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World Psychiatry : Official Journal of... Feb 2021Experiencing psychological trauma during childhood and/or adolescence is associated with an increased risk of psychosis in adulthood. However, we lack a clear knowledge...
Experiencing psychological trauma during childhood and/or adolescence is associated with an increased risk of psychosis in adulthood. However, we lack a clear knowledge of how developmental trauma induces vulnerability to psychotic symptoms. Understanding the psychological processes involved in this association is crucial to the development of preventive interventions and improved treatments. We sought to systematically review the literature and combine findings using meta-analytic techniques to establish the potential roles of psychological processes in the associations between developmental trauma and specific psychotic experiences (i.e., hallucinations, delusions and paranoia). Twenty-two studies met our inclusion criteria. We found mediating roles of dissociation, emotional dysregulation and post-traumatic stress disorder (PTSD) symptoms (avoidance, numbing and hyperarousal) between developmental trauma and hallucinations. There was also evidence of a mediating role of negative schemata, i.e. mental constructs of meanings, between developmental trauma and delusions as well as paranoia. Many studies to date have been of poor quality, and the field is limited by mostly cross-sectional research. Our findings suggest that there may be distinct psy-chological pathways from developmental trauma to psychotic phenomena in adulthood. Clinicians should carefully ask people with psychosis about their history of developmental trauma, and screen patients with such a history for dissociation, emotional dysregulation and PTSD symptoms. Well conducted research with prospective designs, including neurocognitive assessment, is required in order to fully understand the biopsychosocial mechanisms underlying the association between developmental trauma and psychosis.
PubMed: 33432756
DOI: 10.1002/wps.20841 -
Human Brain Mapping Apr 2024Schizophrenia is a chronic psychiatric disorder with characteristic symptoms of delusions, hallucinations, lack of motivation, and paucity of thought. Recent evidence... (Review)
Review
Schizophrenia is a chronic psychiatric disorder with characteristic symptoms of delusions, hallucinations, lack of motivation, and paucity of thought. Recent evidence suggests that the symptoms of schizophrenia, negative symptoms in particular, vary widely between the sexes and that symptom onset is earlier in males. A better understanding of sex-based differences in functional magnetic resonance imaging (fMRI) studies of schizophrenia may provide a key to understanding sex-based symptom differences. This study aimed to summarize sex-based functional magnetic resonance imaging (fMRI) differences in brain activity of patients with schizophrenia. We searched PubMed and Scopus to find fMRI studies that assessed sex-based differences in the brain activity of patients with schizophrenia. We excluded studies that did not evaluate brain activity using fMRI, did not evaluate sex differences, and were nonhuman or in vitro studies. We found 12 studies that met the inclusion criteria for the current systematic review. Compared to females with schizophrenia, males with schizophrenia showed more blood oxygen level-dependent (BOLD) activation in the cerebellum, the temporal gyrus, and the right precuneus cortex. Male patients also had greater occurrence of low-frequency fluctuations in cerebral blood flow in frontal and parietal lobes and the insular cortex, while female patients had greater occurrence of low-frequency fluctuations in the hippocampus, parahippocampus, and lentiform nucleus. The current study summarizes fMRI studies that evaluated sex-based fMRI brain differences in schizophrenia that may help to shed light on the underlying pathophysiology and further understanding of sex-based differences in the clinical presentation and course of the disorder.
Topics: Humans; Male; Female; Magnetic Resonance Imaging; Sex Characteristics; Brain; Schizophrenia; Brain Mapping
PubMed: 38520370
DOI: 10.1002/hbm.26664 -
Journal of Psychiatric Research Sep 2022Preliminary data suggest that patients with COVID-19 may experience psychiatric symptoms, including psychosis. We systematically reviewed the literature to evaluate the... (Review)
Review
BACKGROUND
Preliminary data suggest that patients with COVID-19 may experience psychiatric symptoms, including psychosis. We systematically reviewed the literature to evaluate the concurrence of new-onset psychosis or exacerbation of clinically stable psychosis through case reports and case series.
METHODS
Six databases were searched, followed by an electronic and manual search of the relevant articles. Studies were identified using predetermined eligibility criteria. We evaluated the demographic characteristics, clinical history, course of illness, management, and prognosis of the patients in these studies.
RESULTS
Case reports and case series, altogether consisting of 57 unique cases were included. The mean patient age for onset of psychotic symptoms was 43.4 years for men and 40.3 years for women. About 69% of patients had no prior history of psychiatric disorders. Most patients had mild COVID-19-related symptoms, with only 15 (26.3%) presenting with moderate to severe COVID-19-related disease and complications. The most commonly reported psychotic symptoms were delusions and hallucinations. Patients with psychotic symptoms were treated with antipsychotics, benzodiazepines, valproic acid, and electroconvulsive treatment. In 36 cases, psychotic symptoms resolved completely or improved significantly. Ten cases had partial improvement with residual psychotic symptoms, and one patient died due to cardiac arrest.
