Ebook Delusions - Understanding the Un- understandable: Part 2
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Ebook Delusions - Understanding the Un- understandable: Part 2
The Neurochemical ConnectionAs psychology struggled to make headway with delusions, another discipline close to the heart of psychiatry, pharmacology, Ebook Delusions - Understanding the Un- understandable: Part 2, was sending out signals that a different approach might be more successful. The psychopharmacological era began in 1952 with the discovery that a drug, chlorpromazine, brought about substantial clinical benefit in schizophrenia, where everything everything else from psychoanalysis to insulin coma Ebook Delusions - Understanding the Un- understandable: Part 2therapy had previously failed. Not only did this and other antipsychotic drugs improve psychotic symptoms, it seemed that other drugs could also inducEbook Delusions - Understanding the Un- understandable: Part 2
e them in healthy people. This became clear a few years later when psychiatry finally accepted what had been staring it in the face for years, that amThe Neurochemical ConnectionAs psychology struggled to make headway with delusions, another discipline close to the heart of psychiatry, pharmacology, Ebook Delusions - Understanding the Un- understandable: Part 2ects by producing a functional decrease in brain dopamine; amphetamine and other stimulants cause a functional increase of the same neurotransmitter. These two complementary findings became the pillars of the dopamine hypothesis of schizophrenia, which reigned supreme for a quarter of a century, unt Ebook Delusions - Understanding the Un- understandable: Part 2il a competitor arrived in the form of a drug with effects on another neurotransmitter. Phencyclidine, which had been introduced in the 1950s, was knoEbook Delusions - Understanding the Un- understandable: Part 2
wn to induce vivid subjective experiences in many patients who were given it as an anaesthetic or for pre-operative sedation, and it had even been invThe Neurochemical ConnectionAs psychology struggled to make headway with delusions, another discipline close to the heart of psychiatry, pharmacology, Ebook Delusions - Understanding the Un- understandable: Part 2vere psychotic states. Later still it was found to act by blocking the N-methyl-D-aspartate (NMDA) receptor, one of several classes of glutamate receptor.The dopamine hypothesis survives to the present day despite a number of reversals of fortune. At the time of writing, the glutamate theory is faci Ebook Delusions - Understanding the Un- understandable: Part 2ng an existential crisis, due mainly to the failure of any of a range of glutamatergic drugs to show therapeutic effectiveness in schizophrenia. But tEbook Delusions - Understanding the Un- understandable: Part 2
his is beside the point; all that matters for present purposes is that disturbances in one or both of these neurotransmitters can cause healthy peopleThe Neurochemical ConnectionAs psychology struggled to make headway with delusions, another discipline close to the heart of psychiatry, pharmacology, Ebook Delusions - Understanding the Un- understandable: Part 2 same league as dopamine and glutamate as a neurochemical theory of schizophrenia, cannabis certainly punches above its weight in terms of its ability to induce psychotic symptoms in healthy people.8990Chapter 6: The Neurochemical ConnectionDopamineStimulant Drug-Induced PsychosisThe apparent abilit Ebook Delusions - Understanding the Un- understandable: Part 2y of amphetamine to induce delusions and other psychotic symptoms was first noted in 1938, in three patients who had started taking the drug for narcoEbook Delusions - Understanding the Un- understandable: Part 2
lepsy (Young & Scoville, 1938). I lundreds of further case reports followed, which also implicated other stimulant drugs such as phenmetrazine and metThe Neurochemical ConnectionAs psychology struggled to make headway with delusions, another discipline close to the heart of psychiatry, pharmacology, Ebook Delusions - Understanding the Un- understandable: Part 2selves recognized the problem of‘speed paranoia’ (Rylander 1972; Schiorring 1981). However, it was only after Connell (1958) published a detailed analysis of 42 cases of amphetamine psychosis that resistance to the idea of a causal link finally evaporated. He demolished the argument that what was be Ebook Delusions - Understanding the Un- understandable: Part 2ing seen was a loxic-confusional slate. His case material also provided little support for an alternative argument that amphetamine psychosis was simpEbook Delusions - Understanding the Un- understandable: Part 2
ly schizophrenia being ‘released’ in predisposed individuals who had drifted into drug use as part of their evolving illness.Nevertheless, stimulant dThe Neurochemical ConnectionAs psychology struggled to make headway with delusions, another discipline close to the heart of psychiatry, pharmacology, Ebook Delusions - Understanding the Un- understandable: Part 2ell. Thus, several of Connell’s (1958) patients had auditory and other hallucinations, and formal thought disorder was also evident in some of the cases he described in detail. Subsequent studies have made it clear that the entire clinical picture of schizophrenia can be reproduced, including negati Ebook Delusions - Understanding the Un- understandable: Part 2ve symptoms and catatonic phenomena up to and including stupor (Tatetsu, 1964; Chen et al., 2003). Nevertheless, there is probably some truth to the wEbook Delusions - Understanding the Un- understandable: Part 2
