Mechanistic insights into the genetics of affective psychosis from Prader-Willi syndrome

Aman, Lucie; Manning, Katherine; Whittington, Joyce; Holland, Anthony

doi:10.1016/s2215-0366(18)30009-9

Cited by 37 publications

(31 citation statements)

References 77 publications

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“…Nowadays, it is clear that AS is caused by loss of the maternal copy of the UBE3A gene in the 15q11‐13 chromosome region (reviewed in Ref. ) (Fig. 1A).…”

Section: Genetic Etiologymentioning

confidence: 99%

Angelman syndrome: a journey through the brain

et al. 2020

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Angelman syndrome (AS) is an incurable neurodevelopmental disease caused by loss of function of the maternally inherited UBE3A gene. AS is characterized by a defined set of symptoms, namely severe developmental delay, speech impairment, uncontrolled laughter, and ataxia. Current understanding of the pathophysiology of AS relies mostly on studies using the murine model of the disease, although alternative models based on patient-derived stem cells are now emerging. Here, we summarize the literature of the last decade concerning the three major brain areas that have been the subject of study in the context of AS: hippocampus, cortex, and the cerebellum. Our comprehensive analysis highlights the major phenotypes ascribed to the different brain areas. Moreover, we also discuss the major drawbacks of current models and point out future directions for research in the context of AS, which will hopefully lead us to an effective treatment of this condition in humans.

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“…Nowadays, it is clear that AS is caused by loss of the maternal copy of the UBE3A gene in the 15q11‐13 chromosome region (reviewed in Ref. ) (Fig. 1A).…”

Section: Genetic Etiologymentioning

confidence: 99%

Angelman syndrome: a journey through the brain

et al. 2020

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“…Gamma-aminobutyric acid (GABA) neural circuits dysfunctionality is involved in both PWS and catatonia. 97 …”

Section: Current Standard Therapiesmentioning

confidence: 99%

Obesity management in Prader–Willi syndrome: current perspectives

Crinò¹,

Fintini²,

Bocchini³

et al. 2018

DMSO

102

106

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Prader–Willi syndrome (PWS) is a complex multisystem disorder due to the absent expression of the paternally active genes in the PWS critical region on chromosome 15 (15q11.2-q13). The syndrome is considered the most common genetic cause of obesity, occurring in 1:10,000–1:30,000 live births. Its main characteristics include neonatal hypotonia, poor feeding, and lack of appetite in infancy, followed by weight gain, lack of satiety, and uncontrolled appetite, frequently after the age of 2–3 years. The clinical picture includes short stature, multiple endocrine abnormalities (hypogonadism, growth hormone/insulin-like growth factor-I axis dysfunction, hypothyroidism, central adrenal insufficiency), dysmorphic features, scoliosis, osteoporosis, mental retardation, and behavioral and psychiatric problems. Subjects with PWS will become severely obese unless their food intake is strictly controlled. Constant and obsessive food seeking behavior can make life very difficult for both the family and caretakers. Prevention of obesity is mandatory in these patients from the first years of life, because once obesity develops it is difficult to maintain the control of food intake. In fact, PWS subjects die prematurely from complications conventionally related to obesity, including diabetes mellitus, metabolic syndrome, sleep apnea, respiratory insufficiency, and cardiovascular disease. The mechanisms underlying hyperphagia in PWS are not completely known, and to date no drugs have proven their efficacy in controlling appetite. Consequently, dietary restriction, physical activity, and behavior management are fundamental in the prevention and management of obesity in PWS. In spite of all available therapeutic tools, however, successful weight loss and maintenance are hardly accomplished. In this context, clinical trials with new drugs have been initiated in order to find new possibilities of a therapy for obesity in these patients. The preliminary results of these studies seem to be encouraging. On the other hand, until well-proven medical treatments are available, bariatric surgery can be taken into consideration, especially in PWS patients with life-threatening comorbidities.

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“…However, there are a number of reasons this may be the case. First, psychotic-like experiences are not equivalent to a psychotic disorder, and prior evidence suggests that psychotic symptoms in individuals with PWS have an uncharacteristically acute onset (Aman et al, 2018;)Holland et al, 2003). The phenomenology of psychosis in PWS also is distinct from 'typical' psychosis presentation, in that there is a strong affective component and a more 'cycloid' pattern (Larson et al 2014).…”

Section: Discussionmentioning

confidence: 99%

Neurobehavioral dimensions of Prader Willi Syndrome: Relationships between sleep disturbance and psychotic experiences

Zhang

Vajdi

Kushan-Wells

et al. 2020

Preprint

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Background: Prader Willi Syndrome (PWS) is a genetic disorder caused by the absence of expression of the paternal copies of maternally imprinted gene(s) located at 15q11–q13. While the physical and medical characteristics of PWS, including short stature, hyperphagia and endocrine dysfunction are well-characterized, systematic investigation of the long-recognized psychiatric manifestations has been recent. Methods: Here, we report on the first remote (web-based) assessment of neurobehavioral traits, including psychotic-like experiences (Prodromal Questionnaire-Brief Version; PQ-B) and sleep behavior (Pittsburgh Sleep Quality Index), in a cohort of 127 participants with PWS, of whom 48% had a paternal deletion, 36% uniparental disomy, 2.4% an imprinting mutation and 13% unknown mutation (mean age 19.2 years+/-8.4 years; 55.2% female). We aimed to identify the most informative variables that contribute to psychosis risk symptoms. Multiple domains of cognition (accuracy and speed) were also assessed in a subset of PWS participants (N=39) using the Penn Computerized Neurocognitive Battery (Penn-CNB). Results: Sleep disturbance, particularly the reasons for sleep difficulty, was most strongly associated with distress related to psychotic-like symptoms. Regarding cognition, individuals with PWS showed the most prominent deficits in accuracy on measures of social cognition involving faces, namely Face Memory, Age Differentiation and Emotion Recognition, and greatest slowing on measures of Attention and Emotion Recognition. However, there were no significant differences in psychotic-like experiences or cognitive performance as a function of PWS genetic subtype. Conclusion: Findings indicate that self/parent-reported neurobehavioral symptoms and cognition can be assessed remotely in individuals with PWS, which has implications for future large-scale investigations of rare neurogenetic disorders. Trial registration: Not applicable.

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Mechanistic insights into the genetics of affective psychosis from Prader-Willi syndrome

Cited by 37 publications

References 77 publications

Angelman syndrome: a journey through the brain

Angelman syndrome: a journey through the brain

Obesity management in Prader–Willi syndrome: current perspectives

Neurobehavioral dimensions of Prader Willi Syndrome: Relationships between sleep disturbance and psychotic experiences

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Mechanistic insights into the genetics of affective psychosis from Prader-Willi syndrome

Cited by 37 publications

References 77 publications

Angelman syndrome: a journey through the brain

Angelman syndrome: a journey through the brain

Obesity management in Prader&ndash;Willi syndrome: current perspectives

Neurobehavioral dimensions of Prader Willi Syndrome: Relationships between sleep disturbance and psychotic experiences

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Product

Resources

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Obesity management in Prader–Willi syndrome: current perspectives