CONCLUSION
Most patients responded to a low-to-moderate dose of antipsychotics with a quick recovery. However, the residual psychiatric symptoms highlight the need for careful monitoring and longer follow-up. Clinicians should be mindful of the occurrence of psychosis due to COVID-19 infection in a subset of COVID-19 patients that can be misdiagnosed as a psychotic disorder alone.
Topics: Adult; Antipsychotic Agents; COVID-19; Female; Hallucinations; Humans; Male; Pandemics; Psychotic Disorders
PubMed: 35797814
DOI: 10.1016/j.jpsychires.2022.06.041 -
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 -
BMJ Open Jul 2022Consumption of the drug khat is high across East Africa and the South-Western Arabian Peninsula despite evidence for its adverse psychiatric effects. This systematic... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Consumption of the drug khat is high across East Africa and the South-Western Arabian Peninsula despite evidence for its adverse psychiatric effects. This systematic review aims to explore cross-sectional research in the field to determine the strength of the association between khat use and psychiatric symptoms METHODS: Six databases were searched in October 2021-Ovid Medline, Embase, APA PsycINFO, CINAHL, Scopus and Proquest-using the following search terms: "khat" OR "qat" OR "qaad" OR "catha" OR "miraa" OR "mairungi" AND "depression" OR "anxiety" OR "mania" OR "psych*" OR "schiz*" OR "mental" OR "hallucinations" OR "delusions" OR "bipolar". Eligible studies were cross-sectional studies of any population or setting comparing the prevalence of psychiatric symptoms in long term or dependent khat users with non-users. The quality of each study was appraised by the Newcastle-Ottawa scale. A meta-analysis was planned using a random effects model to produce an OR with 95% CIs-using the Mantel-Haenszel method-alongside an I statistic to represent heterogeneity. The quality of this meta-analysis was appraised using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) scoring system.
RESULTS
35 studies were eligible for inclusion (total participants=31 893), spanning 5 countries (Ethiopia, Somalia, Kenya, Saudi Arabia, UK). Meta-analysis suggests that khat use is associated with an 122% increased prevalence of psychiatric symptoms (OR 2.22, 95% CIs 1.76 to 2.79, p<0.00001, GRADE score: 'very low').
CONCLUSIONS
The high heterogeneity of the meta-analysis is likely due to the wide variation between the studies within the evidence base. To perform a more accurate systematic review, further primary studies are needed with standardised measurements of variables, particularly khat consumption.
PROSPERO REGISTRATION NUMBER
CRD42020224510.
Topics: Catha; Ethiopia; Humans; Prevalence; Saudi Arabia; Somalia; Substance-Related Disorders
PubMed: 35879018
DOI: 10.1136/bmjopen-2022-061865 -
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 -
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 2023Delusional misidentification syndromes (DMS) are a group of psychopathological experiences occurring in psychosis, involving the misidentification of a person or place....
INTRODUCTION
Delusional misidentification syndromes (DMS) are a group of psychopathological experiences occurring in psychosis, involving the misidentification of a person or place. DMS are often accompanied by hostility towards the object of delusional misidentification. This is of a particular concern in perinatal mental illness due to the potential disruption of the mother-infant bond, and risk of neglect, violence, or infanticide towards a misidentified child. This review aimed to collate all published cases of DMS in postpartum psychosis to further understand how these syndromes present in perinatal mental illness.
METHODS
In August 2021, an online database search was conducted using PubMed, MEDLINE, PsycINFO, CINAHL, and Embase to identify all publications reporting DMS in the perinatal period.
RESULTS
Nine papers were included in the review involving 8 case reports of Capgras syndrome and one case series involving 4 cases of Fregoli syndrome. Three cases identified organic pathology, which may have contributed to the presentation. The most common subject of misidentification was the patient's husband (n = 7), followed by their baby (n = 6), hospital staff (n = 4), other family members (n = 3), and self (n = 1). Five cases remark on the impact of perinatal illness on the maternal-infant bond, of which four result in the mother being unwilling to care for the infant as the result of their delusional beliefs.
CONCLUSION
This is the first systematic review of the literature in this field. Although small in number, these cases reveal several important learning points including that DMS can occur with or without underlying organic disease. Active exploration of the nature of delusions in postpartum psychosis is required to mitigate the risk of harm to the infant and mother-infant bond. It may also uncover that these syndromes are more common in postpartum psychosis than previously realized.
Topics: Female; Child; Humans; Capgras Syndrome; Psychotic Disorders; Delusions; Mothers; Postpartum Period
PubMed: 36116435
DOI: 10.1159/000526129 -
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 -
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