Evidence-Based Mind-Body Interventions for Children and Adolescents with Functional Neurological Disorder.

LEARNING OBJECTIVES: • Develop and implement treatment plans for children and adolescents with functional neurological disorder (FND)• Outline a plan to increase awareness and standardize the care for patients with FND using evidence-based interventions. ABSTRACT: Functional neurological disorder (FND) in children and adolescents involves the biological embedding of lived experience in the body and brain. This embedding culminates in stress-system activation or dysregulation and in aberrant changes in neural network function. In pediatric neurology clinics, FND represents up to one-fifth of patients. Current research shows good outcomes with prompt diagnosis and treatment using a biopsychosocial, stepped-care approach. At present, however-and worldwide-FND services are scarce, the result of long-standing stigma and ingrained belief that patients with FND do not suffer from a real ("organic") disorder and that they therefore do not require, or even deserve, treatment. Since 1994, the Mind-Body Program for children and adolescents with FND at The Children's Hospital at Westmead in Sydney, Australia-run by a consultation-liaison team-has delivered inpatient care to hundreds of patients with FND and outpatient care to hundreds of others. For less-disabled patients, the program enables community-based clinicians to implement biopsychosocial interventions locally by providing a positive diagnosis (by a neurologist or pediatrician), a biopsychosocial assessment and formulation (by clinicians from the consultation-liaison team), a physical therapy assessment, and clinical support (from the consultation-liaison team and the physiotherapist). In this Perspective we describe the elements of a biopsychosocial mind-body program intervention capable of providing, as needed, effective treatment to children and adolescents with FND. Our aim is to communicate to clinicians and institutions around the world what is needed to establish effective community treatment programs, as well as hospital inpatient and outpatient interventions, in their own health care settings.

Progressing our understanding of the impacts of nutrition on the brain and behaviour in anorexia nervosa: a tyrosine case study example.

Anorexia nervosa is a severe and complex illness associated with a lack of efficacious treatment. The effects of nutrition on the brain and behaviour is of particular interest, though an area of limited research. Tyrosine, a non-essential amino acid, is a precursor to the catecholamines dopamine, noradrenaline and adrenaline. Ongoing tyrosine administration has been proposed as an adjunct treatment through increasing blood tyrosine sufficiently to facilitate brain catecholamine synthesis. The effects of tyrosine supplementation in adolescents with anorexia nervosa remain to be tested. This study had approval from the Hunter New England Human Research Ethics Committee (06/05/24/3.06). We aimed to explore the pharmacokinetics of tyrosine loading in adolescents with anorexia nervosa (n = 2) and healthy peers (n = 2). The first stage of the study explored the pharmacological response to a single, oral tyrosine load in adolescents (aged 12-15 years) with anorexia nervosa and healthy peers. Participants with anorexia nervosa then continued tyrosine twice daily for 12 weeks. There were no measured side effects. Peak tyrosine levels occurred at approximately two to three hours and approached baseline levels by eight hours. Variation in blood tyrosine response was observed and warrants further exploration, along with potential effects of continued tyrosine administration in anorexia nervosa.

Pervasive refusal syndrome (PRS) 21 years on: a re-conceptualisation and a renaming.

Twenty-one years ago, Lask and colleagues first described pervasive refusal syndrome (PRS) as a child's "dramatic social withdrawal and determined refusal to walk, talk, eat, drink, or care for themselves in any way for several months" in the absence of an organic explanation. PRS has been conceptualised in a variety of ways since then. These have included a form of post-traumatic stress disorder, learnt helplessness, 'lethal mothering', loss of the internal parent, apathy or the 'giving-up' syndrome, depressive devitalisation, primitive 'freeze', severe loss of activities of daily living and 'manipulative' illness, meaning the possibility that the children have been drugged to increase chances of asylum in asylum-seeking families. Others have insisted that PRS is simply depression, conversion disorder, catatonia or a factitious condition. This paper reviews these conceptualisations, explores some of the central complexities around PRS and proposes a neurobiological explanatory model, based upon autonomic system hyper-arousal. It touches upon the clinical implications and suggests a new name for the condition reflecting what we believe to be a more sophisticated understanding of the disorder than was available when it was first described.

Conversion disorder in Australian pediatric practice.

OBJECTIVES: To describe the incidence and clinical features of children presenting to Australian child health specialists with conversion disorder. METHOD: Active, national surveillance of conversion disorder in children younger than 16 years of age during 2002 and 2003. RESULTS: A total of 194 children were reported on. The average age was 11.8 years; 23% were younger than 10 years of age. Presentations were complex, with 55% presenting with multiple conversion symptoms. The most common presentations were disturbance of voluntary motor function (64%), sensory symptoms (24%), pseudoseizure (23%), and respiratory problems (14%). Hospital admission was required for 70%, with an average stay of 10.2 days. Antecedent stressors were also reported in 62% and a history of mental health concerns in 42%, with 14% of children taking psychotropic medications for comorbid anxiety or depression. The incidence of conversion disorder in Australian specialist child health practice is estimated to be between 2.3 and 4.2/100,000. CONCLUSIONS: Conversion disorder is associated with a significant burden for the child, family, and the health system. This study emphasizes the comorbidity with anxiety, depression, and symptoms of pain and fatigue. It also highlights the potential impact of "commonplace" stressors such as family conflict and children's loss of attachment figures.

