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Social Defeat Is a Risk Factor for Schizophrenia?

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Social Defeat Is a Risk Factor for Schizophrenia? BRITISH JOURNAL OF PSYCHIATRY (2007), 191 (suppl. 51), s9^s12. doi: 10.1192/bjp.191.51.s9 EDITORIAL Hypothesis: social defeat is a risk factor for migrants from lower and middle- income versus high income countries and for schizophrenia? a remarkably high risk for migrants from countries where the majority of the population is Black (RR¼4.8, 95% CI JEAN-PAUL SELTENand ELIZABETH CANTOR-GRAAE 3.7–6.2). It is important to note, however, that very high risks have also been noted for non-Black immigrant groups. Denmark has received many immigrants from its former colony Greenland and the risk for second-generation Greenlanders, who are ethnic Inuit, is 12.4 (95% CI 4.7–33.1) Summary The increased really ‘begins’. Interestingly, a study of dis- times the risk for ethnic Danes (Cantor- schizophrenia risks for residents of cities cordant twins has shown that divergence in Graae & Pedersen, 2007). In the Nether- school performance precedes the onset of lands, the risk for second-generation with high levels of competition and for psychosis by an average of 10 years (van Moroccan males is 6.8 times (95% CI members of disadvantaged groups (for OelOel et aletal, 2002). This suggests that certain 3.3–14.1) the risk for Dutch males (Veling example migrants fromlow- and middle- causal factors may operate long before the et aletal, 2006). Selective migration of geneti- income countries, people with low IQ, emergence of psychotic symptoms and that cally vulnerable individuals has been ruled hearingimpairments or a history of abuse) the time frame of life-event studies is inade- out as the sole explanation for the increased quate. The purpose of this paper is to pre- risk in migrants (Cantor-Graae & Selten, suggestthat social factors are important sent evidence in support of the hypothesis 2005).2005). for aetiology.Dopaminergic that a chronic andlong-term experience of A third risk factor for schizophrenia is dysfunctioning is a key mechanism in social defeat may lead to sensitisation of low intelligence. A follow-up study of pathogenesis.This editorialis a selective the mesolimbic dopamine system (and/or to Swedish conscripts, for instance, showed increased baseline activity of this system) that the risk for schizophrenia was strongly literature review to delineate a and thereby increase the risk for schizo- and linearly related to low IQ (Zammit etet mechanism whereby social factors can phrenia. The hypothesis is based on epidemi- alal, 2004). Subjects with an average IQ, for disturbdisturbdopaminefunctioninthebrain. dopamine function in the brain. ological findings, studies of dopamine example, had a significantly greater risk of Experiments withwithrodents rodents have shown function in humans and animal experiments. developing schizophrenia than those with that social defeat leads to dopaminergic an IQ of more than 126 (RR¼1.3, 95%1.3,95% CI 1.04–1.54). hyperactivity and to behavioural EPIDEMIOLOGICAL FINDINGS It has been estimated that the use ofuseof sensitisation, whereby the animal displays cannabis and other dopamine-enhancing an enhanced behavioural and dopamine Some established risk factors for schizo- drugs approximately doubles the risk (Ar- response to dopamine agonists. phrenia, which are not purely genetic, are seneaultseneault et aletal, 2004). Hearing impairment Neuroreceptor imaging studies have the urban environment, migration, low and deafness are well-established risk fac- IQ, hearing impairment and the use of illicit tors for psychosis, but the magnitude of demonstrated the same phenomena in drugs.drugs. the relative risk for narrow schizophrenia patientswith schizophreniawhohadneverschizophreniawho hadnever Krabbendam & van Os (2005) per- associated with these factors is not precisely received antipsychotics.In humans, the formed a meta-analysis of studies that ex- known (Thewissen et aletal, 2005). Finally, ac- chronic experience of social defeat may amined the rate of schizophrenia in urban cumulating evidence indicates that a history as compared to rural areas, and obtained of physical or sexual abuse during upbring- lead to sensitisation (and/or increased a mean weighted relative risk (RR) of ing is a risk factor for schizophrenia, but baseline activity) ofthe mesolimbic 1.72 (95% CI 1.53–1.92). The available opinions are still divided as to whether it dopamine system and thereby increase evidence suggests that causation (urban is a causal risk factor (Read et aletal, 2005).,2005). the risk for schizophrenia. environment causes psychosis) is more im- portant than selection (high-risk individuals Declaration of interest None. move into urban areas) and that the effect SOCIAL DEFEAT of the environmental factors in the urban environment is conditional on genetic risk. Previously, we have proposed that the long- Current textbooks of psychiatry remain un- Considerable interest has been gener- term experience of social defeat, defined as decided about a causal role for psychosocial ated by studies of first- and second-genera- a subordinate