summarize in bullet points: The onset of schizophrenia was initially hypothesized to stem from abnormally high concentrations of the brain neurotransmitter dopamine. This dopamine... summarize in bullet points: The onset of schizophrenia was initially hypothesized to stem from abnormally high concentrations of the brain neurotransmitter dopamine. This dopamine hypothesis of schizophrenia was proposed on the basis of pharmacologic studies showing that antipsychotic drugs were potent blockers of brain dopamine receptors. A strong positive correlation was found between the clinical potencies of first-generation antipsychotic drugs (e.g., chlorpromazine, fluphenazine, and haloperidol) and their affinity for the dopamine D2 receptor. In addition, drugs at high doses that dramatically increased dopaminergic transmission—such as levodopa (L-dopa), cocaine, and amphetamine—produced schizophrenic-like psychosis, which was reversed by dopamine blockers. A current view of the dopamine hypothesis of schizophrenia is that brain dopamine pathways are altered in different ways (Fig. 19.4). For example, the negative symptoms and cognitive alterations in schizophrenia are proposed to result from reduced dopaminergic neurotransmission in the mesocortical dopamine pathway. This hypodopaminergic transmission in the prefrontal cortex contrasts with the hypothesized hyperdopaminergic secretion in mesolimbic brain regions that may contribute to the production of positive schizophrenia symptoms. The mesolimbic dopamine pathway innervates temporal lobe structures including the hippocampal formation and amygdala, as well as the nucleus accumbens and anterior cingulate cortex. Another neurotransmitter system that may underlie the pathogenesis of schizophrenia is the excitatory neurotransmitter glutamate and its actions on the N-methyl-D-aspartate (NMDA) receptor subtype. The glutamate hypothesis of schizophrenia proposes that the underactivation of glutamate receptors contributes to schizophrenia. In schizophrenia, glutamate concentrations in the cerebrospinal fluid (CSF) are reduced along with a decrease in cortical glutamate synthesis. Furthermore, in unaffected individuals, blocking the glutamate NMDA receptor with antagonists, such as phencyclidine (PCP) and ketamine, facilitates the positive and negative symptoms of schizophrenia. PCP users report auditory hallucinations and disorientation and may become violent from their delusions. In monkeys, chronic PCP treatment impairs cognitive performance in a test associated with prefrontal cortical damage. Clinical Manifestations The symptoms of schizophrenia are currently divided into three broad categories of positive, negative, and cognitive symptoms. Positive symptoms frequently occur during a psychotic episode, when an individual loses touch with reality and experiences something that should be absent (e.g., hallucinations). Negative symptoms are characterized by disruptions in normal emotional states and expressions. Cognitive symptoms are fairly common and involve problems with thought processes that severely impair the ability to perform routine daily tasks that involve attention, planning, and social skills. According to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the diagnosis of schizophrenia begins by eliminating other mental disorders and symptoms not caused by substance abuse, medication, or medical condition. The individual will then be diagnosed with schizophrenia when at least two of the following symptoms (1) delusions, (2) hallucinations, (3) disorganized speech, (4) disorganized or catatonic behavior, and (5) negative symptoms are experienced most of the time during a 1-month-period with some disturbance present over 6 months. In addition, one of the symptoms must be delusions, hallucinations, or disorganized speech. Read more