by Ashild Kummen

Whereas last week we talked about the association between psychotic disorders and moving to a different country (which you can read about here), another one of our recent papers, published in last month’s issue of JAMA Psychiatry, found that, before age 20, the greater the distance moved within a country, the greater the risk to be diagnosed with a non-affective psychotic disorder (such as schizophrenia).

It is not uncommon to move house during childhood and adolescence, for example due to financial problems or a change of parental employment in the household. These time periods are important for social development and may be a central stressor when migrating is the breaking up of social networks. Moving during childhood may be associated with changing schools, meaning young people could be faced with the challenges of fitting in with a new peer group. Social isolation and lack of peer relationships have been previously found to be associated with psychotic disorders (Winsper, Wolke, Bryson, Thompson, & Singh, 2016), and consistent with this, research has also found a link between psychotic disorders and moving houses during childhood and adolescence (Paksarian, Eaton, Mortensen, & Pedersen, 2015).

Until now, it has remained unclear whether this impact extended beyond mid-adolescence, and into moves in late adolescence and adulthood. We hypothesized that there would be a positive relationship between amount of times moved during childhood and adolescence and later risk of non-affective psychotic disorders. Additionally, we predicted that the greater the distance moved, the greater this risk would be, being strongest when distances moved were most likely to indicate a breakup of social networks (we set this to be 30 km, a distance we hypothesised would likely involve changing schools) .

Our study included 1.4 million participants, all Swedish residents born between 1982 and 1995. They were followed from birth to age 29. We were interested in four time periods: early childhood (0-6 years), childhood (7-15 years), adolescence (16-19 years) and early adulthood (20-29 years). Data on non-affective psychotic diagnoses were collected, as well as additional information such as sex, family income, educational attainment, and parental history of mental illness from the Swedish registers.

As predicted, residential mobility was associated with non-affective psychosis. For all time periods, a change in residence significantly increased the risk, often by number of times moved. For example; moving once over the time period of 16-19 years old increased the risk with 28% but moving four times or more doubled the risk. The pattern was different in early adulthood, where increased risk was notable only when the amount of times moved was 3 or more. Also consistent with our predictions, greater distance moved led to greater risk. However, this was only true during childhood and adolescence, as early adulthood yielded a decrease in risk compared to the general Swedish population (see graph).

During childhood and adolescence, a change in residence is likely initiated by guardians. Our results could be explained in that the breakup of social networks when moving disrupts the developing ability to make new friends and maintain friendships. This could lead to increased social isolation, which again makes one vulnerable to mental illness including psychotic disorders. However, past 20 years old, moving is likely a personal choice by the individual. We found that longer distances moved predicted a lower likelihood of being diagnosed with a non-affective psychotic disorder past 20 years old. This could be explained by the fact that the personal choice made reflects health and independence as the individual moves out from their parent’s house and enters work or attends university. Meanwhile, it would be more difficult for individuals vulnerable to non-affective psychotic disorders to move out and enter work or university, due to symptoms revolved around cognitive deficits as well as the strong association between psychotic disorders and social defeat (Dickson, Laurens, Cullen, & Hodgins, 2012; Selten, van der Ven, Rutten, & Cantor-Graae, 2013).

Our paper published last week found that for all ages investigated, including childhood, adolescence and early adulthood, migrating to a different country increased the risk of being diagnosed with a psychotic disorder. This paper, as well as the one on moving houses within a country, support the idea that migration involving disruption of social networks appear to increase risk, especially for international migrants. This might be particularly difficult for visible minorities. Greater differences, both visible and not, involves greater difficulty for a child to fit in with a peer group.  A good network of social support, including both family and peer-relationships, is crucial as a preventive measure against psychotic disorders. Hence, it is important that children and adolescents receive the necessary attention and support when migrating, both internationally and within a country, to minimize risks of a future diagnosis.

References:

Paksarian, D., Eaton, W. W., Mortensen, P. B., & Pedersen, C. B. (2015). Childhood residential mobility, schizophrenia, and bipolar disorder: a population-based study in Denmark. Schizophr Bull, 41(2), 346-254.

Selten, J. P.,van der Ven, E., Rutten, B. P. F., & Cantor-Graae E. (2013).  The social defeat hypothesis of schizophrenia: an update. Schizophr Bull, 39 (6), 1180-1186.

