Summary NURS 660 Exam 1 Study Guide 2023

NURS 660 Exam 1 Study Guide 2023. The mesocortical dopamine pathway also projects from the midbrain ventral tegmental area but sends its axons to areas of the prefrontal cortex, where they may have a role in mediating cognitive symptoms (dorsolateral prefrontal cortex, DLPFC) and affective symptoms (ventromedial prefrontal cortex, VMPFC) of schizophrenia. Expression of these symptoms is thought to be associated with hypoactivity of this pathway.  The tuberoinfundibular dopamine pathway projects from the hypothalamus to the anterior pituitary gland and controls prolactin secretion into the circulation. Dopamine inhibits prolactin secretion. In untreated schizophrenia, activation of this pathway is believed to be “normal.”.  The thalamic dopamine pathway arises from multiple sites, including the periaqueductal gray, ventral mesencephalon, hypothalamic nuclei, and lateral parabrachial nucleus, and it projects to the thalamus. Its function is not currently well known but may be involved in sleep and arousal mechanisms by gating information 2 passing through the thalamus to the cortex and other brain areas. There is no evidence at this point for abnormal functioning of this dopamine pathway in schizophrenia. 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