UNDERESTIMATED PSYCHOMETABOLIC ASPECTS IN

CHILD PSYCHIATRYBY:

SAMIR M MONIRLECTURER OF NEUROPEDIATRICS

MINIA UNIVERSITY

(METABOLISM AND PSYCHE)

Still offering an amazing area in research

“Inherited” and “metabolic diseases” two words send chills down the

spine of a junior doctor and represent endless hours one spent learning

all about mutations, enzymes, co‐enzymes and substrate deficiencies and

still failed to grasp the complexity of the problem.

Dr: Clarke. 2006; Cambridge University

BRAIN

• 1.36 kg

• Over 100 billion neurons, or signaling units.

• Controls everything we do

• If injured, it may affect basic functions, including thought, behavior, memory and speech

• Underappreciated organ

• Metabolism (from Greek, metabolē, "change") can refer to all

chemical reactions that occur in living organisms.

• Metabolism is usually divided into : Catabolism, that breaks down

organic matter and produces energy by way of cellular respiration

and anabolism that uses energy.

METABOLIC PATHWAYS

We will discuss:

Historical Background

Psychiatric Presentation of Metabolic Disorders

Metabolic Disorders and Common Neurodevelopmental Syndromes

Diet , Nutritional Disorders and Child Psychiatry

Psychopharmacologicl Aspects

Family Aspects

Acknowledgement

Historical Background:

Inherited disorders have accompanied humanity since its

earliest existence as remarkable in many prehistoric and

historic sites. In Egypt, investigation of mummies from the

huge necropolis of Thebes-West in Upper Egypt revealed

osseous manifestations suggestive of metabolic disorders.

Pharaoh Akhenaten, might had the aromatase excess syndrome.

The periodic “madness” of King George III has been attributed to acute intermittent porphyria (AIP)

Van Gogh.

Metabolic disorders caused by genetic mutations resulting in

enzyme deficiencies in an intermediary metabolic pathway,

constitute a wide spectrum of diseases in clinical practice.

The term ‘inborn errors of metabolism’ was introduced by

Sir Archibald Garrod at the beginning of the twentieth

century.

More than 6500 inherited disorders, known to affect world populations. The

overall incidence was estimated to be 1 in 1,400 live births. However, this rate

may be an underestimation, as new disorders continue to be discovered

because improvement in diagnostic techniques sensitivity and accuracy.

Although individually rare, they are collectively numerous. Prevention of

death or permanent neurological sequele is dependent on early diagnosis and

initiation of appropriate therapy . Diagnosis is done by clinical assessment,

imaging studies, electrophysiological, histopathological and biochemical

studies).

Raghuveer et al; 2006

Psychiatric Presentation of Inborn Errors of Metabolism

• Neurological dysfunction is an important manifestation of inherited

metabolic disorders.

• Over one-third of the inherited metabolic disorders are characterized by the central nervous system involvement. Neurological symptoms are the presenting and the most prominent clinical problems associated with them. Among the neurometabolic disorders, there are particularly five common neurological presentations: chronic encephalopathy, acute encephalopathy, movement disorder, myopathy and psychiatric or behavioral abnormalities

Child psychiatry, in particular, needs miracles to unravel all its

mysteries. Inborn errors of metabolism (IEMs) may present in

childhood, adolescence as well as adulthood as a phenocopy of a

psychiatric disorder. Fortunately, many of these IEMs are treatable.

However, diagnostic procedures and specific therapeutic modalities

should be early at the 'psychiatric stage' to be effective. After that the

occurrence of irreversible neurological lesions or profound mental delay

will appear.

It is important to detect metabolic disorders for several reasons:

• (1) Specific treatments may be available

• (2) Metabolic decompensation may be avoided

• (3) Accurate counselling may be given.

• Sedel et al did a schematic classification of metabolic disorders into three groups

according to the type of psychiatric signs at onset.

