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Treatment of a Prader-Willi Patient with Recurrent Catatonia



Prader-Willi is a genetic disorder characterized by neonatal hypotonia, hyperphagia, short stature, hypogonadism, and mental delay. This disorder can result from multiple mechanisms, most commonly a deletion of paternal chromosome 15, leaving a single maternally derived chromosome 15. Individuals who have a maternal uniparental disomy of chromosome 15 have a higher risk for developing psychosis compared to other forms of Prader-Willi. The following report details the treatment course of a 24-year-old female with Prader-Willi and recurrent catatonia. The patient initially had a positive lorazepam challenge test but subsequently failed treatment with benzodiazepines. She then received eight electroconvulsive therapy (ECT) treatments after which she showed improvement from initial catatonic state. However, the resolution in her symptoms did not follow a linear course but would show periods of improvement followed by a return of catatonic features. This case provides an example of the complexity of treatment of a patient with a genetic disorder and recurrent catatonia.
Case Report
Treatment of a Prader-Willi Patient with Recurrent Catatonia
Hana M. Poser1and Alexandru E. Trutia2
Correspondence should be addressed to Hana M. Poser;
Received  January ; Revised  April ; Accepted  April 
Academic Editor: Toshiya Inada
Copyright ©  H. M. Poser and A. E. Trutia. is is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
Prader-Willi is a genetic disorder characterized by neonatal hypotonia, hyperphagia, short stature, hypogonadism, and mental
delay. is disorder can result from multiple mechanisms, most commonly a deletion of paternal chromosome , leaving a single
maternally derived chromosome . Individuals who have a maternal uniparental disomy of chromosome  have a higher risk for
developing psychosis compared to other forms of Prader-Willi. e following report details the treatment course of a -year-old
female with Prader-Willi and recurrent catatonia. e patient initially had a positive lorazepam challenge test but subsequently
failed treatment with benzodiazepines. She then received eight electroconvulsive therapy (ECT) treatments aer which she showed
improvement from initial catatonic state. However, the resolution in her symptoms did not follow a linear course but would show
periods of improvement followed by a return of catatonic features. is case provides an example of the complexity of treatment of
a patient with a genetic disorder and recurrent catatonia.
1. Introduction
Prader-Willi syndrome (PWS) is a genetic disorder with
an incidence of one in , [] characterized by absence
of expression of one or more paternally inherited genes
on chromosome q-q. ose with PWS have a char-
acteristic phenotype which includes neonatal hypotonia,
hypogonadism, short stature, decreased cognition, and most
classically extreme overeating that can lead to obesity without
food restriction. ere are four genetic mechanisms which
can result in the Prader-Willi genotype. Approximately %
of individuals aected have a de novo deletion of the
paternal chromosome  (q-q), % of individuals have
a maternal uniparental disomy (mUPD) with two copies
of maternal chromosome , and the remaining % result
from an imprinting defect or unbalanced chromosomal
translocation []. Previous studies have shown that those
individuals with the mUPD are at a much higher risk for
psychosis than those with PWS due to some other genetic
causes [,]. In addition, individuals with the mUPD had a
greater incidence of recurrent psychiatric episodes and oen
those with recurrences showed deterioration from premorbid
functioning []. e limited studies on PWS consist of case
reports and cohort studies with relatively small sample sizes
due to the low prevalence of this syndrome. One case report
exists describing a -year-old male with Prader-Willi who
presented with catatonia that was resp onsive to pharmacolog-
ical therapy alone []. e goal of this case report is to detail
the clinical course and treatment of catatonia in a patient with
PWS of the mUPD type.
2. Case Report
Ms. Z is a -year-old Caucasian female with Prader-Willi
mUPD type, mild mental retardation (IQ ), and unspeci-
ed mood disorder who presented to the emergency depart-
ment aer her parents reported one month of increasingly
manic behavior and a ten-pound weight loss in ten days.
e patient’s behavior ve to six days before hospital admis-
sion was described as hyperverbal, euphoric, and illogical
with decreased sleep. She then suddenly became mute and
withdrawn exhibiting purposeless movements prompting her
parents to bring her to the hospital.
