761:(NMDARs), in addition to dopamine in the etiology of schizophrenia. Abnormal NMDAR transmission may alter communication between cortical regions and the striatum. Mice with only 5% of the normal levels of NMDAR's expressed schizophrenic-like behaviors seen in animal models of schizophrenia while mice with 100% of NMDAR's behaved normally. Schizophrenic behavior in low NMDAR mice has been effectively treated with antipsychotics that lower dopamine. NMDAR's and dopamine receptors in the prefrontal cortex are associated with the cognitive impairments and working memory deficits commonly seen in schizophrenia. Rats that have been given a NMDAR antagonist exhibit a significant decrease in performance on cognitive tasks. Rats given a dopamine antagonist (antipsychotic) experience a reversal of the negative effects of the NMDAR antagonist. Glutamate imbalances appear to cause abnormal functioning in dopamine. When levels of glutamate are low dopamine is overactive and results in the expression schizophrenic symptoms.
605:, or specific variants of genes, that code for mechanisms involved in dopamine function, which may be more prevalent in people experiencing psychosis or diagnosed with schizophrenia. Advanced technology has led to the possibility of performing Genome-Wide Association (GWA) studies. These studies identify frequently seen single nucleotide polymorphisms (SNP) that are associated with common, yet complex disorders. Genetic variants found due to GWA studies may offer insight concerning impairments in dopaminergic function
193:, which comprehends language but does not create it. Note that variation in distribution is observed within individuals, so abnormalities of this characteristic likely play a significant role in all psychological illnesses. Individual alterations are produced by differences within glutamatergic pathways within the limbic system, which are also implicated in other psychotic syndromes. Among the alterations of both synaptic and global structure, the most significant abnormalities are observed in the
213:(LTP) from the abnormally strong signals transversely across the brain. This, combined with a relative deficit in GABAergic input to Wernicke's area, shifts the balance of bilateral communication across the corpus callosum posteriorly. Through this mechanism, hemispherical communication becomes highly shifted towards the left/dominant posterior. As such, spontaneous language from Broca's can propagate through the limbic system to the tertiary
431:
suggestions are made for improving future longitudinal neuroimaging studies of treatment effects in schizophrenia A recent review of imaging studies in schizophrenia shows confidence in the techniques, while discussing such operator error. In 2007 one report said, "During the last decade, results of brain imaging studies by use of PET and SPECT in schizophrenic patients showed a clear dysregulation of the dopaminergic system."
25:
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an explanation. Some migrants who have had adverse experiences in their host country, such as racism, xenophobia, and poor living conditions, were found to have high stress levels, which increased dopaminergic neurotransmission. This increase in dopaminergic neurotransmission can be seen in the striatum and amygdala, both of which are areas in the brain that process aversive stimuli.
624:
While genetics play an important role in the occurrence of schizophrenia, other biopsychosocial factors must also be taken into consideration. While focusing on the risk of schizophrenia in second generation migrants, Hennsler and colleagues relay that the dopamine hypothesis of schizophrenia may be
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receptors in drug-free patients with schizophrenia, but the degree of overlap between patients and controls makes it unlikely that this is clinically meaningful. While the review by
Laruelle acknowledged more sites were found using methylspiperone, it discussed the theoretical reasons behind such an
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agonism can facilitate the self-reinforcing, illogical patterns of language found in such patients. In schizophrenia, this feedback loop has progressed, which produced the widespread neural atrophy characteristic of this disease. Patients on neuroleptic or antipsychotic medication have significantly
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McEvoy JP, Lieberman JA, Stroup TS, Davis SM, Meltzer HY, Rosenheck RA, Swartz MS, Perkins DO, Keefe RS, Davis CE, Severe J, Hsiao JK (April 2006). "Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical
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increase the levels of dopamine in the synaptic space and exacerbate acute psychotic episodes in schizophrenic patients. It should be noted, however, that this does not occur when patients with schizophrenia are not in an acute psychotic state. In fact, low-dose amphetamine (10mg) has been shown to
220:
In addition, significant cortical grey matter volume reductions are observed in this disorder. Specifically, the right hemisphere atrophies more, while both sides show a marked decrease in frontal and posterior volume. This indicates that abnormal synaptic plasticity occurs, where certain feedback
430:
receptor density compared to controls. Comparable findings in longitudinal studies show: " Particular emphasis is given to methodological limitations in the existing literature, including lack of reliability data, clinical heterogeneity among studies, and inadequate study designs and statistic,"
237:
receptor, leading to dopamine release in the structures where 5-HT2C is expressed; striatum, prefrontal cortex, nucleus accumbens, amygdala, hippocampus (all structures indicated in this disease), and currently thought to be a reason why antipsychotics with 5HT2C antagonistic properties improves
