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1.
Reduced Jumping to Conclusion Bias after Experimentally Induced Enhancement of Subjective Body Boundaries in Psychosis.
Lyons, N, Dietrich, DE, Graser, J, Juckel, G, Koßmann, C, Krauß, H, Müller, B, Michalak, J
Psychopathology. 2021;(2):92-97
Abstract
INTRODUCTION A disturbed sense of self is frequently discussed as an etiological factor for delusion symptoms in psychosis. Phenomenological approaches to psychopathology posit that lacking the sense that the self is localized within one's bodily boundaries (disembodiment) is one of the core features of the disturbed self in psychosis. The present study examines this idea by experimentally manipulating the sense of bodily boundaries. METHODS Seventy-three patients with psychosis were randomly assigned to either a 10-min, guided self-massage in the experimental group (EG) to enhance the sense of bodily boundaries or a control group (CG), which massaged a fabric ring. Effects on an implicit measure (jumping to conclusion bias; JTC) and an explicit measure (Brief State Paranoia Checklist; BSPC) of delusion processes were assessed. The JTC measures the tendency to make a decision with little evidence available, and the BSPC explicitly measures the approval of paranoid beliefs. RESULTS Patients in the EG showed a lower JTC (M = 4.11 draws before decision) than the CG (M = 2.43; Cohen's d = 0.64). No significant difference in the BSPC was observed. DISCUSSION/CONCLUSION Our results indicate that enhancing the sense of body boundaries through a self-massage can reduce an implicit bias associated with delusional ideation and correspondingly support the idea that disembodiment might be a relevant factor in the formation of psychotic symptoms.
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Late life psychotic features in prodromal Parkinson's disease.
Pachi, I, Maraki, MI, Giagkou, N, Kosmidis, MH, Yannakoulia, M, Dardiotis, E, Hadjigeorgiou, G, Sakka, P, Ntanasi, E, Xiromerisiou, G, et al
Parkinsonism & related disorders. 2021;:67-73
Abstract
INTRODUCTION Some case series have suggested that psychotic features could occur even before the onset of motor symptoms of Parkinson's Disease (PD). Our aim was to investigate a possible association between psychotic symptoms and prodromal Parkinson's disease in a population-based cohort, the Hellenic Longitudinal Investigation of Aging and Diet study. METHODS This cross-sectional study included participants aged ≥65 years without dementia or PD. We defined psychotic symptoms as the presence of at least one new hallucinatory or delusional feature, assessed with the Neuropsychiatric Inventory scale and the Columbia University Scale for Psychopathology in Alzheimer's Disease, exhibited only at follow-up and not present at baseline visit. We calculated the probability of prodromal PD (pPD) for every participant, according to the 2019 International Parkinson and Movement Disorders Society research criteria for prodromal PD. RESULTS Participants who developed psychotic manifestations over a three-year follow up (20 of 914) had 1.3 times higher probability of pPD score (β [95%CI]: 1.3 [0.9-1.5], p=0.006) compared to non-psychotic subjects. This association was driven mostly by depressive symptoms, constipation and subthreshold parkinsonism (p<0.05). CONCLUSION Our data indicate that emerging psychotic features evolve in parallel with the probability of pPD. This is the first study that provides evidence for the presence of psychotic experiences in pPD. The association detected needs to be confirmed in longitudinal studies.
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Prescribing antipsychotics in child and adolescent psychiatry: guideline adherence.
Dinnissen, M, Dietrich, A, van der Molen, JH, Verhallen, AM, Buiteveld, Y, Jongejan, S, Troost, PW, Buitelaar, JK, Hoekstra, PJ, van den Hoofdakker, BJ
European child & adolescent psychiatry. 2020;(12):1717-1727
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Abstract
Antipsychotics are often prescribed to children and adolescents, mostly off-label. We aimed to assess adherence to recommendations of guidelines for antipsychotic prescription. We reviewed 436 medical records from 155 clinicians from 26 clinics within three Dutch child and adolescent psychiatry organizations (n = 398 outpatient, n = 38 inpatient care). We assessed target symptoms, diagnostic process, prior and concomitant treatment, and consideration of contra-indications. Multiple logistic regression assessed the role of age, sex, and psychiatric diagnosis on adherence to three main recommendations: to (1) prescribe antipsychotics only after other treatments proved insufficient, (2) always combine antipsychotics with psychosocial interventions, and (3) not prescribe multiple antipsychotics simultaneously. Most patients received off-label antipsychotics. Main target symptoms were inattention/hyperactivity (25%), aggression (24%), and other disruptive behaviors (41%). Most patients underwent diagnostic evaluation before the first prescription; however, screening of contra-indications was low (0.2-19%). About 84% had previously received psychosocial treatment and 48% other psychoactive medication, but 9% had not received any treatment. Notably, only 37% continuously received concomitant psychosocial treatment. Simultaneous use of multiple antipsychotics occurred in 3.2%. Younger children were at higher risk of non-adherence to guideline recommendations regarding prior and concomitant treatment, children with autism spectrum disorder or attention-deficit/hyperactivity disorder more likely not to receive concomitant psychosocial treatment. Sex did not significantly affect adherence. Our findings implicate insufficient adherence to important recommendations regarding antipsychotic use in children and adolescents. Especially younger children are at higher risk of receiving suboptimal care. There is an urgency to consistently offer psychosocial interventions during antipsychotic treatment.
