Genetic Basis Underlying Neuropsychiatric Disorders

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

Deadline for manuscript submissions: closed (20 October 2022) | Viewed by 24751

Special Issue Editor

Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA
Interests: neuropsychiatric disorders; schizophrenia; depression; ADHD; autism; substance dependence; genetics; risk SNPs; mRNA expression
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Numerous neuropsychiatric disorders, endophenotypes, personality and neuroimaging traits share common genetic bases, which may underlie their common symptoms/characters, high rate of comorbidity, or common neuropathogenesis. However, these shared genetic factors have not been comprehensively and systematically investigated. The aim of this Special Issue is to collect the research findings on this topic. The reliable findings with independent self-validation, innovative study designs, cutting-edge analytic approaches, and/or at genome-wide scale are especially welcomed.

Dr. Xingguang Luo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Neuropsychiatric disorders
  • Genetics
  • Neuroimaging
  • Shared heritability
  • Genome-wide
  • Comorbidity
  • Common pathogenesis base

Published Papers (10 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

16 pages, 482 KiB  
Article
Phenotypic Spectrum of NFIA Haploinsufficiency: Two Additional Cases and Review of the Literature
by Veronica Bertini, Francesca Cambi, Alessandro Orsini, Alice Bonuccelli, Aureliano Fiorini, Andrea Santangelo, Massimo Scacciati, Maurizio Elia, Ornella Galesi, Diego Peroni and Angelo Valetto
Genes 2022, 13(12), 2249; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13122249 - 30 Nov 2022
Cited by 3 | Viewed by 1541
Abstract
The NFIA (nuclear factor I/A) gene encodes for a transcription factor belonging to the nuclear factor I family and has key roles in various embryonic differentiation pathways. In humans, NFIA is the major contributor to the phenotypic traits of “Chromosome 1p32p31 deletion syndrome”. [...] Read more.
The NFIA (nuclear factor I/A) gene encodes for a transcription factor belonging to the nuclear factor I family and has key roles in various embryonic differentiation pathways. In humans, NFIA is the major contributor to the phenotypic traits of “Chromosome 1p32p31 deletion syndrome”. We report on two new cases with deletions involving NFIA without any other pathogenic protein-coding gene alterations. A cohort of 24 patients with NFIA haploinsufficiency as the sole anomaly was selected by reviewing the literature and public databases in order to analyze all clinical features reported and their relative frequencies. This process was useful because it provided an overall picture of the phenotypic outcome of NFIA haploinsufficiency and helped to define a cluster of phenotypic traits that can facilitate clinicians in identifying affected patients. NFIA haploinsufficiency can be suspected by a careful observation of the dysmorphisms (macrocephaly, craniofacial, and first-finger anomalies), and this potential diagnosis is strengthened by the presence of intellectual and developmental disabilities or other neurodevelopmental disorders. Further clues of NFIA haploinsufficiency can be provided by instrumental tests such as MRI and kidney urinary tract ultrasound and confirmed by genetic testing. Full article
(This article belongs to the Special Issue Genetic Basis Underlying Neuropsychiatric Disorders)
Show Figures

Figure 1

8 pages, 810 KiB  
Article
Genetic Dysruption of the Histaminergic Pathways: A Novel Deletion at the 15q21.2 locus Associated with Variable Expressivity of Neuropsychiatric Disorders
by Carla Lintas, Roberto Sacco, Alessia Azzarà, Ilaria Cassano, Luigi Laino, Paola Grammatico and Fiorella Gurrieri
Genes 2022, 13(10), 1685; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13101685 - 20 Sep 2022
Viewed by 1285
Abstract
The involvement of the Histaminergic System (HS) in neuropsychiatric disease is not well-documented, and few studies have described patients affected by different neuropsychiatric conditions harbouring disruptions in genes involved in the HS. In humans, histamine is synthetised from histidine by the histidine decarboxylase [...] Read more.
The involvement of the Histaminergic System (HS) in neuropsychiatric disease is not well-documented, and few studies have described patients affected by different neuropsychiatric conditions harbouring disruptions in genes involved in the HS. In humans, histamine is synthetised from histidine by the histidine decarboxylase enzyme encoded by the HDC gene (OMIM*142704). This is the sole enzyme in our organism able to synthetise histamine from histidine. Histamine is also contained in many different food types. We hereby describe a twenty-one-year-old female diagnosed with a borderline intellectual disability with autistic traits and other peculiar neuropsychological features carrying a 175-Kb interstitial deletion on chromosome 15q21.2. The deletion was inherited from the mother, who was affected by a severe anxiety disorder. The deleted region contains entirely the HDC and the SLC27A2 genes and partially the ATP8B4 gene. The HDC gene has been previously associated with Tourette Syndrome (TS). Based on the functional role of the HDC, we propose this gene as the best candidate to explain many traits associated with the clinical phenotype of our patient and of her mother. Full article
(This article belongs to the Special Issue Genetic Basis Underlying Neuropsychiatric Disorders)
Show Figures