• Group 1 represents emergencies, in which disorders can present with acute and recurrent attacks

of confusion, sometimes misdiagnosed as acute psychosis. Diseases in this group include urea

cycle defects, homocysteine remethylation defects and porphyrias.

• Group 2 includes diseases with chronic psychiatric symptoms arising in adolescence or

adulthood. Catatonia, visual hallucinations, and aggravation with treatments are often observed.

This group includes homocystinurias, Wilson disease, adrenoleukodystrophy and some lysosomal

disorders.

• Group 3 is characterized by mild mental retardation and late-onset behavioural or personality

changes. This includes homocystinurias, cerebrotendinous xanthomatosis, nonketotic

hyperglycinaemia, monoamine oxidaseA deficiency, succinic semialdehyde dehydrogenase

deficiency, creatine transporter deficiency, and a and b mannosidosis.

• The need to screen for an inborn error of metabolism arises out of the fact that most cases take to irreversible effects as time progress. Emphasis has to be laid on early detection and prompt management,

Algorithm for patients with a number of treatable inherited metabolic conditions.

organic causes of psychosis should be considered among patients with atypical

psychiatric symptoms After further diagnostic processes, easy-to-apply

screening tests are now available that can assist in confirming diagnoses

• Treatment used in psychiatry and which may aggravate metabolic diseases

Psychiatric features of inherited metabolic disorders by Turnacioglu et al., 2013

Psychosis

Psychosis

• Certain inborn errors of metabolism as homocysteine metabolism disorders, urea cycle disorders, porphyria, Wilson disease, cerebrotendinous xanthomatosis and Niemann-Pick disease type C can present as psychosis. It should be considered in patients with atypical psychiatric symptoms. Some IEMs are treatable especially during the early stages of disease (sometimes simply with vitamin replacement or supplementation) and new treatments continue to appear.

• Atypical psychiatric symptoms including: acute onset and /or early onset, fluctuating course, confusion, catatonia, visual hallucinations, progressive cognitive decline, intellectual disability, treatment resistance Unusual or severe side effects

Spectrum of Childhood Behavioral and Neurodevel;opmental Disorders by: Greenspan et al.,

1998

Inborn Errors of Metabolism and Common Neurodevelopmental Syndromes

• Although each disorder is distinct, some clinicians do not see these

conditions as discrete entities, but a continuum of disorders with related

features. All share similar etiologies, common presentations as well as

responsiveness to common treatment approaches.

• All share common triggers: nutrient deficiencies; fatty acid abnormalities;

hyper-sensitivities or intolerances to food; adverse responses to food

additives, preservatives, artificial colors and flavorings, sulfites, salicylates

and phenols; all as co-existing problems in many of these disorders.

• Researchers suggest that incomplete digestion of wheat and other gluten

containing grains as well as milk/dairy products can be linked to behavioral

symptoms recognized in those with developmental problems

AUTISM

Autism• Autism spectrum disorder (ASD) is the broad term includes autistic disorder,

Asperger syndrome, and pervasive developmental disorder, not otherwise

specified. These disorders share common features of impaired social

relationships, impaired communication and language, and stereotypic

mannerisms or a narrow range of interests, associated with behavioral

problems, such as hyperactivity and aggression. Although it's exact cause is

not known, several factors have been implicated in its etiology, including

inborn errors of metabolism. Although relatively uncommon, it's more likely

to occur in certain countries, such as in the Middle East, where recessive

conditions are common because of consanguinity. • The following disorders were identified: phenylketonuria, glucose-6-

phosphatase deficiency, propionic acidemia, adenosine deaminase deficiency, mitochondrial disorders, and branched chain ketoacid dehydrogenase kinase deficiency.

