Kufor-Rakeb syndrome-associated psychosis: a novel loss-of-function ATP13A2 variant and response to antipsychotic therapy.

Biallelic (autosomal recessive) pathogenic variants in ATP13A2 cause a form of juvenile-onset parkinsonism, termed Kufor-Rakeb syndrome. In addition to motor symptoms, a variety of other neurological and psychiatric symptoms may occur in affected individuals, including supranuclear gaze palsy and cognitive decline. Although psychotic symptoms are often reported, response to antipsychotic therapy is not well described in previous case reports/series. As such, we describe treatment response in an individual with Kufor-Rakeb syndrome-associated psychosis. His disease was caused by a homozygous novel loss-of-function ATP13A2 variant (NM_022089.4, c.1970_1975del) that was characterized in this study. Our patient exhibited a good response to quetiapine monotherapy, which he has so far tolerated well. We also reviewed the literature and summarized all previous descriptions of antipsychotic treatment response. Although its use has infrequently been described in Kufor-Rakeb syndrome, quetiapine is commonly used in other degenerative parkinsonian disorders, given its lower propensity to cause extrapyramidal symptoms. As such, quetiapine should be considered in the treatment of Kufor-Rakeb syndrome-associated psychosis when antipsychotic therapy is deemed necessary.

Clozapine Use in 22q11.2 Deletion Syndrome: A Systematic Review of the Literature.

BACKGROUND: 22q11.2 deletion syndrome confers significant risk for the development of schizophrenia. While current recommendations regarding the management of psychotic symptoms in affected individuals are generally in keeping with treatment guidelines for general schizophrenia populations, evidence for the use of clozapine has come from case reports and retrospective observational data. As no reviews on the topic currently exist, a systematic review of clozapine use in 22q11.2 deletion syndrome was completed. METHODS: In November 2023, a literature search was completed using both PubMed and Scopus to identify English-language articles that reported the use of clozapine in humans with 22q11.2 deletion syndrome. RESULTS: Twenty-six articles describing 57 individuals were deemed eligible for inclusion. Most individuals had a diagnosis of treatment-resistant schizophrenia. Where reported, the mean or median dose of clozapine was relatively low, and the majority of individuals exhibited a good response (approximately 65.5% across individual case reports/series). While seizures were unsurprisingly the most commonly reported serious adverse effect, the majority of individuals were able to remain on (or be restarted on) clozapine by having their dose decreased and/or by adding an anticonvulsant (most commonly valproate). CONCLUSIONS: This review reaffirms that individuals with 22q11.2 deletion syndrome may benefit from clozapine therapy even at a low dose, assuming they meet criteria for treatment-resistant schizophrenia and provided no contraindications exist. However, given the increased incidence of seizures in 22q11.2 deletion syndrome, the use of prophylactic anticonvulsant therapy should be considered, and hypoparathyroidism/hypocalcemia screened for and corrected before the initiation of clozapine. It is also recommended that clozapine blood levels be monitored.

Quetiapine, Clozapine, and Pimavanserin Treatment Response in Monogenic Parkinson's Disease Psychosis: A Systematic Review.

Psychotic symptoms frequently occur in idiopathic Parkinson's disease (PD) and often require treatment with antipsychotic therapy. Most antipsychotics have the potential to worsen the motor symptoms of PD; quetiapine, clozapine, and pimavanserin are commonly used for the treatment of idiopathic PD because these medications tend to be comparatively well tolerated. Although psychotic symptoms may also occur in monogenic forms of PD, no reviews have focused on the use of antipsychotic medications in this context. The objective of the present systematic review was to characterize the effectiveness and tolerability of quetiapine, clozapine, and pimavanserin in monogenic PD-associated psychosis. A literature search was performed with PubMed, Scopus, and Embase. The search yielded 24 eligible articles describing 30 individuals, although treatment response with respect to psychotic symptoms was described in only 11 cases; of these, six individuals experienced symptomatic improvement or remission (four with clozapine and two with quetiapine), two exhibited a poor therapeutic response (one to clozapine and one to quetiapine), and the other three responded initially to antipsychotic therapy before experiencing a recurrence of symptoms. The use of quetiapine and clozapine in GBA variant-associated PD is briefly reviewed separately. Notably, no reports of pimavanserin therapy were identified. In keeping with the idiopathic PD literature, relatively low doses of medication were used in most cases. Lastly, side effects were rarely reported. Although quetiapine and particularly clozapine may be effective and well tolerated in the treatment of monogenic PD psychosis, this review highlights the paucity of available evidence to guide clinical decision making in this context.

A Unique Case of SCN2A Variant-Associated Catatonia and Response to Electroconvulsive Therapy.

