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UNIT 3 ■ Care of Patients With Psychiatric Disorders
Cortex
Thalamus
Striatum
Substantia nigra
Frontal cortex
Hypothalamus
Mesolimbic pathway
Mesocortical pathway
Pituitary
Nigrostriatal pathway
Tuberoinfundibular pathway
Amygdala
Hippocampus
Ventral tegmentum area
FIGURE 15–1 Neurobiology of schizophrenia.
NEUROTRANSMITTERS A number of neurotransmitters have been implicated in the etiology of schizophrenia: dopamine, norepinephrine, serotonin, gluta- mate, and gamma-aminobutyric acid (GABA). The dopaminergic system has been most widely studied and closely linked to the symp- toms associated with the disease. AREAS OF THE BRAIN AFFECTED Four major dopaminergic pathways (the pathways that transmit dopamine to different areas of the brain) have been identified: • Mesolimbic pathway: Originates in the ventral tegmentum area (VTA) and projects to areas of the limbic system, including the nucleus accumbens, amygdala, and hippocampus. The mesolimbic pathway is associated with functions of memory, emotion, arousal, and pleasure. Excess activity in the mesolimbic tract has been implicated in the positive symptoms of schizophrenia (e.g., hallucinations, delusions). Dopamine blockade in this pathway is the target of antipsychotic medication to reduce hallucinations and delusions. • Mesocortical pathway: Originates in the VTA and projects into the cortex. The mesocortical pathway is concerned with cognition, social behavior, planning, problem-solving, motivation, and reinforcement in learning. Negative symptoms of schizophrenia (e.g., flat affect, apathy, lack of motivation, and anhedonia) have been associated with diminished activity in the mesocortical tract, particularly at D 3 receptors. • Nigrostriatal pathway: Originates in the substantia nigra and terminates in the striatum of the basal ganglia. This pathway is associ- ated with the function of motor control. Degeneration in this pathway is associated with Parkinson’s disease, and because typical anti- psychotics may also block dopamine here, drug-induced Parkinson-like extrapyramidal side effects and tardive dyskinesia can occur. • Tuberoinfundibular pathway: Originates in the hypothalamus and projects to the pituitary gland. It is associated with endocrine function, digestion, metabolism, hunger, thirst, temperature control, and sexual arousal. Dopamine blockade in this pathway is asso- ciated with an increase in prolactin levels (hyperprolactinemia), which can result in galactorrhea (milk discharge from the nipples) in both men and women, erectile disorder, and anorgasmia. ANTIPSYCHOTIC MEDICATIONS Type Receptor Affinity Associated Side Effects First Generation (Typical) Antipsychotics Phenothiazines Haloperidol (ease positive symptoms such as hallucinations and delusions but worsen negative symptoms) Strong D 2 (dopamine) Varying degrees of affinity for: ACh (acetylcholine) α 1 (norepinephrine) H 1 (histamine) Weak 5-HT (serotonin) Extrapyramidal symptoms (EPS), hyperprolactinemia, neuroleptic malignant syndrome Anticholinergic effects Tachycardia, tremors, insomnia, postural hypotension
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