cell homeostasis. Although changes in mitochondrial function are implicated in a wide range of diseases, our understanding is challenged by a lack of reliable ways to extract spatial features from the cristae, the detailed visualization of which requires electron microscopy (EM). Here, we present a semi-automatic method for the segmentation, 3D reconstruction, and shape analysis of mitochondria, cristae, and intracristal spaces based on 2D EM images of the murine hippocampus. We show that our method provides a more accurate characterization of mitochondrial ultrastructure in 3D than common 2D approaches and propose an operational index of mitochondria’s internal organization. With an improved …

Journal of Neuropsychology

The pathophysiological development of Alzheimer's disease (AD) begins in the brain years before the onset of clinical symptoms. The accumulation of beta‐amyloid (Aβ) is thought to be the first cortical pathology to occur. Carrying one apolipoprotein E (APOE) ε4 allele increases the risk of developing AD at least 2–3 times and is associated with earlier Aβ accumulation. Although it is difficult to identify Aβ‐related cognitive impairment in early AD with standard cognitive tests, more sensitive memory tests may be able to do this. We sought to examine associations between Aβ and performance on three tests within three subdomains of memory, verbal, visual, and associative memory, to elucidate which of these tests were sensitive to Aβ‐related cognitive impairment in at‐risk subjects. 55 APOE ε4 carriers underwent MRI, 11C‐Pittsburgh Compound B (PiB) PET, and cognitive testing. A composite cortical PiB SUVR cut …

Cognitive Modelling of the Intra-Extra Dimensional Set Shift Task in Children at Familial High Risk of Schizophrenia or Bipolar Disorder — Aarhus University Skip to main navigation Skip to search Skip to main content Aarhus University Home Aarhus University Logo Help & FAQ English Dansk Home Profiles Research units Projects Research output Prizes Activities Courses Press/Media Search by expertise, name or affiliation Cognitive Modelling of the Intra-Extra Dimensional Set Shift Task in Children at Familial High Risk of Schizophrenia or Bipolar Disorder Arndis Simonsen * , Oskar Hougaard Jefsen, Nicoline Hemager, Ditte Lou Langhoff Gantriis, Birgitte Klee Burton, Ditte Ellersgaard, Kerstin Jessica Plessen, Anne AE Thorup, Jens Richardt Møllegaard Jepsen, Merete Nordentoft, Ole Mors, Aja Neergaard Greve, Riccardo Fusaroli * Corresponding author for this work Department of Clinical Medicine - Psychosis …

Alzheimer's & Dementia

INTRODUCTION Capillary dysfunction, characterized by disturbances in capillary blood flow distribution, might be an overlooked factor in the development of Alzheimer's disease (AD). This study investigated microvascular blood flow in preclinical and prodromal AD individuals. METHODS Using dynamic susceptibility contrast magnetic resonance imaging and positron emission tomography, we examined alterations in microvascular circulation and levels of Aβ deposition in two independent cohorts of APOE ε4 carriers. RESULTS Capillary dysfunction was elevated in both prodromal and preclinical AD individuals compared to age‐matched controls. Additionally, the prodromal group exhibited higher levels of capillary dysfunction compared to the preclinical group. DISCUSSION These findings suggest that capillary dysfunction can be detected at the preclinical stage of AD and indicates a worsening of capillary …

Psychiatry Research

In bipolar disorder, dysregulation of affect is a core feature while knowledge on affective lability in schizophrenia is sparse. Research on affective lability in partners to individuals with schizophrenia or bipolar disorder is also lacking. The objective of this study was to investigate affective lability in parents with schizophrenia or bipolar disorder, and their co-parents without these disorders. The Danish High Risk and Resilience Study – VIA 7 is a population-based cohort study. This study focuses on parents diagnosed with schizophrenia (n = 148), their co-parents (n = 157), parents with bipolar disorder (n = 98), their co-parents (n = 89) and control parents (n = 359). The Affective Lability Scale – short form (ALS-SF) was used to measure affective lability. We found significantly higher levels of affective lability in parents with schizophrenia and bipolar disorder compared with controls, but no significant differences between …

Journal of Affective Disorders

BackgroundDespite the genetic overlap between bipolar disorder and schizophrenia, working memory impairments are mainly found in children of parents with schizophrenia. However, working memory impairments are characterized by substantial heterogeneity, and it is unknown how this heterogeneity develops over time. We used a data-driven approach to assess working memory heterogeneity and longitudinal stability in children at familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP).MethodsBased on the performances on four working memory tasks by 319 children (FHR-SZ, N = 202, FHR-BP, N = 118) measured at age 7 and 11, latent profile transition analysis was used to test for the presence of subgroups, and the stability of subgroup membership over time. Population-based controls (VIA 7, N = 200, VIA 11, N = 173) were included as a reference group. The working memory subgroups …

