Schizophrenia In African Americans Research Articles

Overdiagnosis of Schizophenia Said to Be Persistent Among Black Patients

Overdiagnosis of Schizophenia Said to Be Persistent Among Black Patients

Multiple genes in the 15q13-q14 chromosomal region are associated with schizophrenia.

The chromosomal region, 15q13-q14, including the α7 nicotinic acetylcholine receptor gene, CHRNA7, is a replicated region for schizophrenia. This study fine-mapped genes at 15q13-q14 to determine whether the association is unique to CHRNA7. Family-based and case-control association studies were performed on Caucasian-non-Hispanic and African-American individuals from 120 families as well as 468 individual patients with schizophrenia and 144 well-characterized controls. Single-nucleotide polymorphism (SNP) markers were genotyped, and association analyses carried out for the outcomes of schizophrenia, smoking, and smoking in schizophrenia. Three genes were associated with schizophrenia in both ethnic populations: TRPM1, KLF13, and RYR3. Two SNPs in CHRNA7 were associated with schizophrenia in African-Americans, and a second SNP in CHRNA7 was significant for an association with smoking and smoking in schizophrenia in Caucasians. Results of these studies support association of the 15q13-q14 region with schizophrenia. The broad positive association suggests that more than one 15q gene may be contributing to the disorder, either in combination or through a regulatory mechanism.

Natural contact and stigma towards schizophrenia in African Americans: Is perceived dangerousness a threat or challenge response?

This research extends our understanding of the relationship of social contact theory to stigma in a sample of mainly African American college students. In Phase 1, 75 participants with high levels of contact reported significantly lower negative affect and less social distance toward the mentally ill as compared to 89 participants with low contact. Despite this, the high contact group attributed significantly higher levels of dangerousness to the mentally ill. Thus while social contact was associated with reductions in some dimensions of stigma, it was associated with higher levels of self-reported perceived dangerousness. These results were obtained while controlling for social desirability bias in the self-report measures of stigma. The results from Phase 1 of this study may indicate fundamental differences between incidental social contact and that which occurs in an assistive context. In Phase 2, a subset of convenience from the high contact group (n=27) and the low contact group (n=38) were compared on cardiovascular reactivity measures while imagining social interactions with people labeled with schizophrenia. Post hoc testing revealed that when participants from the high contact group imagined interacting with people labeled as schizophrenic they exhibited significant decreases in total peripheral resistance (TPR), the challenge pattern, compared to their reactions when they imagined interacting with unstigmatized people. This finding suggests the higher dangerousness ratings of the mentally ill sometimes found in African American samples may be related to factors other than direct threat.

Is it time to trial vitamin D supplements for the prevention of schizophrenia?

Is it time to trial vitamin D supplements for the prevention of schizophrenia?

A 2-base pair deletion polymorphism in the partial duplication of the α7 nicotinic acetylcholine gene ( CHRFAM7A) on chromosome 15q14 is associated with schizophrenia

Multiple genetic linkage studies support the hypothesis that the 15q13–14 chromosomal region contributes to the etiology of schizophrenia. Among the putative candidate genes in this area are the α7 nicotinic acetylcholine receptor gene ( CHRNA7) and its partial duplication, CHRFAM7A. A large chromosomal segment including the CHRFAM7A gene locus, but not the CHRNA7 locus, is deleted in some individuals. The CHRFAM7A gene contains a polymorphism consisting of a 2 base pair (2 bp) deletion at position 497–498 bp of exon 6. We employed PCR-based methods to quantify the copy number of CHRFAM7A and the presence of the 2 bp polymorphism in a large, multi-ethnic population. The 2 bp polymorphism was associated with schizophrenia in African Americans (genotype p = 0.005, allele p = 0.015), and in Caucasians (genotype p = 0.015, allele p = 0.009). We conclude that the presence of the 2 bp polymorphism at the CHRFAM7A locus may have a functional significance in schizophrenia.

Effects of cultural themes in psychotic symptoms on the diagnosis of schizophrenia in African Americans

Cultural themes focusing on race-related issues and religiosity were identified via content analysis in the delusions and hallucinations of a sample of 118 African American psychiatric patients. The purpose of the study was to determine whether cultural themes in psychotic symptoms influence the diagnosis from different sources (i.e., chart, SCID, and best estimate) of schizophrenia for Black patients. It was hypothesized that the best estimate diagnoses of cultural experts would diagnose schizophrenia in African Americans more frequently when they exhibit race-related themes in their psychotic symptoms. It was also hypothesized that diagnosis of the paranoid subtype would yield a stronger difference among the sources than the broader category of schizophrenia. The results did not support the hypotheses. Implications for understanding the relationship between culture and psychosis among African Americans are discussed.