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Bosch-Boonstra-Schaaf Optic Atrophy Syndrome Presenting as New-Onset Psychosis in a 32-Year-Old Man: A Case Report and Literature Review.
Hobbs, MM, Wolters, WC, Rayapati, AO
Journal of psychiatric practice. 2020;(1):58-62
Abstract
Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is a recently described autosomal dominant disorder caused by mutations in the nuclear receptor subfamily 2 group F member 1 (NR2F1) gene. Its common features include optic atrophy and/or hypoplasia, developmental delay, intellectual disability, attention deficit disorder, autism spectrum disorder, seizures, hearing defects, spasticity, hypotonia, and thinning of the corpus callosum. Mitochondrial involvement has also been described with BBSOAS. Currently, 31 cases of BBSOAS have been described in the literature. Here we report a case of undiagnosed BBSOAS presenting as psychosis in a 32-year-old man with a history of bilateral optic nerve atrophy, intellectual disability, epilepsy, and mitochondrial complex I abnormality on muscle biopsy. Whole-genome sequencing identified a heterozygous de novo nonsense mutation in the NR2F1 gene [c.253 G>T (guanine to thymine mutation in coding position 253) in exon 1, p.E85X variant (GAG>TAG) (glutamic acid to stop codon mutation; protein truncated to 85 amino acids)]. A pathogenic nonsense mutation has not previously been reported in the literature in association with BBSOAS and represents an expansion of clinically relevant variants. Psychosis has also not been previously reported in this syndrome and may represent a phenotypic expansion of BBSOAS, a manifestation of prolonged disease, or a result of disease management.
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Efavirenz as a psychotropic drug.
Zareifopoulos, N, Lagadinou, M, Karela, A, Pouliasi, F, Economou, I, Tsigkou, A, Velissaris, D
European review for medical and pharmacological sciences. 2020;(20):10729-10735
Abstract
OBJECTIVE Antiretroviral drugs are the mainstay of treatment for human immunodeficiency virus (HIV) infection. Lifelong highly active antiretroviral therapy (HAART) is indicated to prevent disease progression to acquired immunodeficiency syndrome (AIDS). Efavirenz was a first-line component of HAART across the world for many years. The purpose of this article is to review the psychotropic properties of efavirenz, which are the most important adverse events associated with the drug and commonly result in treatment discontinuation. MATERIALS AND METHODS A PubMed search was conducted using efavirenz as a search term, which returned 4655 results. Titles and abstracts of articles were screened for relevance, and all relevant articles published in English were included in the narrative review. RESULTS Acute exposure to efavirenz may cause profound perceptual disturbances (delusions and hallucinations) whereas chronic exposure may be associated with abnormal dreams and other sleep disturbances, anxiety, depressed mood and suicidality. It may also be abused as a hallucinogen, especially in individuals with a history of poly-substance abuse. Recent research indicates that efavirenz directly affects monoaminergic neurotransmission and may partially substitute for psychedelic drugs, such as lysergic acid diethylamide (LSD). Efavirenz acts as a serotonin 5-HT2A receptor antagonist, a serotonin-dopamine reuptake inhibitor, an inhibitor of monoamine oxidase (MAO) and a vesicular monoamine transporter 2 (VMAT2) inhibitor, which are mechanisms common with many psychotropic drugs. Efavirenz interacts with many of the same molecular targets as the empathogen methylendioxymethamphetamine (MDMA), but the effects of the 2 drugs may differ. CONCLUSIONS The exact mechanism of action of efavirenz as a psychotropic drug remains unclear and future studies should focus on evaluating whether prolonged exposure could lead to irreversible side effects.
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Prenatal and perinatal risk and protective factors for psychosis: a systematic review and meta-analysis.
