Early-onset catatonia associated with SHANK3 mutations: looking at the autism spectrum through the prism of psychomotor phenomena.

Background: Individuals with Phelan-McDermid syndrome (PMS) present with a wide range of diagnoses: autism spectrum disorder, intellectual disability, or schizophrenia. Differences in the genetic background could explain these different neurodevelopmental trajectories. However, a more parsimonious hypothesis is to consider that they may be the same phenotypic entity. Catatonic disturbances occasionally reported from adolescence onwards in PMS prompts exploration of the hypothesis that this clinical entity may be an early-onset form of catatonia. The largest cohort of children with childhood catatonia was studied by the Wernicke-Kleist-Leonhard school (WKL school), which regards catatonia as a collection of qualitative abnormalities of psychomotricity that predominantly affecting involuntary motricity (reactive and expressive). The aim of this study was to investigate the presence of psychomotor signs in three young adults carrying a mutation or intragenic deletion of the SHANK3 gene through the prism of the WKL school conception of catatonia. Methods: This study was designed as an exploratory case study. Current and childhood psychomotor phenomena were investigated through semi-structured interviews with the parents, direct interaction with the participants, and the study of documents reporting observations of the participants at school or by other healthcare professionals. Results: The findings show catatonic manifestations from childhood that evolved into a chronic form, with possible phases of sub-acute exacerbations starting from adolescence. Conclusion: The presence of catatonic symptoms from childhood associated with autistic traits leads us to consider that this singular entity fundamentally related to SHANK3 mutations could be a form of early-onset catatonia. Further case studies are needed to confirm our observations.

Catatonia in neurodevelopmental disorders: assessing catatonic deterioration from baseline.

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.

Case Report: A Case of Pediatric Catatonia: Role of the Lorazepam Challenge Test.

A case of a 12-year-old boy who developed catatonia is presented. He had no previous psychiatric history but has a family history of affective disorder. An extensive medical workup was negative. Despite a negative lorazepam challenge test, lorazepam was titrated up to 24 mg/day, with resolution of most catatonic symptoms. The case highlights an important point in the management of catatonia that may be a source of confusion, i.e., a positive lorazepam challenge test corroborates the diagnosis of catatonia; however, a negative lorazepam challenge test does not negate the diagnosis of catatonia, and subsequent focused benzodiazepine treatment may still be effective.

Electroconvulsive Treatment for Catatonia in Autism Spectrum Disorders.

Catatonia has been increasingly recognized in people with autism spectrum disorders (ASD). Assessment, diagnosis, and treatments are reviewed and illustrated with 2 new case vignettes. The use of electroconvulsive treatment (ECT) is recommended in patients who fail to respond to medical treatments, including a trial of lorazepam or another benzodiazepine. The importance of maintenance ECT is discussed. There is an urgent need for prospective studies of catatonia in ASD and for controlled treatment trials.

Electroconvulsive Therapy for Catatonia in Children and Adolescents.

Catatonia may be more common in children and adolescents than previously thought. A boost for the recognition of pediatric catatonia comes from changes in Diagnostic and Statistical Manual of Mental Disorders, 5th edition, facilitating the diagnosis in a wide range of pediatric and adult patients with associated developmental and autistic spectrum disorders; and schizophrenic, affective, and medical disorders. The current status, assessment, and treatment of pediatric catatonia are described. Two case vignettes illustrate diagnostic assessment and treatment. Theories modeling the mechanism of catatonia are reviewed, including a vagal theory.

Neuroleptic Malignant Syndrome/Malignant Catatonia in Child Psychiatry: Literature Review and a Case Series.

OBJECTIVE: To describe the presentation of neuroleptic malignant syndrome (NMS) and malignant catatonia (MC) in children and adolescents. BACKGROUND: NMS and MC are life-threatening, neuropsychiatric syndromes, associated with considerable morbidity and mortality. NMS is diagnosed when there is a recent history of treatment with an antipsychotic (AP) medication, while MC is diagnosed when the symptoms resemble NMS but without a history of exposure to an AP agent. Some authorities believe that apart from the history of exposure to an AP medication, the two conditions are identical. The symptoms of NMS/MC include severe agitation, behavior disregulation, motor and speech changes, self-injury and aggression, autonomic instability, and a range of psychiatric symptoms (affective, anxiety, or psychotic symptoms). Patients may be misdiagnosed with another disorder leading to extensive tests and a delay in treatment. Untreated, the condition may be fatal in 10%-20% of patients, with death sometimes occurring within days of disease onset. METHOD: We describe the presentation and management of five children and adolescents with NMS/MC. CONCLUSION: MC and NMS are life-threatening medical emergencies, which if diagnosed promptly, can be successfully treated with known effective treatments (benzodiazepines and/or electroconvulsive therapy).

