A Mini Review on the Contribution of the Anterior Cingulate Cortex in the Risk of Psychosis in 22q11.2 Deletion Syndrome

AbstractBackgroundThe 22q11.2 deletion syndrome (22q11DS) is caused by a deletion on chromosome 22 locus q11.2. This copy number variant results in haplo-insufficiency of the catechol-O-methyltransferase (COMT) gene, and is associated with a significant increase in the risk for developing cognitive impairments and psychosis. The COMT gene encodes an enzyme that primarily modulates clearance of dopamine (DA) from the synaptic cleft, especially in the prefrontal cortical areas. Consequently, extracellular DA levels may be increased in prefrontal brain areas in 22q11DS, which may underlie the well-documented susceptibility for cognitive impairments and psychosis in affected individuals. This study aims to examine DA D2/3 receptor binding in frontal brain regions in adults with 22q11DS, as a proxy of frontal DA levels.MethodsThe study was performed in 14 non-psychotic, relatively high functioning adults with 22q11DS and 16 age- and gender-matched healthy controls (HCs), who underwent DA D2/3 receptor [18F]fallypride PET imaging. Frontal binding potential (BPND) was used as the main outcome measure.ResultsBPND was significantly lower in adults with 22q11DS compared with HCs in the prefrontal cortex and the anterior cingulate gyrus. After Bonferroni correction significance remained for the anterior cingulate gyrus. There were no between-group differences in BPND in the orbitofrontal cortex and anterior cingulate cortex.ConclusionsThis study is the first to demonstrate lower frontal D2/3 receptor binding in adults with 22q11DS. It suggests that a 22q11.2 deletion affects frontal dopaminergic neurotransmission.

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Large-scale brain network dynamics provide a measure of psychosis and anxiety in 22q11.2 deletion syndrome

10.1101/551796 ◽

2019 ◽

Author(s):

Daniela Zöller ◽

Corrado Sandini ◽

Fikret Işik Karahanoğlu ◽

Maria Carmela Padula ◽

Marie Schaer ◽

...

Keyword(s):

Large Scale ◽

Brain Networks ◽

Network Dynamics ◽

22Q11.2 Deletion Syndrome ◽

Brain Network ◽

Anterior Cingulate ◽

Deletion Syndrome ◽

Psychotic Symptoms ◽

22Q11.2 Deletion ◽

Network Activation

AbstractProdromal positive psychotic symptoms and anxiety are two strong risk factors for schizophrenia in 22q11.2 deletion syndrome (22q11DS). The analysis of large-scale brain network dynamics during rest is promising to investigate aberrant brain function and identify potentially more reliable biomarkers. We retrieved and examined dynamics of large-scale functional brain networks using innovation-driven co-activation patterns (iCAPs) and probed into functional signatures of prodromal psychotic symptoms and anxiety. Patients with 22q11DS had shorter activation in cognitive brain networks and longer activation in emotion processing networks. Functional signatures of prodromal psychotic symptoms confirmed an implication of cingulo-prefrontal salience network activation duration and coupling. Functional signatures of anxiety un-covered an implication of amygdala activation and coupling, indicating differential roles of dorsal and ventral sub-divisions of anterior cingulate and medial prefrontal cortices. These results confirm that the dynamic nature of brain network activation contains essential function to develop clinically relevant imaging markers of psychosis vulnerability.

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Psychotic symptoms influence the development of anterior cingulate BOLD variability in 22q11.2 deletion syndrome

Schizophrenia Research ◽

10.1016/j.schres.2017.08.003 ◽

2018 ◽

Vol 193 ◽

pp. 319-328 ◽

Cited By ~ 8

Author(s):

Daniela Zöller ◽

Maria Carmela Padula ◽

Corrado Sandini ◽

Maude Schneider ◽

Elisa Scariati ◽

...

Keyword(s):

22Q11.2 Deletion Syndrome ◽

Anterior Cingulate ◽

Deletion Syndrome ◽

Psychotic Symptoms ◽

22Q11.2 Deletion

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Glutamatergic and GABAergic reactivity and cognition in 22q11.2 deletion syndrome and healthy volunteers: A randomized double-blind 7-Tesla pharmacological MRS study

Journal of Psychopharmacology ◽

10.1177/0269881120922977 ◽

2020 ◽

Vol 34 (8) ◽

pp. 856-863

Author(s):

Claudia Vingerhoets ◽

Desmond HY Tse ◽

Mathilde van Oudenaren ◽

Dennis Hernaus ◽

Esther van Duin ◽

...

