Special Issue "Genetics of Psychiatric Disease and the Basics of Neurobiology"

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (15 August 2021).

Special Issue Editors

Dr. Laia Rodriguez-Revenga
E-Mail Website
Guest Editor
Hospital Clinic de Barcelona, Centro de Diagonóstico Biomédico, Barcelona, Catalonia, Spain
Interests: fragile X syndrome; intellectual disorders; chromosome rearrangement research; molecular genetics
Dr. Maria Isabel Álvarez
E-Mail Website
Guest Editor
Centro de Diagonóstico Biomédico, Hospital Clinic de Barcelona, Barcelona, Catalonia, Spain
Interests: neurodegenerative diseases; next-generation sequencing; genetic analysis; genomics

Special Issue Information

Dear Colleagues,

Psychiatric disorders are the leading cause of disability worldwide. Most psychiatric disorders, including schizophrenia, bipolar disorder, attention deficit hyperactivity disorder (ADHD), and autism have a clear genetic component estimated at 80% or higher. The etiology of the major psychiatric disorders is a complex combination of both genetic and environmental components. Advances in our understanding of the genome, together with the advent of new high throughput technologies and analytical methods, are providing new clues to better understand the biology of psychiatric disorders. It is forecasted that new genetic testing and therapeutic strategies will result from this knowledge.

It is my great privilege and pleasure to introduce this Special Issue on Genetics of Psychiatric Disease and the Basics of Neurobiology. Psychiatric disorders constitute a major public health burden with high economic and social impact worldwide. The aim of this Special Issue is to present state-of-the-art advancements and research done in this area. In recent years, there has been an increasing number of detection of genetic variants associated with neuropsychiatric disorders. These promising findings suggest that we are at the beginning of a new era with new efforts fostering the translation of this knowledge into a precision medicine framework. Original research and review papers dealing with all aspects of “Genetics of Psychiatric Disease and the Basics of Neurobiology” are welcome for inclusion in this Special issue of Genes.

Dr. Laia Rodriguez-Revenga
Dr. Maria Isabel Álvarez
Guest Editors

Manuscript Submission Information

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Keywords

  • Psychiatric disorders
  • Brain biology
  • Genetics
  • Pharmacogenetics
  • Complex trait

Published Papers (8 papers)

