Summary NURS 660 Exam 1 Study Guide 2023

NURS 660 Exam 1 Study Guide 2023. GLUTAMATE  Excitatory NT, can excite and turn on all virtually ALL CNS neurons. Known as the master switch  Glutamate is released from synaptic vesicles, interacts with neighbor cells (glia) is taken up into glia VIA excitatory amino acid transporters (EAATs), it is converted to glutamine inside glia by enzyme glutamine synthetase, glutamine is released and SNAT (specific neutral amino acid transporters) takes it back into presynaptic neuron where its converted back to glutamate, then goes back into synaptic vesicles by vGluT transporters to be stored.  NMDA receptors are glutamate receptors and requires cotransmitter glycine or d-serine, made by neighboring glial cells (some neurons make glycine to put in synaptic vesicle but most comes from glial cells). Glial cells convert l-serine to d-serine Glutamate receptors:  NMDA, AMPA, and kainite- these are all ionotropic. So glutamate is released, attaches to receptor, sodium channels open and depolarize the cell, glutamate flows in, then Gaba is released. Glutamate pathways:  Cortico-brainstem-descending projects from cortical pyramidal neurons to brainstem NT centers including raphe for serotonin, VTA and substantia nigra for dopamine, ad locus coeruleus for NE. These excitatory cortico brainstem neurons stimulate NT release.  Corticostriatal-descending from cortical pyramidal neurons to striatal complex. AKA cortico-accumbens when project to NA. These neurons terminate on GABA neurons.  Hippocampal accumbens-projects from hippocampus to NA-this path is linked to schizo.  Thalamo-cortical pathways-brings info from thalamus back to cortex to process sensory info.  Corticothalamic-projets back to thalamus  Cortico-cortical-glutamate pathways in cortex  Indirect cortico-cortico-one neuron inhibit another neuron via interneurons that release GABA. Positive and negative symptoms of Schizophrenia  Positive symptoms: these are psychotic behaviors that are not generally seen in healthy individuals. Those with positive symptoms may lose touch with some aspects of reality. Symptoms: delusions, hallucinations, thought disorders (unusual or dysfunctional ways 3 of thinking), movement disorder (agitated body movements) (Arising from the mesolimbic dopamine pathway) i. Positive symptoms of schizophrenia are hypothetically modulated by malfunctioning mesolimbic circuits. 1. Delusions, Hallucinations, Distortions or exaggerations in language and communication, Disorganized speech, Disorganized behavior, Catatonic behavior, and Agitation  Negative symptoms: disruptions to normal emotions and behaviors. Characterized by: flat affect, reduced feelings of pleasure in everyday life, difficulty beginning and sustaining activities, decreased communication. (Arising from the mesocortical dopamine pathway) ii. Negative symptoms are hypothetically linked to malfunctioning mesocortical circuits and may also involve mesolimbic regions such as the nucleus accumbens. 1. Alogia – Poverty of speech; e.g., talks little, uses few words 2. Affective blunting – Reduced range of emotions (perception, experience and expression); e.g., feels numb or empty inside, recalls few emotional experiences, good or bad 3. Asociality – Reduced social drive and interaction; e.g., little sexual interest, few friends, little interest in spending time with (or little time spent with) friends 4. Anhedonia – Reduced ability to experience pleasure; e.g., finds previous hobbies or interests unpleasurable 5. Avolition – Reduced desire, motivation, persistence; e.g., reduced ability to undertake and complete everyday tasks; may have poor personal hygiene iii. Affective symptoms of schizophrenia 1. Affective symptoms are associated with the ventromedial prefrontal cortex. a. Depressed mood, Anxious mood, Guilt, Tension, Irritability, and Worry iv. Cognitive symptoms of schizophrenia 1. Cognitive symptoms are associated with problematic information processing in the dorsolateral prefrontal cortex. a. Problems representing and maintaining goals, Problems allocating attentional resources, Problems focusing and sustaining attention , Problems evaluating functions , Problems modulating behavior based upon social cues, Problems monitoring performance , Problems prioritizing , Problems with serial learning, Impaired verbal fluency, and Difficulty with problem solving 4 DSM five: two of the following during one month (one must be 1-3)  delusions  hallucinations  disorganized speech  grossly disorganized or catatonic behavior  negative symptoms Know the following brain regions and what mental health symptoms originate from them: Dorsolateral prefrontal cortex – cognitive symptoms  Nucleus accumbens – negative symptoms/reward circuits  Orbital frontal cortex – aggressive symptoms  Substantia nigra – motor function and movement  Mesolimbic – positive symptoms  Ventromedial prefrontal cortex – affective symptoms ***Suicidal ideation:VMPFC, amygdala Important to note: Negative symptoms can also be linked to mesolimbic system which involves the nucleus accumbens which is part of the brain's reward circuitry and plays a role in motivation. NA may also be involved in