Discussion

Although findings indicate that migrants are at increased risk of developing APD and NAPD, the findings were heterogeneous, which precludes a conclusion about ‘the’ RR among migrants in general. While there was no evidence of a greatly increased risk among migrants in Israel or Canada, the risk among migrants in Europe, in particular those from developing countries outside Europe and/or those with a black skin, was greatly increased. Overall, the risk became somewhat attenuated after adjustment for SES at first contact. A comparison of risks for first- and second-generation migrants based on effect estimates derived from the same study yielded no significant difference. This indicates that membership of a disadvantaged ethnic minority group, rather than a personal history of migration, is an important determinant of risk. There was insufficient evidence to conclude that there is a difference in risk between refugees and non-refugees.

It is unlikely that the findings can be explained by bias. Some researchers (e.g. Zandi et al., Reference Zandi, Havenaar, Smits, Limburg-Okken, van Es, Cahn, Algra, Kahn and van den Brink2010) have argued that Western psychiatrists misunderstand patients from a different culture, but most studies of clinical presentation and long-term outcome do not indicate that there is a major diagnostic bias (e.g. Morgan et al., Reference Morgan, Fearon, Lappin, Heslin, Donoghue, Lomas, Reininghaus, Onyejiaka, Croudace, Jones, Murray, Doody and Dazzan2017).

Furthermore, this meta-analysis showed that the risk of PDs was high among migrants from Eastern Europe, who do not differ greatly in culture from Western Europeans. For a thorough discussion of these issues, see previous reviews (Cantor-Graae and Selten, Reference Cantor-Graae and Selten2005; Bourque et al., Reference Bourque, van der Ven and Malla2011). Selection bias is an unlikely explanation, because field studies of major mental disorders have shown that the ratio of treated to untreated cases is negatively associated with SES (Link and Dohrenwend, Reference Link, Dohrenwend, Dohrenwend, Dohrenwend, Gould, Link, Neugebauer and Wunsch-Hirzig1980). There was evidence of publication bias, but its effect was modest.

Strengths of this meta-analysis are the large number of studies included, and, with reference to Europe, the diversity of the migrant groups examined. By using a ‘pairwise’ comparison of effect sizes derived from the same study (e.g. effect sizes adjusted and non-adjusted for SES), it was often possible to avoid confounding by study.

Our meta-analysis has several limitations. First, our results apply mainly to Europe. Of note, studies of first hospital admissions published before 1977 reported a modestly increased risk of schizophrenia among migrants to the USA. Malzberg (Reference Malzberg1964), for example, reported that the first admission rates among foreign-born white individuals in New York City, standardized for age and sex, exceeded those among the native-born white individuals by 16%. To our knowledge, no investigation has reported a greatly increased risk among migrants to the USA or Canada (Selten and Cantor-Graae, Reference Selten, Cantor-Graae, Gattaz and Hafner2004).

Second, the quality of information on the risk for refugees was limited. Only one study compared the risk for refugees to non-refugees from the same part of the world (Hollander et al., Reference Hollander, Dal, Lewis, Magnusson, Kirkbride and Dalman2016). The result of this investigation, a significantly higher risk for refugees, remains inconclusive, however, because the parts of the world were as large as Asia. Since Asia comprises countries as diverse as Afghanistan and China, the comparability of refugees and non-refugees remains uncertain. Leao et al. (Reference Leao, Sundquist, Frank, Johansson, Johansson and Sundquist2006) designated migrants from particular countries (e.g. African countries) refugees, while the authors did not know whether these subjects were the victims of political persecution. Consequently, the outcome of our meta-analysis, i.e. insufficient evidence of a difference in risk between refugees and non-refugees, should not be interpreted as evidence of no difference.

Third, the adjustment for current, rather than parental SES. This is problematic because low SES at onset of psychosis may also be the result of a disturbed neuro-development. Of note, there is a larger potential for downward mobility during the pre-psychotic period among natives than among migrants or their children, many of whom already belong to a lower social class. The situation is complex, because many migrants may have belonged to a higher social class before migration. Also, the definitions of SES varied considerably.

Fourth, the lower rates for migrants within Europe might be explained to some extent by the fact that it is relatively easy to seek support in the country of origin.

