Nervous System Flashcards
WHO classifies the most significant mental / neurological disorders into these 4 categories:
- learning and dev disabilities
- neurological disorders
- mental diseases
- substance abuse disorders
What are learning & dev disabilities?
disorders / injuries to NS young, limits development and thus function later in life
genetic, nutritional, infections, toxic expxosures, injury, poverty, multifactorial causes
down syndrome, fragile X syndrome, neural tube defects, thalidomide
What are the features of Alzheimer’s disease & other dementias?
deterioration of intellectual function and other cognitive skills that is severe enough to interfere with social or occupational functioning
AD is incurable, nearly untreatable, most common form of dementia
Explain the biological basis of AD (Alzheimers)
- characterized by deposition of amyloid proteins
- disruption of neuronal cytoskeleton (neurofibrillary tangles from tau)
- however, language systems seem to be preserved
The cytoskeleton consists of 3 main protein polymers. What are they?
- microtubule - microtubule associated proteins like tau get unstable microtubule formation and aggregates of tau proteins fall apart and aggregate/tangled
- Neurofilament / intermediate - vary from cell to cell
- Microfilament - actin
tau proteins in Alzheimer’s disease become abnormally modified, leading to the destabilization of microtubules and the formation of toxic aggregates. These changes disrupt neuronal function and contribute to the progressive cognitive decline observed in Alzheimer’s patients.
How does a buildup of amyloid result in Alzheimers?
- Alzheimers is caused by a build-up of an abnormal config of a protein amyloid
- may cause neurons to produce abnormal intracellular aggregations of tau protein
- tau protein is normally present in neurons where is stabilizes microtubules, in brains producing amyloid, intracellular tau forms aggregates (neurofibrillary tangles) this may cause neuronal death
Which areas are vulnerable and which areas are not (In AD)?
Vulnerable: medial temporal lobe - hippocampus & neocortex affected = memory
Not vulnerable: primary motor/sensory cortex, parental regions, visual cortex relatively unaffected
btw, what is the difference or distinction between a neurological disease and a
mental illness?
It’s largely a historical distinction based on what were thought
to be disorders caused by an “organic process”, such as degeneration or
inflammation (the neurological disorders), and disorders of the mind (mental disorders) due to it not working properly rather than being damaged by some disease process – a software rather than hardware issue. This distinction is not really as valid as it once seemed
Define epilepsy
common brain disorder characterized by 2 or more unprovoked seizures
affects ~ 1% of population (50-70 M worldwide)
Features of seizures
- seizures are discrete events caused by transient, hyper/highly-synchronous abnormal neuronal activity
- may occur in close temporal association w acute stroke, sepsis, or alcohol withdrawal
- associated w loss of consciousness
can be linked to a toxic event
vast majority of seizures have no immediate identifiable cause
Epilepsy is more of a SYMPTOM of a disease than a disease itself. It is divided into 3 categories. What are they?
1) Idiopathic epilepsy (such as childhood-onset absence epilepsy - thought to have a genetic basis) ~ 10%
2) Secondary / symptomatic epilepsy (caused a known central NS injury or disorder, e.g. infection, stroke, traumatic injury) ~ 20%
3) Cryptogenic epilepsy - no clear evidence of an etiological factor ~ 60%
Explain the underlying biological cause of idiopathic epilepsy
Genetic Basis:
Gene Involvement: Many genes implicated in epilepsy encode proteins that play roles in neuronal excitability, ion channels, vesicle trafficking, etc.
Subtle Mutations: Even small mutations in these genes can cause familial epilepsies.
Mechanism of Dysfunction:
Protein Function: The issue is not that the proteins are non-functional, but that there are subtle changes affecting their function.
Neurotransmitter Binding and Ion Channel Function: Minor changes in the affinity for neurotransmitters or the duration of ion channel opening can lead to increased neuronal excitability, contributing to epileptic activity.
Define mental disorders
diseases that affect cognition, emotion, and behavioural control and substantially interfere both with ability of children to learn and with ability of adults to function in their families, at work, and in the broader society. Mental disorders tend to begin early in life and often run a chronic recurrent course.