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does not change." (In another place Seeman has said methylspiperone possibly binds with dimers) With this difference in measurement technique in mind, the above-mentioned meta-analysis uses results from 10 different ligands. Exaggerated ligand binding results such as SDZ GLC 756 (as used in the
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receptors, which may be related to negative symptoms and cognitive impairment. The overactivity and underactivity in these different regions may be linked, and may not be due to a primary dysfunction of dopamine systems but to more general neurodevelopmental issues that precede them. Increased
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Some animal models of psychosis are similar to those for addiction – displaying increased locomotor activity. For those female animals with previous sexual experience, amphetamine stimulation happens faster than for virgins. There is no study on male equivalent because the studies are meant to
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receptor number may reflect presynaptic factors such as increased endogenous dopamine levels (16). In either case, our findings support the hypothesis that dopamine receptor abnormalities are present in untreated schizophrenic patients." (The experiment used 3-N-methylspiperone – the same as
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Wong DF, Wagner HN, Tune LE, Dannals RF, Pearlson GD, Links JM, Tamminga CA, Broussolle EP, Ravert HT, Wilson AA, Toung JK, Malat J, Williams JA, O'Tuama LA, Snyder SH, Kuhar MJ, Gjedde A (December 1986). "Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive
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in controlling psychosis, but more effective in controlling the negative symptoms, despite the fact that they have lower affinity for dopamine receptors than for various other neurotransmitter receptors. More recent work, however, has shown that atypical antipsychotic drugs such as
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receptors blocked by antipsychotic drugs, but showed little reduction in their psychoses. This primarily occurs in patients who have had the psychosis for ten to thirty years. At least 90-95% of first-episode patients, however, respond to antipsychotics at low doses and do so with
286:, the common target for all antipsychotics, typical or atypical. Combined with less inhibitory signalling from the thalamus and other basal ganglic structures, from atrophy the abnormal activation of the cingulate cortex, specifically around Broca's and Wernicke's areas, abnormal D
775:
suggested in a review of 2018 that in many cases of psychosis, including schizophrenia, three interconnected networks based on dopamine, serotonin, and glutamate - each on its own or in various combinations - contributed to an overexcitation of dopamine D2 receptors in the
221:
loops become so potentiated, others receive little glutaminergic transmission. This is a direct result of the abnormal dopaminergic input to the striatum, thus (indirectly) disinhibition of thalamic activity. The excitatory nature of dopaminergic transmission means the
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less atrophy within these crucial areas. As such, early medical intervention is crucial in preventing the advancement of these profound deficits in bilateral communication at the root of all psychotic disorders. Advanced, chronic schizophrenia can not respond even to
670:
Furthermore, although dopamine-inhibiting medications modify dopamine levels within minutes, the associated improvement in patient symptoms is usually not visible for at least several days, suggesting that dopamine may be indirectly responsible for the illness.
537:
dopamine receptors are substantially increased in schizophrenic patients who have never been treated with neuroleptic drugs raises the possibility that dopamine receptors are involved in the schizophrenic disease process itself. Alternatively, the increased
152:
effects. The theory, however, does not posit dopamine overabundance as a complete explanation for schizophrenia. Rather, the overactivation of D2 receptors, specifically, is one effect of the global chemical synaptic dysregulation observed in this disorder.
734:. It appears, therefore, that there are multiple causes for psychosis and schizophrenia, including gene mutations and anatomical lesions. Many argue that other theories concerning the cause of schizophrenia may be more reliable in some cases, such as the
320:
improve auditory discrimination training in patients with schizophrenia. Repeated, high doses of amphetamine are neurotoxic to dopamine neurons, and can cause a psychotic syndrome resembling schizophrenia. Similarly, those treated with dopamine enhancing
567:
dopamine sensitivity may be a common final pathway. Gründer and
Cumming assert that of those living with schizophrenia and other dopaminergic related illnesses, up to 25% of these patients may appear to have dopaminergic markers within the normal range.
470:
ratio, and the 'cooperativity' model. Cooperativity is a chemical function in the study of enzymes. Dopamine receptors interact with their own kind, or other receptors to form higher order receptors such as dimers, via the mechanism of cooperativity.
719:) receptors, are known to cause psychosis at least somewhat resembling schizophrenia, further suggesting that psychosis and perhaps schizophrenia cannot fully be explained in terms of dopamine function, but may also involve other neurotransmitters.
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receptors in the high-affinity state for dopamine. This latter work implies that there are multiple genes and neuronal pathways that can lead to psychosis and that all these multiple psychosis pathways converge via the high-affinity state of the
2176:
Seeman P, Guan HC, Civelli O, Van Tol HH, Sunahara RK, Niznik HB (October 1992). "The cloned dopamine D2 receptor reveals different densities for dopamine receptor antagonist ligands. Implications for human brain positron emission tomography".