NeuroImage

IntroductionFunctional MRI with spatial resolution in the submillimeter domain enables measurements of activation across cortical layers in humans. This is valuable as different types of cortical computations, e.g., feedforward versus feedback related activity, take place in different cortical layers. Laminar fMRI studies have almost exclusively employed 7T scanners to overcome the reduced signal stability associated with small voxels. However, such systems are relatively rare and only a subset of those are clinically approved. In the present study, we examined if the feasibility of laminar fMRI at 3T could be improved by use of NORDIC denoising and phase regression.Methods5 healthy subjects were scanned on a Siemens MAGNETOM Prisma 3T scanner. To assess across-session reliability, each subject was scanned in 3–8 sessions on 3–4 consecutive days. A 3D gradient echo EPI (GE-EPI) sequence was used …

Biological psychiatry

BackgroundEducation is essential for socioeconomic security and long-term mental health; however, mental disorders are often detrimental to the educational trajectory. Genetic correlations between mental disorders and educational attainment do not always align with corresponding phenotypic associations, implying heterogeneity in the genetic overlap.MethodsWe unraveled this heterogeneity by investigating associations between polygenic risk scores for 6 mental disorders and fine-grained school outcomes: school grades in language and mathematics in ninth grade and high school, as well as educational attainment by age 25, using nationwide-representative data from established cohorts (N = 79,489).ResultsHigh polygenic liability of attention-deficit/hyperactivity disorder was associated with lower grades in language and mathematics, whereas high polygenic risk of anorexia nervosa or bipolar disorder was …

Journal of Clinical Psychopharmacology

BackgroundBipolar disorder and attention-deficit/hyperactivity disorder are common comorbidities. Attention-deficit/hyperactivity disorder is commonly treated with stimulants (eg, methylphenidate), which, however, have been suggested to cause treatment-emergent mania in patients with bipolar disorder. Here, we assessed the risk of mania, depressive episodes, and psychiatric admissions after initiation of methylphenidate treatment in patients with bipolar disorder.MethodsUsing Danish health registries, we identified all individuals registered with a diagnosis of bipolar disorder from January 1, 2000, to January 1, 2018, who were treated with methylphenidate. We applied a 1-year mirror-image model to compare the occurrence of mania, depression, and psychiatric admissions in the period leading up to and after methylphenidate treatment initiation. We furthermore assessed the trend in these outcomes from 4 …

Schizophrenia Bulletin

Background and Hypotheses Impaired executive control is a potential prognostic and endophenotypic marker of schizophrenia (SZ) and bipolar disorder (BP). Assessing children with familial high-risk (FHR) of SZ or BP enables characterization of early risk markers and we hypothesize that they express impaired executive control as well as aberrant brain activation compared to population-based control (PBC) children. Study Design Using a flanker task, we examined executive control together with functional magnetic resonance imaging (fMRI) in 11- to 12-year-old children with FHR of SZ (FHR-SZ) or FHR of BP (FHR-BP) and PBC children as part of a register-based, prospective cohort-study; The Danish High Risk and Resilience study—VIA 11. Study Results We included 85 (44% female) FHR-SZ, 63 (52% female) FHR-BP and 98 (50% female) PBC in …

Neurobiology of Aging

Alterations in cerebral perfusion is increasingly considered to play a crucial role in Alzheimer's disease (AD) and together with accumulated amyloid-β, deficiencies in the brain microvascular circulation may result in local hypoxia. Here, we studied alterations in cerebral circulation and the correlation between amyloid-β load and cerebral perfusion in prodromal AD (pAD). Using dynamic susceptibility contrast MRI and PET, we evaluated cerebral perfusion and amyloid-β levels in 19 individuals with mild cognitive impairment (MCI) and high amyloid-β load (pAD-MCI), 13 MCI individuals without AD pathology and 21 healthy controls. The pAD-MCI group showed significantly lower microvascular blood flow and significantly higher heterogeneity of microvascular blood transit times (p < 0.01) compared with the other 2 groups. Additionally, in the pAD-MCI group raised amyloid-β levels correlated with decreased …

3D mitochondrial ultrastructure using volume electron microscopy — Aarhus University Skip to main navigation Skip to search Skip to main content Aarhus University Home Aarhus University Logo Help & FAQ English Dansk Home Profiles Research units Projects Research output Prizes Activities Courses Press/Media Search by expertise, name or affiliation 3D mitochondrial ultrastructure using volume electron microscopy Chenhao Wang, Leif Østergaard, Stine Hasselholt, Jon Sporring Department of Clinical Medicine - Center of Functionally Integrative Neuroscience Research output: Contribution to conference › Conference abstract for conference › Research › peer-review Overview Original language English Publication date 31 Oct 2023 Publication status Published - 31 Oct 2023 Event 6th Annual Research Meeting at the Department of Clinical Medicine - Aarhus Universitetshospital, Aarhus N, Denmark Duration: …

