Week 7, Lec 2 Flashcards
what is a delusion
Belief is held despite being presented with evidence against it (“fixed” – firmly maintained)
what disorders can delusions be seen in
▪ Can be due to: mental disorder, neurological or
medical disorder
▪ Examples: schizophrenia, substance abuse, bipolar disorder, major depressive disorder (MDD), delirium and dementia
delusion
▪ A belief that is clearly false and indicates an
abnormality in content of thought
what is hallucination
sensory perception in the absence of a corresponding external or somatic stimulus and described according to the sensory domain in which it occurs
types of hallucinations
- Most common are visual, auditory, tactile, olfactory
▪ gustatory, nociceptive, thermoceptive, proprioceptive are possible
formed vs unformed hallucinations
Formed (i.e. voice making a command) or unformed (i.e.non- specific sound)
hallucinations with insight or without insight
With insight–px is aware that she is experiencing a hallucination - OR without insight – patient believes the perception is real
causes of hallucinations
▪ Can occur in illness or during an adjustment disorder or without mental illness (i.e. grief)
▪ Can be due to: psychiatric, neurological or medical disorder
*Delirium, substance withdrawal, intoxication, CNS infection, seizures can all cause hallucinations
DSM criteria for schizophrenia
- delusions
- hallucinations
- disorganized speech (e.g. frequent derailment or incoherence)
- grossly disorganized or catatonic behaviour
- negative symptoms (i.e. diminished emotional expression or avolition)
must have 2+ of these and one of them has to be #1,2,or3
how long must have signs and how long for active symptoms of schizophrenia for DSM5 criteria
6 months have signs
1 month of active symptoms
other DSM criteria of schizo
- Level of functioning in work/school, social relationships, self-
care is markedly decreased - Can’t be due to another condition
ALONG WITH
(2+ characteristics) and last 6 months
what is disorganized speech and thoughts (schizophrenia)
Speech and thought – derailment, poverty of speech, tangentiality, lack of logic, perserveration, neologism, thought blocking, clanging, echolalia… these are part of a phenomenon known as “thought disorders”
catatonia in schizo
move their body erratically or not at all.
- Psychomotor disturbances motor immobility
- Stupor, rigidity, strange postures, “waxy
flexibility”
▪ excessive activity
* Echolalia, echopraxia
▪ Sometimes both can be present at different times
derailment in schizo
Also known as “loose associations,” this is when a person’s thoughts shift abruptly from one topic to another unrelated topic, making their speech difficult to follow. There may be a lack of logical connection between ideas.
poverty of speech in schizo
This refers to limited verbal output, where the person’s speech is reduced in quantity or content. They might give brief or monosyllabic answers, which lack detail or elaboration, even when more is expected.
tangentiality in schizo
this occurs when a person goes off-topic or provides an irrelevant answer during conversation. The response is loosely related or completely unrelated to the question or topic at hand.
lack of logic (illogical thinking) in schizo
This involves making conclusions or statements that don’t follow a logical sequence or have faulty reasoning. The person may present ideas in a way that defies conventional logic.
perseveration in schizo
Repetitive thoughts or speech, where a person repeats the same word, phrase, or idea over and over, often despite a change in the topic or context.
neologism in schizo
The creation of new, often nonsensical, words that only have meaning to the person using them. These made-up words are often unrecognizable and not based on any known language.
thought blocking in schizo
This is when a person’s thoughts are interrupted or stopped abruptly, often in the middle of speaking. The person may pause for an extended period or appear to lose their train of thought.
clanging in schizo
Speech characterized by the use of rhyming or alliteration, often with words linked together based on sound rather than meaning. The focus is on the phonetic aspects of words, which can make the content nonsensical.
echolalia in schizo
The repetition or mirroring of words or phrases spoken by someone else, often without understanding the meaning. This behavior can be seen in individuals with autism or certain types of psychosis.
disorganized behaviour in schizophrenia
-incoherent or erratic behaviour (i.e. inappropriate dressing, cant complete tasks, aimless wandering)
-inappropriate emotional responses (laugh cry at wrong time)
-difficulty planning an sequencing (i.e. make a meal, hygiene)
catatonia
omplex psychomotor syndrome characterized by abnormal movements, behaviors, and reactions.