2488:""Amphetamine psychosis has been proposed as a model for some features of schizophrenia... This model of amphetamine sensitization has also been adopted as a paradigm for researchers interested in the addictive powers of drugs of abuse.""
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Williams J, Spurlock G, McGuffin P, Mallet J, Nöthen MM, Gill M, Aschauer H, Nylander PO, Macciardi F, Owen MJ (May 1996). "Association between schizophrenia and T102C polymorphism of the 5-hydroxytryptamine type 2a-receptor gene".
2744:
Seeman P, Guan HC, Nobrega J, Jiwa D, Markstein R, Balk JH, Picetti R, Borrelli E, Van Tol HH (February 1997). "Dopamine D2-like sites in schizophrenia, but not in
Alzheimer's, Huntington's, or control brains, for benzquinoline".
2062:
Seeman P, Schwarz J, Chen JF, Szechtman H, Perreault M, McKnight GS, Roder JC, Quirion R, Boksa P, Srivastava LK, Yanai K, Weinshenker D, Sumiyoshi T (September 2006). "Psychosis pathways converge via D2high dopamine receptors".
2400:
Cropley VL, Innis RB, Nathan PJ, Brown AK, Sangare JL, Lerner A, Ryu YH, Sprague KE, Pike VW, Fujita M (June 2008). "Small effect of dopamine release and no effect of dopamine depletion on fallypride binding in healthy humans".
295:, regarded as the most effective antipsychotic, as such, a cure for highly advanced schizophrenia is likely impossible through the use of any modern antipsychotics, so the value of early intervention cannot be stressed enough.
699:
receptors, meaning serotonin abnormalities are also involved in the complex constellation of neurologic factors predisposing one to the self reinforcing language-based psychological deficits found in all forms of psychosis.
348:) than non-psychotic individuals. However, the acute effects of dopamine stimulants include euphoria, alertness and over-confidence; these symptoms are more reminiscent of mania than schizophrenia. Since the 2000s, several
637:
scanning to examine drug action in the brain of living patients) challenged the view that the amount of dopamine blocking was correlated with clinical benefit. These studies showed that some patients had over 90% of their
399:
dopamine receptors seemed to be inversely proportional to their therapeutic dose. This correlation, suggesting that receptor binding is causally related to therapeutic potency, was reported by two laboratories in 1976.
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receptors to be elevated in the striata of patients with schizophrenia". However, the authors were concerned the effect of medication may not have been fully accounted for. The study introduced an experiment by
328:
can experience psychotic side effects mimicking the symptoms of schizophrenia. Up to 75% of patients with schizophrenia have increased signs and symptoms of their psychosis upon challenge with moderate doses of
277:), or making brain lesions in newborn animals, or delivering animals abnormally by Caesarian section, all induce a marked behavioural supersensitivity to dopamine and a marked rise in the number of dopamine D
217:. This retrograde signaling to the temporal lobes that results in the parietal lobes not recognizing it as internal results in the auditory hallucinations typical of chronic schizophrenia.
2444:
Abi-Dargham A, van de
Giessen E, Slifstein M, Kegeles LS, Laruelle M (June 2009). "Baseline and amphetamine-stimulated dopamine activity are related in drug-naïve schizophrenic subjects".
233:
receptor regulates cortical input to the basal ganglia and many typical and atypical antipsychotics are antagonists at this receptor. Several antipsychotics are also antagonists at the
745:
has argued that drug companies have inappropriately promoted the dopamine hypothesis of schizophrenia as a deliberate and calculated simplification for the benefit of drug marketing.
722:
Similarly, there is now evidence to suggest there may be a number of functional and structural anomalies in the brains of some people diagnosed with schizophrenia, such as changes in
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function and having somewhat less of a dopamine blocking effect. In addition, dopamine pathway dysfunction has not been reliably shown to correlate with symptom onset or severity.
2514:"Sexual behavior induction of c-Fos in the nucleus accumbens and amphetamine-stimulated locomotor activity are sensitized by previous sexual experience in female Syrian hamsters"
42:
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receptor between these areas and the rest of the brain may also be implicated in schizophrenia, specifically in the acute phase. A relative excess of these receptors within the
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increase (including the monomer-dimer equilibrium) and called for more work to be done to 'characterise' the differences. In addition, newer antipsychotic medication (called
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Vernaleken I, Eickhoff SB, Veselinovic T, Klomp M, Spreckelmeyer K, Schäfer W, Gründer G (2008). "Elevated D2/3-receptor availability in schizophrenia: A fallypride study".
1408:
Whitford TJ, Kubicki M, Schneiderman JS, O'Donnell LJ, King R, Alvarado JL, Khan U, Markant D, Nestor PG, Niznikiewicz M, McCarley RW, Westin CF, Shenton ME (July 2010).
