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Frontiers in Genetics 2019Childhood-onset schizophrenia (COS), a very rare and severe chronic psychiatric condition, is defined by an onset of positive symptoms (delusions, hallucinations and...
Childhood-onset schizophrenia (COS), a very rare and severe chronic psychiatric condition, is defined by an onset of positive symptoms (delusions, hallucinations and disorganized speech or behavior) before the age of 13. COS is associated with other neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit and hyperactivity disorder. Copy number variations (CNVs) represent well documented neurodevelopmental disorder risk factors and, recently, single nucleotide variations (SNVs) in genes involved in brain development have also been implicated in the complex genetic architecture of COS. Here, we aim to review the genetic changes (CNVs and SNVs) reported for COS, going from previous studies to the whole genome sequencing era. We carried out a systematic review search in PubMed using the keywords "childhood(early)-onset schizophrenia(psychosis)" and "genetic(s) or gene(s) or genomic(s)" without language and date limitations. The main inclusion criteria are COS (onset before 13 years old) and all changes/variations at the DNA level (CNVs or SNVs). Thirty-six studies out of 205 met the inclusion criteria. Cytogenetic abnormalities (n = 72, including 66 CNVs) were identified in 16 autosomes and 2 sex chromosomes (X, Y), some with a higher frequency and clinical significance than others (e.g., 2p16.3, 3q29, 15q13.3, 22q11.21 deletions; 2p25.3, 3p25.3 and 16p11.2 duplications). Thirty-one single nucleotide mutations in genes principally involved in brain development and/or function have been found in 12 autosomes and one sex chromosome (X). We also describe five SNVs in X-linked genes inherited from a healthy mother, arguing for the X-linked recessive inheritance hypothesis. Moreover, (19q13.2) is the only gene carrying more than one SNV in more than one patient, making it a strong candidate for COS. Mutations were distributed in various chromosomes illustrating the genetic heterogeneity of COS. More than 90% of CNVs involved in COS are also involved in ASD, supporting the idea that there may be genetic overlap between these disorders. Different mutations associated with COS are probably still unknown, and pathogenesis might also be explained by the association of different genetic variations (two or more CNVs or CNVs and SNVs) as well as association with early acquired brain lesions such as infection, hypoxia, or early childhood trauma.
PubMed: 31921276
DOI: 10.3389/fgene.2019.01137 -
Frontiers in Psychiatry 2024Moyamoya disease (MMD) is a life-threatening condition characterized by stenosis of intracranial arteries. Despite the frequency and the impact of psychiatric symptoms...
INTRODUCTION
Moyamoya disease (MMD) is a life-threatening condition characterized by stenosis of intracranial arteries. Despite the frequency and the impact of psychiatric symptoms on the long-term prognosis and quality of life of MMD patients, no systematic review on this topic exists.
METHODS
This systematic review and meta-analysis included 41 studies (29 being case reports), from PubMed, Scopus, Embase until 27/3/2023, on MMD patients exhibiting psychiatric symptoms.
RESULTS
Despite a fair average quality of the articles, quantitative synthesis through logistic regression was possible only for case reports, due to heterogeneity between the other studies. Psychosis, the most frequent psychiatric symptom reported in case reports, was more frequent in MMD patients with left hemisphere involvement. Neurological symptoms occurrence increased the odds of MMD diagnosis preceding psychiatric symptoms. Psychiatric symptoms are highly prevalent in MMD patients and are relatively often the only presenting symptoms.
DISCUSSION
We discuss the diagnostic, therapeutic, and prognostic implications of recognizing and characterizing specific psychiatric symptoms in MMD, outlining preliminary guidelines for targeted pharmacological and psychotherapeutic interventions. Lastly, we outline future research and clinical perspectives, striving to enhance the oft-overlooked psychiatric care for MMD patients and to ameliorate their long-term outcome.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023406303.
PubMed: 38585478
DOI: 10.3389/fpsyt.2024.1371763 -
Psychopathology 2023Heautoscopy refers to a pathological experience of visual reduplication of one's body with an ambiguous sense of self-location and a disturbing sensation of owning the...
BACKGROUND
Heautoscopy refers to a pathological experience of visual reduplication of one's body with an ambiguous sense of self-location and a disturbing sensation of owning the illusory body. It has been recognized to occur in the course of strikingly diverse psychiatric and neurological disorders, such as schizophrenia, space-occupying lesions, frequently of the temporal or parietal lobes, migraine, epilepsy, and depression. The literature on the subject suffers from numerous conceptual inconsistencies, scarcity of clinical data, and a lack of theoretical integratory framework that could explain the uniqueness of these symptoms.