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Research

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Article
A Common CDH13 Variant Is Associated with Low Agreeableness and Neural Responses to Working Memory Tasks in ADHD
Genes 2021, 12(9), 1356; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12091356 - 29 Aug 2021
Viewed by 624
Abstract
The cell—cell signaling gene CDH13 is associated with a wide spectrum of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism, and major depression. CDH13 regulates axonal outgrowth and synapse formation, substantiating its relevance for neurodevelopmental processes. Several studies support the influence of CDH13 on [...] Read more.
The cell—cell signaling gene CDH13 is associated with a wide spectrum of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism, and major depression. CDH13 regulates axonal outgrowth and synapse formation, substantiating its relevance for neurodevelopmental processes. Several studies support the influence of CDH13 on personality traits, behavior, and executive functions. However, evidence for functional effects of common gene variation in the CDH13 gene in humans is sparse. Therefore, we tested for association of a functional intronic CDH13 SNP rs2199430 with ADHD in a sample of 998 adult patients and 884 healthy controls. The Big Five personality traits were assessed by the NEO-PI-R questionnaire. Assuming that altered neural correlates of working memory and cognitive response inhibition show genotype-dependent alterations, task performance and electroencephalographic event-related potentials were measured by n-back and continuous performance (Go/NoGo) tasks. The rs2199430 genotype was not associated with adult ADHD on the categorical diagnosis level. However, rs2199430 was significantly associated with agreeableness, with minor G allele homozygotes scoring lower than A allele carriers. Whereas task performance was not affected by genotype, a significant heterosis effect limited to the ADHD group was identified for the n-back task. Heterozygotes (AG) exhibited significantly higher N200 amplitudes during both the 1-back and 2-back condition in the central electrode position Cz. Consequently, the common genetic variation of CDH13 is associated with personality traits and impacts neural processing during working memory tasks. Thus, CDH13 might contribute to symptomatic core dysfunctions of social and cognitive impairment in ADHD. Full article
(This article belongs to the Special Issue Genetics of Psychiatric Disease and the Basics of Neurobiology)
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Article
SLC6A3 (DAT1) as a Novel Candidate Biomarker Gene for Suicidal Behavior
Genes 2021, 12(6), 861; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12060861 - 04 Jun 2021
Viewed by 763
Abstract
It has been previously shown that the serotonin and dopamine neurotransmitter systems might influence the predisposition to suicidal behavior. This study aims to estimate the contribution of 11 polymorphisms in the genes SLC6A4 (5HTT), HTR1A, HTR2A, HTR1B, SLC6A3 [...] Read more.
It has been previously shown that the serotonin and dopamine neurotransmitter systems might influence the predisposition to suicidal behavior. This study aims to estimate the contribution of 11 polymorphisms in the genes SLC6A4 (5HTT), HTR1A, HTR2A, HTR1B, SLC6A3 (DAT1), DRD4, DRD2, COMT, and BDNF to suicidal behavior and severity of symptoms of depression and anxiety in the Russian population. The study was performed on 100 patients with repeated suicide attempts and 154 controls. We first found an association between SLC6A3 (DAT1) 40 bp VNTR locus and suicidal behavior. This association was significant; when using the codominant (p = 0.006), dominant (p = 0.001), overdominant (p = 0.004), and log-additive (p = 0.004) models, LL genotype played a protective role (OR = 0.48, 0.29–0.82, p = 0.005). Difference in the distribution of COMT rs4680 genotypes was significant in the codominant (p = 0.04), dominant (p = 0.013), and log-additive (p = 0.02) models, and AA genotype might protect against suicide (OR = 0.49, 0.26–0.91, p = 0.025). SLC6A4 5-HTTLPR + rs25531 locus was significant in the recessive model (p = 0.024), and also affected the severity of symptoms of depression (p = 0.044) and personal anxiety (p = 0.029). Our results suggest that allelic variants of SLC6A3, COMT, and SLC6A4 genes might be considered as risk factors for suicidal attempts. Full article
(This article belongs to the Special Issue Genetics of Psychiatric Disease and the Basics of Neurobiology)
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Article
Towards a Change in the Diagnostic Algorithm of Autism Spectrum Disorders: Evidence Supporting Whole Exome Sequencing as a First-Tier Test
Genes 2021, 12(4), 560; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12040560 - 12 Apr 2021
Cited by 2 | Viewed by 769
Abstract
Autism spectrum disorder (ASD) is a prevalent and extremely heterogeneous neurodevelopmental disorder (NDD) with a strong genetic component. In recent years, the clinical relevance of de novo mutations to the aetiology of ASD has been demonstrated. Current guidelines recommend chromosomal microarray (CMA) and [...] Read more.
Autism spectrum disorder (ASD) is a prevalent and extremely heterogeneous neurodevelopmental disorder (NDD) with a strong genetic component. In recent years, the clinical relevance of de novo mutations to the aetiology of ASD has been demonstrated. Current guidelines recommend chromosomal microarray (CMA) and a FMR1 testing as first-tier tests, but there is increasing evidence that support the use of NGS for the diagnosis of NDDs. Specifically in ASD, it has not been extensively evaluated and, thus, we performed and compared the clinical utility of CMA, FMR1 testing, and/or whole exome sequencing (WES) in a cohort of 343 ASD patients. We achieved a global diagnostic rate of 12.8% (44/343), the majority of them being characterised by WES (33/44; 75%) compared to CMA (9/44; 20.4%) or FMR1 testing (2/44; 4.5%). Taking into account the age at which genetic testing was carried out, we identified a causal genetic alteration in 22.5% (37/164) of patients over 5 years old, but only in 3.9% (7/179) of patients under this age. Our data evidence the higher diagnostic power of WES compared to CMA in the study of ASD and support the implementation of WES as a first-tier test for the genetic diagnosis of this disorder, when there is no suspicion of fragile X syndrome. Full article
(This article belongs to the Special Issue Genetics of Psychiatric Disease and the Basics of Neurobiology)
Article
Identification of Common Pathogenetic Processes between Schizophrenia and Diabetes Mellitus by Systems Biology Analysis
Genes 2021, 12(2), 237; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12020237 - 07 Feb 2021
Cited by 2 | Viewed by 981
Abstract
Schizophrenia (SCZ) is a psychiatric disorder characterized by both positive symptoms (i.e., psychosis) and negative symptoms (such as apathy, anhedonia, and poverty of speech). Epidemiological data show a high likelihood of early onset of type 2 diabetes mellitus (T2DM) in SCZ patients. However, [...] Read more.
Schizophrenia (SCZ) is a psychiatric disorder characterized by both positive symptoms (i.e., psychosis) and negative symptoms (such as apathy, anhedonia, and poverty of speech). Epidemiological data show a high likelihood of early onset of type 2 diabetes mellitus (T2DM) in SCZ patients. However, the molecular processes that could explain the epidemiological association between SCZ and T2DM have not yet been characterized. Therefore, in the present study, we aimed to identify underlying common molecular pathogenetic processes and pathways between SCZ and T2DM. To this aim, we analyzed peripheral blood mononuclear cell (PBMC) transcriptomic data from SCZ and T2DM patients, and we detected 28 differentially expressed genes (DEGs) commonly modulated between SCZ and T2DM. Inflammatory-associated processes and membrane trafficking pathways as common biological processes were found to be in common between SCZ and T2DM. Analysis of the putative transcription factors involved in the regulation of the DEGs revealed that STAT1 (Signal Transducer and Activator of Transcription 1), RELA (v-rel reticuloendotheliosis viral oncogene homolog A (avian)), NFKB1 (Nuclear Factor Kappa B Subunit 1), and ERG (ETS-related gene) are involved in the expression of common DEGs in SCZ and T2DM. In conclusion, we provide core molecular signatures and pathways that are shared between SCZ and T2DM, which may contribute to the epidemiological association between them. Full article
(This article belongs to the Special Issue Genetics of Psychiatric Disease and the Basics of Neurobiology)
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Article
Bullying Victimization in Young Females with Fragile-X-Syndrome
Genes 2020, 11(9), 1069; https://0-doi-org.brum.beds.ac.uk/10.3390/genes11091069 - 11 Sep 2020
Viewed by 849
Abstract
The aim of this study is to investigate the risk associated with girls with fragile X syndrome (FXS) suffering bullying in the role of a victim and its effects on their adaptive behavior, socialization style, and emotional state. A neuropsychological assessment was carried [...] Read more.
The aim of this study is to investigate the risk associated with girls with fragile X syndrome (FXS) suffering bullying in the role of a victim and its effects on their adaptive behavior, socialization style, and emotional state. A neuropsychological assessment was carried out on a sample of 40 participants (26 FXS positive and 14 control group) using the following instruments: WISC-V, SENA, BAS-2, ABAS-II. The results show that the group of girls with FXS presented higher ratios of lack of social support and isolation from classmates. This finding suggests that problems with social interaction and communication in the group of girls with FXS could lead to difficulties in interpreting social signals and identifying situations of bullying correctly, placing them in a very vulnerable situation. Full article
(This article belongs to the Special Issue Genetics of Psychiatric Disease and the Basics of Neurobiology)
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Review