1504:
Swerdlow, Neal R.; Tarasenko, Melissa; Bhakta, Savita G.; Talledo, Jo; Alvarez, Alexis I.; Hughes, Erica L.; Rana, Brinda; Vinogradov, Sophia; Light, Gregory A. (2016).
937:
McIntosh AM, Muñoz
Maniega S, Lymer GK, McKirdy J, Hall J, Sussmann JE, et al. (December 2008). "White matter tractography in bipolar disorder and schizophrenia".
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Another finding is a six-fold excess of binding sites insensitive to the testing agent, raclopride; Seeman said this increase was probably due to the increase in D
1324:
Gur RE, Maany V, Mozley PD, Swanson C, Bilker W, Gur RC (December 1998). "Subcortical MRI volumes in neuroleptic-naive and treated patients with schizophrenia".
983:
Haznedar MM, Buchsbaum MS, Hazlett EA, Shihabuddin L, New A, Siever LJ (December 2004). "Cingulate gyrus volume and metabolism in the schizophrenia spectrum".
201:. The combination of these creates a profound dissymmetry of prefrontal inhibitory signaling, shifted positively towards the dominant side. Eventually, the
418:
to chronic antipsychotic treatment. Compared to the success of postmortem studies in finding profound changes of dopamine receptors, imaging studies using
344:
studies have also shown that, after taking amphetamine, patients diagnosed with schizophrenia show greater levels of dopamine release (particularly in the
1175:
Harvey I, Ron MA, Du Boulay G, Wicks D, Lewis SW, Murray RM (August 1993). "Reduction of cortical volume in schizophrenia on magnetic resonance imaging".
1827:
Davis CE, Jeste DV, Eyler LT (October 2005). "Review of longitudinal functional neuroimaging studies of drug treatments in patients with schizophrenia".
2314:
Abi-Dargham A, Rodenhiser J, Printz D, Zea-Ponce Y, Gil R, Kegeles LS, Weiss R, Cooper TB, Mann JJ, Van
Heertum RL, Gorman JM, Laruelle M (July 2000).
3260:"NMDA receptor antagonists impair prefrontal cortex function as assessed via spatial delayed alternation performance in rats: modulation by dopamine"
2024:
Maas JW, Contreras SA, Seleshi E, Bowden CL (June 1988). "Dopamine metabolism and disposition in schizophrenic patients. Studies using debrisoquin".
1725:
Creese I, Burt DR, Snyder SH (April 1976). "Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs".
89:
61:
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Berg KA, Harvey JA, Spampinato U, Clarke WP (December 2005). "Physiological relevance of constitutive activity of 5-HT2A and 5-HT2C receptors".
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receptors in people with schizophrenia and showing a correlation between this magnitude and the result of amphetamine stimulation experiments.
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794:
735:
222:
1028:"Evidence for plasticity in white-matter tracts of patients with chronic Broca's aphasia undergoing intense intonation-based speech therapy"
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or other dopamine-like compounds, all given at doses at which control normal volunteers do not have any psychologically disturbing effects.
68:
1981:
Stone JM, Morrison PD, Pilowsky LS (June 2007). "Glutamate and dopamine dysregulation in schizophrenia--a synthesis and selective review".
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Levitzki A, Schlessinger J (December 1974). "Cooperativity in associating proteins. Monomer-dimer equilibrium coupled to ligand binding".
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827:
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sought to clarify whether the increase was solely due to medication by using drug-naive people with schizophrenia: "The finding that D
75:
3307:
Javitt DC (2007). "Glutamate and schizophrenia: phencyclidine, N-methyl-D-aspartate receptors, and dopamine-glutamate interactions".
2758:
1911:
Meisenzahl EM, Schmitt GJ, Scheuerecker J, Möller HJ (August 2007). "The role of dopamine for the pathophysiology of schizophrenia".
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2999:
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receptors involved in the schizophrenic process and more dopamine. Since then another study has shown such elevated percentages in D
108:
387:) and reduce positive psychotic symptoms. This observation was subsequently extended to other antipsychotic drug classes, such as
408:
57:
843:
Heinz A (March 2002). "Dopaminergic dysfunction in alcoholism and schizophrenia--psychopathological and behavioral correlates".
395:. The link was strengthened by experiments in the 1970s which suggested that the binding affinity of antipsychotic drugs for D
46:
3354:"Beyond the dopamine hypothesis of schizophrenia to three neural networks of psychosis: dopamine, serotonin, and glutamate"
2151:
2613:
Abi-Dargham A, Moore H (October 2003). "Prefrontal DA transmission at D1 receptors and the pathology of schizophrenia".
634:
423:
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may contribute to the 'positive symptoms' of schizophrenia, whereas problems concerning dopamine function within the
1369:"A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia"
742:
487:
1409:
82:
35:
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Seeman P, Lee T, Chau-Wong M, Wong K (June 1976). "Antipsychotic drug doses and neuroleptic/dopamine receptors".