Keyword(s):

Single Dose ◽

22Q11.2 Deletion Syndrome ◽

Anterior Cingulate ◽

7 Tesla ◽

Deletion Syndrome ◽

Resonance Spectroscopy ◽

Long Term Effects ◽

22Q11.2 Deletion ◽

Double Blind ◽

Metabolite Concentrations

Aims: 22q11.2 deletion syndrome (22q11.2DS) is associated with impaired cognitive functioning. Glutamatergic pathways have been linked with cognition and are hypothesized to be disrupted in 22q11.2DS patients, possibly ‘shifting’ the excitatory (glutamate)/inhibitory (GABA) balance. Hence, the glutamate/GABA balance may constitute a target for pharmacological treatment. We aimed to examine alterations of glutamate/GABA metabolites in 22q11.2DS in vivo using riluzole, a compound with glutamate/GABA-modulating action, as pharmacological challenge. Methods: Seventeen 22q11.2DS patients and 20 matched healthy controls were enrolled in this randomized double-blind placebo-controlled crossover study. Glutamate and glutamine concentrations in the anterior cingulate cortex (ACC) and striatum, as well as ACC GABA concentrations were obtained after placebo and after a single dose of 50 mg riluzole using 7-Tesla magnetic resonance spectroscopy (MRS). Within the 22q11.2DS group, the relationship between metabolite concentrations and cognition was examined. Results: No group differences were found in ACC and striatal metabolite concentrations following placebo. Riluzole numerically decreased ACC ( η2 = 0.094) but not striatal glutamate concentrations as well as ACC GABA concentrations ( η2 = 0.176) in all subjects. In both regions, riluzole did not alter glutamine concentration. No interaction effects were found. Although not significant after Bonferroni correction, ACC glutamate concentrations were inversely correlated with cognitive functions in 22q11.2DS patients. Discussion: We did not demonstrate altered ACC and striatal metabolite concentrations in 22q11.2DS. Nevertheless, these results suggest that glutamate and GABA can be modulated with a single dose of riluzole. Possibly, riluzole may have memory-enhancing effects in 22q11.2DS. Future studies should examine the long-term effects of riluzole on cognition.

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Surgical Management of Patients With 22q11.2 Deletion Syndrome

Perspectives of the ASHA Special Interest Groups ◽

10.1044/2019_pers-sig5-2019-0004 ◽

2019 ◽

Vol 4 (5) ◽

pp. 857-869

Author(s):

Oksana A. Jackson ◽

Alison E. Kaye

Keyword(s):

Surgical Management ◽

Preoperative Evaluation ◽

Preoperative Assessment ◽

22Q11.2 Deletion Syndrome ◽

Deletion Syndrome ◽

22Q11.2 Deletion ◽

Surgical Decision ◽

Obstructive Sleep ◽

Spine Abnormalities ◽

Speech Assessment

Purpose The purpose of this tutorial was to describe the surgical management of palate-related abnormalities associated with 22q11.2 deletion syndrome. Craniofacial differences in 22q11.2 deletion syndrome may include overt or occult clefting of the palate and/or lip along with oropharyngeal variances that may lead to velopharyngeal dysfunction. This chapter will describe these circumstances, including incidence, diagnosis, and indications for surgical intervention. Speech assessment and imaging of the velopharyngeal system will be discussed as it relates to preoperative evaluation and surgical decision making. Important for patients with 22q11.2 deletion syndrome is appropriate preoperative screening to assess for internal carotid artery positioning, cervical spine abnormalities, and obstructive sleep apnea. Timing of surgery as well as different techniques, common complications, and outcomes will also be discussed. Conclusion Management of velopharyngeal dysfunction in patients with 22q11.2 deletion syndrome is challenging and requires thoughtful preoperative assessment and planning as well as a careful surgical technique.

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Psychosocial Risks and Management for Children and Adolescents With 22q11.2 Deletion Syndrome

Perspectives of the ASHA Special Interest Groups ◽

10.1044/2019_pers-sig5-2019-0002 ◽

2019 ◽

Vol 4 (4) ◽

pp. 633-640 ◽

Cited By ~ 1

Author(s):

Canice E. Crerand ◽

Ari N. Rabkin

Keyword(s):

Cognitive Abilities ◽

Psychotic Disorders ◽

Developmental Stages ◽

Early Adulthood ◽

22Q11.2 Deletion Syndrome ◽

Deletion Syndrome ◽

22Q11.2 Deletion ◽

Psychosocial Risks ◽

Empirically Supported ◽

Specific Education

Purpose This article reviews the psychosocial risks associated with 22q11.2 deletion syndrome, a relatively common genetic condition associated with a range of physical and psychiatric problems. Risks associated with developmental stages from infancy through adolescence and early adulthood are described, including developmental, learning, and intellectual disabilities as well as psychiatric disorders including anxiety, mood, and psychotic disorders. Other risks related to coping with health problems and related treatments are also detailed for both affected individuals and their families. Conclusion The article ends with strategies for addressing psychosocial risks including provision of condition-specific education, enhancement of social support, routine assessment of cognitive abilities, regular mental health screening, and referrals for empirically supported psychiatric and psychological treatments.

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