scholarly journals Brain structural abnormalities in six major psychiatric disorders: shared variation and network perspectives

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 356
Author(s):  
Euclides José de Mendonça Filho ◽  
Márcio Bonesso Alves ◽  
Patricia Pelufo Silveira
Keyword(s):  
Network Analysis ◽  
Psychiatric Disorders ◽  
Regional Distribution ◽  
Principal Component ◽  
Autism Spectrum ◽  
Brain Abnormalities ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Component Loading ◽  
Shared Variation

Common brain abnormalities are a possible explanation for comorbidities in psychiatric disorders. Challenges in understanding these conditions are likely due to the paucity of studies able to analyze the extent and regional distribution of shared morphometric abnormalities between disorders. Recently, Opeal et al. presented an elegant rationale to investigate shared and specific morphometric measures of cortical thickness and subcortical gray matter volume between healthy individuals and subjects across six major psychiatric disorders. Although their approach has the potential to systematically portrait shared brain alterations, the chosen principal component analysis solution may not address the central question of the observed shared versus specific brain alterations due to misspecification of the number of components. Given how this misspecification can lead to different conclusions, we reanalyzed Opel et al. data to thoroughly determine the number of factors to be considered, explore the alternative solution, and visualize the patterns of shared brain matter correlations using network analysis. Our approach suggests that a unidimensional solution was appropriate in this situation. The unidimensional solution indicated that brain alterations in autism spectrum disorder (ASD) had a significant negative component loading, suggesting that brain abnormalities found in ASD carry more similarities with major depressive disorder (MDD), bipolar disorder (BD), schizophrenia (SCZ), and obsessive-compulsive disorder (OCD) than demonstrated by the original work. Network analysis indicated that SCZ had the highest strength, BD the highest closeness, and BD and MDD had the highest betweenness in the network. This work highlights how different component solutions can lead to different conclusions, with important implications for the understanding of overlapped patterns of symptoms among six major psychiatric diseases. The network approach is complementary in indicating central markers of specific psychopathology domains. Investigations using shared-variation and network perspectives are promising for the study of pathophysiological patterns of common brain alterations.

scholarly journals Comprehensive exploration of the genetic contribution of the dopaminergic and serotonergic pathways to psychiatric disorders

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Judit Cabana-Domínguez ◽  
Bàrbara Torrico ◽  
Andreas Reif ◽  
Noèlia Fernàndez-Castillo ◽  
Bru Cormand
Keyword(s):  
Psychiatric Disorders ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Genetic Contribution ◽  
Obsessive Compulsive ◽  
Gene Set ◽  
Compulsive Disorder ◽  
Kegg Pathways ◽  
Gene Sets ◽  
Psychiatric Conditions

AbstractPsychiatric disorders are highly prevalent and display considerable clinical and genetic overlap. Dopaminergic and serotonergic neurotransmission have been shown to play an important role in many psychiatric disorders. Here we aim to assess the genetic contribution of these systems to eight psychiatric disorders (attention-deficit hyperactivity disorder (ADHD), anorexia nervosa (ANO), autism spectrum disorder (ASD), bipolar disorder (BIP), major depression (MD), obsessive-compulsive disorder (OCD), schizophrenia (SCZ) and Tourette’s syndrome (TS)) using publicly available GWAS analyses performed by the Psychiatric Genomics Consortium that include more than 160,000 cases and 275,000 controls. To do so, we elaborated four different gene sets: two ‘wide’ selections for dopamine (DA) and for serotonin (SERT) using the Gene Ontology and KEGG pathways tools, and two’core’ selections for the same systems, manually curated. At the gene level, we found 67 genes from the DA and/or SERT gene sets significantly associated with one of the studied disorders, and 12 of them were associated with two different disorders. Gene-set analysis revealed significant associations for ADHD and ASD with the wide DA gene set, for BIP with the wide SERT gene set, and for MD with the core SERT set. Interestingly, interrogation of a cross-disorder GWAS meta-analysis of the eight psychiatric conditions displayed association with the wide DA gene set. To our knowledge, this is the first systematic examination of genes encoding proteins essential to the function of these two neurotransmitter systems in these disorders. Our results support a pleiotropic contribution of the dopaminergic and serotonergic systems in several psychiatric conditions.

