Clinical Psychopharmacology

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Oct 30, 2023

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Clinical Psychopharmacology The big 5 -Schizophrenia -Depression -Bipolar Disorder -Anxiety Disorder -Attention Deficit/Hyperactivity Disorder
Cognitive impairments in schizophrenic patients include deficits in memory, abstraction, and attention Schizophrenia Schizophrenia spectrum disorders are defined by abnormalities in at least one of the five domains: delusions, hallucinations, disorganized thinking (speech), grossly disorganized or abnormal motor behavior (including catatonia), and negative symptoms (flattened affect, alogia, apathy, avolition and social withdrawal) • Criterion A: At least two of the previous five domains (one of which must be either delusions, hallucinations, or disorganized speech) • Criterion B: Impairment for a significant portion of time in a major area of functioning • Criterion C: Signs of the disturbance continuously for at least six months • Criterion D: Schizoaffective, depressive, or bipolar dis- order with psychotic features have been ruled out • Criterion E: The symptoms are not attributed to the effects of some substance (medications) or medical condition • Criterion F: There is no history of autism spectrum disorder or a communication disorder during childhood dopaminergic pathway includes the connections between the ventral tegmental area (VTA) and the nucleus accumbens and mostly the D1 and D2 receptors mesocortical pathway includes connections from the VTA to the temporal cortex, frontal cortex, and PFC, and mostly D1 receptors with some presence of D2 and D5 receptors substantia nigra to the corpus striatum (the nigrostriatal) and from the hypothalamus to the anterior pituitary (the tuberoinfundibular)
Two Main Categories of Antipsychotics 1. First generation (FGA, typical ) -FGAs, like chlorpromazine and haloperidol, have high affinity for dopamine receptors, specifically the D2, especially within the mesolimbic path- way, thereby decreasing the presence of positive symptoms 2. Second generation (SGA, atypical ) -SGAs (like clozapine, risperidone, olanzapine, quetiapine, and aripiprazole) have slightly decreased affinity for the D2 receptors, but are believed to have some serotonin antagonism Main Side Effect of FGAs include: 1. Extrapyramidal side effects (EPS). EPS is defined as parkinsonism (rigidity, bradykinesia, shuffling gait, tremor), dystonia (fixed upper gaze, neck twisting, facial muscle spasms), and akathisia (inability to sit still, restlessness, tapping of feet). It is believed that it is D2 inhibition within the basal ganglia that leads to EPS, as is similar to Parkinson’s disease EPS is mostly treated with anticholinergic drugs, although some studies have shown that these may lead to further cognitive impairment 2. Tardive dyskinesia (TD) is defined as involuntary movements, especially of the lower face. One proposed etiol- ogy of TD is an adaptive hypersensitivity of D2 receptors in the striatum. Main Side Effect of SGAs (main benefit no EPS or TD- increased serotonergic inhibition of dopamine block) include: sedation, weight gain, and diabetes mellitus type II https://www.frontiersin.org/articles/10.3389/fnins.2014.00395/full
Cognitive impairments: overall poor performance on cognitive tests; issues with - psychomotor speed, attention, and visual learning, memory, executive dysfunction Depression Depression, as defined in the DSM-5, consists of a pervasive feeling of sadness or irritability that results in significant disturbances in energy, sleep, appetite, sexual drive, weight, or the ability to express or seek pleasure • Major depressive disorder (MDD) is defined as depression that lasts for at least a two-week period, with symptoms that cause clinically significant impairment at work, with the family, or in other important areas • MDD Types: typical (melancholic), atypical, and psychotic • MDD can present at any age, but has an increased likelihood during puberty • MDD is also highly associated with many other health issues, including coronary artery disease, metabolic syndrome, diabetes, and other chronic illness Norepinephrine: molecule mostly produced in the locus ceruleus (LC) and is involved in vigilance, stress response, neuroendocrine function, pain control, and the sympathetic nervous system Serotonin, on the other hand, is produced within the raphe nucleus, and is involved in modulation of mood, the sleep–wake cycle, motivation and reward, cognition function, and pain perception, as well as neuroendocrine function After being released into the synaptic cleft, these molecules are then transported back through a nonspecific transporter, vesicular monoamine transporter (VMAT), or through specific serotonin trans- porter (SERT) and norepinephrine transporters (NET). Both of these molecules then get degraded intracellularly by an enzyme called monoamine oxidase (MAO), of which there are two types: MAO-A degrades serotonin, norepinephrine, and dopamine, while MAO-B degrades dopamine only!
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