Finally, the arbitrary and imperfect classification of subjects on the basis of their skin colour. One could argue, for instance, that subjects from the Indian subcontinent are often darker than Africans and that the group ‘other’, consisting of people from South-America and the larger part of Asia is very heterogeneous. However, given the relatively small number of studies, we opted for this classification. With the designation of a group as white (e.g. Eastern Europeans), we do not suggest that this group is not exposed to prejudice or discrimination.

How should the findings be interpreted? It was previously thought that individuals with a genetic predisposition for psychosis are more likely to migrate than others (Odegaard, Reference Odegaard1932), but not a single study has supported this negative selection hypothesis (Cantor-Graae and Selten, Reference Cantor-Graae and Selten2005). On the contrary, many studies from the USA and Canada have reported a better (somatic) health among migrants than among native-born individuals, while the results of similar studies from Europe vary greatly across migrant populations (Ikram et al., Reference Ikram, Mackenbach, Harding, Rey, Bhopal, Regidor, Rosato, Juel, Stronks and Kunst2016). In any event, due to the self-selection of healthy, resilient people who have the courage to move to a new environment, migrants from developing countries are probably healthier than those who stay behind. Current knowledge about the years before the first hospital admission, during which the patient often exhibits a lack of initiative (Hafner et al., Reference Hafner, Loffler, Maurer, Hambrecht and an der Heiden1999), provides additional evidence against the negative selection hypothesis. Receiving countries can reinforce a positive selection process through their immigrant admission policies. Since such policies are more rigorous in Canada and Australia than in Europe, the relatively low risk of PDs among many migrant groups in the first two countries may be due to positive selection (Vang et al., Reference Vang, Sigouin, Flenon and Gagnon2017). Lastly, selective migration cannot explain the increased risk among Ethiopian Jews, because the whole population moved to Israel (Spector, Reference Spector2005).

There is no evidence that the high incidence of psychosis among migrants from developing countries in Europe reflects a similarly high incidence in the country of origin. While there have been no high-quality incidence studies from Africa, studies from the Caribbean (Bhugra et al., Reference Bhugra, Hilwig, Hossein, Marceau, Neehall, Leff, Mallett and Der1996), Surinam (Selten et al., Reference Selten, Zeyl, Dwarkasing, Lumsden, Kahn and Van Harten2005), India and China (Baxter et al., Reference Baxter, Charlson, Cheng, Shidhaye, Ferrari and Whiteford2016) have reported ‘normal’ incidence or prevalence rates. This also implies that poverty by itself is an unlikely cause of psychosis.

However, as many migrants who move from a developing country to Europe find themselves in the lowest strata of European society, the effect of migration might be due, at least in part, to a (relative) social disadvantage (Morgan et al., Reference Morgan, Kirkbride, Hutchinson, Craig, Morgan, Dazzan, Boydell, Doody, Jones, Murray, Leff and Fearon2008) or social defeat. Indeed, a case–control study from the UK found strong associations between indicators of social disadvantage and psychosis. Indicators of disadvantage and isolation were more common in Black Caribbean subjects than in White British subjects (Morgan et al., Reference Morgan, Kirkbride, Hutchinson, Craig, Morgan, Dazzan, Boydell, Doody, Jones, Murray, Leff and Fearon2008).