Winsper, C., Wolke, D., Bryson, A., Thompson, A., & Singh, S. P. (2016). School mobility during childhood predicts psychotic symptoms in late adolescence. J Child Psychol Psychiatry, 57 (8), 957-966.

Dickson, H., Laurens, K. R., Cullen, A. E., & Hodgins, S. (2012). Meta-analyses of cognitive and motor function in youth aged 16 years and younger who subsequently develop schizophrenia. Psychol Med, 42(4), 743-755.

by Ashild Kummen

Migration can be a difficult process, involving a multitude of stressors. This may make some migrants more vulnerable to mental health problems, and previous research have found migrants to be at an elevated risk for psychotic disorders, especially with visible minorities, such as people from black Caribbean and African backgrounds in the UK . In regard to bipolar disorders, however, the research is more mixed, and enquiries have rarely distinguished between bipolar disorders with and without psychotic symptoms.

A new paper from our Ph.D. student Jennifer Dykxhoorn, published today in Psychological Medicine, sheds light on whether the increased risk of psychotic disorders extends to bipolar disorder with and without psychosis. In her paper, Jen hypothesised that migrants were at elevated risk for schizophrenia and affective psychoses (such as bipolar disorder with psychotic features), but not for bipolar disorders without psychotic symptoms. Longitudinal data from almost 1.8 million Swedish residents born between 1982-1996 were collected, with differences by migrant status, age-at-migration and region of origin investigated. Consistent with previous findings , we predicted that migration during early childhood would increase the risk of being diagnosed with a psychotic disorder.

Findings

Compared with the Swedish-born population, migrants and their children were at elevated risk for all psychotic disorders. This included schizophrenia and schizoaffective disorder, where migrants and their children were, on average, twice as likely to be diagnosed. First-generation migrants were also at double the risk for other types of non-affective psychoses. Rates of bipolar disorder with psychosis were also elevated in migrants and their children by 42% and 22%, respectively, compared to the Swedish-born population. In stark contrast,  migrants were up to 40% less likely to be diagnosed with non-psychotic bipolar disorders than the Swedish-born population. For second-generation migrants, risk of non-psychotic bipolar disorder was similar to Swedish-born rates.

While we predicted that migrating during early childhood would elevate risk of psychotic disorders, our findings did not support this. Instead, there was a pattern of increased risk at all ages of immigration to Sweden for psychotic disorders.. By contrast, all ages at immigration were associated with lower risk for bipolar disorder, except for those who migrated during infancy, where incidence rates were closer to the Swedish-born population.

In accordance with previous research by the PsyLife team , African migrants were at highest risk for all psychotic outcomes, including being five times more likely to be diagnosed with schizophrenia. In total, migrants from all origins (except other Nordic origin) were at elevated risk for all psychotic disorders, compared to the Swedish-born population.

Possible explanations

Migrants are exposed to several difficulties relating to the process of migrating and the minority status. Jen’s paper found that the incidence rates for psychotic disorder and bipolar disorders (without psychotic symptoms) is largely different, with higher risk for psychotic disorders and lower risk for bipolar disorders compared to the Swedish-born population. This could suggest that the stressors of migrating and post-migration life have a specific effect on developing psychotic disorders. This is consistent with some research on the neurodevelopmental origins of psychotic and non-psychotic bipolar disorders, conveying these origins are distinct. For example, patients with schizophrenia and bipolar disorders with psychotic features are observed to have premorbid cognitive deficits, which have not been consistently found in non-psychotic affective disorders (Reichenberg et al., 2002; Trotta et al., 2014). Our research suggests further work is now required to test whether certain environmental factors impact on specific neurobiological pathways to influence the occurrence of certain types of mental health problem.