Ms. Z was diagnosed clinically with Prader-Willi at a
young age with the key features of hyperphagia, short stature,
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Case Reports in Psychiatry
Volume 2015, Article ID 697428, 4 pages
Case Reports in Psychiatry
hypogonadism, and mental delay all present. It was not until
the age of  that she underwent genetic testing revealing
mUPD form of Prader-Willi. In the past, Ms. Z had two
prior hospitalizations at age of  and  for depression with
catatonia that responded to therapy with lorazepam and
haloperidol. Before her rst hospitalization, Ms. Z had no
signicant psychological history. Since her rst hospitaliza-
tion, she had been maintained on a variety of antipsychotic
and antidepressant regimes for varying diagnosis of mood
disorder not otherwise specied (ICD- F), schizoaec-
tive disorder (ICD- F.), and depression with psychosis
(ICD- F.) while being followed regularly by a pediatric
psychiatrist. Her current home regimen on presentation
consisted of aripiprazole  mg daily, lamotrigine  mg
daily, and lithium  mg two times a day that the patient
was compliant with. At baseline, Ms. Z is able to work part-
time with children under supervision at a local gym and is
described by her parents as very friendly and happy. She lives
with her parents who are very involved in her care.
At initial exam, Ms. Z appeared a well-groomed, obese
young female with stooped posture and mild hand tremor
present bilaterally. She appeared drowsy, lethargic, was tearful
at times, and did not make eye contact but was able to
follow simple commands. She displayed mutism, posturing,
waxy exibility, purposeless movements, repeated shoulder
shrugging, and stereotypy with nger pointing, among other
behaviors. Bush-Francis Catatonia Rating Scale score totaled
/. Her aect was blunted and she was orientated to
person but not place or time. Other portions of the exam
questioning. Physical exam was otherwise unremarkable.
During the interview, Ms. Z responded to mg lorazepam
challenge with improved verbal responses although speech
was very slow, so, and words were slurred. Head CT did
not reveal any acute intracranial abnormality and there
was no evidence of seizure on EEG. She was diagnosed
with catatonia with depressed features and admitted to the
inpatient psychiatric unit where she was started on treatment
with lorazepam mg three times a day as well as her home
regimen of antipsychotics.
Over the next  days Ms. Z showed minimal improve-
ment with lorazepam which was increased to  mg every 
hours. Her symptoms would uctuate minimally; at times
she would be more interactive with sta and family and then
return to being withdrawn. During this time, her home regi-
men was adjusted by decreasing the aripiprazole and lithium
and initiating therapy with ziprasidone to help with mood
and psychosis. Due to lack of response to pharmacological
therapy and concern for patient’s well-being with weight loss
and dehydration noted on initial presentation, the decision
was made to begin ECT therapy with a goal of – treatments
delivered every other day. Ms. Z’s parents were supportive of
this decision and provided consent for her treatment.
Lithium was discontinued before the start of ECT (refer
to Table  for treatment details) and her morning dose
of lorazepam was held on ECT days. Aer the rst ECT
treatment, Ms. Z had improved mental status for about 
minutes and then returned to initial catatonic state. Following
her second treatment with ECT, Ms. Z displayed increased
eye contact, was more verbally responsive, had more energy,
described her mood as “happier,” and showed decreased
psychomotor slowing. During her third ECT session, two
stimuli were given due to poor initial motor and EEG
seizure responses. e following day, Ms. Z appeared more
withdrawn, appeared less interactive with sta, and again
appeared to be responding to internal stimuli. Lamotrigine
was decreased and held nights before ECT treatment to
achieve better ECT response. Lorazepam was also decreased
to improve motor response to ECT.
Aer ECT , the patient’s progress halted. She displayed
increased psychomotor slowing that was very apparent and
Ms. Z became very sedated and some of her presenting
features of catatonia such as waxy exibility returned. She
was spending more time talking to herself and remained
awake for most of the night pacing the hallway. Aer this
notable change, lorazepam was increased due to concern that
the lower dosage was responsible for a return back towards
catatonic state. Ziprasidone was also increased to help with
e following morning, Ms. Z became even more sedated
lorazepam was held due to concern over increased sedation
, she was talkative, interactive, and more energetic. She
was able to participate in group activities and took part in
dancing, one of her favorite past times. Mini-mental status
exam was performed and the patient received / only
missing points for day of the week and date. Her father
reported at this point that she was “close to baseline.’’