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dopamine receptor. More specifically, "an increase in monomers, may be one basis for dopamine supersensitivity".
404:
262:
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Jacobs D, Silverstone T (May 1986). "Dextroamphetamine-induced arousal in human subjects as a model for mania".
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receptor has been attempted by a significant minority. Radioligand imaging measurements involve the monomer and
3186:
242:. More research is needed to explain the exact nature of the altered chemical transmission in this disorder.
1410:"Corpus callosum abnormalities and their association with psychotic symptoms in patients with schizophrenia"
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Nakamura M, McCarley RW, Kubicki M, Dickey CC, Niznikiewicz MA, Voglmaier MM, et al. (September 2005).
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It is still thought that dopamine mesolimbic pathways may be hyperactive, resulting in hyperstimulation of D
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receptors is brain-wide (using a different ligand, which did not need dopamine depletion). In a 2009 study,
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341:
1954:
Laruelle M (September 1998). "Imaging dopamine transmission in schizophrenia. A review and meta-analysis".
2895:"New Genetic Findings in Schizophrenia: Is there Still Room for the Dopamine Hypothesis of Schizophrenia?"
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325:
210:
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Recent evidence on a variety of animal models of psychosis, such as sensitization of animal behaviour by
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Lieberman JA, Kane JM, Alvir J (1987). "Provocative tests with psychostimulant drugs in schizophrenia".
679:
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353:
1085:"Fronto-temporal disconnectivity in schizotypal personality disorder: a diffusion tensor imaging study"
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However, there was controversy and conflicting findings over whether postmortem findings resulted from
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Seeman P, Weinshenker D, Quirion R, Srivastava LK, Bhardwaj SK, Grandy DK, et al. (March 2005).
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380:
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Seeman P (2008). "All
Psychotic Roads Lead to Increased Dopamine D2High Receptors: A Perspective".
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Seeman P, Guan HC, Van Tol HH (September 1993). "Dopamine D4 receptors elevated in schizophrenia".
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Even in 1986 the effect of antipsychotics on receptor measurement was controversial. An article in
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also regulates monoamine neurotransmitters, including dopaminergic transmission. Specifically, the
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1506:"Amphetamine Enhances Gains in Auditory Discrimination Training in Adult Schizophrenia Patients"
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Further experiments, conducted as new methods were developed (particularly the ability to use
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Recent findings from meta-analyses suggest that there may be a small elevation in dopamine D
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Zakzanis KK, Hansen KT (August 1998). "Dopamine D2 densities and the schizophrenic brain".
1264:"Dopamine supersensitivity correlates with D2High states, implying many paths to psychosis"
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Weinstein JJ, Chohan MO, Slifstein M, Kegeles LS, Moore H, Abi-Dargham A (January 2017).
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methods in drug naive patients have generally failed to find any difference in dopamine D
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2705:
2575:
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1738:
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3219:"Mice with reduced NMDA receptor expression display behaviors related to schizophrenia"
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et al. in which it was shown medication-free live people with schizophrenia had more D
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Richtand NM, Welge JA, Logue AD, Keck PE, Strakowski SM, McNamara RK (August 2007).
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Henssler J, Brandt L, Müller M, Liu S, Montag C, Sterzer P, Heinz A (April 2020).
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receptors and positive symptoms. There is also growing evidence that, conversely,
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Influence Behavior. Englewood Cliffs: Prentice Hall, 1996.
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According to Seeman, "...Numerous postmortem studies have consistently revealed D
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738:, GABA hypothesis, dysconnection hypothesis, and Bayesian inference hypothesis.
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Proceedings of the
National Academy of Sciences of the United States of America
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Proceedings of the
National Academy of Sciences of the United States of America
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Proceedings of the National Academy of Sciences of the United States of America
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1994:
518:. confirmed the findings of her previous study regarding increased baseline D
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Valton V, Romaniuk L, Douglas Steele J, Lawrie S, Seriès P (December 2017).
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2316:"Increased baseline occupancy of D2 receptors by dopamine in schizophrenia"
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2002:
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levels correlate trendwise to symptoms severity. During the application of
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receptor. All of these drugs exhibit inverse agonistic effects at the 5-HT
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Gründer G, Cumming P (2016). "The Dopamine Hypothesis of Schizophrenia".
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10.1002/(SICI)1098-2396(199702)25:2<137::AID-SYN4>3.0.CO;2-D
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studies have confirmed an altered synthesis capacity of dopamine in the
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figure) were explained by reference to this monomer-dimer equilibrium.