AIMS
In the study, we aimed to review all case reports on heautoscopy we could cull from the literature with an attempt to extract common factors and to foster a theoretical synthesis.
METHODS
All medical and psychological databases were rigorously searched, along with reference lists of the preselected articles. First-person reports were classified according to aspects of bodily self-consciousness primarily affected: body ownership, self-location, sense of agency and consequently, collated with their etiological backgrounds.
RESULTS
Out of over 140 case studies, a total of only 9 patients with heautoscopy were selected as satisfying functional criteria, carefully distinguishing heautoscopy from other typically conflated full-body anomalies: autoscopy, out-of-body experience, or feeling of presence. Numerous cases turned out to be mislabeling autoscopy or out-of-body experience as heautoscopy. In addition, several problems with existing neuroimaging experiments were identified.
CONCLUSION
Phenomenological analysis revealed that from the patients' perspective, heautoscopy resembles a somatesthetic-proprioceptive illusion, rather than a cognitive delusion, and occurs much less frequently than reported. A most peculiar symptom, described by some as a sense of "bilocation," appears to stem from dynamic shifts in self-location and expanded body ownership, rather than an expanded first-person perspective. Although extremely rare in its pure form, heautoscopy gives a unique opportunity to explore the brain limits to the plasticity of bodily boundaries and the origin of the first-person spatial perspective.
Topics: Humans; Body Image; Illusions; Brain; Proprioception; Mental Disorders
PubMed: 36349795
DOI: 10.1159/000526869 -
Schizophrenia Bulletin Jan 2019Psychotic disorders often have been linked with violence. However, studies have shown that people with a psychotic disorder are more often victim than perpetrator of... (Meta-Analysis)
Meta-Analysis
Psychotic disorders often have been linked with violence. However, studies have shown that people with a psychotic disorder are more often victim than perpetrator of violence. The objective of this meta-analysis was to review prevalence rates for different types of victimization and to identify risk factors associated with victimization. Based on a search in MEDLINE, PsycINFO, and Web of Science, 27 studies were found with samples consisting of adults with a psychotic disorder and possible victimization occurring during adulthood and data on "violent victimization," "sexual victimization," "non-violent victimization," and/or "victimization not otherwise specified." The median prevalence rate for violent victimization was 20%, for sexual victimization 20%, nonviolent victimization 19%, and for victimization not otherwise specified 19%. Victimization rates were approximately 4-6 times higher than in the general community. Meta-analyses showed the following significant risk factors: delusion (OR = 1.69), hallucinations (OR = 1.70), manic symptoms (OR = 1.66), drugs (OR = 1.90) or alcohol abuse (OR = 2.05), perpetration of a crime (OR = 4.33), unemployment (OR = 1.31), and homelessness (OR = 2.49). Other risk factors like previous victimization, impaired social functioning, personality disorder, and living in a disadvantaged neighborhood were found only in 1 or 2 studies. Based on the results, we conclude that, depending on the examined time period, 1 in 5 (assessment period ≤3 y) or 1 in 3 (assessment period entire adulthood) people with a psychotic disorder was victim of a crime. Clinical, behavioral, and sociodemographic factors were significantly associated with victimization, as well as previous victimization. Prospective research into risk factors is needed to capture causal trajectories of victimization.
Topics: Adult; Crime Victims; Humans; Prevalence; Psychotic Disorders; Risk Factors; Schizophrenia
PubMed: 29547958
DOI: 10.1093/schbul/sby020 -
The Cochrane Database of Systematic... Nov 2020Psychosis is an illness characterised by the presence of hallucinations and delusions that can cause distress or a marked change in an individual's behaviour (e.g.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Psychosis is an illness characterised by the presence of hallucinations and delusions that can cause distress or a marked change in an individual's behaviour (e.g. social withdrawal, flat or blunted effect). A first episode of psychosis (FEP) is the first time someone experiences these symptoms that can occur at any age, but the condition is most common in late adolescence and early adulthood. This review is concerned with FEP and the early stages of a psychosis, referred to throughout this review as 'recent-onset psychosis.' Specialised early intervention (SEI) teams are community mental health teams that specifically treat people who are experiencing, or have experienced, a recent-onset psychosis. SEI teams provide a range of treatments including medication, psychotherapy, psychoeducation, educational and employment support, augmented by assertive contact with the service user and small caseloads. Treatment is time limited, usually offered for two to three years, after which service users are either discharged to primary care or transferred to a standard adult community mental health team. Evidence suggests that once SEI treatment ends, improvements may not be sustained, bringing uncertainty about the optimal duration of SEI to ensure the best long-term outcomes. Extending SEI has been proposed as a way of providing continued intensive treatment and continuity of care, of usually up to five years, in order to a) sustain the positive initial outcomes of SEI; and b) improve the long-term trajectory of the illness.