With this improvement, lorazepam was further
decreased. ECT  was then performed. e night following
ECT , Ms. Z was noted to be extremely sedated and dicult
to arouse. e next morning she provided minimal responses
to questioning, was seen smiling to herself most of the day,
displayed unsteady gait, increased psychomotor retardation,
and was again very drowsy. She did not have any rigidity or
purposeless movements. It was unclear whether Ms. Z was
moving back towards her catatonic state or if this was just
a normal uctuation of her catatonic state in response to
ECT treatment. Lorazepam was discontinued at this time.
ECT  was given and over the next three days Ms. Z
continued to show psychomotor retardation and was mostly
mute but began to engage more on the fourth day. Lastly
ECT  was given at % bitemporal energy due to decreased
seizure and waxing/waning mutism displayed at the time.
Following her nal treatment, Ms. Z still displayed some
psychomotor retardation and decreased energy but did have
spontaneous speech. Her parents felt she was about % of
home aer  days of inpatient treatment. She was discharged
on lamotrigine  mg daily, lithium  mg three times a day,
and ziprasidone  mg daily. At her tenth week of follow-up,
Ms. Z’s mood had improved. She was able to return to work
although she was experiencing some episodes of cataplexy.
Case Reports in Psychiatry
T : ECT treatment course.
ECT Medications Energy/charge Motor/EEG response Clinical response
Ziprasidone  mg twice daily, lamotrigine  mg
before bed, and lorazepam mg three times daily
% bifrontal
. mc  sec motor/ sec EEG
Improved verbal response for  min and then back
to catatonic state. roughout the day, patient
became more verbal and coherent and even
expressed humor.
Identical regimen as time point  % bifrontal
. mc  sec motor/ sec EEG Less interactive, disoriented, with repetitive
Identical regimen as time point 
. mc
 sec motor/ sec EEG
 sec motor/ sec EEG
Less energetic, increasingly drowsy, minimal
interaction, decreased sleep, and pacing hallways.
Ziprasidone  mg twice daily,
lamotrigine  mg b efore b ed, and lorazepam
. mg three times daily
% bifrontal
. mc  sec motor/ sec EEG Very drowsy, psychomotor retardation, decreased
sleep, waxy exibility, and increased speech latency.
Ziprasidone  mg twice daily,
lamotrigine  mg b efore b ed, and lorazepam
. mg three times daily
% bifrontal
. mc  sec motor/sec EEG Much more engaged, aware, conversational, and
oriented to situation.
Ziprasidone  mg twice a day,
lamotrigine  mg before bed (held before ECT),
and lorazepam . twice daily
% bifrontal
. mc sec motor/ sec EEG Waxing/waning mutism, repetitive movements, and
psychomotor retardation.
Ziprasidone  mg twice daily,
lamotrigine  mg before bed (held before ECT),
and d/c lorazepam
% bifrontal
. mc  sec motor/ sec EEG Improved but still with low energy and very drowsy.
Ziprasidone  mg am/ mg pm, lamotrigine
 mg before bed
% bitemporal
. mc sec motor/ sec EEG Regaining energy, more engaged, with improved
Morning dose of lorazepam was held in mornings of ECT for better seizure response.
Treatment required two stimuli due to poor motor response.
Case Reports in Psychiatry
Six months aer hospitalization, she had made a full recovery
with no return of catatonic features.
3. Discussion
Catatonia is a recognized syndrome characterized by its
unique set of behavioral abnormalities and response to
benzodiazepines and ECT. Multiple models have been pro-
posed to explain the etiology of these behaviors including
theories on dysfunctional GABA receptors and alterations
to hypothalamic-pituitary axis []. Some also suspect that
there could be a genetic component to the development
of catatonia. Catatonia can be one of the displayed forms
caused by an abnormality in chromosome . Similar genes
have been implicated in catatonic schizophrenia and autism
Due to the lack of randomized controlled trials address-
ing the treatment of catatonia, protocol for therapy is mainly
benzodiazepines followed by ECT or simultaneous use of
both represents the standard of care. Case series suggest that
benzodiazepines alone have a response rate of %–% [].