Male vs Female mental disorders
Males have higher rates of attention deficit hyperactivity disorder,
autism, and substance use disorders;
Females have higher rates of major depressive disorder, most anxiety
disorders, and eating disorders
What does prodromal mean?
preceding the more obvious, diagnosable symptoms of an illness or disease
Prodromal signs of schizophrenia
- social withdrawal
- neglect of personal hygiene
- odd ideas & behaviour
- flattened affect & paucity of speech (not much emotional expression)
these are NEGATIVE symptoms (absence of normal actions)
Non-psychotic signs of schizophrenia
- certain tendencies to become overloadeed with info
- difficulty in crowded rooms or when lots of people are talking
- easily distracted
- periods of great mental activity & creativity & excitement
Psychotic epiodes (in schizophrenia) might entail. . .
distortions in thinking, perception, emotions, language, sense of self and behaviour
hallucinations (voices that instruct or comment on the person) & delusions (fixed false belliefs or suspicions that are firmly held contrary to evidence)
Acute psychotic episodes are characterized by delusions of paranoia and grandiosity and spiritual or supernatural experiences; the feeling that there are being controlled by external forces or privileged to special information
Misattributions of significance (acute psychotic episodes)
- See something and think thats about me - normal stimulus and
misunderstood message - Making judgements every time you see, evaluate things how
important things are
Schizophrenia is not a homogenous disorder. But a common pathology is to see. . .
enlargement of ventricles = possible neuronal loss?
Which regions of the brain are involved in the dopamine system?
striatum
substantia nigra
vental tegmental area
frontal lobe
What are some problems with the dopamine hypothesis?
- dopamine antagonists can be shown to bind to receptors a short time after administration, but relief of symptoms takes SEVERAL weeks (as w antidepressants)
- PCP (angel dust) is a drug that causes psychotic states with similarities to schizophrenia (like paranoid delusions & auditory hallucinations that take control of the person) but it acts on a subclass of glutamate receptors NOT dopamine receptors
- Some people with schizophrenia don’t respond to D2 blockers, but to drugs that show broad monamine antagonism
factors like genetics, onset of symptoms, and the distribution of abnormalities make it challenging to fully understand the condition.
Treament efficacy for schizophrenia can be related to . . .
both the quantity of medication needed and how tightly it binds to D2 receptors
VTA projections and dopamine. . .
The ventral tegmental area (VTA) sends dopamine projections to several key brain regions, incl. the prefrontal cortex (PFC) & nucleus accumbens
Drugs that effectively treat schizophrenia often impact these brain regions, suggesting their dysfunction may be involved in the disorder’s pathology.
How does the DSM-5 describe major depressive episode?
DSM-5 is an attempt to classify disorders by looking at criteria where if you exhibit a certain number of symptoms, you may have a major depressive episode
Particular interest in criteria of ahedonia (↓interest/pleasure) and erroneous self evaluation (↑worthlessness/guilt everyday)
Symptoms include depressed mood and feelings of worthlessness or guilt, cognitive and somatic
symptoms but also behavioral symptoms including social withdrawal and agitation.
Manic depression
- Manic episodes greatly elevated mood, creativity, profusion of thought and pressured speech.
- May manifest as grandiosity and confidence or anxiety and aggression.
- Feeling of increased or limitless energy, including reduced need for sleep.
- Typically highly distractible, irritable, and exhibiting poor judgment.
- Extreme mania may include disordered (pyschotic) thought.
bipolar disorder — Rather that becoming stuck in uninteresting world, instead alternate and oscillate between high
and low
Brain region affected in depression
orbital / medial prefrontal cortex
amygdala
dorsolateral prefrontal cortex
ventromedial prefrontal cortex
hippocampus
eduction in abnormal high blood flow coincides with resolution of depres
lateral region is implicated in schizophrenia
What are 3 treatments of depression?
- EEG
- Psychotherapy
- antidepresssant drugs
EEG
Involve passing large currents through head and has dramatic appearance, controversial, line of last resort, very effective for some people, not a one shot cure, require additional treatments, mechanism unknown
Psychotherapy
o Engage in discussion with therapist, about things that trigger the depression, how to avoid
those things,
o Controversial - is related to type of interactions with therapist, or someone listening, some
good effects
Antidepressant drugs
o Biggest treatments, first line of attack is to try some sort of drug therapy, all drugs interact on same NT system
o Work after a period of weeks, why it takes so long unknown