OBJECTIVES
To compare extended SEI teams with treatment as usual (TAU) for people with recent-onset psychosis. To compare extended SEI teams with standard SEI teams followed by TAU (standard SEI + TAU) for people with recent-onset psychosis.
SEARCH METHODS
On 3 October 2018 and 22 October 2019, we searched Cochrane Schizophrenia's study-based register of trials, including registries of clinical trials.
SELECTION CRITERIA
We selected all randomised controlled trials (RCTs) comparing extended SEI with TAU for people with recent-onset psychosis and all RCTs comparing extended SEI with standard SEI + TAU for people with recent-onset psychosis. We entered trials meeting these criteria and reporting usable data as included studies.
DATA COLLECTION AND ANALYSIS
We independently inspected citations, selected studies, extracted data and appraised study quality. For binary outcomes we calculated the risk ratios (RRs) and their 95% confidence intervals (CIs). For continuous outcomes we calculated the mean difference (MD) and their 95% CIs, or if assessment measures differed for the same construct, we calculated the standardised mean difference (SMD) with 95% CIs. We assessed risk of bias for included studies and created a 'Summary of findings' table using the GRADE approach.
MAIN RESULTS
We included three RCTs, with a total 780 participants, aged 16 to 35 years. All participants met the criteria for schizophrenia spectrum disorders or affective psychoses. No trials compared extended SEI with TAU. All three trials randomly allocated people approximately two years into standard SEI to either extended SEI or standard SEI + TAU. The certainty of evidence for outcomes varied from low to very low. Our primary outcomes were recovery and disengagement from mental health services. No trials reported on recovery, and we used remission as a proxy. Three trials reported on remission, with the point estimate suggesting a 13% increase in remission in favour of extended SEI, but this included wide confidence intervals (CIs) and a very uncertain estimate of no benefit (RR 1.13, 95% CI 0.97 to 1.31; 3 trials, 780 participants; very low-certainty evidence). Two trials provided data on disengagement from services with evidence that extended SEI care may result in fewer disengagements from mental health treatment (15%) in comparison to standard SEI + TAU (34%) (RR 0.45, 95% CI 0.27 to 0.75; 2 trials, 380 participants; low-certainty evidence). There may be no evidence of a difference in rates of psychiatric hospital admission (RR 1.55, 95% CI 0.68 to 3.52; 1 trial, 160 participants; low-certainty evidence), or the number of days spent in a psychiatric hospital (MD -2.70, 95% CI -8.30 to 2.90; 1 trial, 400 participants; low-certainty evidence). One trial found uncertain evidence regarding lower global psychotic symptoms in extended SEI in comparison to standard SEI + TAU (MD -1.90, 95% CI -3.28 to -0.52; 1 trial, 156 participants; very low-certainty evidence). It was uncertain whether the use of extended SEI over standard SEI + TAU resulted in fewer deaths due to all-cause mortality, as so few deaths were recorded in trials (RR 0.38, 95% CI 0.09 to 1.64; 3 trials, 780 participants; low-certainty evidence). Very uncertain evidence suggests that using extended SEI instead of standard SEI + TAU may not improve global functioning (SMD 0.23, 95% CI -0.29 to 0.76; 2 trials, 560 participants; very low-certainty evidence). There was low risk of bias in all three trials for random sequence generation, allocation concealment and other biases. All three trials had high risk of bias for blinding of participants and personnel due to the nature of the intervention. For the risk of bias for blinding of outcome assessments and incomplete outcome data there was at least one trial with high or unclear risk of bias.
AUTHORS' CONCLUSIONS
There may be preliminary evidence of benefit from extending SEI team care for treating people experiencing psychosis, with fewer people disengaging from mental health services. Evidence regarding other outcomes was uncertain. The certainty of evidence for the measured outcomes was low or very low. Further, suitably powered studies that use a consistent approach to outcome selection are needed, but with only one further ongoing trial, there is unlikely to be any definitive conclusion for the effectiveness of extended SEI for at least the next few years.