position or as outsider status, stress in the aetiology of schizophrenia. Re- tion migrants. A meta-analysis of incidence may well be the common denominator for searchers who are opposed to this possibil- studies found an even greater increase in these findings (Selten & Cantor-Graae, ity often point out that studies of life events psychosis risk for the second generation 2005). This interpretation is compatible occurring shortly before the first psychotic (RR(RR¼4.5, 95% CI 1.5–13.1) than for the with the high levels of competition in urban episode have yielded negative or inconclu- first (RRfirst(RR¼2.7, 95% CI 2.3–3.2) (Cantor- areas, the fewer career opportunities for sive results. In actuality, we have no idea Graae & Selten, 2005). Further subgroup people with low IQ, the social exclusion ex- when a so-called schizophrenic disorder comparisons showed greater effect sizes perienced by immigrants and people with s9s9 Downloaded from https://www.cambridge.org/core. 26 Sep 2021 at 08:14:48, subject to the Cambridge Core terms of use. SELTEN & CANTOR-GRAAE hearing impairments and the humiliation of The experience of social defeat will lead the most viable interpretation of the avail- being abused. to a greater need for illicit drugs and to a able epidemiological data. The pattern of findings among immi- greater susceptibility to these substances grants supports this idea. A greater effect (see below). Finally, since males may feel DOPAMINE FUNCTION size for the second generation than for the more pressed to achieve a social rank than IN SCHIZOPHRENIA first can be expected, because it is more hu- females, the hypothesis may also explain miliating to feel unwelcome in the country the higher risk and earlier onset in males Evidence for the role of dopamine in the de- that you are born in than to feel unwelcome (Aleman(Aleman et aletal, 2003), but this is uncertain. velopment of schizophrenia is provided by because you are born abroad. Furthermore, the increased occupancy of striatal D2 re- the immigrants with the highest risks ceptors by dopamine in patients who have (Moroccan males in the Netherlands, the CONCEPTUAL ISSUES not received medication, the psychotogenic Inuit in Denmark and African–Caribbeans effects of dopamine-enhancing drugs and in the UK) belong to the least successful The experience of defeat is in the eye of the the known mode of action of antipsychotic and/or the most heavily discriminated beholder. Consequently, the absence of an drugs, i.e. blockade of dopamine D2 recep- groups. Moroccan males in the Netherlands association between socio-economic status tors (reviewed by Laruelle, 2003). Further- are known for the highest crime and of the parents and risk for schizophrenia more, current evidence indicates that the unemployment rates and have reported in the child does not necessarily argue mesolimbic dopamine system is sensitised the highest frequency of the experience of against the hypothesis. Children of high so- in schizophrenia. Sensitisation is a process discrimination. Remarkably, the schizo- cio-economic status, who may feel pres- whereby exposure to a given stimulus re- phrenia risk for first- or second-generation sured to meet the high expectations of sults in an enhanced response at subsequent Moroccan females is not increased (Veling their parents, may feel more easily defeated exposures, in this example excess release of et aletal, 2006). They have an inferior position than other children. Furthermore, social de- dopamine or the development of psychotic in Moroccan society, but receive many feat is neither a necessary nor a sufficient symptoms. The notion that patients with opportunities for education and career in condition for the development of schizo- schizophrenia show dopamine sensitisation the Netherlands. Since migration has con- phrenia, is not always followed by the de- is supported by neuroreceptor imaging stu- ferred upon them a considerable rise in so- velopment of a psychiatric disorder and is dies which have shown that amphetamine- cial status, their low risk accords with the also a risk factor for depression and addic- induced dopamine release is increased in hypothesis. (Moroccans of either gender tion. Other factors, including those under a neuroleptic-naive individuals with schizo- are exposed to the stress of acculturation strong genetic control, would determine the phrenia; and many patients display in- and this type of stressor is therefore un- nature of the outcome of exposure to social creased sensitivity to the psychotogenic likely to explain the pattern of findings.) defeat. The important consideration here is effects of illicit drugs. This means that they In Denmark, first- and second-generation that the genetic vulnerability to schizo- develop psychotic symptoms after exposure Greenlanders have higher rates of schizo- phrenia may be present in 10–20% of the to doses that do not induce psychosis in phrenia than most other ethnic groups. It population. Thus, the likelihood that gene healthy subjects. However, dopamine only should be noted that Greenlanders and citi- carriers may go on to develop the schizo- mediates psychosis.
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