7 psychomotor disturbances seen in catatonia (decrease vs increase activity)
- motor immobility (reduced or lack of movement)
- stupor (unresponsive)
- ridigity (muscle stiff)
- strange postures (catalepsy)
- excessive motor activity
- echolalia (autonmatic repetition of words)
- echopraxia (imitate or mirror movements)
echolalia and echopraxia
echolalia- repeat words
echopraxia- imitate or mirror movements
negatove symptoms in schizophrenia
-less speech
-less emotions
-less social activity
-less motivation
-less psychomotor activity
onset of schizo
3rd decade
pathogenesis of schizophrenia
▪ Psychosis and other positive symptoms thought to be
associated with dysregulation in dopaminergic systems
▪ Neurological basis for cognitive symptoms are poorly understood
cognitive symptoms of schizophrenia
- Problems with working memory and attention
- Executive functions, such as ability to organize information
- Social cognition – difficulty understanding/noticing subtle interpersonal cues, difficulty with forming relationships with others
what happens to the dopaminergic system in schizophrenia
hyper responsive
2 things that prove dopaminergic system is hyperresponsive in schizophrenia
▪ (1) Antipsychotic drugs block DA via D2 receptors
▪ (2) Drugs that increase DA (L-dopa, amphetamines)
will cause increase in psychosis
what are the last interneurons to be incorporated into the Brian and are vulnerable to developmental insults
GABA interneurons
what is GABA interneurons susceptible to damage from
Highly susceptible to damage from oxidative stress and glutamatergic drive – particularly in the early postnatal developmental period before puberty
monoamines in the dipaminergic system
dopamine, norepinephrine, serotonin
where are most of the neuronal cell bodies that release dopamine located
midbrain
2 midbrain area for releasing dopamine
ventral tegmental area (VTA) and substantia nigra
which midbrain area for reward and motivation
VTA
which midbrain area for motor function
substantia nigra
which midbrain area for executive fucntion
VTA and dorsal substantia nigra
where does VTA project to for reward
nucleus accumbens and ventral striatum (of the basal ganglia)
where does substantia nigra project to for motor function
striatum (of basal ganglia)
where do VTA and dorsal susbstantia nigra project to for executive function
many cortical areas
what is tonic firing
Dopaminergic (DA) neurons fire in a slow, pacemaker fashion “at rest”
what area of the brain slows down tonic firing and by release of what
the ventral pallidum (basal ganglia) slows down this activity via GABA release
what is phasic firing
reticular activating system detects a stimulus ! glutamate release onto DA neurons ! rapid bursts of action potentials
what happens in interesting or acutely stressful stimuli
Activation of part of the hippocampus (subiculum)! enhanced tonic firing ! “stronger” phasic firing in response to a stimulus
2 types of firing in dopaminergic system
tonic firing (at rest) and phasic firing
what happens to firing in chronic stress
Activation of the amygdala ! decreased tonic firing ! “weaker” phasic firing
acute vs chronic stress effects on firing of DA system
acute: increase tonic and phasic firing
chronic: decrease tonic and phasic firing
what do antipsychotic medications block? what symptoms does this make worse?
block D2 receptors, and L- dopa (dopamine precursor) as well as amphetamines (cause “leak” of dopamine into synaptic cleft) worsen positive symptoms
▪ However, antipsychotics do not seem to help cognitive or negative symptoms
what areas in the DA system are hyper functioning in schizophrenia
he hippocampal areas that stimulate tonic activity are hyperfunctioning! inappropriately increased tonic activity
▪ VTA neurons that release dopamine do not seem to be abnormal
▪ Reduced inhibitory GABA-ergic neurons in the hippocampus
changes to gaba and dopamine in schizo
▪ VTA neurons that release dopamine do not seem to be abnormal
▪ Reduced inhibitory GABA-ergic neurons in the hippocampus
what is the theory for delusions/hallucinations in schizo in relation to DA system
hyperactive dopaminergic activity due to “hippocampal overdrive” –> all stimuli are seen as “important” or real –> delusions/hallucinations
DA system and getting cognitive and negative symptoms in schizo?
