Neuro 5 and 6) Neurobiology and neurochemistry in mental health Flashcards
What are the symptoms of schizophrenia?
Positive - voices, delusions, thought insertion / withdrawal / broadcast
Negative - neglect, isolation, lack of emotional expression, avolition
Cognitive - reduced concentration and attention. Reduced executive functioning
What is dopamine?
Monoamine neurotransmitter
What is the precursor of dopamine?
Tyrosine
What are the functions of dopamine?
Executive functions Motor control Motivation Reward Lactation Nausea
Why do typical antipsychotics cause side effects?
Reduce dopamine causing hyperprolactinaemia
Too little dopamine in nigrostriatum causes extrapyramidal side effects
Describe the link between glutamate and psychosis
Too little cortex in prefrontal cortex causes psychosis
Reduction in glutamate release leads to direct loss of dopamine in the prefrontal cortex via the mesocortiyal pathway.
Reduction in glutamate release increases positive symptoms by mesolimbic pathway
Describe the link between GABA and psychosis
Reduction in glutamate release decreases GABA so there is less inhibition. This increases positive symptoms due to hyperactivity in the mesolimbic pathway
What neuroanatomical changes occur in schizophrenia?
Enlarged ventricles
Reduced grey matter volumes
Decreased gyrification
Loss of asymmetry of planet temporale
Why is it important to understand the neuroanatomical changes in schizophrenia?
Understand therapeutic drug development
Identify appropriate treatment goals in schizophrenia
Understand side effect profiles
What are some organic causes of psychosis?
NMDA receptor autoimmune encephalitis Huntington's chorea Temporal lobe epilepsy Wilson's disease Parkinson's disease
Describe NMDA receptor autoimmune encephalitis
Associated with teratomas
Presents with flu like illness, encephalitis or psychotic symptoms
Requires immunosuppression with steroids.
May need ITU due to autonomic instability
How does NMDA receptor autoimmune encephalitis cause psychosis?
Antibodies form against NR1 and NR2 subunits of NMDA receptor which reduces glutamate binding
Describe the genetics of Huntington’s chorea
Autosomal dominant
CAG triplet repeats in Huntington gene
Every generation increases instability of CAG triplets and risks increasing the number of repeats (genetic anticipation)
Describe the link between temporal lobe epilepsy and psychosis
May have no impairment of consciousness during seizure
Depending on part of temporal lobe, can have hallucinations in all modalities, extreme fear, amnesia, dissociation
Post-ictal or inter-octal psychosis
What is Wilson’s disease and how does it cause psychosis?
Autosomal recessive
Faulty ATP7B gene affecting Wilson’s disease protein which leads to copper deposition in liver and brain
Affects basal ganglia
Neuropyschiatric complications including cognitive impairment, depression and psychosis
Will have Kayser-Flesicher rings
Describe the link between Parkinson’s disease and psychosis
Multiple contributing factors: PD medications (L-DOPA) Visual dysfunction brainstem, sleep dysfunction Cortical pathology Deep brain stimulation surgery Genetic, neurochemical abnormalities
What is autism?
Spectrum from severe classical autism to high functioning asperger’s
Deficits in social interaction, restricted repertoire, communication
What is classical autism?
Tapping feet Screeches Spins in circles Struggles when routine is changed Can be aggressive Obsessed with numbers
What is high functioning ASC?
Wears same clothes
Eats same coloured foods
Interest in playing violin and practices every evening and weekend
Excels at maths
What are the current autism theories?
Empathising - systemising theory
- decreased empathy
- increased systemising
Theory of mind
- empathy deficit
Navon test
- over systemising
Describe autism and the social brain
Hypoactivation of fusiform gyrus in response to faces leading to reduced ability to recognise emotions in others
Hypoactivation of social brain on fMRI
- IFG during facial expression imitation
- pSTS during perception of facial expression and gaze tasks
- SFG during theory of mind tasks
What is ADHD?
Neurodevelopmental disorder
Triad of attention difficulties, impulsivity, hyperactivity
What is the DSM criteria for ADHD?
