Neurodevelopmental Disorders and Schizophrenia: Recent Developments

2020 ◽  
pp. 213-220
Author(s):  
Kimberley Kendall ◽  
Jeremy Hall ◽  
Michael Owen
Keyword(s):  
Intellectual Disability ◽  
Neurodevelopmental Disorders ◽  
Psychotic Disorders ◽  
Autism Spectrum ◽  
Biological Pathways ◽  
The Other ◽  
Psychotic Symptoms ◽  
Clinical Implications ◽  
Recent Developments ◽  
Genetic And Environmental Factors

In this chapter the occurrence of schizophrenia, other psychotic disorders, psychotic symptoms in intellectual disability, and autism spectrum disorder is considered, as are the similarities in clinical features between these disorders. Also reviewed are the evidence for genetic overlaps between these disorders and their convergence on specific biological pathways. Finally, the evidence for overlap in environmental risk factors between these disorders is considered. Taken together these findings suggest that schizophrenia and the other functional psychoses may be related aetiologically and pathogenically with the group of neurodevelopmental disorders to which intellectual disability and autism belong. Indeed these disorders might be better conceptualized as lying on a spectrum of clinical outcomes that result from disruption to the developing brain induced by genetic and environmental factors. The chapter concludes with a discussion of the clinical implications of these findings.

scholarly journals Immunity and mental illness: findings from a Danish population-based immunogenetic study of seven psychiatric and neurodevelopmental disorders

2019 ◽  
Vol 27 (9) ◽  
pp. 1445-1455 ◽  
Author(s):  
Ron Nudel ◽  
Michael E. Benros ◽  
Morten Dybdahl Krebs ◽  
Rosa Lundbye Allesøe ◽  
Camilla Koldbæk Lemvigh ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Protective Effect ◽  
Neurodevelopmental Disorders ◽  
Association Studies ◽  
Human Leukocyte ◽  
Population Based ◽  
Autism Spectrum ◽  
Small Samples ◽  
Hla Association ◽  
Hla Genes

AbstractHuman leukocyte antigen (HLA) genes encode proteins with important roles in the regulation of the immune system. Many studies have also implicated HLA genes in psychiatric and neurodevelopmental disorders. However, these studies usually focus on one disorder and/or on one HLA candidate gene, often with small samples. Here, we access a large dataset of 65,534 genotyped individuals consisting of controls (N = 19,645) and cases having one or more of autism spectrum disorder (N = 12,331), attention deficit hyperactivity disorder (N = 14,397), schizophrenia (N = 2401), bipolar disorder (N = 1391), depression (N = 18,511), anorexia (N = 2551) or intellectual disability (N = 3175). We imputed participants’ HLA alleles to investigate the involvement of HLA genes in these disorders using regression models. We found a pronounced protective effect of DPB1*1501 on susceptibility to autism (p = 0.0094, OR = 0.72) and intellectual disability (p = 0.00099, OR = 0.41), with an increased protective effect on a comorbid diagnosis of both disorders (p = 0.003, OR = 0.29). We also identified a risk allele for intellectual disability, B*5701 (p = 0.00016, OR = 1.33). Associations with both alleles survived FDR correction and a permutation procedure. We did not find significant evidence for replication of previously-reported associations for autism or schizophrenia. Our results support an implication of HLA genes in autism and intellectual disability, which requires replication by other studies. Our study also highlights the importance of large sample sizes in HLA association studies.

scholarly journals Risk of neurodevelopmental disorders in children born from different ART treatments: a systematic review and meta-analysis

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Tono Djuwantono ◽  
Jenifer Kiem Aviani ◽  
Wiryawan Permadi ◽  
Tri Hanggono Achmad ◽  
Danny Halim
Keyword(s):  
Systematic Review ◽  
Cerebral Palsy ◽  
Intellectual Disability ◽  
Assisted Reproductive Technology ◽  
Risk Ratio ◽  
Neurodevelopmental Disorders ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Reproductive Technology ◽  
Multiple Birth