Waist circumference does not predict insulin resistance in African American schizophrenia patients

The objective of the study was to determine whether race plays a role in the relationship between waist circumference and insulin resistance in an African American and white sample of subjects with schizophrenia. A cross-sectional comparison was conducted to determine the relationship between waist circumference and insulin resistance in 55 subjects treated with antipsychotic medication. Each subject underwent an anthropometric assessment of waist and hip circumference, height, weight and body mass index. Laboratory assays were performed to assess insulin resistance by the homeostasis model assessment for insulin resistance (HOMA-IR). Data for fifty-five subjects are reported: white/Caucasian (n=38) and African American (n=17). Mean waist circumference was higher in whites (98 cm±11 cm) compared with African Americans (94 cm±11 cm) but not statistically significant (p=0.181). There was no correlation between waist circumference and insulin resistance calculated by HOMA-IR in the African American subject s...

Association of SNPs and haplotypes in APOL1, 2 and 4 with schizophrenia

Prior work found the APOL1, 2 and 4 genes, located on chromosome 22q12.3–q13.1, to be upregulated in brains of schizophrenic patients. We performed a family-based association study using 130 SNPs tagging the APOL gene family (APOL1-6). The subjects were 112 African-American (AA), 114 European-American (EA), 109 Chinese (Ch) and 42 Japanese (Jp) families with schizophrenia (377 families, 1161 genotyped members and 647 genotyped affected in total). Seven SNPs had p-values<0.05 in the APOL1, 2 and 4 regions for the AA, EA and combined (AA and EA) samples. In the AA sample, two SNPs, rs9610449 and rs6000200 showed low p-values; and a haplotype which comprised these two SNPs yielded a p-value of 0.00029 using the global test (GT) and the allele specific test (AST). The two SNPs and the haplotype were associated with risk for schizophrenia in African-Americans. In the combined (AA and EA) sample, two SNPs, rs2003813 and rs2157249 showed low p-values; and a three SNP haplotype including these two SNPs was significant using the GT (p=0.0013) and the AST (p=0.000090). The association of this haplotype with schizophrenia was significant for the entire (AA, EA, Ch and Jp) sample using the GT (p=0.00054) and the AST (p=0.00011). Although our study is not definitive, it suggests that the APOL genes should be more extensively studied in schizophrenia.

The Role of Treatment Setting and High Acuity in the Overdiagnosis of Schizophrenia in African Americans

Multiple studies have shown that significant disparities exist in the diagnosis of schizophrenia between African Americans (AAs) and Whites with severe mental illness. This phenomenon has been a topic in the literature for nearly three decades, yet it remains unclear what factors contribute most conclusively to the overdiagnosis of schizophrenia in AAs. The purpose of this article was to collectively examine the contributing factors identified in the literature and to discuss the role of acuity and treatment setting in overdiagnosis as well. A variety of client-level (higher rates of use of psychotomimetic substances in AAs) and care process-level (misinterpretation of cultural mistrust as paranoia, under detection of depression, similarities in diagnostic criteria between mood and psychotic disorders, provider bias, miscommunication between patient and provider, changes in diagnostic criteria, differences in diagnostic practice between providers, and a lack of sufficient data obtained) factors emerged as influential in overdiagnosis. However, in this review, it also emerged that AAs tendency to use emergency and acute care services, a systems level factor, could be related as well. It is possible that assessment at a time when symptom acuity is severe might increase the likelihood of a schizophrenia diagnosis in AAs.

Researching protective and promotive factors in mental health

This issue of the Journal features two cohort studies which show a marked excess of schizophrenia in African Americans, and a dose–response relationship between perceived discrimination and excess rates of schizophrenia in different minority groups in The Netherlands. These studies mirror one another, and numerous other studies carried out in developed countries, in inferring that minority groups are at elevated risk for schizophrenia, and that social factors—particularly discriminationrelated disadvantages—are partially responsible. That these elevated rates have been the subject of scientific investigations is fully justified—if the higher rate of schizophrenia in minority groups were ignored, we would feel rightly outraged. Likewise, we believe ignoring the mental health needs of other disadvantaged groups—for example, women or conflict-affected people—is both scientifically and morally indefensible. It is scientifically indefensible because these groups are particularly vulnerable to suffering from poor mental health. It is morally indefensible because in the context of other important disadvantages across multiple axes, attempting to understand and address mental health inequalities becomes still more pressing as a matter of social justice. Nevertheless, in this editorial we add our voices to those who call for a broadening of the research agenda beyond the risk factors for poor mental health and the mental health problems of socially vulnerable groups. Instead, we propose that more attention needs to be paid to the protective factors which decrease the probability of suffering mental health problems, and to the promotive factors which actively enhance positive psychological well-being. Our argument is that protective and promotive factor epidemiology is not simply the converse of risk factor epidemiology, either conceptually, methodologically or in its potential public health benefits; and that a failure to investigate protective and promotive factors rigorously may therefore hamper our ability to understand mental health problems and to promote good mental health. Investigating protective factors at the group level

