Neurodevelopmental Disorders

Development of the central nervous system (CNS) is a complex, controlled, and highly organized process, involving the following mechanisms – neurogenesis, neuronal migration, cellular differentiation, synaptogenesis, axon myelination and molecular specification (1). Development starts in utero and continues up to the age of twenty. This extended time course of development coupled with the lack of a fully formed blood brain barrier until after birth, places the CNS at risk of disturbance by multiple prenatal (both intrauterine and extrauterine) and postnatal factors (2). Intrauterine factors impact the immediate environment of the fetus, whilst extrauterine factors are the ones that indirectly impact the fetus via the mother (e.g. alcohol) (1). Such environmental factors include nutrition (e.g. iodine deficiency results in Cretinism), hormone levels, immune responses (Sydenham’s Chorea), infections, medicine, severe childhood neglect (Autism), and trauma. These environmental factors typically interact with a genetic predisposition towards the disorder resulting in its onset (1).

The prognosis of neurodevelopmental disorders varies based on the brain regions or developmental mechanisms that are impacted, and also on the degree to which the high plasticity of the brain during development can compensate for the loss of these systems. Recent research has provided new hope for treatment of these disorders as it has been theorised that it is possible to change the signalling involved in neurodevelopment (working with excitatory and inhibitory synapses) in order to redirect the developmental mechanisms back towards their original paths, a phenomenon that is known to occur when development is disrupted due to oxidative stress (1).

There are a number of common neurodevelopmental disorders, which include: Angelman Syndrome, Autism, Cretinism, Fetal Alcohol Spectrum Disorders, Phenylketonuria, Rett Syndrome, Sydenham’s Chorea, and Tourette Syndrome. It is important to study these disorders as they result in cognitive, emotional and physical abnormalities that significantly impact the entire lives of affected individuals.


  1. Angelman Syndrome (Marlena Kodzhahincheva)
    1. Symptoms and Diagnostics
      1. Symptoms and testing for the syndrome
      2. Prognosis for affected children
    2. Genetic factors
    3. The Ube3a gene and its function in the brain
      1. Topoisomerase inhibitors and activation of the silenced allele of the gene.
      2. Successful trials in mice
      3. Possible treatments for Angelman Syndrome
  2. Autism(Yanbo Gao)
    1. Possible genetic causes
      1. Copy number variants
    2. Possible environmental cause
      1. Pre-natal exposure to valproic acid
    3. Neurobiology (animal models)
      1. Environmentally-induced model (valproic acid treated rats)
      2. Genetic linked model (Shank3 mutant mice)
    4. Theories
      1. The Weak Central Coherence Theory
      2. The Empathizing-Systemizing Theory
      3. The Intense World Theory
    5. Potential Treatments
  3. Cretinism(Ekaterina Kouzmina)
    1. Symptoms
      1. Neurological cretinism
      2. Hypothyroid cretinism
    2. Causes and Treatments
      1. Changes in fetal brain
      2. Problems during pregnancy and their treatment
      3. Genetic mutations
    3. Animal models
      1. Environmental manipulations
      2. Genetic manipulations
    4. Homo floresiensis
  4. Fetal Alcohol Spectrum Disorders(Lyudmila Gavroussenko)
    1. Causes and diagnosis
      1. Alcohol exposure and effects on neuroanatomy and neurophysiology
        1. Inhibited cholesterol synthesis
        2. Reactive oxygen species
        3. Retinoic acid formation and deficiency
      2. Symptoms
        1. CNS abnormalities
        2. Behavioural, cognitive and motor defecits
      3. Animal models
        1. Assessment of disease in mice
        2. Potential treatment using mice
          1. Lobeline
          2. Lithium
  5. Phenylketonuria(Nariman Hossein-Javaheri)
    1. Phenylketonuria detection test
    2. Symptoms of phenylketonuria
    3. Genetic mutation in phenylketonuria
    4. Metabolic pathway affected in phenylketonuria
    5. Neuronal structural changes associated with phenylketonuria
      1. White matter abnormalities
      2. Grey matter abnormalities
    6. Treatments
  6. Rett Syndrome(Nathalie Cardenas-Zelaya)
    1. Symptoms
      1. Loss of motor control
      2. Stereotopies
    2. Mechanisms
      1. Mutation of the MeCP2 gene
      2. X-chromosome inactivation
    3. Diagnosis
      1. Clinical observations vs. actual analysis of the MeCP2 gene
    4. Animal model
      1. Drasophila
      2. Two different mice models
    5. Potential treatments
      1. Prevent cardia arrhythmias
    6. Phosphorylation of S421 area of MeCP2
  7. Sydenham's Chorea (Lisa Bilston)
    1. Epidemiology
    2. Prognosis
    3. Symptoms
      1. Motor
      2. Cognitive
      3. Neuropsychiatric and emotional
      4. Neuroanatomy
    4. Etiology
      1. Immune-Mediated Hypothesis
      2. The Dopamine Hypothesis
      3. Animal models
    5. Co-morbid Disorders and Genetic Implications
      1. Prevalence of co-morbid neuropsychiatric disorders
      2. Family studies: Anxiety disorders
    6. Persistent SC and Long-term effects
  8. Tourette Syndrome (Maisie Kamal Alddin)
    1. Symptoms and Diagnosis
      1. Motor and Vocal Tics
      2. Co-morbidities
    2. Causes and Neural Correlates
      1. of Tic generation
      2. of Co-morbidities
    3. Treatment Options
      1. Pharmaco-therapy
      2. Cognitive-Behavioural Therapy

1.Connors, S. L., et al. Fetal mechanisms in neurodevelopmental disorders. Pediatric Neurology. (2008) 38(3): 163-176
2.Rodier, P.M. Vulnerable periods and processes during central nervous system development. Environmental Health Perspectives. (1994) 102: 121-124