PsyLife references

Other references

• Reichenberg, A., Weiser, M., Rabinowitz, J., Caspi, A., Schmeidler, J., Mark, M., Kaplan, Z, & Davidson, M. (2002). A population-based cohort study of premorbid intellectual, language and behavioural functioning in patients with schizophrenia, schizoaffective disorder, and nonpsychotic bipolar disorder. Psychiatry: Interpersonal and Biological Processes, 159, 2027-2035.
• Trotta, A., Murray, R. M & MacCabe, J. H. (2014). Do premorbid and post-onset cognitive functioning differ between schizophrenia and bipolar disorder? A systematic review and meta-analysis. Psychological Medicine, 45, 381-394.

by Ashild Kummen

Whilst it is known that the first episode of a psychotic disorder usually occurs during adolescence or early adulthood (Kessler et al., 2007), there is a considerable amount of people also experiencing the onset in old age, termed very late-onset of schizophrenic-like psychosis (VLOSLP).Over a year, between 0.1- 0.5% of the population past 65 years old are diagnosed with or have an existing diagnosis of schizophrenia (Howard, Rabins, Seeman & Jeste, 2000).

Robust research in regard to the variance in incidences of VLOSLP and its associated risk factors is important to inform public mental health in hopes of improving interventions for affected individuals. Yet, there is a limited amount of epidemiological research on VLOSLP. The studies that do investigate an onset of a psychotic disorder past 60 or 65 years old, are mostly cross-sectional studies of small samples with limited generalisability. Furthermore, their findings lack in replication. In tackling these limitations, Jean Stafford, one of our PhD students in the PsyLife team has conducted a systematic review on the research there is on incidence rates and different risk factors for VLOSLP. She also conducted a longitudinal cohort study looking into risk factors identified in previous research, including gender, age and sensory impairment as well as unexplored areas such as social economic status, migrant status, social isolation and trauma.

The systematic review and meta-analysis found 41 papers (dated between 1960 and March 2016) that looked at incidence cases of patients diagnosed with a psychotic disorder past 65 years old, not including cases related to dementia, organic and drug-induced psychoses. The majority of these papers were rated of high and average quality, and 25 were included for quantitative analysis. The pooled incidence rate showed that, every year, 7.5 out of 100 000 people over 65 years old were diagnosed with schizophrenia. Moreover, psychoses related to an affective disorder had a yearly rate of 30.9 new cases per 100 000 people. Incidence rates for non-affective psychoses differed largely between studies, and a pooled estimate was not possible. However, the cohort study offers some clarification as it investigated only non-affective psychotic disorders.

The cohort study consisted of over 3 million participants past age 60, all Swedish residents born between 1920 and 1949. Large-scale data collection was possible as every resident in Sweden is given a national identification number that is recorded within a range of health and administrative services. This revealed an incidence rate for non-affective psychotic disorders of 37.66 per 100 000 people every year.

Stafford also investigated the influence of gender and age. The systematic review found reports that women were more likely to be diagnosed than men past age 65 within all branches of psychotic disorders analysed (non-affective, affective psychoses and schizophrenia). The cohort study supported this, with participants diagnosed with a non-affective psychotic disorder past 60 years old being 60% female. In regard to age, the systematic review revealed previous research has been mixed. However, the cohort study revealed a significant increase with age, with differing patterns between men and women. Past 80 years old, women were at risk for VLOSLP at an accelerated rate.

The cohort study also collected data on other possible risk factors, such as migrant status, income, family and sensory impairments. Migrants from Africa, North America and Europe were at elevated risk compared to the rest of the population. This is an association also found in younger populations , possibly explained by the stressors encompassed in migration. Furthermore, low income at age 60 significantly predicted a higher future risk of VLOSLP. In an investigation of family history, it was found that participants with children diagnosed with a psychotic disorder were twice as likely to have VLOSLP. Looking at social isolation; participants with no children and/or no partner 2 years before exiting the study were at elevated risk. Experiencing the death of a partner 2 years before also led to increased risk, whilst the death of a child before age 18 had no association and the death of a child at infancy had weak evidence for elevated risk. These could be indicators of the influence of trauma. Contradictory to previous research (Cooper & Porter, 1976; Cooper et al. 1974), participants with sensory impairments were less likely have VLOSLP compared to the general Swedish population. However, this result could reflect an under-detection of psychiatric disorders in people with physical health issues (Roberts, Roalfe, Wilson & Lester, 2007)

In conclusion, these results indicate that people with VLOSLP were more likely to have social disadvantages, such as lower income and social isolation. This could be interpreted two ways; either there is causal link where the stressors of inequalities lead to increased risk of a psychotic disorder, or that those with premorbid symptoms of a psychotic disorder will subsequently suffer disadvantages due to lower functioning, although VLOSLP patients have been shown to have higher premorbid functioning (Castle et al., 1997). Older women are at particularly prominent risk, indicating this is a group deserving of more clinical recognition.