The Lancet Psychiatry

BackgroundMotor abnormalities have clinical relevance as a component of psychotic illness; they are not only a proxy of altered neurodevelopment, but also intimately related to psychotic risk. We aimed to assess motor development and its association with psychotic experiences in children with familial high risk (FHR) of schizophrenia or bipolar disorder compared with controls.MethodsThe Danish High Risk and Resilience Study is a prospective longitudinal cohort study, for which participants were extracted from Danish registers. Children born in Denmark between Sept 1, 2004, and Aug 31, 2009, with no, one, or two parents born in Denmark with schizophrenia or bipolar disorder, could be included in the study. No ethnicity data were collected. Children with no biological parent diagnosed with schizophrenia spectrum disorder or bipolar disorder were matched to children with FHR of schizophrenia (one or two …

Psychological Medicine

Background Sex differences in brain structure and neurodevelopment occur in non-clinical populations. We investigated whether sex had a similar effect on developmental domains amongst boys and girls with a familial risk of schizophrenia (FHR-SZ), bipolar disorder (FHR-BP), and controls. Methods Through Danish registries, we identified 522 7-year-old children (242 girls) with FHR-SZ, FHR-BP, and controls. We assessed their performance within the domains of neurocognition, motor function, language, social cognition, social behavior, psychopathology, and home environment. Results FHR-SZ boys compared with FHR-SZ girls had a higher proportion of disruptive behavior and attention-deficit hyperactivity disorder (ADHD) and exhibited lower performance in manual dexterity, balance, and emotion recognition. No sex differences were found between boys and girls within FHR-BP group. Compared with …

Frontiers in Psychiatry

Introduction Studies have consistently demonstrated increased stress sensitivity in individuals with psychosis. Since stress sensitivity may play a role in the onset and maintenance of psychosis, this could potentially be a promising target for treatment. The current study was the first to investigate whether reactivity to and recovery from daily-life stressors in psychosis change in response to treatment, namely virtual-reality-based cognitive behavioral therapy (VR-CBT). Methods 116 patients were randomized to either VR-CBT or the waiting list control group (WL). Pre-treatment and post-treatment participants completed a diary ten times a day during six to ten days. Multilevel analyses were used to model the time-lagged effects of daily stressful events on negative affect (NA) and paranoia symptoms to examine reactivity and recovery. Results There was a significant difference in NA reactivity. VR-CBT showed higher NA at post-treatment compared to pre-treatment than WL (bpre=0.14; bpost=0.19 vs bpre=0.18; bpost=0.14). There was a significant difference in NA recovery and paranoia recovery between the groups at lag 1: VR-CBT showed relatively lower negative affect (bpre=0.07; bpost=-0.06) and paranoia (bpre= 0.08; bpost=-0.10) at post-treatment compared to pre-treatment than WL (bpre=0.08; bpost=0.08; bpre=0.04; bpost=0.03). Conclusion Negative affect and paranoia recovery improved in response to treatment. Increased NA reactivity may be explained by a decrease in safety behavior in the VR-CBT group. The discrepancy between reactivity and recovery findings may be explained by the inhibitory learning theory that suggests that an …

Frontiers in psychiatry

Introduction Treatment-resistant depression (TRD) is commonly defined as the failure of at least two trials with antidepressant drugs, given at the right dose and for an appropriate duration. TRD is associated with increased mortality, compared to patients with a simple major depressive episode. This increased rate was mainly attributed to death from external causes, including suicide and accidents. The aim of our study is to identify socio-demographic and psychopathological variables associated with suicidal attempts in a sample of outpatients with TRD. Material and methods We performed a monocentric observational study with a retrospective design including a sample of 63 subjects with TRD referred to an Italian outpatient mental health centre. We collected socio-demographic and psychopathological data from interviews and clinical records. Results 77.8% of the sample (N=49) were females, the mean age was 49.2 (15.9). 33.3% (N=21) of patients had attempted suicide. 54% (N=34) of patients had a psychiatric comorbidity. Among the collected variables, substance use (p=0.031), psychiatric comorbidities (p=0.049) and high scores of HAM-D (p=0.011) were associated with the occurrence of suicide attempts. In the regression model, substance use (OR 6.779), psychiatric comorbidities (OR 3.788) and HAM-D scores (OR 1.057) were predictive of suicide attempts. When controlling for gender, only substance use (OR 6.114) and HAM-D scores (OR 1.057) maintained association with suicide attempts. Conclusion The integrated treatment of comorbidities and substance abuse, which involves different mental health services, is fundamental …