substance abuse. Dopamine hypothesis: AKA: dopamine hypothesis of schizophrenia)  The mesolimbic dopamine pathway projects from dopaminergic cell bodies in the ventral tegmental area of the brainstem to axon terminals in one of the limbic areas of the brain, mainly the nucleus accumbens located in the ventral striatum. This pathway is said to have an important functional role in many emotional behaviors (positive symptoms of psychosis - delusions & hallucinations). This pathway also plays a role in motivation, pleasure, and reward. Drugs that increase dopamine will increase or produce positive symptoms of psychosis. The opposite is true for drugs that decrease dopamine - decrease or stop positive symptoms. All antipsychotics that treat positive symptoms are blockers of the dopamine D2 receptor. Ex: stimulants such as cocaine/amphetamines: release dopamine, if taken repeatedly, can cause paranoid psychosis that is hard to differentiate from positive symptoms of schizophrenia.  The dopamine hypothesis or the mesolimbic dopamine hypothesis of positive symptoms of schizophrenia. Since it is believed that hyperactivity in the mesolimbic pathway, mediates positive symptoms of psychosis. Hyperactivity of this path accounts for positive symptoms whether symptoms are a part of schizophrenia or a drug induced psychosis, or psychosis from depression or dementia. IT IS NOT KNOWN what causes dopamine hyperactivity, but they think its consequence of dysfunction in prefrontal cortex and hippocampal glutamate 5  May also play a role in aggression and hostile symptoms  Evidence of dopamine hypotheses: amphetamine, cocaine increases dopamine levels which can cause symptoms that look like psychosis. Levodopa can do the same. Know the neurotransmitters and their role related to schizophrenia.  Dopamine is the main neurotransmitter in schizophrenia. There are four main dopamine receptors and all are blocked by some atypical antipsychotics. The dopamine 2 receptors are presynaptic and block the release of dopamine into the synaptic cleft.  The mesolimbic dopamine pathway projects from the tegmental area of the brainstem to axons in the limbic system in the nucleus accumbens in the ventral striatum. This area is associated with emotional behaviors including positive symptoms of psychosis, but it also creates motivation, pleasure, and rewards. Stimulants like amphetamine and cocaine increase dopamine which can increase the presence of psychosis. Whereas medications that block dopamine will reduce positive symptoms.  All antipsychotics that can block dopamine can treat the positive symptoms of schizophrenia. Hyperactivity of the mesolimbic dopamine pathway may also play a role in the hostility and aggression found with schizophrenia. The mesocortical dopamine pathway branches into the dorsolateral prefrontal cortex which is thought to regulate cognitive and executive functioning and branches into the ventromedial parts of the prefrontal cortex to regulate emotions and affect. This means that these pathways will produce cognitive, affective, and some negative symptoms with a dopamine deficit.  Another important area affected in the brain by dopamine is the nigrostriatal dopamine pathway stemming from the substantia nigra in the brainstem to the basal ganglia or striatum. This is part of the extrapyramidal nervous system which controls motor movements and deficits of dopamine will lead to movement disorders. Deficiency in the basal ganglia can also cause akathisia and dystonia. If there is too much dopamine in these areas you will see hyperkinetic movements such as chorea, dyskinesia, and tics.  With the tuberoinfundibular dopamine pathway, deficiencies can affect prolactin levels leading to galactorrhea, amenorrhea, and sexual dysfunction. This is often seen when antipsychotics are given and the dopamine is blocked.  Glutamate - is the major neurotransmitter in the central nervous system and sometimes to be considered the “master switch” of the brain, since it can excite and turn on virtually all CNS neurons.  Glutamate is the major excitatory neurotransmitter of the CNS as it can “turn on” nearly all the CNS neurons. There are six pathways of relevance to schizophrenia. The corticobrainstem glutamate pathway is a regulator or neurotransmitter release where direct innervation of monoamine neurons in the brainstem stimulates release and indirect innervation via GABA interneurons blocks release.  The cortico-striatal glutamate pathway projects to the dorsal striatum terminate on GABA neurons. The hippocampal-accumbens glutamate pathway has specific theories that link 6 this to schizophrenia and also terminate on GABA neurons. The thalamo-cortical glutamate pathway helps to process sensory information by carrying information from the thalamus to the cortex. The cortico-thalamic glutamate pathway projects back into the thalamus and may affect the manner in which neurons react to sensory information. The direct cortico-cortical glutamate pathway allows pyramidal neurons to excite one another. Finally, the indirect cotrico-cortical glutamate pathway allows for one pyramidal neuron to inhibit another via indirect input on the intraneurons releasing GABA.