Davies, C, Segre, G, Estradé, A, Radua, J, De Micheli, A, Provenzani, U, Oliver, D, Salazar de Pablo, G, Ramella-Cravaro, V, Besozzi, M, et al
The lancet. Psychiatry. 2020;(5):399-410
Abstract
BACKGROUND Prenatal and perinatal insults are implicated in the aetiopathogenesis of psychotic disorders but the consistency and magnitude of their associations with psychosis have not been updated for nearly two decades. The aim of this systematic review and meta-analysis was to provide a comprehensive and up-to-date synthesis of the evidence on the association between prenatal or perinatal risk and protective factors and psychotic disorders. METHODS In this systematic review and meta-analysis, we searched the Web of Science database for articles published up to July 20, 2019. We identified cohort and case-control studies examining the association (odds ratio [OR]) between prenatal and perinatal factors and any International Classification of Diseases (ICD) or Diagnostic and Statistical Manual of Mental Disorders (DSM) non-organic psychotic disorder with a healthy comparison group. Other inclusion criteria were enough data available to do the analyses, and non-overlapping datasets. We excluded reviews, meta-analyses, abstracts or conference proceedings, and articles with overlapping datasets. Data were extracted according to EQUATOR and PRISMA guidelines. Extracted variables included first author, publication year, study type, sample size, type of psychotic diagnosis (non-affective psychoses or schizophrenia-spectrum disorders, affective psychoses) and diagnostic instrument (DSM or ICD and version), the risk or protective factor, and measure of association (primary outcome). We did random-effects pairwise meta-analyses, Q statistics, I2 index, sensitivity analyses, meta-regressions, and assessed study quality and publication bias. The study protocol was registered at PROSPERO, CRD42017079261. FINDINGS 152 studies relating to 98 risk or protective factors were eligible for analysis. Significant risk factors were: maternal age younger than 20 years (OR 1·17) and 30-34 years (OR 1·05); paternal age younger than 20 years (OR 1·31) and older than 35 years (OR 1·28); any maternal (OR 4·60) or paternal (OR 2·73) psychopathology; maternal psychosis (OR 7·61) and affective disorder (OR 2·26); three or more pregnancies (OR 1·30); herpes simplex 2 (OR 1·35); maternal infections not otherwise specified (NOS; OR 1·27); suboptimal number of antenatal visits (OR 1·83); winter (OR 1·05) and winter to spring (OR 1·05) season of birth in the northern hemisphere; maternal stress NOS (OR 2·40); famine (OR 1·61); any famine or nutritional deficits in pregnancy (OR 1·40); maternal hypertension (OR 1·40); hypoxia (OR 1·63); ruptured (OR 1·86) and premature rupture (OR 2·29) of membranes; polyhydramnios (OR 3·05); definite obstetric complications NOS (OR 1·83); birthweights of less than 2000 g (OR 1·84), less than 2500 g (OR 1·53), or 2500-2999 g (OR 1·23); birth length less than 49 cm (OR 1·17); small for gestational age (OR 1·40); premature birth (OR 1·35), and congenital malformations (OR 2·35). Significant protective factors were maternal ages 20-24 years (OR 0·93) and 25-29 years (OR 0·92), nulliparity (OR 0·91), and birthweights 3500-3999 g (OR 0·90) or more than 4000 g (OR 0·86). The results were corrected for publication biases; sensitivity and meta-regression analyses confirmed the robustness of these findings for most factors. INTERPRETATION Several prenatal and perinatal factors are associated with the later onset of psychosis. The updated knowledge emerging from this study could refine understanding of psychosis pathogenesis, enhance multivariable risk prediction, and inform preventive strategies. FUNDING None.
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Effects of Transcranial Direct Current Stimulation (tDCS) and Approach Bias Modification (ABM) training on food cravings in people taking antipsychotic medication.
Grycuk, L, Gordon, G, Gaughran, F, Campbell, IC, Schmidt, U
Trials. 2020;(1):245
Abstract
BACKGROUND Antipsychotic drug-induced weight gain puts individuals with schizophrenia at increased cardiometabolic risk. As a potential intervention for this problem, we describe the theoretical background and a protocol for a feasibility randomised controlled trial (RCT) of approach bias modification (ABM) training combined with real versus sham (placebo) transcranial direct current stimulation (tDCS). The primary aim of this trial is to obtain information that will guide decision making and protocol development in relation to a future large-scale RCT of ABM and tDCS in this group of participants. Second, the study will assess the preliminary efficacy of ABM + tDCS in reducing food cravings in people who take antipsychotic medication. METHODS Thirty adults with a DSM-V diagnosis of schizophrenia or schizoaffective disorder treated with anti-psychotic medication will be randomly allocated to receive five sessions that will combine ABM and real or sham tDCS, in a parallel group design. In this feasibility study, a broad range of outcome variables will be examined. Measures will include food craving, psychopathology (e.g. symptoms of schizophrenia and depression), neuropsychological processes (such as attentional bias and impulsiveness), and the tolerability and acceptability of tDCS. The feasibility of conducting a large-scale RCT of ABM + tDCS and appropriateness of tDCS as a treatment for antipsychotic drug-induced weight gain will be evaluated by assessment of recruitment and retention rates, acceptability of random allocation, blinding success (allocation concealment), completion of treatment sessions and research assessments (baseline, post-treatment and follow-up). DISCUSSION The effect sizes generated and other findings from this trial will inform a future large-scale RCT with respect to decisions on primary outcome measures and other aspects of protocol development. In addition, results from this study will provide a preliminary indication of the efficacy of ABM + tDCS treatment for antipsychotic drug-induced weight gain. TRIAL REGISTRATION ISRCTN Registry, ISRCTN13280178. Registered on 16 October 2018.