For patients with severe catatonia or catatonia refractory to
treatment with benzodiazepines, ECT is the recommended
form of therapy. ere are no current ECT guidelines for
duration of treatment, frequency, strength of treatment, or
electrode placement in patients with catatonia due to lack of
controlled studies using ECT in this target population. One
recent study of  patients treated with ECT for catatonia
found the average number of ECT sessions per patient to
be 7.25 ± 2.54 withan.%responserate[]. Varia-
tions in electrical charge delivered and duration of motor
and EEG response can been seen between retrospective
As seen in this case, the treatment course becomes
complex when dealing with catatonic patients with comorbid
genetic and mood disorders being treated with mood stabi-
lizers and antipsychotics. It becomes dicult to discern what
aspects of treatment are contributing to improvement and
those that may be hindering it. In addition, the response to
ECT can be highly variable among patients and symptoms
can seem to uctuate throughout the course of treatment
as seen with Ms. Z. e study by Raveendranathan et al.
suggests that characteristics such as younger age, duration
of catatonia, and higher Bush Francis may predict bet-
ter response to ECT. One consistent nding among stud-
ies was that earlier diagnosis and treatment of catatonia
led to better outcomes. is stresses the importance of
early recognition of symptoms, diagnosis, and treatment of
A database search locates one other case report of catato-
nia in a patient with Prader-Willi. is case study described
the treatment of a -year-old male with Prader-Willi, who
was diagnosed clinically and had acute onset catatonia which
responded to treatment with lorazepam and risperidone over
atwo-weekperiod[]. Ms. Z who was described here with
Prader-Willi of the maternal uniparental disomy type was
known to have a preexisting mood disorder and received
treatment for recurrent catatonia refractory to treatment with
Verbal consent for publication was given by patient’s mother.
Conflict of Interests
e authors declare that there is no conict of interests
regarding the publication of this paper.
[] J.E.Whittington,A.J.Holland,T.Webb,J.Butler,D.Clarke,and
H. Boer, “Population prevalence and estimated birth incidence
UK Health Region,Journal of Medical Genetics, vol. , no. ,
pp. –, .
[] R. D. Nicholls and J. L. Knepper, “Genome organization,
function, and imprinting in Prader-Willi and Angelman syn-
dromes,Annual Review of Genomics and Human Genetics,vol.
[] H.Boer,A.Holland,J.Whittington,J.Butler,T.Webb,andD.
Clarke, “Psychotic illness in people with Prader Willi syndrome
due to chromosome  maternal uniparental disomy,” e
[] S. Soni, J. Whittington, A. J. Holland et al., “e course
and outcome of psychiatric illness in people with Prader-
Willi syndrome: implications for management and treatment,
Journal of Intellectual Disability Research,vol.,no.,pp.
, .
[] D. M. Dhossche and N. H. Bouman, “Catatonia in an adolescent
with Prader-Willi Syndrome,Annals of Clinical Psychiatry,vol.
, no. , pp. –, .
[] D.M.Dhossche,L.Stoppelbein,andU.K.Rout,“Etiopatho-
genesis of catatonia: generalizations and working hypotheses,
Journal of ECT,vol.,no.,pp.,.
[] A. Francis, “Catatonia: diagnosis, classication, and treatment,
Current Psychiatry Reports,vol.,no.,pp.,.
[] D. Raveendranathan, J. C. Narayanaswamy, and S. V. Reddi,
“Response rate of catatonia to electroconvulsive therapy and its
clinical correlates,European Archives of Psychiatry and Clinical
... 21 Catatonia has also been reported in individuals with 22q11 deletion syndrome, Prader-Willi syndrome, and many other genetic syndromes that we discuss in this Personal View. [22][23][24][25] Catatonia has the highest mortality risk of any paediatric psychiatric diagnosis, with up to 20% mortality rate in untreated malignant catatonia. 26 ...
... These atypicalities include bradykinesia and parkinsonism in juvenile Huntington's disease, 64 Rett syndrome, 65 and dopa-responsive dystonia; 66 motoric stereotypies in 22q11.2 mutation; 23 dystonia in cerebral palsy; 67 hypotonia in Prader-Willi syndrome; 25 and ataxia in Niemann-Pick type C. 68 The presence of catatonia in complex epilepsy syndromes, such as Lafora disease, has also been reported. 69 Neurobehavioral symptoms can create confusion for clinicians in the setting of catatonia. ...