Neurofuturity: a theory of change.

Our experience is dominated by familiar sameness and unfamiliar change. This article is about change and why and how people change. The capacity to change is critical to the ability to adapt to a changing environment. Our brains help us to manage change by constructing possible futures and enabling us to behave in a way that prepares us for those futures. Capturing the world outside of us to make it into an internal experience is called perception. Some therapies aim to capture the work as it is. Capturing our world as it has been is termed 'memory'. Therapies which aim to revisit and remould this work so that the present and future are easier to deal with, help adaptation. Capturing the possible worlds to come is described here as neurofuturity. It is much broader than expectations and includes our feelings towards the future as well as our beliefs. Therapies are described in terms of which questions they answer and which time frame they address. Therapies and therapists address these big questions and work in different time frames. Reconstructing patients' experience of the future and acceptance of what cannot change are two of the main tasks of clinicians.

Gene-gene interaction between the monoamine oxidase A gene and solute carrier family 6 (neurotransmitter transporter, noradrenalin) member 2 gene in anorexia nervosa (restrictive subtype).

We earlier found an association between anorexia nervosa (AN) restrictive subtype (AN-R) and an inserted sequence within the NETpPR, a polymorphic region located in the promoter of the solute carrier family 6 (neurotransmitter transporter, noradrenalin) member 2 (SLC6A2) gene. To further examine the noradrenergic system in AN-R we performed an association study with a functional polymorphism (MAOA-uVNTR) in the promoter of the monoamine oxidase A (MAOA) gene. Since monoamine oxidase A metabolises noradrenalin, a positive association with the MAOA gene would be biologically plausible. The transmission disequilibrium test and 95 trios/duos (AN-R females+biological parents) showed the main effect of the longer, more transcriptionally active form of the MAOA-uVNTR (MAOA-L) to be statistically non-significant (McNemar's chi(2)=1.4, df=1, P=0.238, odds ratio: 1.4, 95% CI 0.8-2.7). A case-control approach supported this finding. We then stratified the MAOA-uVNTR TDT data according to the (a) NETpPR genotype of the AN-R females, and (b) NETpPR allele transmitted from NETpPR-S4/L4 heterozygous mothers. In both cases, contingency table analysis revealed previously unreported gene-gene interaction between the MAOA and SLC6A2 genes (P=0.019 and 0.019, respectively). Receiving an MAOA-L allele more than doubles the risk for developing AN-R, conditional on an individual also being a NETpPR-L4 homozygote (stratum-specific odds ratio: 2.4, 95% CI 1.1-6.0). These results suggest important involvement of the noradrenergic system in the biological underpinnings of AN-R.

Investigation of epistasis between the serotonin transporter and norepinephrine transporter genes in anorexia nervosa.

Weight-restored patients with anorexia nervosa (AN) respond favorably to the selective serotonin reuptake inhibitor fluoxetine, which justifies association studies of the serotonin transporter gene (SLC6A4, alias SERT) and AN. Case-control studies suggest that the least transcriptionally active allele of the SERT gene promoter polymorphism (5-HTTLPR) has an increased frequency in AN patients. However, this finding was not replicated with 55 trios (AN child+parents) and the transmission disequilibrium test (TDT). To clarify the role of the 5-HTTLPR in susceptibility to AN, we used the TDT and 106 Australian trios to provide 93% power to detect a genotypic relative risk (GRR) of 2.0. Our results were negative for this GRR (McNemar's chi(2)=0.01, df=1, p=0.921, odds ratio 1.0, 95% CI 0.7-1.5). Additionally, we found no association with AN females, AN subtype, age at onset, or minimum BMI. We then performed the first reported investigation of epistasis between the SERT gene and norepinephrine transporter gene (SLC6A2, alias NET) in AN, as an earlier study suggested that atypical AN responds to the dual serotonin-norepinephrine reuptake inhibitor venlafaxine. We observed no epistasis between the 5-HTTLPR and a polymorphism within the NET gene promoter polymorphic region (NETpPR) (chi(2)=0.48, df=1, p=0.490). Although 5-HTTLPR modulates serotonin reuptake by the serotonin transporter, our analyses provide no evidence that susceptibility to AN is modified by 5-HTTLPR alone, nor in concert with as yet undetermined functional effects of the NETpPR polymorphism.