L15-17 Autism

These flashcards cover key terms and concepts related to autism and pervasive developmental disorders, highlighting definitions and characteristics essential for understanding the subject.

Pervasive Developmental Disorders (PDD)

disorders characterized by impairments in social interaction, communication, and restricted interests or repetitive behavior.

Autistic Spectrum Disorders (ASD)

A range of neurodevelopmental disorders characterized by challenges with social skills, repetitive behaviors, and communication.

Synaptopathy

A term describing disorders that arise from dysfunction of synapses, potentially implicated in autism.

Neuroligin

A protein essential for synapse formation and function, implicated in autism when mutated.

• involved in cell-cell contact + synapse maturation/stabilization

• trans synaptic molecule

• single-pass transmembrane protein

• structural acetylcholinesterase domain for trans synaptic communication via neurexin (does not metabolise ACh)

Autistic Triad

The three core areas of impairment in autism: social interaction, communication, and restricted/repetitive behaviors.

Asperger’s Syndrome

A developmental disorder previously considered a distinct type of autism, characterized by difficulties in social interaction and nonverbal communication, with no significant delay in language.

Fragile X Syndrome

A genetic disorder causing intellectual disability, often associated with autistic features, particularly in males. not considered ASD

Rett Syndrome

A neurodevelopmental disorder affecting mostly females, characterized by normal early development followed by a loss of purposeful hand skills, gait abnormalities, and other symptoms related to ASD. not considered ASD

E/S Quotient

A measure proposed by Baron-Cohen to assess empathy and systematizing skills in individuals.

Polygenic Risk

The combined effect of many genes that contribute to the likelihood of developing a disorder such as autism.

Cognitive Dysfunction

Impairment in cognitive functions such as memory, attention, or problem-solving, which can complicate the diagnosis of autism.

astroglyosis

the proliferation of astrocytes in response to injury or disease, often associated with neuroinflammation in autism.

where are smaller cortical minicolumns found?

on the cerebral cortex

which neuroligin is found at the INHIBITORY synapse

N2 (GABA)

which neuroligins are found at the EXCITATORY synapse

N1, 3, 4 (glutamatergic)

why is splicing important

variation allows selectivity between synapses and synapse formation

neuroligin knockout

knock out N1, 2, 3 to see obvious phenotype association (almost the entire neuroligin component in the brain)

neuroligin deficiency

lower synaptic drive in both excitatory and inhibitory transmitters

synaptic deficiency in absence of synapse loss or degradation

NL3 genetic mutation

missense mutation of a single AA in extracellular domain (451Arg → Cys) (R451C)

de novo mutation
misfolded, never gets to surface, identical to null mutation

phenotype for hyper motor learning is found in the :

ventral tegmentum area - involved in REWARD PATHWAY

consequence of NLG-3 loss of function (KO or R451C)

reduces inhibitory signals from GABA released on D1 neurons but not D2 neurons without affecting excitation → unbalanced D1 output (too much) → favours repeated behavioural sequence learning

which single penetrant gene is disrupted in ASD

syntaxin binding protein 1

DSM V definition of ASD triad

• deficits in communication + social interaction

• restricted, repetitive patterns of behaviour, interest/activites

• symptoms must be present in early childhood, may not become fully manifested until adulthood

what % of autistics is associated with seizures

30%

unusual level of electrical activity in ASD

% of coincidence of ASD between MZ twins

90% - strong penetrance of genetic mechanisms in ASD (one of the most strongly penetrant psychiatric disorders) - polygenic

what are the findings of Zhang et al and Litman et al (2025)

cohort studied autistic vs control

1. timeline - when was diagnosis

2. associated traits (along with comorbidities)

3. genetic signatures associated with autistic cohort

findings

• sub-cohort/ classifications within diagnosis = autism is a spectrum

• early diagnosis does not impact challenges associated with autism / early diagnosis does not mean autism is more serious/challenging

limitations

• sub-classification is loosely based on symptomology, time of expression + genetics

• papers do not give insight into underlying biological mechanisms and genetics that interact to generate sub-cohorts

animal model using neuroligin

1. NLG3 knockout mice

2. functional null NLG-3R451C mutated mice

3. WT mice

40rotations per minute = mice could stay on rotary rod

increase to 80rpm = only mice without NLG could adapt + stay on rod. WT fell off

findings

• shared ability to hyper-function in motor control → propensity to repetitive behaviour seen as autistic trait

behavioural therapies for ASD - to induce ‘behavioural plasticity’

1. sensory/ play therapies to refine behaviour

2. encourage interaction with environment + others

3. cognitive therapy: indentify deficiencies, instill awareness, teach autistics to develop strategies to overcome

drug therapies for ASD (treats symptoms, not cause)

1. targets neurochemistry underpinning autistic traid

• serotonergic + dopaminergic drugs

• haloperidol (DA receptor antagonist)

• resperidone (DA + serotonin receptor antagonsit)

• SSRIs - to treat repetetive behaviours

2. transmitter pathways underlying behavioural symptoms

• adrenergic antagonists used to for sleep disorders or aggression

3. organic interventions

• vitamin supplements (Mg2+, VB6, VB12)