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sites rises, reflecting an increase in monomers, while the density of
316:
144:. The model draws evidence from the observation that a large number of
2946:"Migration and schizophrenia: meta-analysis and explanatory framework"
2414:
2076:
407:; the therapeutic effect likely occurs through dopamine modulation by
189:, which can produce illogical language, has an abnormal connection to
2713:
1797:
234:
230:
174:
3022:"Dopamine and serotonin receptor binding and antipsychotic efficacy"
2858:
Seeman P, Van Tol HH (July 1994). "Dopamine receptor pharmacology".
1220:"Schizophrenia: A Sub cortical Neurotransmitter Imbalance Syndrome?"
562:
might be hypoactive (underactive), resulting in hypostimulation of D
419:
2945:
1872:"Laterality in functional brain imaging studies of schizophrenia"
483:
sites remains the same, indicating that the total population of D
3162:"Comprehensive review: Computational modelling of schizophrenia"
716:
618:
610:
602:
270:
258:
226:
609:
Dopamine-related genes linked to psychosis in this way include
674:
Similarly, the second generation of antipsychotic drugs – the
18:
526:
explain why females experience addiction earlier than males.
161:
Some researchers have suggested that dopamine systems in the
3217:
Mohn AR, Gainetdinov RR, Caron MG, Koller BH (August 1999).
2119:
Fuxe K, Marcellino D, Guidolin D, Woods A, Agnati L (2009).
225:
is inextricably intertwined with this altered functioning.
1678:"Pathway-Specific Dopamine Abnormalities in Schizophrenia"
462:
Giving a more precise explanation of this discrepancy in D
2950:
European Archives of Psychiatry and Clinical Neuroscience
1132:
Friston KJ (March 1998). "The disconnection hypothesis".
707:
is now also thought to be associated with schizophrenia.
574:
monomers. Such an increase in monomers may occur via the
443:
medication) can be as potent as older medication (called
691:
bind and unbind rapidly and repeatedly to the dopamine D
475:
has said: "In schizophrenia, therefore, the density of
403:
People with Schizophrenia appear to have a high rate of
169:
may be responsible for the 'negative symptoms', such as
765:
Combined networks of dopamine, serotonin, and glutamate
586:, the supersensitive and lowsensitivity states of the D
886:
Mitra S, Mahintamani T, Kavoor AR, Nizamie SH (2016).
1367:
Arinami T, Gao M, Hamaguchi H, Toru M (April 1997).
547:monomers and binding was double that of controls.)
49:. Unsourced material may be challenged and removed.
3187:20.500.11820/4aef208d-7da5-4055-86f4-27cbcaed2bab
3143:"Daring to Think Differently about Schizophrenia"
2257:"Schizophrenia: more dopamine, more D2 receptors"
1592:Curran C, Byrappa N, McBride A (September 2004).
177:. Abnormal expression, thus distribution of the D
2742:For a discussion of opposing studies see p 143:
2893:Nieratschker V, Nöthen MM, Rietschel M (2010).
2121:"Chapter 10 – Dopamine Receptor Oligermization"
205:becomes atrophied towards the anterior, due to
2825:Clinical Schizophrenia & Related Psychoses
678:– were found to be just as effective as older
594:Genetic and other biopsychosocial risk factors
1026:Schlaug G, Marchina S, Norton A (July 2009).
8:
356:demonstrating a dopaminergic dysregulation.
3413:"The Dopamine Hypothesis of Schizophrenia"
2105:Safra, JE (Chairman) 2005 'Cooperativity'
1032:Annals of the New York Academy of Sciences
978:
976:
3465:
3372:
3283:
3234:
3185:
3037:
2920:
2910:
2537:
2341:
2331:
2290:
2280:
2152:"Dopamine Receptors: Clinical Correlates"
2057:
2055:
1956:The Quarterly Journal of Nuclear Medicine
1887:
1701:
1609:
1525:
1436:
1384:
1297:
1287:
1235:
1108:
1059:
913:
903:
601:evidence has suggested that there may be
109:Learn how and when to remove this message
2146:
2144:
1594:"Stimulant psychosis: systematic review"
711:(also known as PCP or "Angel Dust") and
629:Evidence against the dopamine hypothesis
459:, this correlation becomes significant.
1257:
1255:
810:
647:occupancy of 60-70%. The antipsychotic
3166:Neuroscience and Biobehavioral Reviews
1319:
1317:
58:"Dopamine hypothesis of schizophrenia"
3258:Verma A, Moghaddam B (January 1996).
2654:
2652:
1889:10.1093/oxfordjournals.schbul.a033361
795:Glutamate hypothesis of schizophrenia
753:Research has shown the importance of
223:glutamate hypothesis of schizophrenia
7:
3309:International Review of Neurobiology
2899:Frontiers in Behavioral Neuroscience
2512:Bradley KC, Meisel RL (March 2001).