Despite the inclusion of catatonia as a specifier of autism spectrum disorder in DSM-5, we-a team of child and adolescent neuropsychiatrists who specialise in paediatric catatonia and neurodevelopmental disorders-have identified a number of issues with the diagnosis and clinical management of catatonia in our patients. In this Personal View, we summarise the literature regarding catatonia in people with neurodevelopmental disorders, including autism spectrum disorder, describe our concerns, and offer a novel approach to addressing important issues with current diagnostic and treatment paradigms. We emphasise the need for a measure to diagnose and monitor people with catatonia and their history of neurodevelopmental disorders. This measure should consider previous complex and underlying motor, medical, functional, and neurobehavioural symptoms. We propose two concepts for understanding catatonia that relate to the baseline status of an individual: the personalised score at baseline, an estimate of premorbid neurobehavioral and motor symptoms, and the catatonic deterioration from baseline, an estimate of current features that are due to catatonia rather than an underlying neurodevelopmental disorder. We hope this measure will provide a practical tool for clinicians and researchers working with this underserved and high-risk population.
... Catatonia is a state that a person who is awake does not respond to any external stimuli. We have 3 types of catatonia by its etiology (1) includes associated with the mental disorder (2), associated with the medical condition of the patient (3), and unspecified catatonia (4). This disease manifest some signs and symptoms as allogia, Negativism, Echolalia, Echopraxia, Waxy flexibility and Withdrawal (5). ...
Full-text available
Catatonia is a state that a person who is awake does not respond to any external stimuli. Theterm cultural bound syndrome refers to anyone who has recurrences, locality-specific patternsof aberrant behavior and experiences that appear to fall outside conventional Westernpsychiatric diagnostic categories. In this case we are presenting a young woman who hadgiven birth, and it was followed by an acute and extreme stressor. She suffered from severeanxiety and the symptoms of catatonia.
... Catatonia is a state that a person who is awake does not respond to any external stimuli. We have 3 types of catatonia by its etiology (1) includes associated with the mental disorder (2), associated with the medical condition of the patient (3), and unspecified catatonia (4). This disease manifest some signs and symptoms as allogia, Negativism, Echolalia, Echopraxia, Waxy flexibility and Withdrawal (5). ...
Full-text available
study to determine the prevalence of intestinal helminth infections among primary schoolchildren in Nimo Community, Njikoka Local Government Area, Anambra State, Nigeria was undertaken.Four Primary Schools, namely Ugwu-Oye Primary School, Unity Primary School, St. Joseph’s PrimarySchool and Egbengwu Primary School were involved in the study. 120 pupils were selected from theschools and enlisted into the study. Direct smear and zinc sulphate solution (Flotation method) were usedfor the isolation of the helminth eggs. Of the 120 stool samples examined, 26(21.7%) harboured intestinal helminths, Egbengwu Primary School had the highest number of infection 10(33.3%) and St. Joseph’sPrimary School had the lowest 3(10.0%). Intestinal helminth infections observed were hookworms13(10.8%), Ascaris lumbricoides 7(5.83%), Trichuris trichiura 2(1.66%), Schistosoma mansoni 2 (1.66%), Strongyloides stercoralis 1(0.83%) and Taenia spp 1(0.83%). More females 14(23.3%) than the males12(20.0%) were infected. The age specific prevalence in the four schools was highest in 13-16 years agegroup 3(60.0%) and least in 5-8 years age group 8(16.0%). Government schools had higher prevalence of infection 18(30.0%) than private schools 8(13.3%). Generally poor sanitation, socio-economic status andignorance of the epidemiology of infection were related to the prevalence of infection.
... However, there are significant limitations to candidate gene studies in psychiatry 38 , and these associations have not, to our knowledge, been replicated in large-scale population-based genetic studies. Catatonia has been observed in patients with NDDs with established genetic etiologies 39 , such as Prader-Willi syndrome 40 43 , and late-onset Tay-Sachs disease 44 . These rare genetic disorders can shed light on the neurobiological etiology of catatonia. ...
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Individuals with neurodevelopmental disabilities (NDDs) may be at increased risk for catatonia, which can be an especially challenging condition to diagnose and treat. There may be symptom overlap between catatonia and NDD-associated behaviors, such as stereotypies. The diagnosis of catatonia should perhaps be adjusted to address symptom overlap and to include extreme behaviors observed in patients with NDDs, such as severe self-injury. Risk factors for catatonia in individuals with NDDs may include trauma and certain genetic variants, such as those that disrupt SHANK3 . Common etiologic features between neurodevelopmental disabilities and catatonia, such as excitatory/inhibitory imbalance and neuroimmune dysfunction, may partially account for comorbidity. New approaches leveraging genetic testing and neuroimmunologic evaluation may allow for more precise diagnoses and effective treatments.
