Psychiatric Manifestations in Patients with Biopterin Defects.

Psychiatric manifestations in patients with tetrahydrobiopterin (BH4) defects are common, and may occur even with treatment of the underlying disorder. The neurobiological background of these conditions has been linked to abnormalities of neurotransmitters, such as dopamine, serotonin, norepinephrine, and gamma-aminobutyric acid. Here, we review the psychiatric profile of all patients with BH4 defects followed in the pediatric and adult metabolic clinics at our center. Three patients with autosomal recessive (AR) guanosine triphosphate cyclohydrolase (GTPCH) deficiency and three patients with 6-pyruvoyl tetrahydropterin synthase (PTPS) deficiency were reviewed.All patients had behavioral disturbances and two had significant psychiatric comorbidities. These included attention deficit/hyperactivity disorder, anxiety, depression, aggression, or oppositional defiant disorder. One patient with PTPS deficiency had a severe psychiatric presentation, requiring inpatient admission and temporary placement into foster care for intensive behavioral therapy. Another with AR GTPCH deficiency was diagnosed with aggressive behavioral dysregulation requiring intensive psychiatric treatment. Management of the psychiatric manifestations of BH4 defects can be challenging, due to lack of information and studies of interactions between psychiatric medications on the deficient neurotransmitters and their receptors in these conditions. Further studies are needed to establish safety and efficacy of these treatments.

Lifesaving Electroconvulsive Therapy for a Child With Autism Spectrum Disorder, Severe Self-Injurious Behavior, and Neuroleptic Malignant Syndrome.

We present a case of a preteen with autism spectrum disorder and severe self-injurious behavior who developed neuroleptic malignant syndrome on antipsychotics and required urgent electroconvulsive therapy and continued maintenance electroconvulsive therapy for ongoing clinical stability.

Characteristics of children with autism and unspecified intellectual developmental disorder (intellectual disability) presenting with severe self-injurious behaviours.

Objective: This study aims to delineate the characteristics of severe self-injurious behaviors (SIB) in a cohort of children with autism and unspecified intellectual developmental disorder (UIDD) (intellectual disability) and examine potential risk factors for developing SIB. Methods: A retrospective chart review studied characteristics of severe SIB in 30 children with autism spectrum disorder (ASD) and UIDD referred to a tertiary care center. Characteristics examined include genetic syndromes, brain MRI abnormalities, verbal ability, adaptive functioning, SIB frequency and severity, age of onset, number of psychopharmacological agents, irritability, hyperactivity, stereotypy, psychiatric and physical comorbidities, among others. Descriptive and bivariate analysis were applied to explore potential relationships between factors. Results: Children with severe SIB exhibit this behaviour with high frequency, inflicting moderate to severe injury. Most children in the study sample are non-verbal and have ASD (93.3%; n = 28) with psychiatric (96.7%; n = 29) and physical (90%; n = 27) comorbidities. Overall SIB improvement using the Clinical Global Impression, Improvement Score (CGI-I) was 3.0 (minimally improved). A minority were much or very much improved following appropriate intervention. Conclusions: The severity of SIB is much higher in this sample than previously noted in the literature. Severe SIB is associated with ADHD, early onset mood disorders, tics, avoidant restrictive food intake disorder and Obsessive-Compulsive Disorder.

Iron Deficiency and Restless Sleep/Wake Behaviors in Neurodevelopmental Disorders and Mental Health Conditions.

Iron deficiency (ID) and restlessness are associated with sleep/wake-disorders (e.g., restless legs syndrome (RLS)) and neurodevelopmental disorders (attention deficit/hyperactivity and autism spectrum disorders (ADHD; ASD)). However, a standardized approach to assessing ID and restlessness is missing. We reviewed iron status and family sleep/ID history data collected at a sleep/wake behavior clinic under a quality improvement/quality assurance project. Restlessness was explored through patient and parental narratives and a 'suggested clinical immobilization test'. Of 199 patients, 94% had ID, with 43% having a family history of ID. ADHD (46%) and ASD (45%) were common conditions, along with chronic insomnia (61%), sleep-disordered breathing (50%), and parasomnias (22%). In unadjusted analysis, a family history of ID increased the odds (95% CI) of familial RLS (OR: 5.98, p = 0.0002, [2.35-15.2]), insomnia/DIMS (OR: 3.44, p = 0.0084, [1.37-8.64]), and RLS (OR: 7.00, p = 0.01, [1.49-32.93]) in patients with ADHD, and of insomnia/DIMS (OR: 4.77, p = 0.0014, [1.82-12.5]), RLS/PLMS (OR: 5.83, p = 0.009, [1.54-22.1]), RLS (OR: 4.05, p = 0.01, [1.33-12.3]), and familial RLS (OR: 2.82, p = 0.02, [1.17-6.81]) in patients with ASD. ID and restlessness were characteristics of ADHD and ASD, and a family history of ID increased the risk of sleep/wake-disorders. These findings highlight the need to integrate comprehensive blood work and family history to capture ID in children and adolescents with restless behaviors.

