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Underestimated Psychometabolic Aspects in Child Psychiatry


discussing psychometabolism: meaning the relation between child psychopathology and inborn error of metaboism – PowerPoint PPT presentation

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Title: Underestimated Psychometabolic Aspects in Child Psychiatry

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Underestimated Psychometabolic Aspects in
Child PsychiatryBySamir m monirlecturer of
neuropediatricsminia 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

  • 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, metabole, "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.

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Metabolic pathways
  • We will discuss
  • Historical BackgroundPsychiatric Presentation of
    Metabolic DisordersMetabolic 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

  • The periodic madness of King George III has
    been attributed to acute intermittent porphyria

  • 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.

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  • 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
  • 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

  • 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
  • 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.

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  • 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
  • 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

  • Inborn Errors of Metabolism and Common
    Neurodevelopmental Syndromes

Spectrum of Childhood Behavioral and
Neurodevelopmental Disorders by Greenspan et
al., 1998
  • 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
  • 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 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
  • The following disorders were identified
    phenylketonuria, glucose-6- phosphatase
    deficiency, propionic acidemia, adenosine
    deaminase deficiency, mitochondrial disorders,
    and branched chain ketoacid dehydrogenase kinase

  • ADHD

  • ADHD
  • ADHD occurs in approximately 46 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

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Overview of all causal therapies (n91). Van
Karnebeek and Stockler (2012)
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  • Diet
  • There's another face of food we dont know
    enough, called behavior. Nutrition plays a direct
    role in cognition and behavior in children and
  • Dietary treatment of children with behavioral
    disorders has had a controversy since the 1920s.
  • 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
  • Common Dietary Interventions Additive-free diet,
    sugar elimination diet, food allergies, fatty
    acid supplementation and gluten-free, casein-free

  • Obesity
  • Worldwide 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
  • 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

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  • 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
  • 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.

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  • 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.

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