... A wide range of both psychiatric and medical conditions have been found to be associated with catatonia including autism [9,[17][18][19][20][21], schizophrenia [22,23], trauma [24,25], affective disorders [8], Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) [26], Tourette syndrome, mutism, and obsessive-compulsive disorder (OCD) [27]. Medical conditions associated with catatonia have included anti-Nmethyl-D-aspartate (anti-NMDA) encephalitis and other forms of autoimmune encephalitis [28][29][30][31][32][33], autoimmune disorders [34], systemic lupus erythematosus [35,36], encephalitis [37], infection [38], seizures [39], drug reactions [40][41][42][43], genetic disorders [44], and inborn errors of metabolism [39]. Dhossche and Wachtel reported on a host of other pediatric disorders that can present with catatonia, leading him to refer to the disorder as "hidden in plain sight" (1). ...
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Objective: We present a narrative review of pediatric catatonia and a case report illustrating the complexity of management of psychosis in a child with catatonia. Method: The literature search used the text terms pediatric, catatonia, and antipsychotics and the search engines PubMed and EBSCO. All references from peer-reviewed journals were reviewed for treatment strategies specific to management in children who are also psychotic. Findings. This 8-year-old girl presented with psychotic symptoms which were initially treated with antipsychotics and evolved into life-threatening catatonia that was eventually stabilized with a total daily dose of 46 mg of lorazepam. Lower doses led to recurrence. Once catatonia improved, she tolerated combined benzodiazepine and antipsychotic treatment. Long-term maintenance over 5 years required maintenance treatment with both benzodiazepines and antipsychotics to prevent relapse. Conclusions: The extraordinary doses of benzodiazepines found to be optimal for management of catatonia in this child led to improved alertness and orientation, without evident sedation. Catatonia did not recur with later management of psychosis using neuroleptics when added to lorazepam. The current literature on pediatric catatonia does not provide guidance on dose maintenance or when and if to rechallenge with antipsychotics.
Prader-Willi syndrome (PWS) has a complex neurobehavioral phenotype that evolves over the course of development reflecting differences in genetic subtype. Although it is well known that environmental management (controlled food access) has been lifesaving and psychological intervention (FOOD SECURITY) has improved the quality of life, there are few evidence-based studies evaluating the efficacy of psychotropic medications as an adjunctive management tool for PWS. In this chapter, the pertinent history and current status of psychotropic medication management in PWS will be reviewed, including a historical overview, the evidence base for efficacy, potential adverse effects, alternative treatment strategies, and future directions in research. In summary, there are no psychiatric medications that are specifically recommended for PWS nor are there any medications that are excluded. However, dosing parameters in PWS are affected by pharmacogenetics, pharmacokinetics, and pharmacodynamics. Safeguards for proper dose selection and monitoring of drug-induced adverse events are essential. Given the current state of polypharmacy in PWS, it is prudent to appreciate the impact of drug-drug, drug-hormone, and drug-environment interactions that are unique to PWS. Most importantly, there must be a rationale for using a given medication, and if the outcome of treatment is not as expected, the clinician must be open to questioning whether an environmental, psychological, or environmental intervention might be a better option, rather than adding another medication. This chapter will summarize what is known about (1) historical perspectives on pharmacotherapy in PWS; (2) overview of studies looking at pharmacological management in PWS; (3) efficacy of pharmacotherapy in PWS; (4) pharmacogenetic, pharmacokinetic, and pharmacodynamic factors related to drug selection, drug metabolism, drug dosing, and schedule of administration in PWS; (5) adverse events associated with medication management across different classes of drugs and their effects on body systems; and (6) recommendations for pharmacological intervention going forward.