Frontiers in Psychiatry

IntroductionPeople living with type 2 diabetes who experience homelessness face a myriad of barriers to engaging in diabetes self-care behaviors that lead to premature complications and death. This is exacerbated by high rates of comorbid mental illness, substance use disorder, and other physical health problems. Despite strong evidence to support lay health coach and behavioral activation, little research has effectively engaged people living with type 2 diabetes who had experienced homelessness (DH).MethodsWe used community engaged research and incremental behavioral treatment development to design the Diabetes HOmeless MEdication Support (D-HOMES) program, a one-on-one, 3 month, coaching intervention to improve medication adherence and psychological wellness for DH. We present results of our pilot randomized trial (with baseline, 3 mo., 6 mo. assessments) comparing D-HOMES to enhanced usual care (EUC; brief diabetes education session and routine care; NCT05258630). Participants were English-speaking adults with type 2 diabetes, current/recent (<24 mo.) homelessness, and an HbA1c‗7.5%. We focused on feasibility (recruitment, retention, engagement) and acceptability (Client Satisfaction Questionnaire, CSQ-8). Our primary clinical outcome was glycemic control (HbA1c) and primary behavioral outcome was medication adherence. Secondary outcomes included psychological wellness and diabetes self-care.ResultsThirty-six eligible participants enrolled, 18 in each arm. Most participants identified as Black males, had high rates of co-morbidities, and lived in subsidized housing. We retained 100% of …

Frontiers in Psychiatry

Suspected adverse drug reactions (ADRs) during treatment with clozapine often prompt therapeutic drug monitoring (TDM) in clinical practice. Currently, there is no official recommendation for pharmacogenetic (PGx) testing in the context of clozapine therapy. In this case report, we demonstrate and discuss the challenges of interpreting PGx and TDM results highlighting the possibilities and limitations of both analytical methods. A 36-year-old male patient with catatonic schizophrenia was treated with clozapine. He experienced multiple hospitalizations due to elevated creatine kinase (CK) levels (up to 9000 U/L, reference range: 30-200 U/L). With no other medical explanation found, physicians suspected clozapine-induced ADRs. However, plasma levels of clozapine were consistently low or subtherapeutic upon admission, prompting us to conduct a PGx analysis and retrospectively review the patient’s TDM data, progress notes, and discharge reports. We investigated two possible hypotheses to explain the symptoms despite low clozapine plasma levels: Hypothesis i. suggested the formation and accumulation of a reactive intermediate metabolite due to increased activity in cytochrome P450 3A5 and reduced activity in glutathione S-transferases 1, leading to myotoxicity. Hypothesis ii. proposed under-treatment with clozapine, resulting in ineffective clozapine levels, leading to a rebound effect with increased catatonic symptoms and CK levels. After considering both data sources (PGx and TDM), hypothesis ii. appeared more plausible. By comprehensively assessing all available TDM measurements and examining them in temporal correlation …

Frontiers in Psychiatry

Introduction Societal perceptions and lack of understanding of autism spectrum disorder can be stigmatizing for autistic individuals and their families. This may be particularly the case for individuals who meet criteria for profound autism. Despite the considerable service needs of this marginalized group, there is little data on the prevalence of profound autism, nor on the experiences of those with profound autism and their families. Methods The current study leveraged a mixed-methods approach to address these gaps. First, the prevalence of profound autism was examined in six samples—three from the United States and three from Western Europe. Second, inductive thematic analysis was used to code interviews from 20 caregivers of profoundly autistic adults. Results The prevalence of profound autism varied widely across the six samples—from 11% to 48%. There were also notable differences between samples in prevalence by gender, race, and ethnicity. Two overarching themes were identified via inductive thematic analysis: Community Perceptions of Autism and Family Support Needs and Advocacy Challenges. Though caregivers were not directly asked about stigmatization during interviews, 85% of caregivers reported at least one instance of perceived stigma. Discussion Future research should continue to examine the unique needs and stigmatization experiences of profoundly autistic individuals and their families across the life course.

Frontiers in Psychiatry

Psychometric properties in psychiatric measurement tools are designed to quantify human characteristics and enhance our understanding of complex behaviors, particularly in adolescent and young adult population (1). Adolescence is a period of turmoil, characterized not only by biological changes but also by evolving psychosocial competencies. The prefrontal cortex, which continues to develop during this time, influences rational decision-making. Concurrently, adolescents struggle to adapt to environmental challenges, notably in forming their identities. Moreover, during this critical period, adolescents intensely seek understanding and acceptance from their peers and environment. Consequently, they may experience feelings of inferiority, inadequate self-esteem, and a lack of self-confidence (2, 3). These conditions can affect adolescents’ mental health literacy, communication styles, and interpersonal relationships, including those with mental healthcare professionals. Therefore, psychiatric measurement tools for the adolescent and young adult population are invaluable for clinical purposes—such as early detection, identification, quantification of the severity of mental health problems/disorders and setting therapeutic goals—as well as for research.It is estimated that adolescents comprise approximately 16% of the global population, with 89% residing in low-and middle-income countries (LMICs)(4). Mental health problems and disorders are estimated to affect 10–20% of adolescents and young adults globally, accounting for approximately 13% of the global burden of disease in this age group (5). Behavioural and emotional problems, such …