Figure 1

7 pages, 905 KiB  
Article
Biallelic Loss of Function Mutation in Sodium Channel Gene SCN10A in an Autism Spectrum Disorder Trio from Pakistan
by Ansa Rabia, Ricardo Harripaul, Anna Mikhailov, Saqib Mahmood, Shazia Maqbool, John B. Vincent and Muhammad Ayub
Genes 2022, 13(9), 1633; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13091633 - 11 Sep 2022
Cited by 1 | Viewed by 1999
Abstract
The genetic dissection of autism spectrum disorders (ASD) has uncovered the contribution of de novo mutations in many single genes as well as de novo copy number variants. More recent work also suggests a strong contribution from recessively inherited variants, particularly in populations [...] Read more.
The genetic dissection of autism spectrum disorders (ASD) has uncovered the contribution of de novo mutations in many single genes as well as de novo copy number variants. More recent work also suggests a strong contribution from recessively inherited variants, particularly in populations in which consanguineous marriages are common. What is also becoming more apparent is the degree of pleiotropy, whereby mutations in the same gene may have quite different phenotypic and clinical consequences. We performed whole exome sequencing in a group of 115 trios from countries with a high level of consanguineous marriages. In this paper we report genetic and clinical findings on a proband with ASD, who inherited a biallelic truncating pathogenic/likely pathogenic variant in the gene encoding voltage-gated sodium channel X alpha subunit, SCN10A (NM_006514.2:c.937G>T:(p.Gly313*)). The biallelic pathogenic/likely pathogenic variant in this study have different clinical features than heterozygous mutations in the same gene. The study of consanguineous families for autism spectrum disorder is highly valuable. Full article
(This article belongs to the Special Issue Genetic Basis Underlying Neuropsychiatric Disorders)
Show Figures

Figure 1

15 pages, 5833 KiB  
Article
Exploring the Core Genes of Schizophrenia Based on Bioinformatics Analysis
by Shunkang Feng, Ping Sun, Chunhui Qu, Xiaohui Wu, Lu Yang, Tao Yang, Shuo Wang, Yiru Fang and Jun Chen
Genes 2022, 13(6), 967; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13060967 - 27 May 2022
Cited by 2 | Viewed by 2411
Abstract
Schizophrenia is a clinical syndrome composed of a group of symptoms involving many obstacles such as perception, thinking, emotion, behavior, and the disharmony of mental activities. Schizophrenia is one of the top ten causes of disability globally, accounting for about 1% of the [...] Read more.
Schizophrenia is a clinical syndrome composed of a group of symptoms involving many obstacles such as perception, thinking, emotion, behavior, and the disharmony of mental activities. Schizophrenia is one of the top ten causes of disability globally, accounting for about 1% of the global population. Previous studies have shown that schizophrenia has solid genetic characteristics. However, the diagnosis of schizophrenia mainly depends on symptomatic manifestations, and no gene can be used as a clear diagnostic marker at present. This study explored the hub genes of schizophrenia by bioinformatics analysis. Three datasets were selected and downloaded from the GEO database (GSE53987, GSE21138, and GSE27383). GEO2R, NCBI’s online analysis tool, is used to screen out significant gene expression differences. The genes were functionally enriched by GO and KEGG enrichment analysis. On this basis, the hub genes were explored through Cytoscape software, and the immune infiltration analysis and diagnostic value of the screened hub genes were judged. Finally, four hub genes (NFKBIA, CDKN1A, BTG2, GADD45B) were screened. There was a significant correlation between two hub genes (NFKBIA, BTG2) and resting memory CD4 T cells. The ROC curve results showed that all four hub genes had diagnostic value. Full article
(This article belongs to the Special Issue Genetic Basis Underlying Neuropsychiatric Disorders)
Show Figures