Prader-Willi syndrome (PWS) is caused by the loss of expression of contiguous genes both inside and outside the imprinted region on ch15q11-13. Gene expression is related to the genetic subtype caused by deletion (DEL), maternal uniparental disomy (UPD) 15, or an imprinting center (IC) defect. In typical persons, the many aspects of genomic imprinting play a major role throughout development. The most sensitive periods for expression of imprinted genes are the stages of greatest change in the central and peripheral nervous systems during fetal development and infancy. The loss of expression of imprinted genes on ch15 creates a specific genetic blueprint that interacts with the normal processes of growth and development to produce the multiphasic behavioral phenotype of PWS. A developmental perspective is essential to capture the many facets of the neuropsychiatric phenotype in PWS. This chapter covers (1) an introduction to brain difference in PWS; (2) a literature review of studies defining the behavioral phenotype; (3) a psychiatric evaluation, neurodevelopmental case formulation, and differential diagnosis; and (4) a descriptive narrative of psychiatric diagnoses as they appear across developmental stages from early childhood through senescence. A comprehensive literature review and extensive clinical experience with infants, children, adolescents, and adults with PWS and their parents have informed the data-based concepts presented in this chapter.
The author recounts how she came to carry out artistic research on guitar multiphonics when composing a piece for solo guitar. Furthermore, she explains how the investigation gave rise to a new form of usage of that unconventional technique.
Cambridge Core - Health and Clinical Psychology - The ECT Handbook - edited by I. Nicol Ferrier
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Catatonia in children and adolescents has received little research attention. Treatment and course of catatonia in an adolescent patient with Prader-Willi Syndrome are presented. Clinical features of a small series of published case reports of catatonia in children and adolescents are reported. The association between catatonia, Prader-Willi Syndrome, and other neurodevelopmental disorders is discussed.
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Catatonia has been rediscovered over the last 2 decades as a unique syndrome that consists of specific motor signs with a characteristic and uniform response to benzodiazepines and electroconvulsive therapy. Further inquiry into its developmental, environmental, psychological, and biological underpinnings is warranted. In this review, medical catatonia models of motor circuitry dysfunction, abnormal neurotransmitters, epilepsy, genetic risk factors, endocrine dysfunction, and immune abnormalities are discussed. Developmental, environmental, and psychological risk factors for catatonia are currently unknown. The following hypotheses need to be tested: neuroleptic malignant syndrome is a drug-induced form of malignant catatonia; Prader-Willi syndrome is a clinical GABAergic genetic-endocrine model of catatonia; Kleine-Levin syndrome represents a periodic form of adolescent catatonia; and anti-N-methyl-d-aspartate receptor encephalitis is an autoimmune type of catatonia.
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Editor—Prader-Willi syndrome (PWS) is a genetically determined disorder in which the absence of expression of one or more maternally imprinted gene(s) in the chromosomal region 15q11-13 results in a characteristic facial appearance, learning disabilities (mental retardation), and severe overeating behaviour owing to an abnormal satiety response to food intake, together with a range of other behaviours. Initially, as reported by Prader et al ,1 PWS was conceived as a syndrome of obesity, short growth, cryptorchidism, and mental retardation following hypotonia in the neonatal period. As more and more people with PWS were reported and research into the syndrome began, behavioural characteristics and other clinical features were added, culminating in the consensus diagnostic criteria.2Concurrently, the genetics of the disorder were receiving attention. First was the discovery that for many there was a visible chromosomal deletion in the proximal part of the long arm of chromosome 15 (15q11-13). Reports of an apparently similar deletion being associated with a phenotypically very different syndrome (Angelman syndrome, AS),3 and the observation that PWS was the result of a deletion on the chromosome 15 of paternal origin, and AS the chromosome 15 of maternal origin, led to the recognition that gender specific imprinting of genes at that locus accounted for two diverse syndromes being associated with apparently similar chromosomal deletions.4 Maternal chromosome 15 disomies, mutations of an imprinting centre, and chromosomal translocations accounted for non-deletion cases of PWS.5 In published reports on Prader-Willi syndrome (PWS), prevalence has been variously quoted as “about 1 in 25 000 live births”,6 “between one in 25 000 and one in 10 000 live born children”,7 “[estimates] vary 6-fold from 1 in 5000 to 10 000; 1 in 10 000; 1 in 15 000; 1 in 25 000; to 1 in 10 000 to 30 000”.8 Only two estimates …
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This study is part of a larger UK-wide study investigating psychiatric illness in people with Prader-Willi syndrome (PWS), and describes the longitudinal aspect of psychiatric illness, in particular psychotic illness, and examines the use and role of psychotropic medication. A total of 119 individuals with genetically confirmed PWS were included in the study. An informant-based questionnaire was administered for each participant to screen for a history of psychopathology. Those who screened positive were visited at their homes to obtain further information. This assessment included a full psychiatric history and mental state examination using the Psychiatric Assessment Schedule for Adults with Developmental Disability and the Operational Criteria Checklist for psychotic and affective illness to collect information regarding phenomenology and course of illness, and a modified life events questionnaire. At the end of the study period, informant-based telephone interviews were again carried out, up to 2.5 years after the initial screening. Information regarding medication usage was collected. The results confirm previous findings that psychiatric illness in people with PWS resembles an affective disorder. Individuals with the maternal uniparental disomy genetic subtype had a more severe course of illness than those with the deletion genetic subtype in terms of a greater risk of recurrence, more episodes, higher incidence and a possibly poorer response to medication with more side-effects. Individuals with a recurrent episode during the follow-up period had a poorer course of illness. Selective serotonin reuptake inhibitor medication is frequently used, and beneficial effects may reflect fundamental pathological processes in PWS. Mood-stabilizing medication was found to be of little benefit and reasons for this are examined. The longitudinal course of psychiatric illness and response to medication in people with PWS is fully described. Further research is needed regarding the effect of psychotropic medications, particularly mood-stabilizing medication. These data will enable informed decisions to be made regarding management options and provide information on the possible long-term outcome of illness.