Frontiers in Psychiatry

BackgroundCatatonia presents itself as a complex neuropsychiatric syndrome, giving rise to various motor, speech, and behavioral challenges. It is noteworthy that approximately 10% of psychiatric hospital admissions can be attributed to this condition. It is imperative to note that cannabis-induced catatonia, while infrequent, has been linked to the use of marijuana. This connection has the potential to disrupt neurotransmitter systems, necessitating further research for a comprehensive understanding and effective treatment, particularly given the evolving trends in cannabis use. In this context, we shall delve into a unique case of recurrent cannabis-induced catatonia.Case presentationA 23-year-old gentleman, who has previously struggled with substance use disorder, experienced the emergence of mutism, social isolation, and a fixed gaze subsequent to his use of cannabis. Remarkably, despite the absence of hallucinations, he exhibited recurrent episodes of catatonia. These episodes were effectively addressed through a combination of electroconvulsive therapy (ECT) and lorazepam administration. Notably, when the lorazepam dosage was gradually reduced to below 2 mg per day, the catatonic symptoms resurfaced; however, they promptly abated upon reinstating the medication. The diagnosis of cannabis-induced catatonia was established, and its management primarily involved a therapeutic approach encompassing ECT and lorazepam. It is pertinent to underscore that this catatonic condition can be directly linked to the individual’s cannabis usage.ConclusionThe connection between cannabis and catatonia is intricate and not entirely …

Frontiers in Psychiatry

Introduction The characteristic behaviors we use to define personality pathology arise from specific interpersonal interactions. In an effort to create a laboratory-based context in which behavior might be expected to be influenced by particular personality traits, we used four 2-person, 2-choice games (the Prisoner’s Dilemma, Chicken, Leader, and Hero games) to create a simulated interaction and focused specifically on narcissism and dependency. Method An online sample of 1137 (35% male, M age = 38.46 years, SD age = 13.20) participants completed brief, self-reported measures of trait narcissism and dependency and played one of the four games. Before deciding how to act or react, participants received either no message, a promise to cooperate, or a threat to defect from a (confederate) partner. Results When receiving no message, those who cooperated in the Prisoner’s Dilemma had lower trait narcissism, while those who defected in the Chicken and Leader games had higher trait narcissism. Also with no message, participants who cooperated in the Hero game had higher trait dependency. Promises only affected the relationship between trait narcissism in the Leader game while threats only affected the relationship between trait dependency in the Chicken game. Discussion These findings add to the limited behavioral research on personality pathology and largely support established interpersonal conceptualizations and models. Future work might extend these findings using even more ecologically valid approaches to explore the behavioral correlates of personality traits that have important implications for interpersonal …

Frontiers in Psychiatry

Neurodevelopmental disorders (NDDs) are a class of pathologies arising from perturbations in brain circuit formation and maturation with complex etiological triggers often classified as environmental and genetic. Neuropsychiatric conditions such as autism spectrum disorders (ASD), intellectual disability (ID), and attention deficit hyperactivity disorders (ADHD) are common NDDs characterized by their hereditary underpinnings and inherent heterogeneity. Genetic risk factors for NDDs are increasingly being identified in non-coding regions and proteins bound to them, including transcriptional regulators and chromatin remodelers. Importantly, de novo mutations are emerging as important contributors to NDDs and neuropsychiatric disorders. Recently, de novo mutations in transcriptional co-factor Zmiz1 or its regulatory regions have been identified in unrelated patients with syndromic ID and ASD. However, the role of Zmiz1 in brain development is unknown. Here, using publicly available databases and a Zmiz1 mutant mouse model, we reveal that Zmiz1 is highly expressed during embryonic brain development in mice and humans, and though broadly expressed across the brain, Zmiz1 is enriched in areas prominently impacted in ID and ASD such as cortex, hippocampus, and cerebellum. We investigated the relationship between Zmiz1 structure and pathogenicity of protein variants, the epigenetic marks associated with Zmiz1 regulation, and protein interactions and signaling pathways regulated by Zmiz1. Our analysis reveals that Zmiz1 regulates multiple developmental processes, including neurogenesis, neuron connectivity, and synaptic …

Frontiers in Psychiatry

“Results: For both modalities, the NPV related to degree of improvement at t10. NPV for 10 Hz was 80%, 63% and 46% at t10 in those who failed to improve> 20,> 10, and> 0% respectively; while iTBS NPV rates were 65, 50, and 35%. There were not significant differences between protocols at any t10 cut-off assessed, whether research defined 50% improvement as response or data driven kernel density estimates (p= 0.22–0.44).”