Figure 1

13 pages, 1213 KiB  
Article
Enhancing DLG2 Implications in Neuropsychiatric Disorders: Analysis of a Cohort of Eight Patients with 11q14.1 Imbalances
by Veronica Bertini, Roberta Milone, Paola Cristofani, Francesca Cambi, Chiara Bosetti, Filippo Barbieri, Silvano Bertelloni, Giovanni Cioni, Angelo Valetto and Roberta Battini
Genes 2022, 13(5), 859; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13050859 - 12 May 2022
Cited by 4 | Viewed by 1949
Abstract
Neurodevelopmental disorders (NDDs) are considered synaptopathies, as they are due to anomalies in neuronal connectivity during development. DLG2 is a gene involved insynaptic function; the phenotypic effect of itsalterations in NDDs has been underestimated since few cases have been thoroughly described.We report on [...] Read more.
Neurodevelopmental disorders (NDDs) are considered synaptopathies, as they are due to anomalies in neuronal connectivity during development. DLG2 is a gene involved insynaptic function; the phenotypic effect of itsalterations in NDDs has been underestimated since few cases have been thoroughly described.We report on eight patients with 11q14.1 imbalances involving DLG2, underlining its potential effects on clinical presentation and its contribution to NDD comorbidity by accurate neuropsychiatric data collection. DLG2 is a very large gene in 11q14.1, extending over 2.172 Mb, with alternative splicing that gives rise to numerous isoforms differentially expressed in brain tissues. A thorough bioinformatic analysis of the altered transcripts was conducted for each patient. The different expression profiles of the isoforms of this gene and their influence on the excitatory–inhibitory balance in crucial brain structures could contribute to the phenotypic variability related to DLG2 alterations. Further studies on patients would be helpful to enrich clinical and neurodevelopmental findings and elucidate the molecular mechanisms subtended to NDDs. Full article
(This article belongs to the Special Issue Genetic Basis Underlying Neuropsychiatric Disorders)
Show Figures

Figure 1

8 pages, 508 KiB  
Article
Schizophrenia and Bipolar Polygenic Risk Scores in Relation to Intracranial Volume
by Sonja M. C. de Zwarte, Rachel M. Brouwer, René S. Kahn and Neeltje E. M. van Haren
Genes 2022, 13(4), 695; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13040695 - 14 Apr 2022
Cited by 1 | Viewed by 2259
Abstract
Schizophrenia and bipolar disorder are neurodevelopmental disorders with overlapping symptoms and a shared genetic background. Deviations in intracranial volume (ICV)—a marker for neurodevelopment—differ between schizophrenia and bipolar disorder. Here, we investigated whether genetic risk for schizophrenia and bipolar disorder is related to ICV [...] Read more.
Schizophrenia and bipolar disorder are neurodevelopmental disorders with overlapping symptoms and a shared genetic background. Deviations in intracranial volume (ICV)—a marker for neurodevelopment—differ between schizophrenia and bipolar disorder. Here, we investigated whether genetic risk for schizophrenia and bipolar disorder is related to ICV in the general population by using the UK Biobank data (n = 20,196). Polygenic risk scores for schizophrenia (SZ-PRS) and bipolar disorder (BD-PRS) were computed for 12 genome wide association study P-value thresholds (PT) for each individual and correlations with ICV were investigated. Partial correlations were performed at each PT to investigate whether disease specific genetic risk variants for schizophrenia and bipolar disorder show different relationships with ICV. ICV showed a negative correlation with SZ-PRS at PT ≥ 0.005 (r < −0.02, p < 0.005). ICV was not associated with BD-PRS; however, a positive correlation between BD-PRS and ICV at PT = 0.2 and PT = 0.4 (r = +0.02, p < 0.005) appeared when the genetic overlap between schizophrenia and bipolar disorder was accounted for. Despite small effect sizes, a higher load of schizophrenia risk genes is associated with a smaller ICV in the general population, while risk genes specific for bipolar disorder are correlated with a larger ICV. These findings suggest that schizophrenia and bipolar disorder risk genes, when accounting for the genetic overlap between both disorders, have opposite effects on early brain development. Full article
(This article belongs to the Special Issue Genetic Basis Underlying Neuropsychiatric Disorders)
Show Figures