At least 6 inattentive symptoms present for 6 months
At least 6 hyperactive-impulsive symptoms present for 6 months
Describe the neurophysiology with ADHD
Can be viewed as deficit in executive functioning and delayed rewards
- executive functioning comes from frontal lobe
- delayed rewards come from amygdala and front lobe
Abnormalities in dopamine and noradrenaline
What medication can be given for ADHD?
Methylphenidate (ritalin) and atomoxetine (non-stimulant options) - noradrenaline and dopamine reuptake inhibitors
What are the 2 types of bipolar affective disorder?
Bipolar type 1 = depression and mania
Bipolar type 2 = depression and hypomania
What are the roles of the limbic system?
Emotional regulation
Memory formation
Learning
What are the components of the limbic system
Cingulate gyrus Fornix Thalamus Hippocampus Amygdala Mammillary bodies Hypothalamus Orbitofrontal cortex Insula
What is the cingulate gyrus involved with?
Smells and sights with pleasant memories, emotional reaction to pain, aggressive behaviour
What is the role of the prefrontal cortex in bipolar disorder?
Underactivation seen using fMRI
Volume loss as disease progresses
Reduced connectivity between PFC and amygdala
What is the role of the amygdala in bipolar disorder?
Overactivity in response to faces
Complex models of toxic signalling, oxidative stress, inflammatory responses and calcium dysregulation
Describe what happens to the PFC and amygdala as bipolar progresses
Loss of prefrontal cortex and progressive hypoactivation
Sustained hyperactivity of amygdala and increasing volume size
Describe the prevalence of depression
Depressive symptoms in 13-20% Depressive disorder 5.8% Major depressive disorder lifetime prevalence 20% Peak 25-35 years Female : male 2:1
What are the symptoms of depression?
Low mood, anhedonia, tiredness
Cognitive - hopelessness, helplessness, guilt, worthlessness, poor concentration, poor attention
Somatic - early morning waking, loss of appetite, weight loss, libido decreased
Slow motor movements
What is the pathophysiology of depression?
Monoamine hypothesis
Receptors act downstream on adenyl cyclase or phospholipase C
Designated monoamine transports
All broken down by monoamine oxidase
Serotonin, dopamine, histamine, adrenaline, noradrenaline
How does reserpine cause depression?
Antihypertensive that causes rapid depletion of serotonin in synaptic cleft
What are the types of anxiety disorders?
Generalised anxiety disorder PTSD Social anxiety Phobia Agoraphobia Panic disorder
What is the role of the amygdala in anxiety?
Differentiates sensory information sent by the thalamus to identify threat from no threat
If a threat is perceived, initiates a physiological response
What parts of the brain does the amygdala act on?
Lateral hypothalamus Dorsal vagal nuclei Parabrachial nuclei Basal forebrain Reticular pontis caudalis Central grey area Paraventricular nuclei
What is the effect of the amygdala on the lateral hypothalamus?
Heart rate
BP
What is the effect of the amygdala on the dorsal vagal nuclei?
Bradycardia
Ulcers
What is the effect of the amygdala on the parabrachial nuclei?
Panting
Respiratory depression
What is the effect of the amygdala on the basal forebrain?
Arousal
Vigilance
Attention
What is the effect of the amygdala on the reticular points caudalis?
Increased startle response
What is the effect of the amygdala on the central grey area?
Freezing
Social interaction
What is the effect of the amygdala on the paraventricular nuclei?
Corticosteroid release
Describe the pathway of HPA overstimulation in anxiety
Sensory input to thalamus to amygdala or prefrontal cortex.
From amygdala to hypothalamus which releases corticotrophin releasing hormone which causes anterior pituitary to release adrenocorticotrophic hormone which causes adrenals to produce cortisol.
Chronic stress with elevated cortisol causes anxiety disorders
What is PTSD characterised by?
Hypervigilance
Flashbacks
Nightmares
Avoidance
Describe the pathology path of PTSD
1) Trigger e.g. smell
2) Hippocampus recalls fragment of memory e.g. image
3) Amygdala reacts to memory causing flashback
4) Prefrontal cortex is unable to rationalise situation and unable to recognise person is safe
5) Person attempts to avoid or escape