ABSTRACT: The SCN2A gene encodes a subunit that forms part of voltage-gated sodium channels in the brain. Gain-of-function mutations are associated with epilepsy as well as numerous movement/motor abnormalities. Loss-of-function mutations may also cause epilepsy in addition to a variety of neurodevelopmental anomalies, including autism and intellectual disability. The occurrence of catatonia has also been described in 1 previous report that involved a 4-year-old boy. We describe a 20-year-old intellectually disabled female patient who developed recurrent catatonic symptoms in her teenage years that remitted with electroconvulsive therapy. This is only the second report of catatonia occurring in relation to an SCN2A mutation and the first involving a female. Moreover, this case is unique given our patient's later age of symptom onset and given that her symptoms responded well to electroconvulsive therapy.

Response to Treatment in 3q29 Deletion Syndrome-Associated Psychosis: A Mini-Review.

3q29 deletion syndrome is characterized by various developmental abnormalities, medical issues, and neuropsychiatric symptoms, including psychosis. Although this syndrome may confer the greatest risk for schizophrenia of any copy number variation, response to antipsychotic medication has infrequently been described in the literature, and no reviews on the topic currently exist. As such, the purpose of this article was to review treatment response in 3q29 deletion syndrome-associated psychosis. A review of the literature was completed in December 2022 for English language articles that described treatment response to antipsychotic medications in affected individuals with schizophrenia-like presentations. Five articles that collectively described eight individuals were included. Four individuals had a poor treatment response to non-clozapine antipsychotic medications, three had a partial response, and one individual's response to treatment was not described, despite having taken psychotropic medications of some kind. Additionally, three individuals received clozapine; one of whom partially responded, while two exhibited a good response. Treatment response did not clearly differ according to developmental history. 3q29 deletion syndrome may be associated with treatment-resistant psychotic symptoms. As such, clozapine therapy should be considered in such individuals, provided they meet criteria for treatment-resistant schizophrenia and no contraindications exist. However, this mini-review also highlights the need for more published case reports/series before more specific treatment recommendations can be made.

Clinically Relevant Anti-Neuronal Cell Surface Antibodies in Schizophrenia Spectrum Disorders.

Schizophrenia is a phenotypically heterogeneous and poorly understood disorder. While its etiology is likely multifactorial, immune system dysfunction has increasingly been implicated in its development. As hallucinations and delusions occur frequently and prominently in autoimmune encephalitis (AE), numerous studies have sought to determine whether a small subset of individuals diagnosed with schizophrenia possess anti-neuronal antibodies implicated in AE. Exploring this possibility is of clinical relevance, as identifying individuals with AE who have been misdiagnosed as having a primary psychotic disorder may allow for the implementation of appropriate immune-related therapies as early as possible in the course of the illness, in order to optimize outcomes, reduce illness chronicity, and minimize adverse events. This qualitative review serves to provide an overview of the existing literature on this topic, as well as to update previously published reviews. Although there is some evidence to suggest that in rare cases AE may be misdiagnosed as a primary psychotic disorder, particularly early in the course of the illness, numerous methodological differences between studies likely account for the highly variable findings, and interpretation of the results is particularly limited by a paucity of cerebrospinal fluid data. Moreover, the prevalence of misdiagnosis in chronic and treatment-resistant populations remains understudied. This is particularly problematic, as treatment resistance may represent an enriched population with respect to the presence of anti-neuronal antibodies, and given that such patients have few evidence-based treatment options available to them beyond clozapine.

Maternal 15q11.2-q13.1 duplication syndrome-associated psychosis and mania: a new case and review of the literature.

Maternal 15q11.2-q13.1 duplication syndrome is associated with a variety of developmental and neuropsychiatric abnormalities. Although schizophrenia-like presentations have been reported, details pertaining to the nature of the corresponding psychotic symptoms and their response to treatment have only been described in a few cases, and no reviews summarizing the literature currently exist. As such, we describe a new case of 15q11.2-q13.1 duplication syndrome-associated schizoaffective disorder and also performed a systematic review of the literature. Our patient's presentation is somewhat unique as she experienced visual hallucinations in the absence of auditory hallucinations. This is also the first report to describe full symptomatic remission in response to relatively low-dose atypical antipsychotic therapy.

The Co-occurrence of Gastrointestinal Symptoms and Psychosis: Diagnostic Considerations.

Gastrointestinal issues are common in schizophrenia and may also co-occur with psychotic symptoms in a variety of other clinical contexts. Although their concurrent development may be coincidental, such presentations may also be attributable to a variety of underlying psychiatric, medical, and neurologic conditions. As patients may first present to mental health services, it is important that both psychiatrists and primary care physicians involved in the care of psychiatric populations have a familiarity with the differential diagnosis of co-occurring gastrointestinal and psychotic symptoms. This narrative review describes the numerous clinical scenarios in which gastrointestinal and psychotic symptoms commonly co-occur and highlights the practical implications thereof.