Frontiers in Psychiatry

BackgroundFrontline staff in psychiatry need to perform at a very high professional level in order to ensure patient and community safety. At the same time they are exposed to high levels of stress and workplace trauma. This may have severe consequences for their professional quality of life. In addition, health care workers in general have higher incidence levels of childhood adversity than the general population. The CRITIC (CRITical Incidents and aggression in Caregivers) Study aims to improve increased understanding of the interaction between personal life history (childhood adversity and benevolence), individual capabilities, exposure to trauma and violence at work and Professional Quality of Life (ProQOL).MethodThe Critic Study is a cross-sectional survey of these aspects in frontline, treatment and administrative staff in clinical and forensic psychiatry. We aim to include 360 participants. Participants will be asked to complete questionnaires on childhood adversity and childhood benevolence (assessing personal life history), professional quality of life, current trauma and violence exposure, current mental health (depression, anxiety and stress), coping, social support, work engagement and resilience. In this study we will examine the moderating role of adverse and benevolent childhood experiences in the association between workplace trauma exposure and professional quality of life. Finally, a theoretical model on the relationships between trauma, stress and coping in the context of professional functioning will be tested using structural equation modelling.DiscussionThe CRITIC study examines which factors influence the complex …

Frontiers in Psychiatry

IntroductionThe precise epidemiological burden of autism is unknown because of the limited capacity to identify and diagnose the disorder in resource-constrained settings, related in part to a lack of appropriate standardised assessment tools and health care experts. We assessed the reliability, validity, and diagnostic accuracy of the Developmental Diagnostic Dimensional Interview (3Di) in a rural setting on the Kenyan coast.MethodsUsing a large community survey of neurodevelopmental disorders (NDDs), we administered the 3Di to 2,110 children aged between 6 years and 9 years who screened positive or negative for any NDD and selected 242 who had specific symptoms suggestive of autism based on parental report and the screening tools for review by a child and adolescent psychiatrist. On the basis of recorded video, a multi-disciplinary team applied the Autism Diagnostic Observation Schedule to establish an autism diagnosis. Internal consistency was used to examine the reliability of the Swahili version of the 3Di, tetrachoric correlations to determine criterion validity, structural equation modelling to evaluate factorial structure and receiver operating characteristic analysis to calculate diagnostic accuracy against Diagnostic Statistical Manual of Mental Disorders (DSM) diagnosis.ResultsThe reliability coefficients for 3Di were excellent for the entire scale {McDonald’s omega (ω) = 0.83 [95% confidence interval (CI) 0.79–0.91]}. A higher-order three-factor DSM-IV-TR model showed an adequate fit with the model, improving greatly after retaining high-loading items and correlated items. A higher-order two-factor DSM-5 model also showed …

Frontiers in Psychiatry

BackgroundAnhedonia, a core diagnostic feature for major depressive disorder (MDD), is defined as the loss of pleasure and interest in daily activities. Its prevalence in MDD patients vary from 35 to 70%. Anhedonia in MDD negatively impacts functioning and is associated with treatment resistance and poorer prognosis for various clinical outcomes. Owing to its complexity, there remains considerable heterogeneity in the conceptualization, diagnosis and clinical management of anhedonia in MDD.MethodsThis modified Delphi panel was conducted to elicit expert opinion and establish consensus on concepts relating to clinical features, diagnosis and treatment of MDD with anhedonia (MDDwA) amongst psychiatrists in the Asia-Pacific region. Seven themes were covered. A three-stage process was adopted for consensus generation (two online survey rounds, followed by a moderated consensus meeting). Statements were developed based on a literature review and input from a steering committee of six regional experts. The panel included 12 psychiatrists practicing in Australia, China, Hong Kong, Japan, South Korea and Taiwan with ≥5 years of specialist clinical experience, including assessment or management of patients with MDDwA.ResultsOverall, consensus was achieved (median ≥8) on 89/103 statements (86%). About half of the statements (55/103, 53%) achieved consensus in Round 1, and 29/36 modified statements achieved consensus in Round 2. At the moderated consensus meeting, five modified statements were discussed by the steering committee and consensus was achieved on all statements (5/5). The findings highlighted …

