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 ◽  
...  

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.

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Judit Cabana-Domínguez ◽  
Bàrbara Torrico ◽  
Andreas Reif ◽  
Noèlia Fernàndez-Castillo ◽  
Bru Cormand

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.


2018 ◽  
Vol 49 (07) ◽  
pp. 1166-1173 ◽  
Author(s):  
E. Pettersson ◽  
P. Lichtenstein ◽  
H. Larsson ◽  
J. Song ◽  
A. Agrawal ◽  
...  

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.


2011 ◽  
Vol 26 (S2) ◽  
pp. 970-970
Author(s):  
V. Goussé ◽  
A. Hagi ◽  
J.-L. Stilgenbauer ◽  
R. Delorme

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.


F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 356
Author(s):  
Euclides José de Mendonça Filho ◽  
Márcio Bonesso Alves ◽  
Patricia Pelufo Silveira

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.


2020 ◽  
Author(s):  
Charles Scelles ◽  
LUIS CARLO BULNES

Eye Movement Desensitization and Reprocessing (EMDR) is a treatment for post-traumatic stressdisorder (PTSD). The technique is known to stimulate the capacity to reprocess maladaptive memoriesthat are thought to be central to this pathology. Here we investigate if EMDR therapy can be used in otherconditions than PTSD. We conducted a systematic literature search on PubMed, ScienceDirect, Scopus, and Web of Science. Wesearched for published empirical findings on EMDR, excluding those centred on trauma and PTSD,published up to 2020. The results were classified by psychiatric categories.   Ninety articles met our research criteria. A positive effect was reported in addictions, somatoformdisorders, sexual dysfunction, eating disorder, disorders of adult personality, mood disorders, reaction tosevere stress, anxiety disorders, performance anxiety, Obsessive-Compulsive Disorder (OCD), pain,neurodegenerative disorders, paedopsychiatry and sleep. The evidence was more consistent in pain, OCD,mood disorders, and reaction to severe stress.EMDR’s efficiency across numerous pathological situations, highlighted the central role of affectivememory in several psychiatric and non-psychiatric conditions. Furthermore, EMDR seems to besuccessful in usually uncooperative (e.g. Dementia) or unproductive cases (e.g. aphasia). Moreover, insome severe medical situations were psychologic distress was an obstacle, EMDR allowed thecontinuation of treatment-as-usual. Our review suggests that it is a safe and economical therapeuticoption, and its effect in non-pathological situations opens new avenues for translational research. Overallmore methodologically rigorous studies are needed.


Author(s):  
Teresa A. Piggott ◽  
Alexandra N. Duran ◽  
Isha Jalnapurkar ◽  
Tyler Kimm ◽  
Stephanie Linscheid ◽  
...  

Women are more likely than men to meet lifetime criteria for an anxiety disorder. Moreover, anxiety is a risk factor for the development of other psychiatric conditions, including major depression. Numerous studies have identified evidence of sex differences in anxiety disorders, and there is considerable research concerning factors that may contribute to vulnerability for anxiety in females. In addition to psychosocial influences, biological components such as the female reproductive hormone cycle have also been implicated. Although psychotropic medication is more likely to be prescribed to women, there is little controlled data available concerning sex differences in the efficacy and/or tolerability of pharmacotherapy in anxiety disorders. This chapter provides an overview of the impact of gender in the epidemiology, phenomenology, course, and treatment response in generalized anxiety disorder (GAD), social anxiety disorder (SAD), posttraumatic stress disorder (PTSD), panic disorder (PD), and obsessive-compulsive disorder (OCD).


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kenneth S. Kendler ◽  
Henrik Ohlsson ◽  
Jan Sundquist ◽  
Kristina Sundquist

AbstractTo clarify the structure of genetic risks for 11 major psychiatric disorders, we calculated, from morbidity risks for disorders in 1st–5th degree relatives controlling for cohabitation effects, in the Swedish population born between 1932 and 1995 (n = 5,830,014), the family genetic risk scores (FGRS) for major depression (MD), anxiety disorders (AD), obsessive-compulsive disorder (OCD), bipolar disorder (BD), schizophrenia (SZ), bulimia (BUL), anorexia nervosa (AN), alcohol use disorder (AUD), drug use disorder (DUD), ADHD, and autism-spectrum disorder (ASD). For all affected individuals, we calculated their mean standardized FGRS for each disorder. The patterns of FGRS were quite similar for MD and AD, and for AUD and DUD, but substantially less similar for BUL and AN, BD and SZ, and ADHD and ASD. While OCD had high levels of FGRS for MD and AD, the overall FGRS profile differed considerably from MD and AD. ADHD FGRS scores were substantially elevated in AUD and DUD. FGRS scores for BD, OCD, AN, ASD, ADHD, and especially SZ were relatively disorder-specific while genetic risk for MD and AD had more generalized effects. The levels of FGRS for BMI, coronary artery disease, and educational attainment across our disorders replicated prior associations found using molecular genetic methods. All diagnostic categories examined had elevated FGRS for many disorders producing, for each condition, an informative FGRS profile. Using a novel method which approximates, from pedigree data, aggregate genetic risk, we have replicated and extended prior insights into the structure of genetic risk factors for key psychiatric illnesses.


2021 ◽  
pp. 1-10
Author(s):  
Cristina V. Torres ◽  
Nuria Martínez ◽  
Marcos Ríos-Lago ◽  
Monica Lara ◽  
Juan Alvarez-Linera ◽  
...  

<b><i>Introduction:</i></b> A subgroup of patients with autism spectrum disorder (ASD) show self or heteroaggression, dyscontrol episodes, and others are of obsessive-compulsive disorder (OCD) profile; some of them are resistant to medical and behavioural treatment. We describe the long-term outcome in a group of these patients, treated with radiofrequency brain lesions or combined stereotactic surgery and Gamma Knife (GK) radiosurgery. <b><i>Methods:</i></b> We reviewed the medical records of 10 ASD patients with pathological aggressiveness and OCD, who had undergone radiofrequency lesions and/or radiosurgery with GK in our institution. <b><i>Results:</i></b> The 10 patients had a significant reduction of their symptoms (PCQ 39.9 and 33, OAS 11.8 and 5, CYBOCS-ASD 30.4 and 20), preoperatively and in the last follow-up, respectively; <i>p</i> &#x3c; 0.005 (in all cases), although all but 2 needed more than 1 treatment to maintain this improvement. <b><i>Conclusions:</i></b> We observed a marked improvement in behaviour, quality of life, and relationship with the environment in all our 10 patients after the lesioning treatments, without long-lasting side effects.


2022 ◽  
Vol 15 ◽  
Author(s):  
Ankur Gupta ◽  
Rohini Bansal ◽  
Hany Alashwal ◽  
Anil Safak Kacar ◽  
Fuat Balci ◽  
...  

Many studies on the drift-diffusion model (DDM) explain decision-making based on a unified analysis of both accuracy and response times. This review provides an in-depth account of the recent advances in DDM research which ground different DDM parameters on several brain areas, including the cortex and basal ganglia. Furthermore, we discuss the changes in DDM parameters due to structural and functional impairments in several clinical disorders, including Parkinson's disease, Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorders, Obsessive-Compulsive Disorder (OCD), and schizophrenia. This review thus uses DDM to provide a theoretical understanding of different brain disorders.


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