2038:10.1001/archpsyc.1988.01800300049005
888:"Negative symptoms in schizophrenia"
655:receptors, but this drug is both an
578:mechanism which is responsible for D
304:Evidence for the dopamine hypothesis
123:dopamine hypothesis of schizophrenia
47:adding citations to reliable sources
3276:10.1523/JNEUROSCI.16-01-00373.1996
3107:Trends in Pharmacological Sciences
2860:Trends in Pharmacological Sciences
2669:10.1016/b978-0-12-801829-3.00015-x
2530:10.1523/JNEUROSCI.21-06-02123.2001
1913:International Review of Psychiatry
1463:The American Journal of Psychiatry
1326:The American Journal of Psychiatry
822:(11th ed.). Boston: Pearson.
375:dopamine binding (particularly at
14:
2661:The Neurobiology of Schizophrenia
1598:The British Journal of Psychiatry
1218:Carlsson M.; Carlsson A. (1990).
715:, both of which block glutamate (
447:medication) while also affecting
409:nicotinic acetylcholine receptors
2379:10.1016/j.neuroimage.2008.04.113
2179:European Journal of Pharmacology
2107:The New Encyclopaedia Britannica
1052:10.1111/j.1749-6632.2009.04587.x
703:The excitatory neurotransmitter
257:, or by removing various genes (
127:dopamine hypothesis of psychosis
23:
3178:10.1016/j.neubiorev.2017.08.022
3141:Berenson A (24 February 2008).
2255:Seeman P, Kapur S (July 2000).
1694:10.1016/j.biopsych.2016.03.2104
137:to a disturbed and hyperactive
129:is a model that attributes the
34:needs additional citations for
2663:. Elsevier. pp. 109–124.
2458:10.1016/j.biopsych.2008.12.007
2026:Archives of General Psychiatry
1429:10.1016/j.biopsych.2010.03.025
1101:10.1016/j.biopsych.2005.04.016
951:10.1016/j.biopsych.2008.07.026
759:N-methyl-D-aspartate receptors
1:
3485:Neuroscience of schizophrenia
3321:10.1016/S0074-7742(06)78003-5
3236:10.1016/S0092-8674(00)81972-8
3076:10.1016/s0140-6736(96)90939-3
2226:10.1016/s0920-9964(98)00041-3
1983:Journal of Psychopharmacology
1146:10.1016/s0920-9964(97)00140-0
892:Industrial Psychiatry Journal
857:10.1016/s0924-9338(02)00628-4
543:mentioned by Seeman detects D
405:self-medication with nicotine
253:(PCP, Angel Dust), or excess
3440:"Dopamine and Schizophrenia"
3417:Schizophrenia Research Forum
2872:10.1016/0165-6147(94)90323-9
2191:10.1016/0922-4106(92)90121-B
1841:10.1016/j.schres.2005.05.009
997:10.1016/j.schres.2004.02.025
558:dopamine projections to the
359:A group of drugs called the
3264:The Journal of Neuroscience
2518:The Journal of Neuroscience
2109:, Vol 3, Micropaedia, p 666
749:Relationship with glutamate
3501:
3119:10.1016/j.tips.2005.10.008
2962:10.1007/s00406-019-01028-7
2154:. Acnp.org. Archived from
1475:10.1176/appi.ajp.163.4.600
1461:antipsychotic treatment".
3467:10.4249/scholarpedia.3634
3374:10.1017/S1092852918001013
1925:10.1080/09540260701502468
1647:10.1017/S0033291700009132
1189:10.1017/S003329170002537X
2912:10.3389/fnbeh.2010.00023
2627:10.1177/1073858403252674
1995:10.1177/0269881106073126
1373:Human Molecular Genetics
3026:Neuropsychopharmacology
2584:10.1126/science.2878495
2333:10.1073/pnas.97.14.8104
2282:10.1073/pnas.97.14.7673
1870:Gur RE, Chin S (1999).
1338:10.1176/ajp.155.12.1711
1289:10.1073/pnas.0409766102
1237:10.1093/schbul/16.3.425
790:Causes of schizophrenia
676:atypical antipsychotics
342:functional neuroimaging
3039:10.1038/sj.npp.1301305
2214:Schizophrenia Research
1876:Schizophrenia Bulletin
1829:Schizophrenia Research
1635:Psychological Medicine
1510:Schizophrenia Bulletin
1224:Schizophrenia Bulletin
1177:Psychological Medicine
1134:Schizophrenia Research
985:Schizophrenia Research
820:Physiology of behavior
680:typical antipsychotics
651:occupies over 90% of D
441:atypical antipsychotic
211:long-term potentiation
2446:Biological Psychiatry
1682:Biological Psychiatry
1611:10.1192/bjp.185.3.196
1518:10.1093/schbul/sbw148
1417:Biological Psychiatry
1089:Biological Psychiatry
939:Biological Psychiatry
905:10.4103/ipj.ipj_30_15
445:typical antipsychotic
150:receptor antagonistic
2123:. In Neve KA (ed.).