ADHD

ADHD

ADHD occurs in approximately 4–6% of the population and is defined by

developmentally inappropriate levels of inattention, hyperactivity, or

impulsivity. A highly heritable condition thought to have its basis. ADHD is

currently categorized into three subtypes with varying rates of prevalence:

ADHD-inattentive subtype, ADHD-hyperactive/impulsive subtype, and ADHD-

combined subtype. Stimulant medications in conjunction with psychosocial

treatments such as behavioral management training for parents, are the most

efficacious treatments for ADHD

Developmental Delay

Developmental Delay

Intellectual disability (developmental delay) affects 2.5% of population

worldwide. It is a life-long and debilitating condition with deficits in cognitive

functioning (IQ less than 70) and adaptive skills, often associated with

behavioural problems (autism, hyperactivity and aggression), epilepsy and other

neurological disabilities, all resulting in psychological, social and economic

burdens. In children less than 5years of age with deficits in two or more

developmental domains (e.g. fine/gross motor skills, speech, interaction, etc.).

The etiology of ID is diverse, including infectious, traumatic and toxic causes.

Genetic etiologies constitute the most frequent cause and are demonstrable in

more than 50% of individuals with ID

Overview of all causal therapies (n=91).

Van Karnebeek and Stockler (2012)

Diet

• There's another face of food we don’t know enough, called behavior. Nutrition plays

a direct role in cognition and behavior in children and adolescents.

• Dietary treatment of children with behavioral disorders has had a controversy since

the 1920’s.

• Dietary management of IEM include: medical foods that provide the majority of

nutrient needs, specialized for individual disorders; and dietary supplements that are

used to enhance diminished catalytic function, replace conditionally essential

nutrients, or provide essential nutrients that may be missing due to dietary

restrictions.

• Common Dietary Interventions: Additive-free diet, sugar elimination diet, food

allergies, fatty acid supplementation and gluten-free, casein-free diet.

ObesityWorldwide estimates of childhood obesity are as high as 43 million and it

continues to increase each year. It has been accompanied by much serious and

severe comorbidity. The psychiatric aspects related to obesity in pediatric age

are still poorly studied and the link between obesity and psychiatric symptoms

appears to be unclarified.

Many propose behavioral problems are a result of the stigmatization associated

with childhood obesity, but there is also evidence supporting that behavioral

problems may precede in some children.

Malnutrition

• Early childhood malnutrition is associated with cognitive and behavioral

impairment during childhood and adolescence. Malnutrition limited to the first

year of life with good health and nutrition documented to 12 years of age, is

associated with a significant overrepresentation of adult personality trait scores

outside of the average range involving: anxiety, depression, lowered

interpersonal orientation, apathy and lowered sense of self-efficacy or

competence.

• Even in mild malnutrition, subtle changes in diet may modulate brain function.

Both vitamins and minerals are essential (esp, vitamin C, folic acid, vitamin B6,

magnesium, calcium, zinc, niacin, niacinamide, and dimethylglycine) which

play a valuable role in the treatment of children with attention deficit disorder

or autism spectrum disorder.

Psychopharmacologicl Aspects

Antipsychotics and Metabolism

• There is a growing evidence supporting the presence of metabolic, neurological and

sexual/reproductive adverse effects in children treated with antipsychotics, mood

stabilizers and selective serotonin reuptake inhibitors (SSRIs).

• Adverse effects include: weight gain, obesity, glucose dysregulation, dyslipidaemia,

hyperprolactinaemia and incident cardiovascular events as orthostatic hypotension.

These side effects could lead to serious complications in children.

• This was more significant with younger ages, females, multiple drug use and with

atypical antipsychotics than typical antipsychotics.

• Special considerations should be given before initiating treatment and clinical

monitoring is essential. More research is needed to develop strategies to minimize

antipsychotic-related adverse effects and to discover treatments with lower risk

potential.

Family

• Little is known about parents' perspectives on child development and social impact on families. Living with a metabolic disorder may cause considerable stress on patients and families (Gramer et al., 2014)

• Parents of children diagnosed with ADHD were more likely to divorce and had a shorter latency to divorce than parents of children without ADHD.

• Mothers of children with mental disorders have poor quality of life, poor sleep and high prevalence of mental disorders; hence child psychiatry clinics need to ensure that mothers receive appropriate care along with the child.