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Review
Neuroplastin in Neuropsychiatric Diseases
Genes 2021, 12(10), 1507; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12101507 - 26 Sep 2021
Viewed by 424
Abstract
Molecular mechanisms underlying neuropsychiatric and neurodegenerative diseases are insufficiently elucidated. A detailed understanding of these mechanisms may help to further improve medical intervention. Recently, intellectual abilities, creativity, and amnesia have been associated with neuroplastin, a cell recognition glycoprotein of the immunoglobulin superfamily that [...] Read more.
Molecular mechanisms underlying neuropsychiatric and neurodegenerative diseases are insufficiently elucidated. A detailed understanding of these mechanisms may help to further improve medical intervention. Recently, intellectual abilities, creativity, and amnesia have been associated with neuroplastin, a cell recognition glycoprotein of the immunoglobulin superfamily that participates in synapse formation and function and calcium signaling. Data from animal models suggest a role for neuroplastin in pathways affected in neuropsychiatric and neurodegenerative diseases. Neuroplastin loss or disruption of molecular pathways related to neuronal processes has been linked to various neurological diseases, including dementia, schizophrenia, and Alzheimer’s disease. Here, we review the molecular features of the cell recognition molecule neuroplastin, and its binding partners, which are related to neurological processes and involved in learning and memory. The emerging functions of neuroplastin may have implications for the treatment of diseases, particularly those of the nervous system. Full article
(This article belongs to the Special Issue Genetics of Psychiatric Disease and the Basics of Neurobiology)
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Review
Schizophrenia: Complement Cleaning or Killing
Genes 2021, 12(2), 259; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12020259 - 11 Feb 2021
Cited by 1 | Viewed by 992
Abstract
Schizophrenia is a psychiatric disorder with a typical onset occurring during adolescence or young adulthood. The heterogeneity of the disorder complicates our understanding of the pathophysiology. Reduced cortical synaptic densities are commonly observed in schizophrenia and suggest a role for excessive synaptic elimination. [...] Read more.
Schizophrenia is a psychiatric disorder with a typical onset occurring during adolescence or young adulthood. The heterogeneity of the disorder complicates our understanding of the pathophysiology. Reduced cortical synaptic densities are commonly observed in schizophrenia and suggest a role for excessive synaptic elimination. A major pathway hypothesised to eliminate synapses during postnatal development is the complement system. This review provides an overview of genetic and functional evidence found for the individual players of the classical complement pathway. In addition, the consequences of the absence of complement proteins, in the form of complement protein deficiencies in humans, are taken into consideration. The collective data provide strong evidence for excessive pruning by the classical complement pathway, contributing to cognitive impairment in schizophrenia. In future studies, it will be important to assess the magnitude of the contribution of complement overactivity to the occurrence and prevalence of phenotypic features in schizophrenia. In addition, more insight is required for the exact mechanisms by which the complement system causes excessive pruning, such as the suggested involvement of microglial engulfment and degradation of synapses. Ultimately, this knowledge is a prerequisite for the development of therapeutic interventions for selective groups of schizophrenia patients. Full article
(This article belongs to the Special Issue Genetics of Psychiatric Disease and the Basics of Neurobiology)
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Other