A novel syndrome with psychiatric features and review of malformation syndromes with psychiatric disorders.

Psychiatric disease occurs with increased frequency in a number of malformation syndromes. We hypothesize that the study of these disorders is helpful for understanding the pathophysiology of psychiatric disease. With this objective, we have been screening for individuals with malformations and prominent psychiatric disease. We report on a man with visual and auditory hallucinations and behavioral problems who was the product of an incestuous relationship and had anomalies primarily of his face, hands and feet. His distinctive features define an undescribed acro-auricular malformation syndrome with a psychiatric component. The study of Mendelian syndromes such as the one presented will likely be helpful for isolating novel genes involved in psychiatric illness.

Characterization of a new X-linked mental retardation syndrome with microcephaly, cortical malformation, and thin habitus.

X-linked mental retardation (XLMR) affects 1-2/1,000 males and accounts for approximately 10% of all mental retardation (MR). We have ascertained a syndromic form of XLMR segregating within a five-generation family with seven affected males. Prominent characteristics include mild to severe MR, cortical malformation, microcephaly, seizures, thin build with distinct facial features including a long and thin face, epicanthic folds, almond-shaped eyes, upslanting palpebral fissures and micrognathia and behavioral problems. Carrier females have normal physical appearance and intelligence. This combination of features is unreported and distinct from Lujan-Fryns syndrome, Snyder-Robinson syndrome, and zinc finger DHHC domain-containing 9-associated MR. We propose the name of this new syndrome to be CK syndrome.

Mental health for persons with intellectual disability in the post-deinstitutionalization era: experiences from British Columbia.

The delivery of mental health services to persons with Intellectual Disability (ID) in British Columbia (BC), Canada, is worth documenting because BC is one of the few jurisdictions in the world to completely close its institutions for people with ID. This paper documents the delivery of mental health care in BC for this population and contrasts the dream versus the reality of community living for people with dual diagnosis (mental illness coupled with an intellectual disability).

Early-onset schizophrenia in children with mental retardation: diagnostic reliability and stability of clinical features.

OBJECTIVES: To investigate the presentation of early-onset schizophrenia in children with mental retardation (MR) and the stability of clinical features over time. METHOD: A purpose-designed assessment protocol was developed based on best-practice recommendations in the research literature. Diagnostic reliability, investigated in a group of 20 children with MR, was found to be very good (kappa = 0.87). Using this protocol, the clinical service identified 10 children with an initial diagnosis of schizophrenia. This group was then reassessed 2 years later. RESULTS: At the end of 2 years, 8 of the 10 children with schizophrenia still warranted this diagnosis. However, there was considerable instability in relation to certain diagnostic criteria, notably delusions and visual hallucinations. In all cases some improvements in severity were seen at follow-up. However, the eight whose schizophrenia was confirmed at follow-up showed major deterioration in cognitive level. CONCLUSIONS: It is possible to make reliable diagnoses of early-onset schizophrenia in people with MR, provided the assessment system is carefully structured and pays attention to all the important sources of information. However, symptoms should be reviewed frequently, particularly those that cannot be substantiated by patient interview.

ECT: use in individuals with mental retardation.

Electroconvulsive therapy (ECT) is an effective treatment of a variety of serious psychiatric and neurologic disorders. There are infrequent case reports of its use in individuals with mental retardation (MR). We describe 10 patients with MR and complex comorbid psychiatric disorder treated with ECT. Seven patients had an excellent response to treatment. Side effects of treatment were minimal and transitory.