Analysis of polymorphisms in AT‐rich domains of neuregulin 1 gene in schizophrenia

Linkage analysis and association studies have pointed to neuregulin 1 (NRG1) as the prime candidate for 8p-linked schizophrenia (SZ). However, so far, no specific functional alleles in the gene's exons, intron-exon junctions and promoters have been identified that are unequivocally associated with SZ. In this study, we analyzed several NRG1 polymorphisms that affect ATTT motifs and AT-rich regions of the gene. We have previously identified a number of such polymorphisms in the promoters of other SZ and bipolar disorder (BD) candidate genes and found positive associations to several of them. In addition, allele specific differences in the binding of brain proteins have been found for many of the polymorphisms. A case control design was used to compare allele frequencies in Caucasian and African American patients with SZ and controls. In the African American group, a significant difference was found in the allele and genotype distribution for several of the markers and haplotype blocks located in the 5'- and 3'-ends of the gene. The most significant result was obtained for rs6150532, an insertion/deletion variant in a conserved region of an intron that separates two small, alternatively spliced exons. Allele-specific and developmental differences were detected in the binding of a brain protein using newborn rat pups when probes containing the two rs6150532 alleles were used in electromobility gel shift assays. There were no significant differences in allele or genotype distribution found for any of the markers in the Caucasian sample. Although the samples size is relatively small, the findings support a role for NRG1 in SZ in African Americans and suggest that polymorphic differences in regions of the gene that recognize AT-binding proteins may be a factor in disease pathogenesis.

Association of schizophrenia in African Americans to polymorphism in synapsin III gene

Linkage studies in families with schizophrenia have pointed to chromosome 22q12-q13 as one of several regions of the genome that may contain a susceptibility gene. The gene coding for synapsin III, an intrinsic synaptic vesicle membrane protein, maps to this target region. Two tightly linked single-nucleotide polymorphisms were recently found in a small subset of patients with SZ - a synonymous variant, L469L (469G>A), and a non-synonymous variant, S470N (470G>A) - which results in the loss of a mitogen-activated protein kinase serine phosphorylation site. We also found a slight increase in 470A in Caucasian patients from the US with schizophrenia. But, the sample size and allele frequency were too small to draw definitive conclusions. However, both single-nucleotide polymorphisms were much more polymorphic in African American controls than in Caucasian controls, thereby providing a better sample cohort to analyze for schizophrenia involvement. For the codon 469 single-nucleotide polymorphisms, a 50-fold increase was observed in the frequency of 469A in African Americans compared with Caucasians. Furthermore, there was an increase in the percentage of African American patients with schizophrenia who were homozygous for the 469A allele compared with controls who were homozygous (11 versus 5%; AA vs. all other genotypes - Fisher statistic=3.08, P=0.04, one-tailed). An increase in 470A heterozygotes was also found, but the results fell short of being statistically significant. The findings support a role for synapsin III in a subset of African American patients with schizophrenia and raises questions about selective pressure in Africa to account for the extraordinary disparity of the 469 and 470 single-nucleotide polymorphisms in different ethnic populations.

A Two-Stage Method for the Study of Cultural Bias in the Diagnosis of Schizophrenia in African Americans

Reasons for diagnostic bias in psychiatric evaluations of African Americans fall into two basic categories: clinician bias, which is the lack of adherence to diagnostic criteria during psychiatric evaluations, and cultural bias, which is true ethnic/racial differences in symptom expression being overlooked or misinterpreted by diagnosticians. The ideal method of studying cultural biases in the psychiatric diagnosis of African Americans is a two-stage procedure with the first stage controlling for clinician bias and the second stage addressing cultural bias. This study evaluated a two-stage procedure that first considers clinician bias by a structured clinical interview followed by a best estimate diagnosis by a mental health clinician who is a cultural expert. The method was developed and evaluated for its reliability and validity in the Culturally Sensitive Diagnostic Interview Research Project. Data from 24 psychiatric inpatients were used to evaluate this diagnostic approach. Several hypotheses were tested, but not all were supported.

