Please enable JavaScript.
Coggle requires JavaScript to display documents.
Unit 13. Biological basis of schizophrenia and other psychoses,…
Unit 13. Biological basis of schizophrenia and other psychoses
Clinical description of psychosis
Psychosis =
diff def and misused
syndrome (= mixture symptoms)
association w/ many disordes > not a disorder itself
main symptoms = delusions and hallucinations
Schizophrenia not synonymous to psychosis but requiered to be diagnose
Diseases required psychosis to be diagnosis : substance-induced psychotic disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder and psychotic disorder du to a medical condition
Forms of psychosis :
paranoid, disorganised-exited or depressive
perceptual distortion and motor alteration
symptoms > mental capacity, affective response, recognize reality, comunication, relate to others is impaired
Symptomatic dimensions of schizophrenia
Prevalence :
1% of world's pop
more frequent in men
high prevalence in low-income pop
5 dimensions of symptoms
Positive syntomps (shouldn't be there, excess of normal functions)
Delusions = misinterpretation of perceptions or xp
Hallucinations (perception of smt which dosen't exist, auditory)
Distortions or exaggeration in language and comm, disorganizaed speech
Cataconic or agitated behaviour
Associated w/ bipolar disorder, psychotic depression and Alzheimer
Negative (= reduction of normal functions)
Blunted affect (= limitation in range and intensity of emotional expression)
Alogia () poor fluency ni speech and tought)
Abulia (little goal-directed behaviour)
Anhedonia (= difficulty in experiencing pleasure)
Impaired attention
Associated w/ emotional and social withdrawal, poor contact and passivity
Cognitive symptoms (ft. negative symptoms)
Though disorder
Bizarre use of language, inconsistencies, inaccurate associations , impaired information processing
impaired verbal fluency (spontaneous speech) and executive functions
Learning prblms
Agressive and hostile symptoms (may overlap w/ positive symptoms)
Accentuate impulse control prblm
Hostility (verbal, physical abuse)
Self injurious behaviour (suicide, damage, lack of sexual restraint
Depressive and anxious symptoms
Guilt, anxious and depressed mood
Tension, irritability and worry
Association symptoms and brain areas
D13 Schéma
Positive symptoms: mesolimbic dopaminergic pathway
Negative symptoms: mesocortical dopaminergic pathway
Cognitive symptoms: dorsolateral prefrontal cortex
Affective symptoms: ventromedial prefrontal cortex
Aggressive symptoms and hostility: orbitofrontal cortex and
amygdala
Biological basis of schizophrenia
3.1. Dopaminergic theory
Precursor = tyrosine
2 enzyme to transforme tyrosine into dopamine :
TOH Tyrosine hydroxylase --> DOPA
DDC DOPA Decarboxylase --> dopamine
Transported in vesicule
Introduce in cells with DAT Dopmine transporter or NET norepinephrine transporter
5 receptors to dopamine : 2 groups
D1 like receptor > D1 and D5 > excitatory and stimulate psotsynaptic neuron
D2 like receptors > D2, D3 and D4 > inhibit postsynaptic neurone
4 dopaminergic pathways (+ 1 unknow)
Tuberoinfundibular pathway (normal / not altered) > hypothalamus to anterior pituitary gland > prolactin secretion
Nigrostriatal pathway (normal) > substantia nigra to basal ganglia > regulate movement > low dopamine can cause parkinsonism > high dopamine can cause hyperkinetic movements
Mesolimbic pathway (not normal, hyperactivated) > from ventral tegmental area VTA to the nucleus accumbens in the ventral striatum > regulate motivation and reward > link with positive symptoms
Mesocortical pathway (not normal, hypofunctioning) > from the VTA to the dorsolateral prefrontal cortex > link to negative, cognitive and affective symptoms
D15, 17,
Theory that explain symptoms
3.2. Role of glutamate
Caracteristics
Amino acid involed in protein biosynthesis
Use as neuroT > synthesized from glutamine in glia
Most important excitatory neuroT (80-90% of synapses) and involved in learning and memory
Glutamine --> enter glutamatergic neuron --> enzyme glutaminase transformed it into glutamate
Glutamate is released > interacts w/ receptors in the synapse > transported into neighboring glia by a reuptake pump EAAT Excitatory aino acid transporter > degraded in glia by the enzyme glutamine synthetase
D23, 24, 25
Receptors
3 ionotropic receptors (postsynaptic)
AMPA
NMDA (control calcium channels, more important) > remove magnesium thanks to glutamte or glycine to make it works
Kainate (control sodium channels)
Metabotropic receptors (G protein-coupled)
postsynaptic > type 1
presynaptic > type 2 and 3
Pathways
Glutamatergic H :
hypofunctioning of NMDA receptors in specific synapse of the prefrontal cortex
Origin : use of phencyclidine (PCP, a NMDA erceptor antagonist) that produce a transient hypofunctioning of these same receptors of these same GABA neurons
Neurone --> excited GABA interneurone --> inhibits the next neurone --> glutamatergic pathway disinhibited --> hyperactivity
Cortico-tronceoencephalic glutamanergic pathway : from pyramidal neurons of the cortex of the brainstem (neuronal bodies of monoaminergic neurons)
Excitatory cortico-brainstem glutamate neurons --> innveration of monoamine neurones in the brainstem --> stimulates neuroT release --> indirect innervation of monoamine neurons via GABA interneurons in the brainstem blocks neuroT release
Mesolimbic pathawy ---> direct stimulation of dopaminergic neurons in VTA
Increase of DA in this pathway with hypofuntional NMDA patient
Masocortical pathway --> inhibition through GABA in VTA
Glutamate cortico-thromboencephalic pathway favour the release of DA in the mesocortical pathway
PAS IMPORTANT Corticostrial glutamanergic pathway : from pyramidal neurons to striatum --> pyramidal neurons synapse onto GABA neurons --> project to the thalamus --> upon excitation act as inhibitory sensory filter preventing excessive sensory traffic
Dopamine > inhibitor of this bilter by inhibiting GABA neurons
YT: The serotonin hypotesis of psychosis (Stalh's essential)
Thalamo-cortical glutamatergic pathway. Ascending pathway from the thalamus to the pyramidal neurons it has an excitatory effect on GABA neurons that filter sensory information. If NMDA receptors are hypofunctioning this inhibitory impulse is reduced.