Topics: Adolescent; Adult; Affective Disorders, Psychotic; Bias; Community Mental Health Services; Confidence Intervals; Early Medical Intervention; Female; Humans; Male; Randomized Controlled Trials as Topic; Remission Induction; Schizophrenia; Time Factors; Young Adult
PubMed: 33135812
DOI: 10.1002/14651858.CD013287.pub2 -
The Cochrane Database of Systematic... Dec 2019People with schizophrenia have a range of different symptoms, including positive symptoms (hallucinations and delusions), negative symptoms (such as social withdrawal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
People with schizophrenia have a range of different symptoms, including positive symptoms (hallucinations and delusions), negative symptoms (such as social withdrawal and lack of affect), and cognitive impairment. The standard medication for people with schizophrenia is antipsychotics. However, these medications may not be effective for all symptoms of schizophrenia, as cognitive and negative symptoms are usually hard to treat. Additional therapies or medications are available for the management of these symptoms. Modafinil, a wakefulness-promoting agent most frequently used in narcolepsy or shift work sleep disorder, is one intervention that is theorised to have an effect of these symptoms.
OBJECTIVES
The primary objective of this review was to assess the effects of modafinil for people with schizophrenia or related disorders.
SEARCH METHODS
On 27 April 2015, 24 May 2017, and 31 October 2019, we searched the Cochrane Schizophrenia Group's register of trials, which is based on regular searches of CENTRAL, MEDLINE, Embase, AMED, BIOSIS, CINAHL, PsycINFO, PubMed, and registries of clinical trials. There are no language, time, document type, or publication status limitations for the inclusion of records in the register.
SELECTION CRITERIA
We selected all randomised controlled trials comparing modafinil with placebo or other treatments for people with schizophrenia or schizophrenia-spectrum disorders.
DATA COLLECTION AND ANALYSIS
We independently extracted data from the included studies. We analysed dichotomous data using risk ratios (RR) and 95% confidence intervals (CI). We analysed continuous data using mean difference (MD) with a 95% CI. We used a random-effects model for the meta-analysis. We used GRADE to complete a 'Summary of findings' table and assessed risk of bias for the included studies.
MAIN RESULTS
Eleven studies including a total of 422 participants contributed to data analyses. Most studies had a small population size (average 38 people per study) and were of short duration. We also detected a high risk of bias for selective outcome reporting in just under 50% of the trials. We therefore rated the overall methodological quality of the included studies as low. We considered seven main outcomes of interest: clinically important change in overall mental state, clinically important change in cognitive functioning, incidence of a clinically important adverse effect/event, clinically important change in global state, leaving the study early for any reason, clinically important change in quality of life, and hospital admission. All studies assessed the effects of adding modafinil to participants' usual antipsychotic treatment compared to adding placebo to usual antipsychotic treatment. Six studies found that adding modafinil to antipsychotic treatment may have little or no effect on overall mental state of people with schizophrenia, specifically the risk of worsening psychosis (RR 0.91, 95% CI 0.28 to 2.98; participants = 209; studies = 6, low-quality evidence). Regarding the effect of modafinil on cognitive function, the trials did not report clinically important change data, but one study reported endpoint scores on the MATRICS Consensus Cognitive Battery (MCCB): in this study we found no clear difference in scores between modafinil and placebo treatment groups (MD -3.10, 95% CI -10.9 to 4.7; participants = 48; studies = 1, very low-quality evidence). Only one study (N = 35) reported adverse effect/event data. In this study one serious adverse event occurred in each group (RR 0.84, 95% CI 0.06 to 12.42; participants = 35; studies = 1, very low-quality evidence). One study measured change in global state using the Clinical Global Impression - Improvement Scale. This study found that adding modafinil to antipsychotic treatment may have little or no effect on global state (RR 6.36, 95% CI 0.94 to 43.07, participants = 21; studies = 1, very low-quality evidence). Nine studies found that modafinil has no effect on numbers of participants leaving the study early (RR 1.26, 95% CI 0.63 to 2.52 participants = 357; studies = 9, moderate-quality evidence). None of the trials reported clinically important change in quality of life, but one study did report quality of life using endpoint scores on the Quality of Life Inventory, finding no clear difference between treatment groups (MD -0.2, 95% CI -1.18 to 0.78; participants = 20; studies = 1, very low-quality evidence). Finally, one study reported data for number of participants needing hospitalisation: one participant in each group was hospitalised (RR 0.84, 95% CI 0.06 to 12.42; participants = 35; studies = 1, very low-quality evidence).