Frontiers in Psychiatry

Background To date, few randomized controlled trials of psilocybin with non-directive support exist for obsessive-compulsive disorder (OCD). Results and participant feedback from an interim analysis of an ongoing single-dose trial (NCT03356483) converged on the possibility of administering a higher fixed dose and/or more doses of psilocybin in future trials for presumably greater benefits. Objectives This trial aims to evaluate the safety, feasibility, tolerability, and clinical effects of two doses of psilocybin paired with non-directive support in the treatment of OCD. This trial also seeks to examine whether two doses of psilocybin lead to greater OCD symptom reduction than a single dose, and to elucidate psychological mechanisms underlying the effects of psilocybin on OCD. Design A randomized (1:1), waitlist-controlled design with blinded ratings will be used to examine the effects of two doses of oral psilocybin paired with non-directive support vs. waitlist control on OCD symptoms. An adaptive dose selection strategy will be implemented (i.e., first dose: 25 mg; second dose: 25 or 30 mg). Methods and analysis This single-site trial will enroll 30 adult participants with treatment-refractory OCD. Aside from safety, feasibility, and tolerability metrics, primary outcomes include OCD symptoms assessed on the Yale-Brown Obsessive-Compulsive Scale – Second Edition (Y-BOCS-II). A blinded independent rater will assess primary outcomes at baseline and the primary endpoint at the end of the second dosing week. Participants will be followed up to 12 months post-second dosing. Participants randomized to waitlist will be rescreened after 7 …

Frontiers in Psychiatry

Background Attention deficit hyperactivity disorder (ADHD) is characterized by impairments in developmental–behavioral inhibition, resulting in impulsivity and hyperactivity. Recent research has underscored cortical inhibition deficiencies in ADHD via the gamma-aminobutyric acid (GABA)ergic system, which is crucial for maintaining excitatory–inhibitory balance in the brain. This study explored postnatal changes in parvalbumin (PV) immunoreactivity, indicating GABAergic interneuron types, in the prefrontal (PFC) and motor (MC) cortices of spontaneously hypertensive rats (SHRs), an ADHD animal model. Methods Examining PV- positive (PV+) cells associated with dopamine D2 receptors (D2) and the impact of dopamine on GABA synthesis, we also investigated changes in the immunoreactivity of D2 and tyrosine hydroxylase (TH). Brain sections from 4- to 10-week-old SHRs and Wistar Kyoto rats (WKYs) were immunohistochemically analyzed, comparing PV+, D2+ cells, and TH+ fiber densities across age-matched SHRs and WKYs in specific PFC/MC regions. Results The results revealed significantly reduced PV+ cell density in SHRs: prelimbic (~20% less), anterior cingulate (~15% less), primary (~15% less), and secondary motor (~17% less) cortices. PV+ deficits coincided with the upregulation of D2 in prepubertal SHRs and the downregulation of TH predominantly in pubertal/postpubertal SHRs. Conclusion Reduced PV+ cells in various PFC regions could contribute to inattention/behavioral alterations in ADHD, while MC deficits could manifest as motor hyperactivity. D2 upregulation and TH deficits may impact GABA synthesis …

Frontiers in Psychiatry

Background Post-traumatic stress disorder (PTSD) and substance use (tobacco, alcohol, and cannabis) are highly comorbid. Many factors affect this relationship, including sociodemographic and psychosocial characteristics, other prior traumas, and physical health. However, few prior studies have investigated this prospectively, examining new substance use and the extent to which a wide range of factors may modify the relationship to PTSD. Methods The Advancing Understanding of RecOvery afteR traumA (AURORA) study is a prospective cohort of adults presenting at emergency departments (N = 2,943). Participants self-reported PTSD symptoms and the frequency and quantity of tobacco, alcohol, and cannabis use at six total timepoints. We assessed the associations of PTSD and future substance use, lagged by one timepoint, using the Poisson generalized estimating equations. We also stratified by incident and prevalent substance use and generated causal forests to identify the most important effect modifiers of this relationship out of 128 potential variables. Results At baseline, 37.3% (N = 1,099) of participants reported likely PTSD. PTSD was associated with tobacco frequency (incidence rate ratio (IRR): 1.003, 95% CI: 1.00, 1.01, p = 0.02) and quantity (IRR: 1.01, 95% CI: 1.001, 1.01, p = 0.01), and alcohol frequency (IRR: 1.002, 95% CI: 1.00, 1.004, p = 0.03) and quantity (IRR: 1.003, 95% CI: 1.001, 1.01, p = 0.001), but not with cannabis use. There were slight differences in incident compared to prevalent tobacco frequency and quantity of use; prevalent tobacco frequency and quantity were associated with PTSD symptoms, while …

Frontiers in Psychiatry

Background People living with HIV (PLWHA) smoke at three times the rate of the general population and respond poorly to cessation strategies. Previous studies examined repetitive transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex (L. dlPFC) to reduce craving, but no studies have explored rTMS among PLWHA who smoke. The current pilot study compared the effects of active and sham intermittent theta-burst stimulation (iTBS) on resting state functional connectivity (rsFC), cigarette cue attentional bias, and cigarette craving in PLWHA who smoke. Methods Eight PLWHA were recruited (single-blind, within-subject design) to receive one session of iTBS (n=8) over the L. dlPFC using neuronavigation and, four weeks later, sham iTBS (n=5). Cigarette craving and attentional bias assessments were completed before and after both iTBS and sham iTBS. rsFC was assessed before iTBS (baseline) and after iTBS and sham iTBS. Results Compared to sham iTBS, iTBS enhanced rsFC between the L. dlPFC and bilateral medial prefrontal cortex and pons. iTBS also enhanced rsFC between the right insula and right occipital cortex compared to sham iTBS. iTBS also decreased cigarette craving and cigarette cue attentional bias. Conclusion iTBS could potentially offer a therapeutic option for smoking cessation in PLWHA.

