Dopamine hypothesis schizophrenia -

Dopamine hypothesis schizophrenia Video

Biological basis of schizophrenia - Behavior - MCAT - Khan Academy dopamine hypothesis schizophrenia Dopamine hypothesis schizophrenia

The dopamine hypothesis of schizophrenia or the dopamine hypothesis of psychosis is a model that attributes the positive symptoms of schizophrenia to a disturbed and hyperactive dopaminergic signal transduction. The model draws evidence from the observation that a large number of antipsychotics have dopamine- receptor antagonistic effects.

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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.

dopamine hypothesis schizophrenia

Some researchers have suggested dopamine hypothesis schizophrenia dopamine systems in the mesolimbic pathway may contribute to the 'positive symptoms' of schizophrenia [1] [2] whereas problems with dopamine function in the mesocortical pathway may be responsible for the 'negative symptoms', such as avolition and alogia. A relative excess of these receptors within the limbic system means Broca's areawhich can produce illogical language, has an abnormal connection to Wernicke's areawhich comprehends language but does not create it. Individual alterations are produced by differences within glutamatergic pathways within the limbic system, which are also implicated dopamine hypothesis schizophrenia other psychotic syndromes.

Among the alterations of both synaptic and global structure, the most significant abnormalities are observed in the uncinate fasciculus [3] and the cingulate cortex. Eventually, the cingulate gyrus becomes atrophied towards the anterior, due to long-term depression LTD and long-term potentiation LTP from the abnormally strong signals transversely across the brain. As such, spontaneous language from Broca's can propagate through the limbic system to the tertiary auditory cortex. 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.

Exploring Schizophrenia Essay

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 is a direct result of dopamine hypothesis schizophrenia abnormal dopaminergic to the striatum, thus indirectly disinhibition of thalamic activity. The excitatory nature of dopaminergic transmission means the glutamate hypothesis of schizophrenia is inextricably intertwined with this altered functioning.

Specifically, the 5-HT2A 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 5-HT2C receptor, leading to dopamine release in the structures where 5-HT2C is expressed; striatum, prefrontal cortex, nucleus accumbens, amygdala, dopamine hypothesis schizophrenia all structures indicated in this diseaseand currently thought to be a reason why antipsychotics with 5HT2C antagonistic properties improves negative symptoms.

More research is needed to explain the exact nature of the altered chemical transmission in dopamine hypothesis schizophrenia disorder. Recent evidence on dopamine hypothesis schizophrenia variety of models of psychosis, such as sensitization of animal behaviour by amphetamineor phencyclidine PCP, Angel Dust[9] or excess steroids [ citation needed ]or by removing various genes COMTDBHGPRK6RGS9RIIbetaor 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 2 receptors in the high-affinity state for dopamine.

Combined with less inhibitory signalling from the thalamus and other basal ganglic structures, from hyoptrophy [11] the abnormal activation of the cingulate cortex, specifically around Broca's and Wernicke's areas, [4] abnormal D 2 agonism can facilitate the self-reinforcing, illogical patterns of language found in such patients. Patients on neuroleptic or antipsychotic medication have significantly less atrophy within these crucial areas.

Stimulants such as amphetamineand cocaine increase the levels of dopamine in the brain and can cause symptoms of psychosis, particularly after large doses or prolonged use. This is often referred to as " amphetamine psychosis " or "cocaine psychosis," but may produce experiences virtually indistinguishable from the positive symptoms associated with schizophrenia. Similarly, those treated with dopamine enhancing levodopa for Parkinson's disease can experience psychotic side effects mimicking the symptoms of schizophrenia.


Some functional neuroimaging studies have also shown that, after taking amphetamine, patients diagnosed with schizophrenia show greater levels of dopamine release particularly in the striatum 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. A group of dopamine hypothesis schizophrenia called the phenothiazinesincluding antipsychotics such as chlorpromazinehas been found to antagonize dopamine binding particularly at receptors known as D 2 dopamine receptors and reduce positive psychotic symptoms.

This observation was subsequently extended to other antipsychotic drug classes, such as butyrophenones including haloperidol. The link was strengthened by experiments in the s which suggested that the binding affinity of antipsychotic drugs for D 2 dopamine receptors seemed to be inversely proportional to their therapeutic dose.

dopamine hypothesis schizophrenia

dopamine hypothesis schizophrenia This correlation, suggesting that receptor binding is causally related to therapeutic potency, was reported by two laboratories in Genetic evidence has suggested that there may be genesor 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. People with Schizophrenia appear to have a high rate of self-medication with nicotine ; the therapeutic effect likely occurs through dopamine modulation by nicotinic acetylcholine receptors. However, dopamine hypothesis schizophrenia was controversy and conflicting findings over whether postmortem findings resulted from drug tolerance to chronic antipsychotic treatment. Compared to the success of postmortem studies in finding profound changes of dopamine receptors, imaging studies using SPET and PET methods in drug naive patients have generally failed to find any difference in dopamine D 2 receptor density compared to controls.

dopamine hypothesis schizophrenia

Comparable findings in longitudinal studies show: " Particular emphasis is given to methodological limitations in the existing literature, including dipamine of reliability data, clinical heterogeneity among studies, and inadequate study designs and statistic," suggestions are made for improving future longitudinal neuroimaging studies of treatment effects in schizophrenia [22] A recent review of imaging studies in schizophrenia shows confidence in the techniques, while discussing such operator error.]

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