AUTHORS' CONCLUSIONS
Due to methodological issues, low sample size, and short duration of the clinical trials as well as high risk of bias for outcome reporting, most of the evidence available for this review is of very low or low quality. For results where quality is low or very low, we are uncertain or very uncertain if the effect estimates are true effects, limiting our conclusions. Specifically, we found that modafinil is no better or worse than placebo at preventing worsening of psychosis; however, we are uncertain about this result. We have more confidence that participants receiving modafinil are no more likely to leave a trial early than participants receiving placebo. However, we are very uncertain about the remaining equivocal results between modafinil and placebo for outcomes such as improvement in global state or cognitive function, incidence of adverse events, and changes in quality of life. More high-quality data are needed before firm conclusions regarding the effects of modafinil for people with schizophrenia or related disorders can be made.
Topics: Antipsychotic Agents; Cognition; Humans; Modafinil; Quality of Life; Randomized Controlled Trials as Topic; Schizophrenia; Wakefulness-Promoting Agents
PubMed: 31828767
DOI: 10.1002/14651858.CD008661.pub2 -
Neuropsychobiology 2020Transcranial magnetic stimulation (TMS) has been proposed as a potential treatment add-on for positive symptoms in schizophrenia. To summarize the current evidence for...
Transcranial magnetic stimulation (TMS) has been proposed as a potential treatment add-on for positive symptoms in schizophrenia. To summarize the current evidence for its efficacy, we reviewed clinical trials from the last 20 years that investigated TMS for positive symptoms. We performed a search on the PubMed database for clinical trials that used TMS for the treatment of positive symptoms published in peer-reviewed journals. We excluded reviews, case reports, and opinion papers. Of the 30 studies included, the majority (n = 25) investigated auditory verbal hallucinations. Twelve studies found evidence for a positive treatment effect of TMS on positive symptoms, while 18 did not find enough evidence to conclude that TMS is effective for positive symptoms. However, the small sample size of the majority of studies is a limiting factor for the reliability of previous findings. In conclusion, evidence for an effect of TMS on positive symptoms was mixed. Since most of the studies were performed in patients with auditory verbal hallucinations, further research of TMS for other positive symptoms including thought disorder and delusions is warranted.
Topics: Hallucinations; Humans; Schizophrenia; Transcranial Magnetic Stimulation
PubMed: 31505508
DOI: 10.1159/000502148 -
Brain and Behavior Feb 2021We reviewed the psychotic symptoms of anti-NMDA receptor encephalitis (NMDARE) to differentiate its presentation from those found in a primary psychiatric disorder. We...
OBJECTIVE
We reviewed the psychotic symptoms of anti-NMDA receptor encephalitis (NMDARE) to differentiate its presentation from those found in a primary psychiatric disorder. We hypothesized that the cycloid psychosis (CP) phenotype would be a frequent clinical presentation in the psychiatric phase of NMDARE.
METHOD
A systematic literature review in PubMed of all case reports published on NMDARE was performed from database inception to March 2020. We included all cases where psychotic symptoms were reported and whose diagnoses were confirmed by the presence of anti-NMDAR antibodies in the cerebrospinal fluid (CSF). An email including a short test (CP phenotype, Perris and Brockington's criteria) was sent to all case report authors asking them to describe the psychotic symptoms.
RESULTS
We identified 335 case reports fulfilling our criteria, and the authors of 200 replied. Our analyses were based exclusively on those answers and data extracted from the articles. Median patient age was 25 years (+-11.4), 81% were female, and 39% had an ovarian teratoma. A complete CP phenotype was identified in 175 patients (87%). These were acute psychotic episodes with a sudden onset and a fluctuating clinical pattern mostly characterized by confusion (97%), delusions (75%), hallucinations (69%), motility disturbances (87%), and mood oscillations (80%).
CONCLUSION
The complete CP phenotype was frequently the expression of psychotic symptoms in NMDARE. We suggest that patients with a first psychotic episode who initially exhibit the CP phenotype should undergo CSF analysis to determine whether antibodies against neuronal cell surface or synaptic receptors are present to rule out a possible diagnosis of autoimmune encephalitis.
Topics: Adult; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Female; Hashimoto Disease; Humans; Psychotic Disorders; Receptors, N-Methyl-D-Aspartate; Teratoma
PubMed: 33270360
DOI: 10.1002/brb3.1980