Psychiatric Disorders and Fragile X Syndrome

Vocabulary and concepts from Lecture 14 covering neurological versus psychiatric disorders, neurodevelopmental milestones, and the genetic and molecular basis of Fragile X Syndrome.

Neurology vs. Psychiatry Distinction

Neurology usually deals with disorders having salient signs of disease in the brain, while psychiatry deals with disorders of thought and behavior with less salient signs in the brain.

Neurodevelopmental Disorders

Brain disorders that manifest during childhood and adolescence, a period when the brain undergoes large-scale changes not occurring in adulthood.

r/K Selection Theory

Evolutionary reproductive strategies where r-selection favors more offspring with less parental care, and K-selection (favored by humans) favors fewer offspring with more parental care and slower growth rates.

Senescence

The normal progression of the gradual deterioration of cognitive function and other functional abilities with age during adulthood.

Synaptic Pruning

The reduction in the number of synapses from a peak in early childhood to a stable level from late childhood through adolescence into adulthood.

UC Davis MIND Institute

The Medical Investigation of Neurodevelopmental Disorders Institute based in Sacramento, focused on autism spectrum disorder, fragile X syndrome, ADHD, and Down syndrome.

Fragile X Syndrome ($FXS$)

A genetic neurodevelopmental disorder caused by a mutation in the $FMR1$ gene on the X chromosome, characterized by intellectual disability, developmental delays, and social impairments.

Fragile X full mutation prevalence

A mutation present in approximately $1$ in $5000$ individuals, usually more severe in males than females.

X-linked Inheritance

Inheritance patterns where a father passes an X-linked allele to all daughters but no sons, while a mother passes it to both with a $50\%$ probability.

X-inactivation

A process in females where one X chromosome copy is randomly packaged into a Barr body to reduce transcription, leading to a mixture of inactivation in later life stages.

Barr body

The special form into which an inactivated X chromosome is packaged, resulting in reduced transcription.

Nucleosome

A structure consisting of a section of DNA wound around $8$ histone cores, serving as the basic unit of DNA packaging.

Chromatin

A dense package consisting of DNA and proteins that makes up the chromosomes.

Epigenetics

Heritable changes in gene function that do not involve changes to the genotype, such as DNA methylation or histone modification.

FMR1 gene

The fragile X messenger ribonucleoprotein $1$ gene located on the X chromosome, containing $17$ exons and a $CGG$ nucleotide repeat section in the $5'$ UTR.

Fragile X Typical Allele

An $FMR1$ gene with fewer than $45$ $CGG$ repeats, resulting in normal expression of $FMRP$ and no $FXS$ symptoms.

Fragile X Full Mutation

An $FMR1$ gene with more than $200$ $CGG$ repeats, leading to epigenetic modifications that reduce transcription and result in a loss of function of $FMRP$.

Fragile X Premutation

A middle range of $CGG$ repeats in $FMR1$ that causes epigenetic modifications increasing transcription, leading to impairments through $RNA$ toxicity.

FMRP (Fragile X messenger ribonucleoprotein)

A protein that normally represses translation by stalling ribosome elongation and blocking ribosome assembly; its loss leads to increased protein synthesis.

mGluR5 (metabotropic glutamate receptor 5)

A receptor that stimulates $mRNA$ translation and can trigger dephosphorylation of $FMRP$ to derepress translation, working with $FMRP$ to control protein expression.

AMPA Receptor Endocytosis

A process promoted by proteins under $FMRP$ control where excitatory glutamate receptors are removed from the synaptic membrane, reducing post-synaptic excitability.

FXS Comorbidity

Fragile X syndrome is frequently comorbid with attention-deficit/hyperactivity disorder ($ADHD$) and is the largest single genetic cause of autism, accounting for $2-6\%$ of cases.