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Case Report
Novel Compound Heterozygous Mutation in TRAPPC9 Gene: The Relevance of Whole Genome Sequencing
Genes 2021, 12(4), 557; https://0-doi-org.brum.beds.ac.uk/10.3390/genes12040557 - 12 Apr 2021
Cited by 1 | Viewed by 545
Abstract
Advances in high-throughput technologies and its implementation worldwide have had a considerable impact on the elucidation of the molecular causes underlying neurodevelopmental psychiatric disorders, especially for autism spectrum disorder and intellectual disability (ID). Nevertheless, etiology remains elusive in close to 50% of cases, [...] Read more.
Advances in high-throughput technologies and its implementation worldwide have had a considerable impact on the elucidation of the molecular causes underlying neurodevelopmental psychiatric disorders, especially for autism spectrum disorder and intellectual disability (ID). Nevertheless, etiology remains elusive in close to 50% of cases, even in those families with multiple affected individuals, strongly hinting at a genetic cause. Here we present a case report of two siblings affected with severe ID and other comorbidities, who embarked on a genetic testing odyssey until diagnosis was reached by using whole genome sequencing (WGS). WGS identified a maternally inherited novel missense variant (NM_031466.7:c.1037G > A; p.Gly346Glu) and a paternally inherited 90 kb intragenic deletion in TRAPPC9 gene. This report demonstrates the clinical utility of WGS in patients who remain undiagnosed after whole exome sequencing. Full article
(This article belongs to the Special Issue Genetics of Psychiatric Disease and the Basics of Neurobiology)
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