Full version of the systematic review can be found here, and the cohort study here.

PsyLife References:

Other references:

• Castle, D.J., Wessely, S., Howard, R., et al. (1997). Schizophrenia with onset at the extremes of adult life. Int J Geriatr Psychiatry, 12, 712–717.
• Cooper, A. F., Curry, A. R., Kay, D. W., Garside, R. F. & Roth, M. (1974). Hearing loss in paranoid and affective psychoses of the elderly. Lancet 2, 7885, 851–54.
• Cooper, A. F. & Porter, R. (1976). Visual acuity and ocular pathology in the paranoid and affective psychoses of later life. Journal of Psychosomatic Research 20, 107–114.
• Howard, R., Rabins, P. V., Seeman, M. V., & Jeste, D. V. (2000). Late-onset schizophrenia and very-late onset schizophrenia-like psychosis: An international consensus. American Journal of Psychiatry, 157, 172–178.
• Kessler, R. C., Amminger, G. P., Aguilar-Gaxiola, S., Alonso, J., Lee S., & Utsun, T. B. (2007). A controlled family study of late-onset non-affective psychosis (late paraphrenia). The British Journal of psychiatry, 170, 511-514.
• Roberts, L., Roalfe, A., Wilson, S., & Lester, H. (2007). Physical health care of patients with schizophrenia in primary care: a comparative study. Fam Pract, 24, 34–40.

It’s an exciting week for the PsyLife group. We’re presenting no fewer than 6 research papers in two of Europe’s most historic cultural capitals – Vienna and Florence.

Recent PsyLife Phd graduate, Dr Hannah Jongsma, and current PhD student Jean Stafford will both be in Florence for the 6th Biennial conference of the Schizophrenia International Research Society  Hannah will be speaking as part of a symposium (Sala Verde, Sat 7 April, 10-12pm) on the prevention of psychosis, talking about her recent findings from the EU-GEI study . Congratulations to Jean, who won a Young Research travel award to attend the conference, and will be giving a poster presentation on variation in the incidence of very-late onset psychotic disorders using nationwide longitudinal cohort data. Her poster is S134 and she will be presenting in Poster Session III on Saturday 7th April, 12-2pm.

Meanwhile, over in Vienna, we have a PsyLife symposium at the 18th 19th(!) Section meeting of European Psychiatric Association’s Epidemiology and Social Psychiatry section. Our symposium, entitled Environments and psychosis: examining the causal evidence will feature our latest findings from the ALSPAC birth cohort and the SEPEA study on how neighbourhood environments are related to psychotic outcomes and comorbid personality disorders. We have talks from Dr James Kirkbride, Dr Francesca Solmi, Ka-Young Ban (PhD student) and Tayla McCloud (rortation PhD student). Do come along and find out more: Kursraum 22, Friday 6th April, 2-3.30pm.

Finally, we wanted to say a massive thank you and congratulations to Francesca, who will be leaving the PsyLife group to begin her own Sir Henry Wellcome Fellowship on the epidemiology of eating disorders. Francesca has published several key papers with the group in her three years here , with several more still to come. We are sure you will go on to great successes, and thank you for being such an inspiring, helpful and knowledgeable member of the group!

References

The PsyLife group are thrilled that group PhD student Hannah Jongsma passed her viva at the University of Cambridge last week, with a recommendation that she be awarded a PhD following (just two) minor corrections to her thesis. In her thesis, entitled The role of the social environment in explaining variance in incidence of psychosis and higher rates of disorder in minorities,  Dr Jongsma explored variation in the incidence and risk of psychotic disorders using epidemiological data from the EU-GEI study. In particular she was interested in understanding variation in incidence by place, and last month published the first output from her thesis in JAMA Psychiatry, in a paper exploring reasons for 10-fold variation in rates of psychotic disorder across 17 centres in the EU-GEI study . She was also interested in understanding variation by ethnicity and migrant status, exploring the roles that psychosocial disadvantage and social distance played on these factors. 

