Motivational Systems And Psychiatry Flashcards
What is schizophrenia a disorder of
Mesolimbic dopamine system and prefrontal cortex
When does schizophrenia emerge
Early adulthood
Positive symptoms of schizophrenia
-hallucinations, paranoid delusions, dissociated from reality. Common type of hallucinations: ‘hearing voices in my head”. Erratic eye movements, related to constantly shifting attention
Negative symptoms of schizophrenia
-impaired attention, executive function, behavioral control, flattening of emotional expression (flat affect)
Neurobiology of schizophrenia
Excessive activity of mesolimbic DA system (opposite of Parkinson’s)
Rx for schizophrenia
Dopamine receptor antagonists, referred as “typical anti-psychotics’ or ‘neuroleptic’ drugs
One potential serious complication of anti-psychotics or neuroleptics
Tardive dyskinesia
- involuntary movements of facial/mastication/tongue muscles.
- can also develop Parkinson’s like signs including cogwheel rigidity
- extra-pyramidal side effects
Role of serotonin in schizophrenia
- some atypical anti-psychotics can also affect serotonin NT
- normal functions of serotonin systems include promoting memory retrieval
- some hallucinogenic act by activating serotonin receptors
- speculative explanation for efficacy of Rx that modulates serotonin: schizophrenia involved excess serotonin signaling which drives hallucinations and delusions
Role of glutamate dysregulation in schizophrenia
- role of dysregulation of glutamate in prefrontal cortex and straitum: excess glutamate release by axon terminals
- dysregulation of glutamate occurs in corticostriatal projections, i.e. Part of the basal nuclei “cognitive loop” or emotive loop
Two major groups of nuclei (multi raphe) of serotonin systems
Ascending/rostral
- caudal midbrain
- rostral pons
Caudal/descending raphe nuclei
-in pons/medulla
Which serotonin system is involved with schizophrenia and how
Rostral/ascending system
- caudal midbrain
- rostral pons
Spritzing serotonin all over cerebrum
Group of nuclei located at the midline in brainstem sections
Nuclei raphe
Early generation diet pills and rostral/ascending system
Act via increasing serotonin in hypothalamus, normally mediates stress-induced interruption of eating
Serotonin levels regulate what
Aggressive behavior, natural reward (eating)
Different raphe nuclei and effects on anxiety
They have opposing affects on anxiety, due to difference in projections targets and receptors types. Ascending serotonin systems have widespread, diffuse projections in cerebrum, but important targets include amygdala, prefrontal cortex, other subcortical sites
What is used for Rx for anxiety/panic/ PTSD, and as anti-depressants
SSRIs
Core symptoms of MMD
- loss of interest, pursuit, and pleasure from usual rewarding activities
- inability/disinterest in performing any daily plan, motivational ‘paralysis’
- feelings of hopelessness/worthlessness
- causes severe dysfunction in daily work/social life
- lasts more than 1 month
Additional diagnostics criteria for MDD
- increases anxiety/agitation
- excessive sleeping or insomnia
- excessive appetite or absence of appetite
- lethargy or high ‘psychomotor’ activity
Crisis point requiring emergency intervention for MDD
Suicidal ideation/planning
Onset of MDD
-chronic/insidious, but often triggered by chronic stress, trauma, grief
Course: may be episodic or chronic state
What do anti depressants target
norepi, serotonin, and dopamine systems
Efectiveness of ant depressant Rx discovery
Through historical/medical accident, not by any pathophysiological understanding of the neurobiology basis of depression
What lead to the monoamine hypothesis of depression
The effectiveness of anti-depressants
What is the monoamine hypothesis of depression
An imbalance of deficiency in monoamines is the cause of depression
Where does the ascending projections come from for the serotonin system
Locus coeruleus
Where does the LC extend
From rostral pons to the caudal midbrain
Key functions of LC
Arousal, support of alertness/selective/sustained attention
What us the LC activated by
Stressors-both positive and negative arousing stimuli
LC and the hippocampus and amygdala
Enhance memory consolidation, including for fear learning/extinction
What does the LC do to feeding
Suppresses feeding via hypothalamus (stress response)
Excess norepinephrine and LC
Linked to anxiety disorders including PTSD
What are the prevailing anti-anxiety Rx
Benzodiazepines (GABA agonists), and SSRIs
Despite norepinephrine being linked to being a cause
How was the first anti-depressant discovered
By accident. Monoamine oxidase inhibitors used to treat movement disorders
What do monoamine metabolic enzyme inhibitors boost synaptic levels of
DA
NA
5-HT
Second generation of anti-depressants
Tricyclic anti depressants: inhibitors of re-uptake transporters for monoamines –DA, NA, 5-HT
3rd generation of anti depressants
More selective inhibitors of re uptake transporters
- selective serotonin re-uptake inhibitors (SSRIs)
- selective norepi reuptake inhibitors
- selective norepi and dopamine re uptake inhibitors
Disadvantages and risks of current anti depressants
- typically requires weeks to achieve noticeable effect
- modest effect vs placebo for many patients
- suicide risk for some adults, higher risk for children, possibly due to increases motivational drive but persistence anxiety and emotional pain
Psychological therapies for MDD
Mainly cognitive behavioral therapy (CBT) with the goal to alter negative thinking patterns, promote reward system function, coping with life circumstances
CBT alone in individuals with MDD
Can produce ciliary changes in prefrontal and amygdala activity as wit RX alone
CBT and Rx treatment for MMD
Common to use them together
New drug targets for MDD
Under investigation, enkephalin receptor agonists (kappa receptor)
New accidental discoveries for MDD treatment
Off label uses for motion sickness (scopolamine)
Experimental in-patient crisis treatment and MDD
Ketamine
NMDA glutamate receptor antagonist
Electroconvulsive therapy (ECT)
Mild electrical current, scalp electrodes
Transcrnial magnetic stimulation and MDD
Non-invasive application of magnetic field over specific cortical region
Depression and deep brain stimulation
- implanted electrode in brain
- current pattern can be adjusted to produce activation of target region. Works in movement disorders, experimental for MDD
Target regions for deep brain stimulation in MDD
Selected based on functional neuroimaging research studies showing altered regional activity relative to healthy control subjects
What is hyperactive in MDD patients and often the target of deep brain stimulation
Subgenual cortex
-inhibiting this produces rapid and significant reduction of symptoms
Nucleus accumbens and MDD
Antlers target for deep brain stimulation
Aim to increase activity
Might need to be combined with psychological therapy to be effective
What 3 areas are often messed up in MDD
Subgenual cortex
Nucleus accumbens
Periventricual zone along the 3rd ventricle
Brain maturation and psychiatric disorders
Brain regions differ in timing of complete maturity: probably involved in age-specific time-windows for vulnerability to psychiatric disorders
Altered mesolimbic dopamine system in schizophrenia may stem from what
Possibly stems from disruption of synaptogensis or mechanisms that stabilize and preserve effective synapses
When is the onset of schizophrenia
Early adult
Onset of depression
Can emerge in children, adolescents, adults of any age
When doesthe amygdala and hippocampus start to mature
About 2 years old
What is the last cerebral cortex to reach maturity
Prefrontal cortex
What is the risk of developing anxiety disorder, PTSD, and depression prior to prefrontal maturity due to
- lack of control of amygdala to prefrontal cortex (anxiety/PTSD)
- lack of amygdala-prefrontal partnership in reward-related learning