idely quoted view that stimulant-induced psychosis tends to take the form of a paranoid-hallucinatory state. For example, in their series of 174 methaThe Neurochemical ConnectionAs psychology struggled to make headway with delusions, another discipline close to the heart of psychiatry, pharmacology, Ebook Delusions - Understanding the Un- understandable: Part 2only around 5 per cent showed disorganized speech (although a further 27 per cent were described as having speech that was odd).Another problem for the model is that the immediate effects of stimulant drugs are euphoria and increased alertness; psychosis is something that occurs later and then not i Ebook Delusions - Understanding the Un- understandable: Part 2n everyone. How much later and with what frequency has never been satisfactorily established. Thirty of Connell’s 42 cases were using amphetamine reguEbook Delusions - Understanding the Un- understandable: Part 2
larly, but 8 developed psychosis after taking a single large dose of the drug. In Chen et al.’s (2003) study of methamphetamine users, less than half The Neurochemical ConnectionAs psychology struggled to make headway with delusions, another discipline close to the heart of psychiatry, pharmacology, Ebook Delusions - Understanding the Un- understandable: Part 2y extensive. ( I his is also the present author’s experience: he and a colleague once administered the lifetime version of the PSE to around 30 regular stimulant drug users. Although some gave clear retrospective descriptions of psychotic symptoms, it was striking how many had never experienced anyt Ebook Delusions - Understanding the Un- understandable: Part 2hing more than vague concerns that the police might be watching them, despite taking the drug in positively veterinary doses.) In an experimental studEbook Delusions - Understanding the Un- understandable: Part 2
y, Griffith Ct al. (1968) administered hourly doses of amphetamine to four abstinent users and found that they all developed paranoid and referential The Neurochemical ConnectionAs psychology struggled to make headway with delusions, another discipline close to the heart of psychiatry, pharmacology, Ebook Delusions - Understanding the Un- understandable: Part 2sychotic states, with the other two showing only at most questionable symptoms, for example becoming hostile and suspicious, or hearing their names being called.Virtually all the evidence points to the psychosis-inducing effects of stimulants being due to an effect on dopamine. As a group, these dru Ebook Delusions - Understanding the Un- understandable: Part 2gs act to increase the synaptic release of theChapter 6: The Neurochemicamonoamine neurotransmitters dopamine and noradrenalin, which is achieved by aEbook Delusions - Understanding the Un- understandable: Part 2
variety of mechanisms (Iversen, 2008a). However, most if not all of the effects in animals appear to be due Io an action on the former transmitter; iThe Neurochemical ConnectionAs psychology struggled to make headway with delusions, another discipline close to the heart of psychiatry, pharmacology, Ebook Delusions - Understanding the Un- understandable: Part 2ptoms are a well-documented side effect of 1-DOPA and other dopamine agonist drugs used in Parkinsons disease (Cummings, 1991). In contrast, despite occasional claims to the contrary (Yamamoto & 1 lornykiewicz, 2004), psychosis is not a recognized complication of treatment with tricyclic antidepress Ebook Delusions - Understanding the Un- understandable: Part 2ants, which block re-uptake of noradrenalin, nor any of a range of other drugs with noradrenergic actions.Many stimulant drugs also lead to increasedEbook Delusions - Understanding the Un- understandable: Part 2
synaptic release of a third monoamine neurotransmitter, serotonin. This also seems to be a red herring, however, since methylphenidate (Ritalin) is weThe Neurochemical ConnectionAs psychology struggled to make headway with delusions, another discipline close to the heart of psychiatry, pharmacology, Ebook Delusions - Understanding the Un- understandable: Part 2even though it has minimal effects on serotonin neurons (Kuczenski & Segal, 1997; see also Iversen, 2008a).What Does Dopamine Do in the Brain?Of a small number of central nervous system pathways that use dopamine, the only one relevant to behaviour is the so-called mesotelencephalic dopamine system. Ebook Delusions - Understanding the Un- understandable: Part 2 As described by Bjorklund and Dunnett (2007) in the most recent summary of their and others’ 30 plus years work in the field, this pathway arises froEbook Delusions - Understanding the Un- understandable: Part 2
m a group of cells in the midbrain, including A9 in the substantia nigra bilaterally and A10 in the midline ventral tegmental area between them; thereThe Neurochemical ConnectionAs psychology struggled to make headway with delusions, another discipline close to the heart of psychiatry, pharmacology, Ebook Delusions - Understanding the Un- understandable: Part 2hat the whole group of cells forms a continuous sheet. If there is a meaningful anatomical division, it is between a dorsal tier (containing cells from all three groups) and a ventral tier (containing representatives only of A9 and A10).The total number of dopamine neurons in A8, A9 and A10 is small Ebook Delusions - Understanding the Un- understandable: Part 2: 40,000-45,000 in rats, 160,000-320,000 in monkeysand 400,000-600,000 in humans (Bjorklund & Dunnett, 2007). However, the area they innervate is wideEbook Delusions - Understanding the Un- understandable: Part 2
: it includes importantly the basal ganglia, specifically the caudate nucleus and pulamen (jointly referred to as the striatum), and the ventral extenGọi ngay
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