scholarly journals A Case for Thalamic Mechanisms of Schizophrenia: Perspective From Modeling 22q11.2 Deletion Syndrome

2021 ◽  
Vol 15 ◽  
Author(s):  
Yanbo Jiang ◽  
Mary H. Patton ◽  
Stanislav S. Zakharenko
Keyword(s):  
Cognitive Deficits ◽  
Neural Circuits ◽  
Social Withdrawal ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Clinical Observations ◽  
Substantial Risk ◽  
22Q11.2 Microdeletion

Schizophrenia is a severe, chronic psychiatric disorder that devastates the lives of millions of people worldwide. The disease is characterized by a constellation of symptoms, ranging from cognitive deficits, to social withdrawal, to hallucinations. Despite decades of research, our understanding of the neurobiology of the disease, specifically the neural circuits underlying schizophrenia symptoms, is still in the early stages. Consequently, the development of therapies continues to be stagnant, and overall prognosis is poor. The main obstacle to improving the treatment of schizophrenia is its multicausal, polygenic etiology, which is difficult to model. Clinical observations and the emergence of preclinical models of rare but well-defined genomic lesions that confer substantial risk of schizophrenia (e.g., 22q11.2 microdeletion) have highlighted the role of the thalamus in the disease. Here we review the literature on the molecular, cellular, and circuitry findings in schizophrenia and discuss the leading theories in the field, which point to abnormalities within the thalamus as potential pathogenic mechanisms of schizophrenia. We posit that synaptic dysfunction and oscillatory abnormalities in neural circuits involving projections from and within the thalamus, with a focus on the thalamocortical circuits, may underlie the psychotic (and possibly other) symptoms of schizophrenia.

scholarly journals Left pulmonary artery in 22q11.2 deletion syndrome. Echocardiographic evaluation in patients without cardiac defects and role of Tbx1 in mice

PLoS ONE ◽  
2019 ◽  
Vol 14 (4) ◽  
pp. e0211170 ◽  
Author(s):  
Gioia Mastromoro ◽  
Giulio Calcagni ◽  
Paolo Versacci ◽  
Carolina Putotto ◽  
Marcello Chinali ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
22Q11.2 Deletion Syndrome ◽  
Left Pulmonary Artery ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Cardiac Defects ◽  
Echocardiographic Evaluation

The role of COMT and plasma proline in the variable penetrance of autistic spectrum symptoms in 22q11.2 deletion syndrome

2016 ◽  
Vol 90 (5) ◽  
pp. 420-427 ◽  
Author(s):  
E. Hidding ◽  
H. Swaab ◽  
L.M.J. de Sonneville ◽  
H. van Engeland ◽  
J.A.S. Vorstman
Keyword(s):  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Autistic Spectrum ◽  
Variable Penetrance

scholarly journals Treatment of 22q11.2 deletion syndrome-associated schizophrenia with comorbid anxiety and panic disorder

2017 ◽  
Vol 9 (2) ◽  
pp. 54-56
Author(s):  
Candace B. Borders ◽  
Amanda Suzuki ◽  
David Safani
Keyword(s):  
Risk Factor ◽  
Panic Disorder ◽  
Adverse Effects ◽  
Late Onset ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Psychiatric Illnesses ◽  
Increased Risk

22q11.2 deletion syndrome (22q11DS) is a risk factor for psychiatric illnesses, including schizophrenia and anxiety. Small studies have shown that several neuroleptic medications are effective in treating psychosis in this population, but are also associated with an increased risk of adverse effects - particularly, seizures. In this case, we discuss a 34-year-old patient presenting with late onset schizophrenia, which ultimately led to her diagnosis of 22q11DS. Subsequent management of the patient's psychosis with asenapine was complicated by concurrent anxiety and panic disorder; thus, we examine the role of anxiolytic therapy in conjunction with antipsychotics in this patient population.

scholarly journals Neuroanatomical underpinnings of autism symptomatology in carriers and non-carriers of the 22q11.2 microdeletion

2020 ◽  
Author(s):  
Maria Gudbrandsen ◽  
Anke Bletsch ◽  
Caroline Mann ◽  
Eileen Daly ◽  
Clodagh M Murphy ◽  
...  
Keyword(s):  
22Q11.2 Deletion Syndrome ◽  
Brain Regions ◽  
Posterior Cingulate Cortex ◽  
Autism Spectrum ◽  
Deletion Syndrome ◽  
Precentral Gyrus ◽  
22Q11.2 Deletion ◽  
Autism Symptomatology ◽  
Main Effect ◽  
22Q11.2 Microdeletion