1747:10.1126/science.3854
770:Psychopharmacologist
736:glutamate hypothesis
556:mesocortical pathway
371:, has been found to
354:nigrostriatal system
207:long-term depression
167:mesocortical pathway
43:improve this article
3458:2007SchpJ...2.3634S
2802:10.1021/bi00722a026
2706:1993Natur.365..441S
2576:1986Sci...234.1558W
2273:2000PNAS...97.7673S
1790:1976Natur.261..717S
1739:1976Sci...192..481C
1386:10.1093/hmg/6.4.577
1280:2005PNAS..102.3513S
1044:2009NYASA1169..385S
845:European Psychiatry
818:Carlson NR (2013).
755:glutamate receptors
488:monomers and dimers
326:Parkinson's disease
195:uncinate fasciculus
142:signal transduction
2837:10.3371/CSRP.1.4.7
2615:The Neuroscientist
2125:Dopamine Receptors
1563:10.1007/BF00216006
1551:Psychopharmacology
501:Anissa Abi-Dargham
385:dopamine receptors
163:mesolimbic pathway
3352:Stahl SM (2018).
2678:978-0-12-801829-3
2570:(4783): 1558–63.
2562:schizophrenics".
2415:10.1002/syn.20506
2077:10.1002/syn.20303
800:Latent inhibition
560:prefrontal cortex
240:negative symptoms
131:positive symptoms
119:
118:
111:
93:
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1798:10.1038/261717a0
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883:
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778:ventral striatum
773:Stephen M. Stahl
199:cingulate cortex
114:
107:
103:
100:
94:
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16:Scientific model
3500:
3499:
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3400:"CNS Spectrums"
3398:
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2737:
2700:(6445): 441–5.
2691:
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2686:
2679:
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2657:
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2607:
2560:
2559:
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2100:
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1953:
1952:
1948:
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1784:(5562): 717–9.
1775:
1774:
1770:
1733:(4238): 481–3.
1724:
1723:
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1632:
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991:(2–3): 249–62.
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945:(12): 1088–92.
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477:methylspiperone
465:
437:
429:
398:
384:
331:methylphenidate
306:
301:
289:
280:
215:auditory cortex
203:cingulate gyrus
191:Wernicke's area
180:
159:
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104:
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3393:External links
3391:
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3367:(3): 187–191.
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3147:New York Times
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369:chlorpromazine
365:antipsychotics
361:phenothiazines
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148:have dopamine-
146:antipsychotics
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3229:(4): 427–36.
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2753:(2): 137–46.
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2621:(5): 404–16.
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32:This article
30:
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3445:Scholarpedia
3443:
3425:. Retrieved
3421:the original
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2790:Biochemistry
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2127:. Springer.
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2064:
2032:(6): 553–9.
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2019:
1986:
1982:
1976:
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363:, including
358:
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187:Broca's area
160:
157:Introduction
139:dopaminergic
126:
122:
120:
105:
96:
86:
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65:
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41:Please help
36:verification
33:
3172:: 631–646.
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851:(1): 9–16.
743:David Healy
724:grey matter
667:receptors.
513:Abi-Dargham
457:debrisoquin
393:haloperidol
335:amphetamine
313:amphetamine
284:D2 receptor
247:amphetamine
99:August 2009
3427:2008-06-08
3361:CNS Spectr
3315:: 69–108.
2498:2017-03-13
2367:NeuroImage
2162:2015-05-26
1512:: sbw148.
806:References
689:quetiapine
661:antagonist
481:raclopride
391:including
373:antagonize
309:Stimulants
299:Discussion
209:(LTD) and
69:newspapers
2992:The Brain
2978:173993492
2387:140206903
705:glutamate
685:clozapine
449:serotonin
379:known as
377:receptors
293:clozapine
171:avolition
3479:Category
3438:(2007).
3436:Seeman P
3383:29954475
3339:17349858
3245:10481908
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713:ketamine
367:such as
346:striatum
322:levodopa
311:such as
255:steroids
197:and the
3454:Bibcode
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2639:S2CID
2596:S2CID
2470:S2CID
2427:S2CID
2383:S2CID
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2238:S2CID
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2007:S2CID
1937:S2CID
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1810:S2CID
1759:S2CID
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1575:S2CID
1487:S2CID
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1201:S2CID
1158:S2CID
1009:S2CID
963:S2CID
869:S2CID
697:2A/2C
603:genes
582:and D
516:et al
468:dimer
420:SPECT
340:Some
267:GPRK6
249:, or
90:JSTOR
76:books
3379:PMID
3335:PMID
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3290:PMID
3241:PMID
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