Abstract Background Various techniques in assisted reproductive technology (ART) have been developed as solutions for specific infertility problems. It is important to gain consensual conclusions on the actual risks of neurodevelopmental disorders among children who are born from ART. This study aimed to quantify the relative risks of cerebral palsy, intellectual disability, autism spectrum disorder (ASD), and behavioral problems in children from different ART methods by using systematic review and meta-analysis. Healthcare providers could use the results of this study to suggest the suitable ART technique and plan optimum postnatal care. Methods Pubmed, Google Scholar, and Scopus databases were used to search for studies up to January 2020. Of the 181 screened full manuscripts, 17 studies (9.39%) fulfilled the selection criteria. Based on the Newcastle-Ottawa scale ratings, 7 studies were excluded, resulting in 10 studies that were eventually included in the meta-analyses. Mantel-Haenszel risk ratio model was used in the meta-analysis, and the results are described using forest plot with 95% confidence interval. Heterogeneity was assessed using the I2 value. Results Pooled evaluation of 10 studies showed that the risk of cerebral palsy in children from assisted reproductive technology (ART) is higher than children from natural conceptions (risk ratio [RR] 1.82, [1.41, 2.34]; P = 0.00001). Risk of intellectual disability (RR 1.46, [1.03, 2.08]; P = 0.03) and ASD (RR 1.49 [1.05, 2.11]; P = 0.03) are higher in intracytoplasmic sperm injection (ICSI) children compared to conventional in vitro fertilization (IVF) children. The differences in the risk of neurodevelopmental disorders in children born after frozen and fresh embryo transfers are not significant. Analysis on potential cofounder effects, including multiple birth, preterm birth, and low birth body weight highlight possibilities of significant correlation to the risks of neurodevelopmental disorders. Conclusions Pooled estimates suggest that children born after ART are at higher risk of acquiring cerebral palsy. ICSI treatment causes higher risk of intellectual disability and ASD. These findings suggest the importance of the availability of intensive care unit at the time of delivery and long-term developmental evaluation particularly in children from ICSI.

scholarly journals Association of maternal diabetes with neurodevelopmental disorders: autism spectrum disorders, attention-deficit/hyperactivity disorder and intellectual disability

2020 ◽  
Author(s):  
Shuyun Chen ◽  
Sixian Zhao ◽  
Christina Dalman ◽  
Håkan Karlsson ◽  
Renee Gardner
Keyword(s):  
Diabetes Mellitus ◽  
Attention Deficit Hyperactivity Disorder ◽  
Autism Spectrum Disorders ◽  
Intellectual Disability ◽  
Attention Deficit ◽  
Neurodevelopmental Disorders ◽  
Maternal Diabetes ◽  
Autism Spectrum ◽  
Hyperactivity Disorder ◽  
Spectrum Disorders

Abstract Background Maternal diabetes has been associated with a risk of neurodevelopmental disorders (NDDs) in offspring, though the common co-occurrence of autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD) and intellectual disability (ID) is rarely considered, nor is the potential for confounding by shared familial factors (e.g. genetics). Methods This population-based cohort study used data from Psychiatry Sweden, a linkage of Swedish national registers, to follow 2 369 680 individuals born from 1987 to 2010. We used population-averaged logit models to examine the association between exposure to maternal type 1 diabetes mellitus (T1DM), pre-gestational type 2 diabetes mellitus (T2DM) or gestational diabetes mellitus (GDM), and odds of NDDs in offspring. Subgroup analysis was then performed to investigate the timings of GDM diagnosis during pregnancy and its effect on the odds of NDDs in offspring. We compared these results to models considering paternal lifetime T1DM and T2DM as exposures. Results Overall, 45 678 individuals (1.93%) were diagnosed with ASD, 20 823 (0.88%) with ID and 102 018 (4.31%) with ADHD. All types of maternal diabetes were associated with odds of NDDs, with T2DM most strongly associated with any diagnosis of ASD (odds ratioadjusted 1.37, 95% confidence interval 1.03–1.84), ID (2.09, 1.53–2.87) and ADHD (1.43, 1.16–1.77). Considering common co-morbid groups, the associations were strongest between maternal diabetes and diagnostic combinations that included ID. Paternal T1DM and T2DM diagnoses were also associated with offspring NDDs, but these associations were weaker than those with maternal diabetes. Diagnosis of GDM between 27 and 30 weeks of gestation was generally associated with the greatest risk of NDDs in offspring, with the strongest associations for outcomes that included ID. Conclusion The association of maternal diabetes with NDDs in offspring varies depending on the co-morbid presentation of the NDDs, with the greatest odds associated with outcomes that included ID. Results of paternal-comparison studies suggest that the above associations are likely to be partly confounded by shared familial factors, such as genetic liability.