The social defeat hypothesis of psychosis, which proposes that the negative experience of being excluded from the majority group increases the risk of psychosis by sensitizing the mesolimbic dopamine system, postulates a link with the brain (Selten and Cantor-Graae, Reference Selten and Cantor-Graae2005; Selten et al., Reference Selten, van Os and Cantor-Graae2016). Sensitization of the mesolimbic dopamine system refers to an increased dopamine function in response to stressors and becomes manifest in excessive presynaptic dopamine synthesis and release (Howes and Murray, Reference Howes and Murray2014). Several lines of evidence support the social defeat hypothesis: (i) the risk of psychosis is increased in other groups exposed to social exclusion, such as individuals with a history of trauma or bullying in childhood, homosexuals, African-Americans, individuals with a low IQ or hearing impairment (for review, see Selten et al., Reference Selten, Booij, Buwalda and Meyer-Lindenberg2017); (ii) the protective effect of high ethnic density, i.e. residence in a neighbourhood where the own ethnic group is well-represented (Schofield et al., Reference Schofield, Thygesen, Das-Munshi, Becares, Cantor-Graae, Pedersen and Agerbo2017); (iii) experiments with rodents that demonstrate dopamine sensitization in defeated animals (Hammels et al., Reference Hammels, Pishva, De Vry, van den Hove, Prickaerts, van Winkel, Selten, Lesch, Daskalakis, Steinbusch, van Os, Kenis and Rutten2015); (iv) a recent positron emission tomography study showing increased dopamine synthesis and increased stress-induced dopamine release in the striatum of individuals (healthy volunteers, clinical high-risk subjects and schizophrenia patients) with a personal or parental history of migration (Egerton et al., Reference Egerton, Howes, Houle, McKenzie, Valmaggia, Bagby, Tseng, Bloomfield, Kenk, Bhattacharyya, Suridjan, Chaddock, Winton-Brown, Allen, Rusjan, Remington, Meyer-Lindenberg, McGuire and Mizrahi2017). Neuro-receptor imaging studies of non-psychotic individuals with a history of hearing impairment or childhood trauma have also reported dopamine sensitization (Gevonden et al., Reference Gevonden, Booij, van den Brink, Heijtel, van Os and Selten2014; Oswald et al., Reference Oswald, Wand, Kuwabara, Wong, Zhu and Brasic2014; Egerton et al., Reference Egerton, Valmaggia, Howes, Day, Chaddock, Allen, Winton-Brown, Bloomfield, Bhattacharyya, Chilcott, Lappin, Murray and McGuire2016). Lastly, the pattern of findings in Israel (i.e. a modest increase in risk among first-generation non-black migrants and the absence of an increase in risk among second-generation migrants) may fit with this interpretation, because the migration of Jews to a Jewish state involves a change from social exclusion to inclusion.

An entirely different interpretation of the increased risk among individuals with a dark skin is that low prenatal levels of vitamin D are a risk factor for psychosis (McGrath, Reference McGrath1999). Indeed, a study from the Netherlands reported that pregnant women and infants from non-European ethnic backgrounds are at high risk of vitamin D deficiency (Vinkhuyzen et al., Reference Vinkhuyzen, Eyles, Burne, Blanken, Kruithof, Verhulst, Jaddoe, Tiemeier and McGrath2016). However, the evidence of a causal role for low vitamin D in the aetiology of psychosis is inconclusive and the hypothesis does not explain the increased risk among first-generation migrants.

Given the fact that substance abuse in the general population is a lot more common among men than among women, the absence of a difference in RR between male and female migrants argues against a major role of drug abuse in the aetiology of the increased incidence.

There is anecdotal evidence and a tiny body of research to suggest that the ratio of risk among migrants and natives is inversed in countries where the original population occupies the weaker position. This may apply, for example, to Aboriginals in Australia, Maori in New Zealand, Native Americans in the USA and Inuit in Canada (Sampath, Reference Sampath1974; Tapsell et al., Reference Tapsell, Hallett and Mellsop2018). This is an important topic for further study.

In conclusion, the results of this meta-analysis confirm earlier European findings of an increased incidence of NAPD among migrants from developing countries, in particular those of African extraction (Cantor-Graae and Selten, Reference Cantor-Graae and Selten2005; Bourque et al., Reference Bourque, van der Ven and Malla2011), and extend them by showing that individuals with an African background are also at an increased risk of PD in Canada and Israel, while migration to the latter countries is generally not associated with an increased risk.

From the large number of research implications, we would like to point out the importance of examining the interaction between ethnic background and host country: does the risk for an immigrant group vary according to the country of destination and which are the determinants of this? A prospective study could test the social defeat hypothesis by comparing striatal dopamine synthesis capacity between migrants and natives in early adult age at two points in time: shortly after arrival in the country of destination and 3–5 years later. The hypothesis predicts a greater rise in striatal dopamine synthesis capacity among migrants than among natives (or a rise in this capacity among migrants and no such rise among natives).

We conclude that the increased psychosis risk among migrants and their children is a major public health problem. Since the lifetime morbid risk for psychosis (affective or non-affective) is about 1–2% for Europeans, our findings suggest that this risk may be 3–6% for migrants from outside Europe. The challenge is to advance our understanding of the underlying mechanisms and to find ways for prevention.