Adverse Childhood Experiences Among Inpatient Youths with Severe and Early-Onset Psychiatric Disorders: Prevalence and Clinical Correlates.

This study aimed to determine the prevalence and the clinical correlates of Adverse Childhood Experiences (ACEs) among 158 inpatient youths with two types of severe psychiatric disorders. ACEs were retrospectively collected with the ACEs scale and the List of Threatening Experiences Questionnaire in 77 patients hospitalized for a catatonic syndrome (average age 15.2 years) and 81 for a manic or mixed episode (average age 15.7 years). ACEs were frequent in youths suffering from bipolar disorder type I (BD-I) (58 %) and from catatonia (57 %), with around one quarter exposed to severe abuse (i.e., physical/sexual/emotional abuse or physical/emotional neglect). Youths with BD-I were more likely to be exposed to family violence compared to those with catatonia. Youths who had been exposed to ACEs did not exhibit a more severe presentation or a poorer response to treatment compared to others, either in the bipolar group or in the catatonic group.

Catatonia in Ugandan children with nodding syndrome and effects of treatment with lorazepam: a pilot study.

BACKGROUND: Nodding syndrome (NS) is a severe neuropsychiatric syndrome of an unknown etiology affecting children and adolescents mostly in Eastern Africa. Symptoms of NS and catatonia seem to overlap. We investigated the presence and types of catatonic symptoms in NS and their response to one or two doses of lorazepam, the first-line treatment for catatonia. METHODS: A cross-sectional descriptive study with systematic assessment of catatonia in 33 patients with NS using a modified version of the Bush Francis Catatonia Rating Scale. Sixteen patients met criteria for catatonia and were observed in an open and uncontrolled study to examine the effects of one or two doses of lorazepam in them. RESULTS: Sixteen of 33 patients with NS had an average of 5 catatonia symptoms and met criteria for catatonia. The highest scores were found for mutism, staring, poor eating/drinking, stupor, and grimacing. Excitement, rigidity, negativism and impulsivity had lower scores. None of the children had echolalia or echopraxia. In 6 children, there was a reduction of more than 50% in catatonia ratings, representing a positive response to lorazepam. Three out of six children whose catatonia ratings did not change after the first dose, responded after administration of a second double dose. There were no unusual or critical side-effects. CONCLUSIONS: About half of a selected sample of children with NS met criteria for catatonia. Catatonia scores decreased in most patients after one or two doses of lorazepam. Larger, longer, and controlled studies are warranted to assess the prevalence of catatonia in NS and to assess the use of lorazepam in NS through its effects on catatonia. TRIAL REGISTRATION: ClinicalTrials.gov NCT02462109 Date of formal registration: June 2, 2015.

A clinical review of the treatment of catatonia.

Catatonia is a severe motor syndrome with an estimated prevalence among psychiatric inpatients of about 10%. At times, it is life-threatening especially in its malignant form when complicated by fever and autonomic disturbances. Catatonia can accompany many different psychiatric illnesses and somatic diseases. In order to recognize the catatonic syndrome, apart from thorough and repeated observation, a clinical examination is needed. A screening instrument, such as the Bush-Francis Catatonia Rating Scale, can guide the clinician through the neuropsychiatric examination. Although severe and life-threatening, catatonia has a good prognosis. Research on the treatment of catatonia is scarce, but there is overwhelming clinical evidence of the efficacy of benzodiazepines, such as lorazepam, and electroconvulsive therapy.

Vagal intimations for catatonia and electroconvulsive therapy.

OBJECTIVES: Catatonia is currently viewed as a unique syndrome that consists of specific motor signs responding to benzodiazepines and electroconvulsive therapy (ECT). Advances in catatonia may provide a new window into the mechanism of ECT. Findings on catatonia are updated and related to the mechanism of ECT. METHODS: Selective literature review. RESULTS: There are several putative models and mechanisms of catatonia concerning motor circuitry dysfunction, abnormal neurotransmitters, epilepsy, genetic risk factors, and endocrine and immune dysfunction. Fear and vagal nerve models are presented casting catatonia in an evolutionary-based autonomic neural substrate of social behaviors, engagement, and disengagement according to perceived level of danger. Benzodiazepines and ECT are thought to have autonomic and vagal effects. CONCLUSIONS: Advances in catatonia provide a new window into the mechanism of ECT. Fear and vagal nerve models call for further anatomical, functional, and clinical studies on the vagal nerve and for further studies on the use of anticholinergic medications in catatonia, on vagal function in catatonia, and on the effects of benzodiazepines, ECT, and induced seizures on cholinergic and vagal function.