scholarly journals Diagnostic and Therapeutic Challenges of Catatonia in an Adolescent With High Functioning Autism Spectrum Disorder: A Case Report

2021 ◽  
Vol 12 ◽  
Author(s):  
Annalisa Traverso ◽  
Caterina Ancora ◽  
Silvia Zanato ◽  
Alessia Raffagnato ◽  
Michela Gatta
Keyword(s):  
Autism Spectrum Disorder ◽  
Neurodevelopmental Disorders ◽  
High Functioning Autism ◽  
Signs And Symptoms ◽  
Autism Spectrum ◽  
Sudden Onset ◽  
Spectrum Disorder ◽  
Psychotic Symptoms ◽  
High Functioning ◽  
Long Time

Catatonia is a psychomotor syndrome with specific clusters of speech, behavioral and motor features. Although potentially life-threatening, especially in its malignant form accompanied with autonomic dysregulation and medical complications, it is a treatable condition, when promptly identified. For a long time catatonia was considered a marker of schizophrenia, thus limiting the possibility of diagnosis and treatment. Due to growing awareness and studies on the subject, it is now known that catatonia can occur in the context of a number of diseases, including psychotic, affective and neurodevelopmental disorders. In recent years, there's been a renewed interest in the recognition and definition of catatonia in neurodevelopmental disorders, such as Autism Spectrum Disorder (ASD), where the differential diagnosis poses great challenges, given the considerable overlapping of signs and symptoms between the conditions. We present the case of a 15 year old boy with High Functioning ASD with a sudden onset of severe catatonic symptoms and the co-existence of psychotic symptoms, whose complex clinical course raises many questions on the differentiation and relation of said disorders.

scholarly journals Male-specific CREB signaling in the hippocampus controls spatial memory deficits in a mouse model of autism and intellectual disability

2018 ◽  
Author(s):  
Marta Zamarbide ◽  
Adele Mossa ◽  
Molly K. Wilkinson ◽  
Heather L. Pond ◽  
Adam W. Oaks ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Mouse Model ◽  
Neurodevelopmental Disorders ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Coiled Coil ◽  
Autism Spectrum ◽  
Behavioral Studies ◽  
Males And Females ◽  
Male Specific

ABSTRACTBackgroundThe prevalence of neurodevelopmental disorders is biased towards males with male: female ratios of 2:1 in intellectual disability (ID) and 4:1 in autism spectrum disorder (ASD). However, the molecular mechanisms of such bias remain unknown. While characterizing a mouse model for loss of the signaling scaffold coiled-coil and C2 domain containing 1A (CC2D1A), which is mutated in ID and ASD, we identified biochemical and behavioral differences between males and females, and explored whether CC2D1A controls male-specific intracellular signaling.MethodsCC2D1A is known to regulate phosphodiesterase 4D (PDE4D). We tested for activation PDE4D and downstream signaling molecules such as CREB in the hippocampus of Cc2d1a-deficient mice. We then performed behavioral studies in females to analyze learning and memory, social interactions, anxiety and hyperactivity. Finally, we targeted PDE4D activation with a PDE4D inhibitor to define how changes in PDE4D and CREB activity affect behavior in males and females.ResultsWe found that in Cc2d1a-deficient males PDE4D is hyperactive leading to a reduction in CREB signaling, but this molecular deficit is not present in females. Cc2d1a-deficient females only show impairment in novel object recognition, and no other cognitive and social deficits that have been found in males. Restoring PDE4D activity using an inhibitor rescues male-specific cognitive deficits, but has no effect on females.ConclusionsOur findings show that CC2D1A regulates intracellular signaling in a male-specific manner in the hippocampus leading to male-specific behavioral deficits. We propose that male-specific signaling mechanisms are involved in establishing sex bias in neurodevelopmental disorders.