Figure 1

10 pages, 1459 KiB  
Article
Possible Catch-Up Developmental Trajectories for Children with Mild Developmental Delay Caused by NAA15 Pathogenic Variants
by Yu Tian, Hua Xie, Shenghai Yang, Shaofang Shangguan, Jianhong Wang, Chunhua Jin, Yu Zhang, Xiaodai Cui, Yanyu Lyu, Xiaoli Chen and Lin Wang
Genes 2022, 13(3), 536; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13030536 - 18 Mar 2022
Cited by 2 | Viewed by 2436
Abstract
Variants in NAA15 are closely related to neurodevelopmental disorders (NDDs). In this study, we investigated the spectrum and clinical features of NAA15 variants in a Chinese NDD cohort of 769 children. Four novel NAA15 pathogenic variants were detected by whole-exome sequencing, including three [...] Read more.
Variants in NAA15 are closely related to neurodevelopmental disorders (NDDs). In this study, we investigated the spectrum and clinical features of NAA15 variants in a Chinese NDD cohort of 769 children. Four novel NAA15 pathogenic variants were detected by whole-exome sequencing, including three de novo variants and one maternal variant. The in vitro minigene splicing assay confirmed one noncanonical splicing variant (c.1410+5G>C), which resulted in abnormal mRNA splicing. All affected children presented mild developmental delay, and catch-up trajectories were noted in three patients based on their developmental scores at different ages. Meanwhile, the literature review also showed that half of the reported patients with NAA15 variants presented mild/moderate developmental delay or intellectual disability, and possible catch-up sign was indicated for three affected patients. Taken together, our study expanded the spectrum of NAA15 variants in NDD patients. The affected patients presented mild developmental delay, and possible catch-up developmental trajectories were suggested. Studying the natural neurodevelopmental trajectories of NDD patients with pathogenic variants and their benefits from physical rehabilitations are needed in the future for precise genetic counseling and clinical management. Full article
(This article belongs to the Special Issue Genetic Basis Underlying Neuropsychiatric Disorders)
Show Figures

Figure 1

14 pages, 1287 KiB  
Article
Polygenic Risk for Schizophrenia Has Sex-Specific Effects on Brain Activity during Memory Processing in Healthy Individuals
by Elise Koch, Lars Nyberg, Anders Lundquist and Karolina Kauppi
Genes 2022, 13(3), 412; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13030412 - 24 Feb 2022
Cited by 2 | Viewed by 1812
Abstract
Genetic risk for schizophrenia has a negative impact on memory and other cognitive abilities in unaffected individuals, and it was recently shown that this effect is specific to males. Using functional MRI, we investigated the effect of a polygenic risk score (PRS) for [...] Read more.
Genetic risk for schizophrenia has a negative impact on memory and other cognitive abilities in unaffected individuals, and it was recently shown that this effect is specific to males. Using functional MRI, we investigated the effect of a polygenic risk score (PRS) for schizophrenia on brain activation during working memory and episodic memory in 351 unaffected participants (167 males and 184 females, 25–95 years), and specifically tested if any effect of PRS on brain activation is sex-specific. Schizophrenia PRS was significantly associated with decreased brain activation in the left dorsolateral prefrontal cortex (DLPFC) during working-memory manipulation and in the bilateral superior parietal lobule (SPL) during episodic-memory encoding and retrieval. A significant interaction effect between sex and PRS was seen in the bilateral SPL during episodic-memory encoding and retrieval, and sex-stratified analyses showed that the effect of PRS on SPL activation was male-specific. These results confirm previous findings of DLPFC inefficiency in schizophrenia, and highlight the SPL as another important genetic intermediate phenotype of the disease. The observed sex differences suggest that the previously shown male-specific effect of schizophrenia PRS on cognition translates into an additional corresponding effect on brain functioning. Full article
(This article belongs to the Special Issue Genetic Basis Underlying Neuropsychiatric Disorders)
Show Figures