scholarly journals Genetic influences on eight psychiatric disorders based on family data of 4 408 646 full and half-siblings, and genetic data of 333 748 cases and controls

2018 ◽  
Vol 49 (07) ◽  
pp. 1166-1173 ◽  
Author(s):  
E. Pettersson ◽  
P. Lichtenstein ◽  
H. Larsson ◽  
J. Song ◽  
A. Agrawal ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Autism Spectrum ◽  
Psychiatric Research ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Hyperactivity Disorder ◽  
Unique Character ◽  
Psychiatric Conditions ◽  
Heritability Estimates ◽  
Study Designs

AbstractBackgroundMost studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders.MethodsWe assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia.ResultsHeritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50.ConclusionsGiven the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.

Lack of mental flexibility as endophenotype in autism spectrum disorder and obsessive comulsive disorder families

2011 ◽  
Vol 26 (S2) ◽  
pp. 970-970
Author(s):  
V. Goussé ◽  
A. Hagi ◽  
J.-L. Stilgenbauer ◽  
R. Delorme
Keyword(s):  
Autism Spectrum Disorder ◽  
Executive Functions ◽  
Principal Component ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Spectrum Disorder ◽  
Central Coherence ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
First Degree Relatives

IntroductionResults from clinical and molecular genetic studies suggest that autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD) could have a shared pattern of heritability. Among a large number of clinical variables evaluated, obsessive compulsive/repetitive behaviors have been found to be highly correlated among autism probands and their relatives. Empirical evidence from neuropsychological studies suggest that an appropriate model for repetitive behaviours is a deficit of executive functions specifically flexibility. Given the lack of flexibility observed in ASD and OCD probands, we hypothesised that it could represent a shared endophenotype in both families.MethodsSeven cognitive tests belonging to executive functions, central coherence and theory of mind were proposed to 58 unaffected first-degree relatives of probands with ASD and 61 unaffected first-degree relatives of OCD patients and compared with 34 healthy controls. A principal component analysis (PCA) was performed.ResultsASD relatives - specifically mothers - performed significantly worse on all the tests than OCD relatives and controls. Moreover, inside the OCD group, female individuals performed significantly worse than males. Finally, the PCA indicate that the cognitive profiles of the ASD relatives and the OCD relatives were similar but distinct from controls.ConclusionLack of cognitive flexibility is observed in ASD and OCD families and might constitute a shared intermediate cognitive phenotype. Our study constitutes an effort to clarify the relationship between ASD and OCD having implications for our nosological understanding of both disorders.

scholarly journals Multilevel neural gradients reflect transdiagnostic effects of major psychiatric conditions on cortical morphology

2021 ◽  
Author(s):  
Bo-yong Park ◽  
Valeria Kebets ◽  
Sara Lariviere ◽  
Meike D. Hettwer ◽  
Casey Paquola ◽  
...  
Keyword(s):  
Multiple Scales ◽  
Principal Component ◽  
Autism Spectrum ◽  
Neural Pathways ◽  
Obsessive Compulsive ◽  
Brain Organization ◽  
Compulsive Disorder ◽  
Working Groups ◽  
Psychiatric Conditions ◽  
Cortical Morphology

It is increasingly recognized that multiple psychiatric conditions are underpinned by shared neural pathways, affecting similar brain systems. Here, we assessed i) shared dimensions of alterations in cortical morphology across six major psychiatric conditions (autism spectrum disorder, attention deficit/hyperactivity disorder, major depression, obsessive-compulsive disorder, bipolar disorder, schizophrenia) and ii) carried out a multiscale neural contextualization, by cross-referencing shared anomalies against cortical myeloarchitecture and cytoarchitecture, as well as connectome and neurotransmitter organization. Pooling disease-related effects on MRI-based cortical thickness measures across six ENIGMA working groups, including a total of 28,546 participants (12,876 patients and 15,670 controls), we computed a shared disease dimension on cortical morphology using principal component analysis that described a sensory-fugal pattern with paralimbic regions showing the most consistent abnormalities across conditions. The shared disease dimension was closely related to cortical gradients of microstructure and intrinsic connectivity, as well as neurotransmitter systems, specifically serotonin and dopamine. Our findings embed the shared effects of major psychiatric conditions on brain structure in multiple scales of brain organization and may provide novel insights into neural mechanisms into transdiagnostic vulnerability.