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Physical health assistance in early recovery of psychosis: Study protocol for a randomized controlled trial.
O'Donoghue, B, Mifsud, NG, Tindall, RM, Foote, L, Hartmann, JA, Obst, K, Simmons, MB, McGorry, PD, Killackey, E
Early intervention in psychiatry. 2020;(5):587-593
Abstract
AIM: Young people with psychotic disorders have poorer physical health compared to their healthy peers, a state compounded by the metabolic side-effects of antipsychotic medications. To address this, Orygen Youth Health has introduced physical health services including exercise physiologists and dieticians. These services are typically coordinated by the case manager and doctor. It is not yet known whether a treating team member dedicated to physical health will improve engagement, adherence and outcomes with these services. Hence, the protocol is presented here for a trial to evaluate the effect of including a physical health nurse in the care of young people with first-episode psychosis. METHODS This will be a single-blind randomized controlled trial that includes 15- to 24-year-olds with first-episode psychosis who have just commenced (within 30 days) antipsychotic medication. The primary outcome will be the event of clinically significant weight gain (≥7% body weight). Participants will be assigned either a physical health nurse in their treating team (in addition to the case manager and doctor) for a 12-week period, or treatment as usual (case manager and doctor). Research assessments will be conducted at baseline, 12 and 26 weeks. Activity trackers worn by participants for the study's duration will measure sleep and physical activity. CONCLUSION The present study will determine whether a physical health nurse will facilitate participants in attending and engaging in physical health interventions and whether this will be associated with physical health improvements or the prevention of worsening physical health.
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The characterization of psychotic symptoms in succinic semialdehyde dehydrogenase deficiency: a review.
Colijn, MA
Psychiatric genetics. 2020;(6):153-161
Abstract
Succinic semialdehyde dehydrogenase (SSADH) deficiency is an ultra-rare inborn error of metabolism that results in disrupted gamma-amino butyric acid (GABA) catabolism. In addition to developmental delay, intellectual disability, hypotonia, ataxia, and seizures, a variety of neuropsychiatric symptoms may occur, including psychosis. By highlighting all available and relevant case reports/series, this qualitative review seeks to characterize the prevalence, clinical manifestation, pathophysiology, and treatment of psychotic symptoms in this population. Psychosis occurs in a minority of SSADH-deficient individuals, and most commonly presents as auditory or visual hallucinations with an onset in adolescence or young adulthood. Although the pathophysiology underlying the development of psychosis in this context is not fully understood, it likely in part relates to increased GABA and/or gamma hydroxybutyric acid activity. Although antipsychotic medications should be used cautiously in SSADH deficiency, they may be effective at treating emergent psychotic symptoms.
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Effectiveness and side effects of psychopharmacotherapy in individuals with 22q11.2 deletion syndrome with comorbid psychiatric disorders: a systematic review.
Mosheva, M, Korotkin, L, Gur, RE, Weizman, A, Gothelf, D
European child & adolescent psychiatry. 2020;(8):1035-1048
Abstract
22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion in humans and is associated with high rates of attention deficit/hyperactivity disorder (ADHD), psychotic spectrum disorders and mood and anxiety disorders. The objective of the study was to systematically review studies regarding pharmacological treatments for psychiatric disorders in individuals with 22q11.2DS and to provide practical guidelines for the psychiatric management and side effect monitoring in 22q11.2DS. A literature search was conducted using the databases PubMed, PsycINFO and Embase. Information regarding study population, drug treatment, side effect profile and efficacy for each trial was extracted. Data collection was completed on May 2018. The search identified 705 studies. A total of seven studies, describing 182 individuals, were included. Pharmacological interventions included three studies for antipsychotic treatment, two studies for stimulants, one study for selective serotonin reuptake inhibitors (SSRIs), one study for S-adenosyl-L-methionine (SAMe), and one case series for metyrosine. The presented data support the clinical impression that individuals with 22q11.2DS and comorbid psychiatric disorders are treated in a manner comparable to non-22q11.2DS individuals. However, distinct medical comorbidities common in individuals with 22q11.2DS may complicate the administration of pharmacotherapy. Further trials with RCT design, larger sample sizes and more syndrome-specific pharmacological agents are needed to improve evidence-based psychiatric care of 22q11.2DS individuals with comorbid mental disorders.