Abstract Background: A crucial step to understanding the mechanistic underpinnings of autism spectrum disorder (ASD), is to examine if the biological underpinnings of ASD in genetic high-risk conditions, like 22q11.2 Deletion Syndrome (22q11.2DS), are similar to those in idiopathic illness. This study aimed to examine if ASD symptomatology in 22q11.2DS is underpinned by the same – or distinct – neural systems that mediate these symptoms in non-deletion carriers. Methods: We examined vertex-wise estimates of cortical volume (CV), surface area (SA), and cortical thickness across 131 individuals between 6 and 25 years of age including (1) 50 individuals with 22q11.2DS, out of which n=25 had a diagnosis of ASD, (2) 40 non-carriers of the microdeletion with a diagnosis of ASD (i.e. idiopathic ASD), and (3) 41 typically developing (TD) controls. We employed a 2-by-2 factorial design to identify neuroanatomical variability associated with the main effects of 22q11.2DS and ASD, as well as their interaction. Further, using canonical correlation analysis (CCA), we compared neuroanatomical variability associated with the complex (i.e. multivariate) clinical phenotype of ASD between 22q11.2 deletion carriers and non-carriers. Results: The set of brain regions associated with the main effect of 22q11.2DS was distinct from the neuroanatomical underpinnings of the main effect of ASD. Moreover, significant 22q11.2DS-by-ASD interactions were observed for CV and SA in the dorsolateral prefrontal cortex, precentral gyrus, and posterior cingulate cortex, suggesting that the neuroanatomy of ASD is significantly modulated by 22q11.2DS ( p <0.01). We further established that the multivariate patterns of neuroanatomical variability associated with differences in symptom profiles significantly differed between 22q11.2 deletion carriers and non-carriers. Limitations: We employed a multicenter design to overcome single-site recruitment limitations, however, FreeSurfer derived measures of surface anatomy have been shown to be highly reliable across scanner platforms and field-strengths’. Further, we controlled for gender to address the differing distribution between idiopathic ASD individuals and the other groups. Nonetheless, the gender distribution in our sample reflects that of the respective populations, adding to the generalizability of our results. Last, we included individuals with a relatively wide age range (i.e. 6-25 years). Conclusions: Our findings indicate that neuroanatomical correlates of ASD symptomatology in carriers of the 22q11.2 microdeletion diverge from those in idiopathic ASD.

scholarly journals Treatment of 22q11.2 deletion syndrome-associated schizophrenia with comorbid anxiety and panic disorder

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Candace B. Borders ◽  
Amanda Suzuki ◽  
David Safani
Keyword(s):  
Risk Factor ◽  
Panic Disorder ◽  
Adverse Effects ◽  
Late Onset ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Psychiatric Illnesses ◽  
Increased Risk

22q11.2 deletion syndrome (22q11DS) is a risk factor for psychiatric illnesses, including schizophrenia and anxiety. Small studies have shown that several neuroleptic medications are effective in treating psychosis in this population, but are also associated with an increased risk of adverse effects - particularly, seizures. In this case, we discuss a 34-year-old patient presenting with late onset schizophrenia, which ultimately led to her diagnosis of 22q11DS. Subsequent management of the patient’s psychosis with asenapine was complicated by concurrent anxiety and panic disorder; thus, we examine the role of anxiolytic therapy in conjunction with antipsychotics in this patient population.

scholarly journals Cognitive deficits in childhood, adolescence and adulthood in 22q11.2 deletion syndrome and association with psychopathology

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sinead Morrison ◽  
Samuel J. R. A. Chawner ◽  
Therese A. M. J. van Amelsvoort ◽  
Ann Swillen ◽  
Claudia Vingerhoets ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion

Executive Functions and Memory Abilities in Children With 22q11.2 Deletion Syndrome

2010 ◽  
Vol 44 (4) ◽  
pp. 364-371 ◽  
Author(s):  
Linda E. Campbell ◽  
Rayna Azuma ◽  
Fiona Ambery ◽  
Angela Stevens ◽  
Anna Smith ◽  
...  
Keyword(s):  
Executive Function ◽  
Cognitive Deficits ◽  
Visual Memory ◽  
22Q11.2 Deletion Syndrome ◽  
Dopamine Metabolism ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Comt Genotype ◽  
Velo Cardio Facial Syndrome ◽  
The Relationship

Objective: Velo-cardio-facial syndrome or 22q11.2 deletion syndrome (22q11DS) is the most common known microdeletion syndrome. One of the genes in the deleted region is the catechol-O-methyltransferase (COMT) gene, which is thought to have significant effects on cognition through its influence on dopamine metabolism. The aim of the present study was to better characterize the cognitive phenotype in a large cohort children with 22q11DS compared with sibling controls and to investigate if the cognitive deficits in 22q11DS were modulated by COMT expression. Method: The memory, executive function and attentional abilities of children with 22q11DS (n = 50) compared to sibling controls (n = 31), were measured. Also, within children with 22q11DS, a preliminary exploration was carried out of the relationship between cognitive ability and COMT genotype. Results: Overall, the 22q11DS group had significantly reduced scores on tests of memory (especially in visual memory) and executive function (particularly in planning, working memory, and motor organization) compared with sibling controls. No association, however, was identified between COMT genotype and cognitive function. Conclusions: Although 22q11DS children have specific cognitive deficits, differences in COMT do not account for these findings.

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