A-90 Personality Tests in Neuropsychological Assessment: Determining the Presence of Psychotic and Obsessive Compulsive Disorders in 3 Individuals with Autism Spectrum Disorder

2021 ◽  
Vol 36 (6) ◽  
pp. 1137-1137
Author(s):  
Kathleen Torsney
Keyword(s):  
Autism Spectrum Disorder ◽  
Psychiatric Disorders ◽  
Case Studies ◽  
Correct Diagnosis ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Future Research ◽  
Obsessive Compulsive ◽  
Personality Tests ◽  
Compulsive Disorder

Abstract Objective The assessment of personality and psychopathology in an individual who has symptoms of autism spectrum disorder (ASD) can be a challenging task due to the overlap of characteristic behaviors associated with ASD and markers of psychopathology. Through the examination of key factors in 3 case studies of neuropsychological assessments, this poster outlines steps to facilitate the correct diagnosis of psychiatric disorders in persons with autism spectrum disorder. Method This poster explores 3 case studies in which an individual exhibited signs of a psychiatric disorder as well as ASD. The author describes how the personality tests such as the MMPI-2 and MMPI-RF were administered and interpreted and how case history and test taking behavior affected the understanding of the results. Results The poster highlights critical factors in differentiating psychiatric disorders and symptoms that are part of the ASD. For example, in all 3 case studies, the individuals had significant difficulty with the computerized version of the test and needed to take it with paper and pencil. The author also outlines examples where the symptoms are manifestations of the ASD, such as perseveration and rigid thinking and when they are attributable to an obsessive–compulsive disorder. Further, the author differentiates signs of psychosis in a person with ASD from the typical tangential and circumstantial speech associated with ASD. Conclusion The author offers suggestions for administering personality tests to persons with ASD, for interpreting the results of the tests, and for conducting future research to facilitate the differentiation between symptoms consistent with ASD and with psychopathology.

Familial coaggregation of major psychiatric disorders among first-degree relatives of patients with obsessive-compulsive disorder: a nationwide study

2020 ◽  
pp. 1-8
Author(s):  
Mao-Hsuan Huang ◽  
Chih-Ming Cheng ◽  
Shih-Jen Tsai ◽  
Ya-Mei Bai ◽  
Cheng-Ta Li ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Psychiatric Disorders ◽  
Obsessive Compulsive Disorder ◽  
Autism Spectrum ◽  
Research Database ◽  
Dependent Manner ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
First Degree Relatives ◽  
Dose Dependent

Abstract Background Whether the first-degree relatives (FDRs) of patients with obsessive-compulsive disorder (OCD) have an increased risk of the major psychiatric disorders, namely schizophrenia, bipolar disorder, OCD, major depressive disorder (MDD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD), remains unclear. Methods Using the Taiwan National Health Insurance Research Database with the whole population sample size (n = 23 258 175), 89 500 FDRs, including parents, offspring, siblings, and twins, of patients with OCD were identified in our study. The relative risks (RRs) of major psychiatric disorders were assessed among FDRs of patients with OCD. Results FDRs of patients with OCD had higher RRs of major psychiatric disorders, namely OCD (RR 8.11, 95% confidence interval (CI) 7.68–8.57), bipolar disorder (RR 2.85, 95% CI 2.68–3.04), MDD (RR 2.67, 95% CI 2.58–2.76), ASD (RR 2.38, 95% CI 2.10–2.71), ADHD (RR 2.19, 95% CI 2.07–2.32), and schizophrenia (RR 1.97, 95% CI 1.86–2.09), compared with the total population. Different familial kinships of FDRs, such as parents, offspring, siblings, and twins consistently had increased risks for these disorders. In addition, a dose-dependent relationship was found between the numbers of OCD probands and the risk of each major psychiatric disorder. Conclusions The FDRs, including parents, offspring, siblings, and twins, of patients with OCD have a higher risk of OCD, schizophrenia, bipolar disorder, MDD, ADHD, and ASD. The familial co-aggregation of OCD with OCD and other major psychiatric disorders was existent in a dose-dependent manner. Given the increased risks of psychiatric disorders, medical practitioners should closely monitor the mental health of the FDRs of patients with OCD.