Frontiers in Psychiatry

Objectives This clinical trial primarily aimed to investigate the effects of blonanserin on social functioning in patients with first-episode schizophrenia. Methods In this prospective, multi-centre, single-arm clinical trial study, blonanserin (flexible oral dose ranging from 8mg to 24mg per day) was given 26 weeks. Outcome measures included the Personal and Social Performance (PSP) scale for evaluating social functioning, the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) for measuring neurocognitive performance, and the Positive and Negative Syndrome Scale (PANSS) for assessing symptom severity. The primary endpoint was social function improvement evaluated by PSP scale at the end of blonanserin treatment. And the secondary endpoint was to validate the efficacy and neurocognitive effects of blonanserin. Adverse drug reactions (ADRs) were also recorded and analysed. Results A total of 96 patients with first-episode schizophrenia were recruited and proceeded to analysis. Fifty-one participants (53.1%) completed the PSP scale measurements at baseline and week 26. Following 26 weeks of blonanserin treatment, all outcome measurements demonstrated significant improvement during the follow-up period. Notably, PSP scores exhibited a continuous increase up to 68.1% ± 103.7% at the end of the treatment (46.6 ± 14.6 at baseline, 69.4 ± 17.4 at week 26, p<0.001), indicating positive effects on social functioning that were already noticeable by week 8. Conclusion Blonanserin treatment exhibited favourable effects on social functioning in individuals with first …

Frontiers in Psychiatry

Background Due to their potential impact on mood and wellbeing there has been increasing interest in the potential of serotonergic psychedelics such as N,N-dimethyltryptamine (DMT) in the treatment of major depressive disorder (MDD). Aim The aim of Part A of this study was to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) profile of escalating doses of SPL026 (DMT fumarate) in psychedelic-naïve healthy participants to determine a dose for administration to patients with MDD in the subsequent Phase 2a part of the trial (Part B: not presented in this manuscript). Methods In the Phase 1, randomized, double-blind, placebo-controlled, parallel-group, single dose-escalation trial, psychedelic-naïve participants were randomized to placebo (n = 8) or four different escalating doses [9, 12, 17 and 21.5 mg intravenously (IV)] of SPL026 (n = 6 for each dose) together with psychological support from 2 therapy team members. PK and acute (immediately following dosing experience) psychometric measures [including mystical experience questionnaire (MEQ), ego dissolution inventory (EDI), and intensity rating visual analogue scale (IRVAS)] were determined. Additional endpoints were measured as longer-term change from baseline to days 8, 15, 30 and 90. These measures included the Warwick and Edinburgh mental wellbeing scale and Spielberger’s state-trait anxiety inventory. Results SPL026 was well tolerated, with an acceptable safety profile, with no serious adverse events. There was some evidence of a correlation between maximum plasma concentration and increased IRVAS, MEQ, and EDI scores …

Frontiers in Psychiatry

Beyond genetic predispositions, the notion that people’s illness profile and clinical outcomes may be driven by the degree of stress throughout their lifespan has become increasingly accepted. Allostatic load (AL), the wear and tear on organic systems due to chronic overactivity or inactivity of physiological processes in response to stress, has emerged as a popular concept to explain different phenotypes within groups with similar chronological ages (1). High AL has been linked to an array of clinical consequences consistently associated with aging, including metabolic diseases, neurodegenerative conditions, mood disorders, and mortality (2). However, the mechanisms underpinning the relationships between age-related changes and stress are still matter of debate. In this Research Topic, authors sought to explore these shortcomings through different approaches.For instance, de Oliveira et al. investigated the impact of aging on neurophysiological reactions to acute stress, namely the startle reflex. In normal conditions, the startle reflex is reduced when the pulse is preceded by a weaker sensory stimulus (prepulse), characterizing the physiological phenomenon named “prepulse inhibition”(PPI). Previous evidence suggested that aging is associated with decreased startle reflex and increased startle latency (3). Moreover, a U-shaped function relationship was found between PPI and age (3). Given that other data indicated a positive correlation between PPI and cognitive performance in young adults (4), the authors hypothesized that PPI alterations could function as a biomarker of cognitive decline in normal aging. The results demonstrated a …