The dopaminergic system projects to a wide variety of brain areas
▪ May explain some of the cognitive or negative symptoms of schizophrenia
risk factors for developing schizo ?
stress in childhood
lead to loss of inhibitory GABA-ergic neurons in the hippocampus
▪ (Over)activation of the amygdala may be linked to loss of these neurons
inflammation and schizo?
Elevations in pro-inflammatory cytokines (TNF-alpha, IL-6, IL-1beta) during psychosis, normalize with antipsychotic treatment
- Pro-inflammatory cytokines –> kynureneic acid production (a metabolite of the amino acid tryptophan)
- Kynurenic acid blocks NMDA receptor, which can cause psychosis
▪ Activation of microglial cells–>Cognitive dysfunction and grey matter volume loss?
* Microglia are key in pruning synapses – possibility that “overactivated” microglia are involved in volume loss
what input does the pain in migraine come from
trigeminovascular input
pathway for migraine
pain in migraine –> trigeminovascular input
* from the meningeal vessels –> trigeminal ganglion–> synapses on second-order neurons in the trigeminocervical complex (TCC) in the brainstem
* TCC–> thalamus–> cortex
what inputs modulate the trigeminovascular nociceptive (pain) input in migraines?
midbrain areas: dorsal raphe nucleus, locus coeruleus, and nucleus raphe magnus
cause of migraines
Problems with modulation of pain sensation from these trigeminal afferents seems to be the cause
▪ Abnormal pain sensation related to vascular dilation and constriction? (vasomotion)
which 2 homrones/ neurotransmitters are acted on by medications in migraines?
serotonin and CGRP
medications effecting migraine
▪ 5-HT1 receptors – important in the trigeminal nucleus and the thalamus, bind to serotonin
* Blocked by drugs known as “-triptans” (i.e. sumatriptan)
▪ CGRP (calcitonin-gene- related peptide) seems to mediate neurotransmission at the trigeminal ganglion and at the vasoactive efferents (it’s a vasodilator and a pain modulator)
neuromuscular theory of migraine
▪ primary neural dysfunction – wave of “spreading depression” (slowly travelling wave of neural excitability) travels through the cortex and leads to activation of the trigeminal complex
- leads to vascular-generated pain
- spreading depression wave thought to be linked to other neurological findings
- may also be linked to modulation of nociceptor afferents by locus ceruleus and dorsal raphe nucleus
central sensitization; what do pro inflammatory cytokines cause the release of
release of nerve growth factor from mast cells –> increase release of BDNF from C fibers
C fibers are pro pain in dorsal horn network
orthodromic and antidromic movement of action potentials in pain C fibre
▪ From periphery –> spinal cord = orthodromic
▪ From spinal cord –> periphery = antidromic
what do C fibers release
substance P and CGRP
rom dendrites into peripheral tissues when action potentials move antidromically
▪ Substance P can cause mast cell degranulation, vasodilation, and edema
▪ CGRP can cause vasodilation
▪ These substances can increase inflammation – this is known as neurogenic inflammation
what does substance P and CGRP cause
neurogenic inflammation via
▪ Substance P can cause mast cell degranulation, vasodilation, and edema
▪ CGRP can cause vasodilation
migraines and gut microbiome?
eradicated h pylori (which triggers CGRP release and sensitizes nerves) –> improve migraine
IBS and migraines
IBS= visceral hypersensitivity
migraine= central hypersensitivity
IBS at risk for migraine
- Food intolerances can trigger both IBS and migraine episodes
- Higher amount of circulating serotonin in IBS
- Pharmaceuticals modulating serotonin receptors are effectively used in both IBS and migraines
how can pro inflammatory cytokines (IL-1Beta, IL-6, IL-8, TNF-alpha, IFN ) that are increased in migraines cause visceral pain
sensitize afferent ending and induce visceral pain
dysbiosis
▪ Increase gut permeability –> LPS leakage –> pro-
inflammatory cytokine release
▪ Some bacterial strains can metabolize tryptophan thus may affect local gut serotonin metabolism
- Serotonin receptors are found on various immune cells (unclear if it is involved in modulating inflammation)