Novel Therapeutics in Childhood Onset Psychiatric Disorders

2013 ◽  
pp. 1061-1064
Author(s):  
Dorothy E. Grice ◽  
Alexander Kolevzon ◽  
Walter E. Kaufmann ◽  
Joseph D. Buxbaum
Keyword(s):  
Autism Spectrum Disorder ◽  
Clinical Trials ◽  
Down Syndrome ◽  
Intellectual Disability ◽  
Neurodevelopmental Disorders ◽  
Autism Spectrum ◽  
Model Systems ◽  
Childhood Onset ◽  
Preclinical Evaluation ◽  
Novel Therapeutics

Neurodevelopmental disorders are frequently the result of genetic and genomic abnormalities associated with high risk for disease. Creating analogous mutations in cell and animal models permits the assessment of underlying neurobiological mechanisms, generates clues about useful therapeutic targets, and provides systems for preclinical evaluation of novel therapeutics. This chapter briefly summarizes several clinical trials in neurodevelopmental disorders, all based on neurobiological findings in model systems, including trials in Down syndrome (DS) and several monogenic forms of intellectual disability (ID) and/or autism spectrum disorder (ASD).

scholarly journals Acute psychotic disorders induced by topiramate: report of two cases

2002 ◽  
Vol 60 (2A) ◽  
pp. 285-287 ◽  
Author(s):  
Florindo Stella ◽  
Dorgival Caetano ◽  
Fernando Cendes ◽  
Carlos A.M. Guerreiro
Keyword(s):  
Antipsychotic Drugs ◽  
Psychotic Disorders ◽  
The Other ◽  
Psychotic Symptoms ◽  
Acute Psychosis ◽  
Visual Hallucinations ◽  
Psychomotor Agitation ◽  
Full Remission ◽  
Epileptic Patients ◽  
Severe Anxiety

We report on two epileptic patients who developed acute psychosis after the use of topiramate (TPM). One patient exhibited severe psychomotor agitation, heteroaggressiveness, auditory and visual hallucinations as well as severe paranoid and mystic delusions. The other patient had psychomotor agitation, depersonalization, derealization, severe anxiety and deluded that he was losing his memory. Both patients had to be taken to the casualty room. After interruption of TPM in one patient and reduction of dose in the other, a full remission of the psychotic symptoms was obtained without the need of antipsychotic drugs. Clinicians should be aware of the possibility of development of acute psychotic symptoms in patients undergoing TPM treatment.

scholarly journals A phenomenological approach to diagnosing psychosis in autism spectrum disorder and intellectual disability: a case series

2018 ◽  
Vol 4 (2) ◽  
pp. 39-48
Author(s):  
Rahul Rai ◽  
Samuel Tromans ◽  
Chaya Kapugama ◽  
Verity Chester ◽  
Ignatius Gunaratna ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Autism Spectrum Disorder ◽  
Intellectual Disability ◽  
Case Series ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Psychotic Symptoms ◽  
Related Case ◽  
Content Type

Purpose The diagnosis of psychosis in individuals with autism spectrum disorder (ASD) poses a unique clinical challenge. The presence of intellectual disability (ID) further complicates the diagnostic picture. Reliable and timely diagnosis of psychosis in such individuals minimises the duration of untreated psychotic symptoms and the subsequent impact on the quality of life of the patients concerned. The paper aims to discuss this issue. Design/methodology/approach The authors present four patients with psychosis, ASD and ID, who have received care within forensic mental health and ID settings. These examples demonstrate the interaction between these conditions, as well as issues pertaining to diagnosis and management. Findings In all four patients, sustained use of antipsychotic medication was objectively associated with an improvement in psychotic symptoms and quality of life. In instances where autistic phenomena were accentuated upon development of psychosis, such features returned to the baseline levels evident prior to the onset of psychosis. Practical implications The discussion and related case examples could improve the understanding of the possibility of psychosis in individuals with ASD and ID, and increase awareness of this diagnostic possibility among healthcare professionals. Originality/value This is the first published case series illustrating the challenges of diagnosing psychosis in individuals with ASD and ID.

