Elevated Striatal Dopamine Function in Immigrants and Their Children: A Risk Mechanism for Psychosis

Abstract

Migration is a major risk factor for schizophrenia but the neurochemical processes involved are unknown. One candidate mechanism is through elevations in striatal dopamine synthesis and release. The objective of this research was to determine whether striatal dopamine function is elevated in immigrants compared to nonimmigrants and the relationship with psychosis. Two complementary case–control studies of in vivo dopamine function (stress-induced dopamine release and dopamine synthesis capacity) in immigrants compared to nonimmigrants were performed in Canada and the United Kingdom. The Canadian dopamine release study included 25 immigrant and 31 nonmigrant Canadians. These groups included 23 clinical high risk (CHR) subjects, 9 antipsychotic naïve patients with schizophrenia, and 24 healthy volunteers. The UK dopamine synthesis study included 32 immigrants and 44 nonimmigrant British. These groups included 50 CHR subjects and 26 healthy volunteers. Both striatal stress-induced dopamine release and dopamine synthesis capacity were significantly elevated in immigrants compared to nonimmigrants, independent of clinical status. These data provide the first evidence that the effect of migration on the risk of developing psychosis may be mediated by an elevation in brain dopamine function.

What causes psychosis? An umbrella review of risk and protective factors

“…In fact, the effect of both factors on the risk of developing psychotic disorders may be explained (mediated) by environmental exposures at an individual level, such as substance use, social isolation, social defeat, social fragmentation, and discrimination 124 . Interestingly, many of these exposures appear to share a common factor of social stress and defeat 125,126 , and have beenmostly indirectly -associated with various neurobiological sequelae of potential relevance to psychotic disorders 127 , such as alterations in the hypothalamic-pituitary-adrenal axis 128,129 , inflammation 130 , altered brain functioning 131,132 , reduced brain volumes 133 , and neurochemical dysfunctions 126,134,135 . However, studies to directly assess the correlations between these factors k -number of samples for each factor, ES -effect size, N -number of cases, PI -prediction interval, CI -confidence interval, SSE -small-study effect, ESBexcess significance bias, LS -largest study with significant effect, eOR -equivalent odds ratio, CE -class of evidence, IRR -incidence rate ratio, OR -odds ratio, k -number of samples for each factor, ES -effect size, N -number of cases, PI -prediction interval, CI -confidence interval, SSE -small-study effect, ESBexcess significance bias, LS -largest study with significant effect, eOR -equivalent odds ratio, CE -class of evidence, IRR -incidence rate ratio, OR -odds ratio, RR -relative risk, Ig -immunoglobulin, NA -not assessable, ns -not significant 133,136 .…”

Dopamine and glutamate in schizophrenia: biology, symptoms and treatment

“…Acute psychosocial stress has been shown to induce striatal dopamine release. Measures of presynaptic dopamine function are raised in migrants, and those that have experienced childhood trauma, both of which are risk factors associated with schizophrenia. However, another risk factor for schizophrenia, heavy cannabis use, is associated with blunted dopamine synthesis capacity and release.…”

30 Years on: How the Neurodevelopmental Hypothesis of Schizophrenia Morphed Into the Developmental Risk Factor Model of Psychosis

“…For example, young adults who were exposed to childhood abuse or who are migrants show increased striatal dopamine synthesis capacity and increased dopamine release to experimentally induced psychosocial stress. 53,54 In general, risk factors for psychosis seem to be associated with increased striatal dopamine. However, two exceptions have been noted so far.…”