scholarly journals Association between polygenic propensity for psychiatric disorders and nutrient intake

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Avina K. Hunjan ◽  
Christopher Hübel ◽  
Yuhao Lin ◽  
Thalia C. Eley ◽  
Gerome Breen
Keyword(s):  
Psychiatric Disorders ◽  
Nutrient Intake ◽  
Autism Spectrum ◽  
Dietary Behaviour ◽  
Obsessive Compulsive ◽  
Higher Alcohol ◽  
Polygenic Score ◽  
Compulsive Disorder ◽  
Genome Wide ◽  
Polygenic Scores

AbstractDespite the observed associations between psychiatric disorders and nutrient intake, genetic studies are limited. We examined whether polygenic scores for psychiatric disorders are associated with nutrient intake in UK Biobank (N = 163,619) using linear mixed models. We found polygenic scores for attention-deficit/hyperactivity disorder, bipolar disorder, and schizophrenia showed the highest number of associations, while a polygenic score for autism spectrum disorder showed no association. The relatively weaker obsessive-compulsive disorder polygenic score showed the greatest effect sizes suggesting its association with diet traits may become more apparent with larger genome-wide analyses. A higher alcohol dependence polygenic score was associated with higher alcohol intake and individuals with higher persistent thinness polygenic scores reported their food to weigh less, both independent of socioeconomic status. Our findings suggest that polygenic propensity for a psychiatric disorder is associated with dietary behaviour. Note, nutrient intake was self-reported and findings must therefore be interpreted mindfully.

scholarly journals Genome wide meta-analysis identifies genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders

2019 ◽  
Author(s):  
◽  
Phil H. Lee ◽  
Verneri Anttila ◽  
Hyejung Won ◽  
Yen-Chen A. Feng ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Pleiotropic Effects ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Hyperactivity Disorder ◽  
Genome Wide ◽  
Genomic Relationships ◽  
The Brain

SummaryGenetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed a meta-analysis of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders identifying three groups of inter-related disorders. We detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning in the second trimester prenatally, and play prominent roles in a suite of neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.

scholarly journals Autoantibody-associated psychiatric syndromes in children: link to adult psychiatry

2021 ◽  
Author(s):  
Niels Hansen ◽  
◽  
Daniel Luedecke ◽  
Berend Malchow ◽  
Michael Lipp ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Psychiatric Symptoms ◽  
Fetal Brain ◽  
Later Life ◽  
Autism Spectrum ◽  
Narrative Review ◽  
Psychiatric Disease ◽  
Obsessive Compulsive ◽  
Disease Manifestation ◽  
Compulsive Disorder

AbstractStudies show that psychiatric symptoms in adults and children are sometimes associated with serum neural autoantibodies. The significance of serum neural autoantibodies associated with psychiatric symptoms in children remains often unclear, but might be relevant for the extent and occurrence of psychiatric disease manifestation in later life, as well as therapy and outcome. For this narrative review, we sought articles listed in PubMed and published between 1988 and 2020 addressing the maternal–fetal transfer of neural autoantibodies and psychiatric disorders associated with serum neural autoantibodies. We identified six major subgroups of psychiatric disorders in children that are associated with serum neural autoantibodies: patients with attentional deficit hyperactivity disorder, autism spectrum disorder, obsessive compulsive disorder, Gilles de la Tourette syndrome, psychosis and catatonia. Furthermore, we summarized study findings from maternal–fetal transfer of Contactin-associated protein-like 2, N-methyl-d-aspartate receptor and fetal brain autoantibodies associated with behavioral effects in animals and humans. We hypothesize that the maternal transfer of serum neuronal autoantibodies during or after birth could result (1) in the ignition of an autoimmune-mediated inflammation having neurodevelopmental consequences for their children (autoimmune-priming-attack hypothesis) and (2) has a potential impact on the later manifestation of psychiatric disorders. Through this narrative review, we propose a diagnostic pathway for the clinical diagnosis of a potentially autoimmune origin of psychiatric symptoms in children while considering recent guidelines.

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