scholarly journals Exome Sequencing in 200 Intellectual Disability/Autistic Patients: New Candidates and Atypical Presentations

2021 ◽  
Vol 11 (7) ◽  
pp. 936
Author(s):  
Floriana Valentino ◽  
Lucia Pia Bruno ◽  
Gabriella Doddato ◽  
Annarita Giliberti ◽  
Rossella Tita ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Intellectual Disability ◽  
Exome Sequencing ◽  
Neurodevelopmental Disorders ◽  
Detection Rate ◽  
Autism Spectrum ◽  
Genetic Syndromes ◽  
Disease Heterogeneity ◽  
Pathogenic Variants ◽  
Atypical Presentations

Intellectual disability (ID) and autism spectrum disorder (ASD) belong to neurodevelopmental disorders and occur in ~1% of the general population. Due to disease heterogeneity, identifying the etiology of ID and ASD remains challenging. Exome sequencing (ES) offers the opportunity to rapidly identify variants associated with these two entities that often co-exist. Here, we performed ES in a cohort of 200 patients: 84 with isolated ID and 116 with ID and ASD. We identified 41 pathogenic variants with a detection rate of 22% (43/200): 39% in ID patients (33/84) and 9% in ID/ASD patients (10/116). Most of the causative genes are genes responsible for well-established genetic syndromes that have not been recognized for atypical phenotypic presentations. Two genes emerged as new candidates: CACNA2D1 and GPR14. In conclusion, this study reinforces the importance of ES in the diagnosis of ID/ASD and underlines that “reverse phenotyping” is fundamental to enlarge the phenotypic spectra associated with specific genes.

scholarly journals First Report of a de novo 10q23.31q23.33 Microdeletion: Obesity, Intellectual Disability and Microcephaly

2021 ◽  
pp. 1-5
Author(s):  
Ayberk Turkyilmaz ◽  
Erdal Kurnaz ◽  
Atilla Cayir
Keyword(s):  
Intellectual Disability ◽  
Array Cgh ◽  
De Novo ◽  
Chromosomal Abnormalities ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Autism Spectrum ◽  
Comparative Genomic ◽  
Facial Dysmorphism ◽  
Genetic And Environmental Factors

Intellectual disability (ID) is characterized by limited or insufficient development of mental abilities, including intellectual functioning impairments, such as learning and understanding cause-effect relationships. Some cases have ID as the only finding and are called isolated cases. Conversely, cases accompanied by facial dysmorphism, microcephaly, autism spectrum disorder, epilepsy, obesity, and congenital anomalies are called syndromic developmental delay (DD)/ID. Isolated and syndromic DD/ID cases show extreme genetic heterogeneity. Genetic etiology can be detected in approximately 40% of the cases, whereas chromosomal abnormalities are observed in 25%. Obesity is a multifactorial disease in which both genetic and environmental factors play important roles. The role of heredity in obesity has been reported to be between 40 and 70%. Array-based comparative genomic hybridization (array-CGH) can detect CNVs in the whole genome at a higher resolution than conventional cytogenetic methods. Array-CGH is currently recommended as the first-tier genetic test for ID cases worldwide. In the present study, we aimed to evaluate clinical, radiological, and genetic analyses of a 12-year and 4-month-old girl with microcephaly, ID, and obesity. In the array-CGH analysis, a 3.1-Mb deletion, arr[GRGh37] 10q23.31g23.33 (92745793_95937944)×1 was detected, and this alteration was evaluated to be pathogenic. We consider that haploinsufficiency of the candidate genes (<i>GPR120</i>, <i>KIF11</i>, <i>EXOC6</i>, <i>CYP26A1</i>, <i>CYP26C1</i>, and <i>LGI1</i>) in the deletion region may explain microcephaly, ID, obesity, seizures, and ophthalmological findings in our patient. The investigation of 10q23.31q23.33 microdeletion in cases with syndromic obesity may contribute to molecular genetic diagnosis.

Sign in / Sign up

Export Citation Format

Share Document