NOTCH4 gene haplotype is associated with schizophrenia in African Americans

Background The goal of this study was to investigate the relationship between the NOTCH4 gene and schizophrenia in African American (AA) and European American (EA) subjects. Methods Two single nucleotide polymorphisms (SNPs) at the NOTCH4 locus were genotyped in 123 AA schizophrenia patients, 223 EA schizophrenia patients, 85 AA healthy control subjects, and 211 EA healthy control subjects. The specific markers studied were -1725T/G and -25T/C. Comparisons of allele and haplotype frequencies between patients and control subjects were performed with the chi-square test, the Fisher's Exact Test, and CLUMP software. Linkage disequilibrium (LD) between these two SNPs was calculated with the 3LOCUS program. Results The haplotype -1725G/-25T associates to schizophrenia in AA subjects ( p = .0008), but not in EA subjects. Alleles -1725G and allele -25T are in positive LD both in AAs and EAs. Allele and haplotype frequencies differ significantly between AAs and EAs. Conclusions The haplotype -1725G/-25T at the NOTCH4 locus, which results from SNPs of NOTCH4 that are in LD, may increase susceptibility to schizophrenia in AAs. Any effect of this locus on risk for schizophrenia is population-specific.

Ethnicity and diagnosis in patients with affective disorders.

Clinically, African American psychiatric patients are disproportionately diagnosed with schizophrenia compared with white patients. Why this occurs is unknown. Extending prior work, the authors hypothesized that first-rank symptoms distract clinicians so that they fail to identify affective disorders in African Americans. 195 African American and white patients with at least 1 psychotic symptom (delusions, hallucinations, or prominent thought disorder) at admission were recruited from January 1, 1998, through May 31, 2001. Each patient received 3 independent DSM-IV diagnoses: a clinical diagnosis, a structured-interview diagnosis, and an expert-consensus diagnosis. The expert-consensus diagnoses were derived from the structured interviews, which were audiotaped and transcribed, and medical records. After reviewing edited transcripts and medical records from which ethnic cues had been eliminated, 2 psychiatrists assigned expert-consensus diagnoses and first-rank symptom ratings. For the 79 patients who received an expert-consensus diagnosis of an affective disorder, clinical variables, diagnoses, and first-rank symptoms were compared between African American (N = 39) and white (N = 40) patients. Seventy-nine (41%) of 195 patients were diagnosed with an affective disorder by expert consensus. African American men with an expert-consensus affective disorder were significantly (p <.03) more likely than other patients to be diagnosed with a schizophrenia spectrum disorder by clinical assessment and structured interview. Although first-rank symptoms were more commonly identified in African American men, this finding did not explain the difference in diagnoses. Post hoc analyses suggested that African American men diagnosed with a schizophrenia spectrum disorder were more likely than other patients to have been identified during structured interview as having psychotic symptoms in the absence of affective symptoms. The apparent misdiagnosis of schizophrenia in African-Americans with mood disorders cannot be ascribed to differences in first-rank symptoms. However, it may be due to a perception that psychotic symptoms are more chronic or persistent than affective symptoms in these patients.

Report of the Chromosome 5 Workshop of the Sixth World Congress on Psychiatric Genetics

The Chromosome 5 Workshop heard new data on a schizophrenia susceptibility locus in the 5q23.3-q31.1 region. Sixty-two pedigrees from Finland gave a lod score of 1.36 at the CSF1R locus approximately 14 cM distal to IL9/D5S393, where positive results from three pedigree collections converged at the 1997 workshop. Though positive at CSF1R, the new data were only weakly positive at the IL9 (lod 0.46) and D5S393 (lod 0.07) loci themselves. The workshop also reviewed new evidence in the 5p14.1-p13.1 region, where a large pedigree of schizophrenia of Puerto Rican extraction has suggested a susceptibility locus with a maximum lod score at D5S111. Twenty-one new pedigrees multiplex for schizophrenia in African Americans gave positive lod scores at D5S111 and flanking loci. In bipolar illness five genetically related pedigrees from the Saguenay-Lac-St. Jean region of Quebec identified a region of interest at 5q31.3-q35.1. This region overlaps with the D5S423 locus and includes the D5S812 locus and the 5q34 region, all of which are consistent with linkage in at least one other study.