We would like to congratulate Dr Jonsgma on her success, and wish her the best of luck in her future career. Dr Jonsgma will continue as a postdoctoral research associate in the Department of Psychiatry at the University of Cambridge, and we look forward to seeing more outputs published from her PhD over the next year or so. 

Well done!

Reference

Over the past few years, a number of scientific studies and media outlets have reported that Toxoplasma Gondii (T. Gondii) infection could increase a person’s risk of experiencing adverse mental health outcomes – including schizophrenia, suicide, and intermittent rage disorder.

Since domestic cats are the primary hosts of T. Gondii (i.e., they provide an environment within which this parasite can reproduce) some people have speculated that cat ownership may put people at increased risk of mental illness, by exposing them to T. Gondii infection. While a handful of small studies have found evidence to support a link between cat ownership and psychosis, most of these investigations had serious methodological limitations (e.g.: relying on recall of past cat ownership, small sample sizes, missing data, lack of control for other explanations), which may have biased their findings.

To tackle these limitations, we used data from a large, longitudinal sample of approximately 5,000 children, a sub-group of 14,000 children born in the former region of Avon, (UK) between 1991 and 1992. Unlike previous studies, we were able to follow people over time, from birth to late adolescence, and address a number of the limitations of previous studies, including controlling for alternative explanations (including socioeconomic status, ethnicity, other pet ownership and over-crowding) and taking into account missing data. We studied whether mothers who owned a cat: 1) while pregnant; 2) when the child was 4 years old; and 3) 10 years old, were more likely to have children who reported psychotic symptoms (e.g.: experiences of visual or auditory hallucinations, and of paranoia) in early (age 13) and late adolescence (age 18).

We found that children who were born and raised in households that included cats at any time period were not at a higher risk of having psychotic symptoms when they were 13 or 18 years old. This finding in a large, representative sample was robust against issues of missing data and alternative explanations. Although most people who experience psychotic symptoms in adolescence will not develop schizophrenia later in life, they can indicate an increased risk for such disorders.

It is important to remember that there is evidence linking T. Gondii exposure in pregnancy to risk of miscarriage and stillbirth or health complications in offspring. We therefore recommend that pregnant women should continue to avoid handling soiled cat litter and other sources of T. Gondii infection (such as raw or undercooked meats or unwashed fruit and vegetables). That said, data from our study suggests that cat ownership during pregnancy or in early childhood does not pose a direct risk for later offspring psychotic symptoms.

New research led by Dr James Kirkbride from the PsyLife group, Division of Psychiatry, UCL, has shown how psychosis risk varies in more rural populations than previously studied in England. The findings, published last week in the American Journal of Psychiatry, reveal that rural regions see a significant rate of new cases of psychotic disorder in their populations. This is important because service planners need to ensure all people developing a first episode of psychosis can get quick, timely access to specialist mental health services such as Early Intervention teams.

The study was conducted in the East of England, in three counties – Cambridgeshire, Norfolk and Suffolk – and tried to identify all young people (aged between 16 and 35 years old) presenting to mental health services for the first time due to psychosis over a 3.5-year period. During this time, the study identified over 680 people who met diagnostic criteria for first episode psychosis living in this region, corresponding to an incidence rate of 34 new cases per 100,000 people per year.

The study also revealed that the risk of developing psychosis varied by important characteristics of both individuals and their environments. For example, although the study was conducted in a more rural setting than many previous epidemiological studies of this type , the authors found that the rate of disorder still varied according to how densely populated and deprived the environment was. Rates of psychotic disorder were relatively stable in most parts of the region, but rose in the most deprived and most densely populated regions. While this data is in keeping with earlier research , the study extends previous knowledge by suggesting that there may be a threshold effect in operation; below a certain level of population density or deprivation, there is no increase in risk, but once a certain level is reached, risk begins to shift. This research has not previously been possible in studies which have tended to be conducted in more urban environments.

The study also found variation by individual level factors. As previously established, men were almost twice as likely to experience a first episode of psychosis than women, particularly in their late teens and early twenties when risk is highest for both sexes. There was some evidence that rates were also raised in black and minority ethnic groups, but another paper from the same study will address this issue in more detail, and is currently under review.

You can read the full version of these findings here, or read about further overage of the findings from Psychiatric News and Medscape.

Reference