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Refining clinical phenotypes by contrasting ethnically different populations with schizophrenia from Australia, India and Sarawak

McLean D, John S, Barrett R, McGrath J, Loa P, Thara R, et al.

Psychiatry Res, 2012 Apr 30;196(2-3):194-200.
PMID: 22401968 DOI: 10.1016/j.psychres.2011.12.027

We contrasted demographic and clinical characteristics in transethnic schizophrenia populations from Australia (n=821), India (n=520) and Sarawak, Malaysia (n=298) and proposed cultural explanations for identified site differences. From these we aimed to identify candidate variables free from significant cultural confounding that are hence suitable for inclusion in genetic analyses. We observed five phenomena: (1) more individuals were living alone in Australia than India or Sarawak; (2) drug use was lower in India than Australia or Sarawak; (3) duration of untreated psychosis (DUP) was longer in India than Australia or Sarawak; (4) the rate of schizoaffective disorder was lower in India than Australia or Sarawak; and (5) age at psychosis onset (AAO) was older in Sarawak than Australia or India. We suggest that site differences for living arrangements, drug use and DUP are culturally confounded. The schizoaffective site difference likely results from measurement bias. The AAO site difference, however, has no obvious cultural or measurement bias explanation. Therefore, this may be an ideal candidate for use in genetic studies, given that genetic variants affecting AAO have already been proposed.
Rates of treated schizophrenia and its clinical and cultural features in the population isolate of the Iban of Sarawak: a tri-diagnostic approach

Barrett R, Loa P, Jerah E, Nancarrow D, Chant D, Mowry B

Psychol Med, 2005 Feb;35(2):281-93.
PMID: 15841685

We present results of a study of treated rates of schizophrenia among the Iban of Sarawak, Malaysia. Most Iban live in longhouses, each comprising a kindred group of up to 300 individuals. Cultural practices such as minimal intermarriage with members of adjacent ethnic groups and in-depth genealogical knowledge make them a population suitable for genetic investigation. Iban culture is conducive to a focus on symptoms and illness, and to patterns of treatment-seeking behaviour that are enthusiastic and persistent.
Fulltext Comparing schizophrenia symptoms in the Iban of Sarawak with other populations to elucidate clinical heterogeneity

McLean D, Barrett R, Loa P, Thara R, John S, McGrath J, et al.

Asia Pac Psychiatry, 2015 Mar;7(1):36-44.
PMID: 24038814 DOI: 10.1111/appy.12093

INTRODUCTION: The symptom profile of schizophrenia can vary between ethnic groups. We explored selected symptom variables previously reported to be characteristic of schizophrenia in the Iban of Sarawak in transethnic populations from Australia, India, and Sarawak, Malaysia. We tested site differences to confirm previous research, and to explore implications of differences across populations for future investigations.
METHODS: We recruited schizophrenia samples in Australia (n = 609), India (n = 310) and Sarawak (n = 205) primarily for the purposes of genetic studies. We analyzed seven identified variables and their relationship to site using logistic regression, including: global delusions, bizarre delusions, thought broadcast/insertion/withdrawal delusions, global hallucinations, auditory hallucinations, disorganized behavior, and prodromal duration.
RESULTS: We identified a distinct symptom profile in our Sarawak sample. Specifically, the Iban exhibit: low frequency of thought broadcast/insertion/withdrawal delusions, high frequency of auditory hallucinations and disorganized behavior, with a comparatively short prodrome when compared with Australian and Indian populations.
DISCUSSION: Understanding between-site variation in symptom profile may complement future transethnic genetic studies, and provide important clues as to the nature of differing schizophrenia expression across ethnically distinct groups. A comprehensive approach to subtyping schizophrenia is warranted, utilizing comprehensively ascertained transethnic samples to inform both schizophrenia genetics and nosology.
Fulltext DSM-IV "criterion A" schizophrenia symptoms across ethnically different populations: evidence for differing psychotic symptom content or structural organization?

McLean D, Thara R, John S, Barrett R, Loa P, McGrath J, et al.

Cult Med Psychiatry, 2014 Sep;38(3):408-26.
PMID: 24981830 DOI: 10.1007/s11013-014-9385-8

There is significant variation in the expression of schizophrenia across ethnically different populations, and the optimal structural and diagnostic representation of schizophrenia are contested. We contrasted both lifetime frequencies of DSM-IV criterion A (the core symptom criterion of the internationally recognized DSM classification system) symptoms and types/content of delusions and hallucinations in transethnic schizophrenia populations from Australia (n = 776), India (n = 504) and Sarawak, Malaysia (n = 259), to elucidate clinical heterogeneity. Differences in both criterion A symptom composition and symptom content were apparent. Indian individuals with schizophrenia reported negative symptoms more frequently than other sites, whereas individuals from Sarawak reported disorganized symptoms more frequently. Delusions of control and thought broadcast, insertion, or withdrawal were less frequent in Sarawak than Australia. Curiously, a subgroup of 20 Indian individuals with schizophrenia reported no lifetime delusions or hallucinations. These findings potentially challenge the long-held view in psychiatry that schizophrenia is fundamentally similar across cultural groups, with differences in only the content of psychotic symptoms, but equivalence in structural form.
Fulltext Ancestry of the Iban is predominantly Southeast Asian: genetic evidence from autosomal, mitochondrial, and Y chromosomes

Simonson TS, Xing J, Barrett R, Jerah E, Loa P, Zhang Y, et al.

PLoS One, 2011;6(1):e16338.
PMID: 21305013 DOI: 10.1371/journal.pone.0016338

Humans reached present-day Island Southeast Asia (ISEA) in one of the first major human migrations out of Africa. Population movements in the millennia following this initial settlement are thought to have greatly influenced the genetic makeup of current inhabitants, yet the extent attributed to different events is not clear. Recent studies suggest that south-to-north gene flow largely influenced present-day patterns of genetic variation in Southeast Asian populations and that late Pleistocene and early Holocene migrations from Southeast Asia are responsible for a substantial proportion of ISEA ancestry. Archaeological and linguistic evidence suggests that the ancestors of present-day inhabitants came mainly from north-to-south migrations from Taiwan and throughout ISEA approximately 4,000 years ago. We report a large-scale genetic analysis of human variation in the Iban population from the Malaysian state of Sarawak in northwestern Borneo, located in the center of ISEA. Genome-wide single-nucleotide polymorphism (SNP) markers analyzed here suggest that the Iban exhibit greatest genetic similarity to Indonesian and mainland Southeast Asian populations. The most common non-recombining Y (NRY) and mitochondrial (mt) DNA haplogroups present in the Iban are associated with populations of Southeast Asia. We conclude that migrations from Southeast Asia made a large contribution to Iban ancestry, although evidence of potential gene flow from Taiwan is also seen in uniparentally inherited marker data.