Figure 1

Review

Jump to: Research

27 pages, 448 KiB  
Review
Psychosis in Parkinson’s Disease: A Lesson from Genetics
by Efthalia Angelopoulou, Anastasia Bougea, Sokratis G. Papageorgiou and Chiara Villa
Genes 2022, 13(6), 1099; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13061099 - 20 Jun 2022
Cited by 5 | Viewed by 3147
Abstract
Psychosis in Parkinson’s disease (PDP) represents a common and debilitating condition that complicates Parkinson’s disease (PD), mainly in the later stages. The spectrum of psychotic symptoms are heterogeneous, ranging from minor phenomena of mild illusions, passage hallucinations and sense of presence to severe [...] Read more.
Psychosis in Parkinson’s disease (PDP) represents a common and debilitating condition that complicates Parkinson’s disease (PD), mainly in the later stages. The spectrum of psychotic symptoms are heterogeneous, ranging from minor phenomena of mild illusions, passage hallucinations and sense of presence to severe psychosis consisting of visual hallucinations (and rarely, auditory and tactile or gustatory) and paranoid delusions. PDP is associated with increased caregiver stress, poorer quality of life for patients and carers, reduced survival and risk of institutionalization with a significant burden on the healthcare system. Although several risk factors for PDP development have been identified, such as aging, sleep disturbances, long history of PD, cognitive impairment, depression and visual disorders, the pathophysiology of psychosis in PD is complex and still insufficiently clarified. Additionally, several drugs used to treat PD can aggravate or even precipitate PDP. Herein, we reviewed and critically analyzed recent studies exploring the genetic architecture of psychosis in PD in order to further understand the pathophysiology of PDP, the risk factors as well as the most suitable therapeutic strategies. Full article
(This article belongs to the Special Issue Genetic Basis Underlying Neuropsychiatric Disorders)
Show Figures

Graphical abstract

17 pages, 684 KiB  
Review
The Molecular Genetics of Dissociative Symptomatology: A Transdiagnostic Literature Review
by Ravi Philip Rajkumar
Genes 2022, 13(5), 843; https://0-doi-org.brum.beds.ac.uk/10.3390/genes13050843 - 08 May 2022
Cited by 1 | Viewed by 4198
Abstract
Dissociative disorders are a common and frequently undiagnosed group of psychiatric disorders, characterized by disruptions in the normal integration of awareness, personality, emotion and behavior. The available evidence suggests that these disorders arise from an interaction between genetic vulnerability and stress, particularly traumatic [...] Read more.
Dissociative disorders are a common and frequently undiagnosed group of psychiatric disorders, characterized by disruptions in the normal integration of awareness, personality, emotion and behavior. The available evidence suggests that these disorders arise from an interaction between genetic vulnerability and stress, particularly traumatic stress, but the attention paid to the underlying genetic diatheses has been sparse. In this paper, the existing literature on the molecular genetics of dissociative disorders, as well as of clinically significant dissociative symptoms not reaching the threshold of a disorder, is reviewed comprehensively across clinical and non-clinical samples. Association studies suggest a link between dissociative symptoms and genes related to serotonergic, dopaminergic and peptidergic transmission, neural plasticity and cortisol receptor sensitivity, particularly following exposure to childhood trauma. Genome-wide association studies have identified loci of interest related to second messenger signaling and synaptic integration. Though these findings are inconsistent, they suggest biologically plausible mechanisms through which traumatic stress can lead to pathological dissociation. However, methodological concerns related to phenotype definition, study power, and correction for the confounding factors limit the value of these findings, and they require replication and extension in studies with better design. Full article
(This article belongs to the Special Issue Genetic Basis Underlying Neuropsychiatric Disorders)
Show Figures

Figure 1

Back to TopTop