I
3.3. Importance of serotonin
Role in 5-HT2A receptor
Mismatch in the excitability of excitatory 5-HT2A receptors of glutamatergic pyramidal neurons
Mismatch in the excitability of excitatory 5-HT2A receptors of glutamatergic
Many patients with Parkinson's disease develope psychosis
Post-mortem studies have shown a loss of serotonergic neurons into PD patients’ cortex, this could produce a compensatory increase in the 5-HT2A receptors of pyramidal neurons. Drugs that block serotonin receptors eliminate
psychotic symptoms in Parkinson's patients.
the neurodegenerative process at some point will affect the GABA and glutamatergic neurons. The surviving GABA neurons cannot stop the stimulation produced by the activation of the serotonin receptors producing a hyperstimulation of these glutamatergic pathways. 5-HT2A antagonists are
also effective in reducing the symptoms of psychosis associated with dementia
Hyperactivity of 5-HT2A will lead to increase of DA release in the mesolimbic
dopaminergic pathway
3.4. Neurodevelopmental impairment or neurodegeneration
Stages in schizophrenia :
premorbid (no specific symptoms) > unitil puberty
prodromal onset / progression
deterioration
chronic/residual
Neuroevolutionary H : abnormalities in fetal brain dvt
Brain dvt > more neurones than necessary so process of selection and migration and synatogenesis
Obstetric complication, viral infections, starvation, autoimmune processes --> structural abnormalities : mis-selection, mis-migration, confusion of neuronal growth signal
Ado > selection of synapsis occurs > dysfunctional genes can be inherited and circuits will be generated abnormally and symptoms of schizophrenia will appear
Neurodegenerative H : neurodegenerative process with loss of neuronal function --> functional and structural abnormalities
Malfunction of NMDA receptor --> affect maintenance of synoopsis throughout the life of the subjects
Evidences :
the response to antipsychotics may decline over the course of the disease, the decreasing response to the treatment is accompanied by loss of brain mass
after a new psychotic relapse the time to experience remission increases
early and continuous treatment is more effective and can prevent the disease from progressing
Anatomical changes in schizophrenia
Anatomical abnormalities
some patients brain ventricles are larger (with high degree of cognitive impairment with social maladjustment)
Limbic system: hypothalamus, amygdala and hippocampus
Neuronal migration → error in the elimination of synapses
Functional abnormalities
Lower metabolic activity in frontal lobe (hypofrontality). Other studies show increased metabolism → cortical “desynchrony”
subjective emotional reaction (difficulty to recognise pleasant smells; using different brain areas) → hypervigilance
More use of prefrontal resources to perform cognitive tasks
More use of prefrontal resources to perform cognitive tasks
Genetics
Epigenetic changes will determine whether the disease develops → polygenic inheritance
Family studies, twin studies and adoption studies support the existence of high genetic component
Genes related to BDNF, encoding dysbindin (protein involved in the formation of synaptic structures), neuregulin (neuronal migration and glial cells genesis) and DISC-I (neurogenesis, neuronal migration and dendritic organization)
Environmental factors
Seasonal effect: more cases in those born in late winter and early spring (exposure to viral epidemics during 1st or 2nd trimester of pregnancy)
Effect of latitude: mora cases further away to the equator (colder and more viral infections)
Low socio-economic status
Area of residence: more cases in urban areas
Maternal malnutrition: vitamin D deficiency (especially in extreme latitudes); thiamine deficiency
Maternal stress and drug abuse, obstetric complications during pregnancy or delivery
Age of the father (after 50) mutations accumulate with age in the spermatogonia
retélécharger diapo avec toutes les info > diapo le plus important 14