Electroconvulsive therapy (ECT) is an important treatment for catatonia. We aimed to study the response rate of catatonia treated with ECT and its clinical correlates in a large sample of inpatients. The ECT parameters of all patients (n = 63) admitted with catatonia between the months of January and December 2007 were examined. The number of ECTs administered, seizure threshold, failure to achieve adequate seizures and clinical signs pertaining to catatonia were analyzed. Response was considered as complete resolution of catatonic symptoms with Bush Francis Catatonia Rating Scale (BFCRS) score becoming zero. ECT was mostly started after failed lorazepam treatment except in 6 patients where ECT was the first choice. Patients who responded in 4 ECT sessions were considered fast responders (mean session number for response is 4 sessions) and response with 5 or more ECTs was considered slow response. Fast responders had significantly lower duration of catatonia (19.67 ± 21.66 days, P = 0.02) and higher BFCRS score at presentation (17.25 ± 6.21, P = 0.03). Presence of waxy flexibility and gegenhalten (22.60% vs. 0%, P = 0.01) predicted faster response, whereas presence of echophenomena (3.2% vs. 24.0%) predicted slow response. The response rate to catatonia appears to be associated with the severity and duration of catatonia, and the presence of certain catatonic signs.
Catatonia is a distinct neuropsychiatric syndrome that is becoming more recognized clinically and in ongoing research. It occurs with psychiatric, metabolic, or neurologic conditions. It may occur in many forms, including neuroleptic malignant syndrome. Treatment with benzodiazepines or electroconvulsive therapy leads to a dramatic and rapid response, although systematic, randomized trials are lacking. An important unresolved question is the role of antipsychotic agents in treatment and their potential adverse effects.
The chromosomal region, 15q11-q13, involved in Prader-Willi and Angelman syndromes (PWS and AS) represents a paradigm for understanding the relationships between genome structure, epigenetics, evolution, and function. The PWS/AS region is conserved in organization and function with the homologous mouse chromosome 7C region. However, the primate 4 Mb PWS/AS region is bounded by duplicons derived from an ancestral HERC2 gene and other sequences that may predispose to chromosome rearrangements. Within a 2 Mb imprinted domain, gene function depends on parental origin. Genetic evidence suggests that PWS arises from functional loss of several paternally expressed genes, including those that function as RNAs, and that AS results from loss of maternal UBE3A brain-specific expression. Imprinted expression is coordinately controlled in cis by an imprinting center (IC), a genetic element functional in germline and/or early postzygotic development that regulates the establishment of parental specific allelic differences in replication timing, DNA methylation, and chromatin structure.
In a population-based study of Prader Willi syndrome (PWS), we investigated the relation between genetic subtypes of the syndrome and psychiatric morbidity. Of 25 patients aged 18 years or older, seven (28%) had severe affective disorder with psychotic features, with a mean age of onset of 26 years (SD 5.9). The seven people affected, all aged 28 years or older, included all five with disomies of chromosome 15, one with a deletion in this chromosome, and one with an imprinting centre mutation in the same chromosome. We postulate that in PWS, an abnormal pattern of expression of a sex-specific imprinted gene on chromosome 15 is associated with psychotic illness in early adult life.