Biomedical subjects

R Murray

Publications and source records attributed to R Murray.

At least 73 records · Page 4Linked to original sources

PubMed1999

Functional MR imaging of confounded hypofrontality.

Comparatively reduced blood flow to frontal brain regions in patients with schizophrenia (hypofrontality) has been frequently observed in the last 25 years. However, there is an inconstant quality to hypofrontality, suggesting either confounded observation of a static (trait-like) abnormality, or that it is a genuinely dynamic (state-like) phenomenon. Possible confounds in functional magnetic resonance imaging (fMRI) studies of hypofrontality are classified. Methods for assessment and correction of stimulus correlated motion (an extracerebral confound) are reviewed in the context of fMRI data acquired from five schizophrenic patients and five comparison subjects during performance of a verbal fluency task. Factorial analysis of these and other data, acquired from the same subjects during a semantic decision task, is used to exclude a number of possible intracerebral confounds. By analogy to the historical controversy concerning the appearance of the planet Saturn viewed through early telescopes, understanding the inconstancy of hypofrontality in schizophrenia is likely to progress more by theoretically driven experiments that exploit the repeatability of fMRI than by further technological development alone.

Analysis of Variance↗

PubMed1998

IL-7 deficiency prevents development of a non-T cell non-B cell-mediated colitis.

IL-7 is a stromal cell-derived cytokine with a well-established physiologic role in lymphocyte biology. This report describes an unexpected role for IL-7 in the development of colitis in a T and B cell-deficient environment. Recombination-activating gene-2 (RAG-2)-deficient mice (RAG-2(-/-)) were exposed to and subsequently maintained a horizontally transmitted microbial flora that included Helicobacter hepaticus. These animals mounted a strong myeloid cell response and developed both systemic and local signs of a severe colitis. A striking infiltration of F4/80 and MHC class II-positive cells was seen in the colon and cecum of animals undergoing the disease. Mice mutant for both IL-7 and RAG-2 (IL-7/RAG-2(-/-)) that were colonized by the same flora showed no signs of myeloid responses or colitis, indicating that IL-7 plays a critical role in exacerbating a non-T cell/non-B cell-mediated chronic inflammatory response. Recombinant IL-10 protein therapy was able to prevent the occurrence of colitis in susceptible mice, suggesting a pivotal role for macrophages. The implications of a role for IL-7 in this disease model with respect to human inflammatory bowel disease are discussed.

Animals↗

PubMed1998

Early and late weight gain following smoking cessation in the Lung Health Study.

The authors examine weight gains associated with smoking cessation in the Lung Health Study (1986-1994) over a 5-year follow-up period. A cohort of 5,887 male and female smokers in the United States and Canada, aged 35-60 years, were randomized to either smoking intervention or usual care. Among participants who achieved sustained quitting for 5 years, women gained a mean of 5.2 (standard error, 5.0) kg in year 1 and a mean of 3.4 (standard error, 5.5) kg in years 1-5. Men gained a mean of 4.9 (standard error, 4.9) kg in year 1 and a mean of 2.6 (standard error, 5.8) kg in years 1-5. In regression analyses, smoking-change variables were the most potent predictors of weight change. Participants going from smoking to quit-smoking in a given year had mean weight gains of 2.95 kg/year (3.61%) in men and 3.09 kg/year (4.69%) in women. Over 5 years, 33% of sustained quitters gained > or = 10 kg compared with 6% of continuing smokers. Also among sustained quitters, 7.6% of men and 19.1% of women gained > or = 20% of baseline weight; 60% of the gain occurred in year 1, although significant weight gains continued through year 5. The average gains and the high proportions of sustained and intermittent quitters who gained excessive weight suggest the need for more effective early interventions that address both smoking cessation and weight control.

Adult↗

PubMed1998

Differences in distribution of ages of onset in males and females with schizophrenia.

An earlier age at onset of schizophrenia in men as opposed to women, has been widely reported, but hitherto, insufficient account has been taken of parameters that might confound this finding. Furthermore, few explanatory models have accounted for the differences in shape of the age-at-onset distributions in males and females with schizophrenia. A catchment area sample of 477 first contact cases with schizophrenia or related disorders was ascertained through a case register. Differences in age at onset distributions between males and females were determined, and adjustment made for potential confounding factors. The most powerful predictors of early illness-onset were poor premorbid occupational functioning, single marital status, and male sex. The earlier onset in males was robust to controlling for other parameters. The shape of the onset distribution also differed between the sexes: SKUMIX analysis revealed a two-peak distribution for males, and a three-peak distribution for females. The mean age at onset for schizophrenia is earlier in males, and the onset distribution differs between the sexes. Psychosocial variables cannot explain these findings. Possible explanations for these gender differences include males and females being differentially susceptible to subtypes of illness with different mean ages at onset; precipitating and/or ameliorating factors operating at different stages of life in males and females; and/or an X-linked susceptibility locus that determines the age at onset.

Age Factors↗

PubMed1998

Defective expression of granulocyte-macrophage colony-stimulating factor/interleukin-3/interleukin-5 receptor common beta chain in children with acute myeloid leukemia associated with respiratory failure.

Deficiency of the granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin-3 (IL-3)/IL-5 receptors common beta chain (betac) is a cause of fatal respiratory failure. betac deficiency manifests as pulmonary alveolar proteinosis (PAP). PAP has heterogenous etiologies that may be genetic or aquired. Some cases of PAP have been reported to be associated with hematologic malignancies such as acute myeloid leukemia (AML). In mice, the PAP phenotype was generated by targeted deletion of the gene for betac and can be treated by transplantation of wild-type bone marrow into betac -/- mice. Thus, our findings in betac -/- mice provide evidence for a causal relationship between the lung disease and the hematopoietic system. We describe here expression defects of betac or betac plus GM-CSF receptor alpha chain (GM-CSFR alpha) in 3 pediatric patients with AML and PAP symptoms. All of the patients' leukemic cells failed to express normal levels of betac. The leukemic cells of patients no. 2 and 3 additionally lacked the expression of GM-CSFR alpha, as shown by flow cytometry. Strikingly reduced or absent function of betac was demonstrated in clonogenic progenitor assays with absent colony-forming unit (CFU) growth after GM-CSF or IL-3 stimulation. The response to growth factors acting via a growth factor receptor distinct from the GM-CSF/IL-3/IL-5 system (recombinant human granulocyte colony-stimulating factor [rhG-CSF]) was normal. After antileukemic treatment, the pulmonary symptoms resolved and betac or betac plus GM-CSFR alpha expression was normal. Our findings provide evidence that a defect in the expression of betac or betac plus GM-CSFR alpha on AML blasts can be associated with respiratory failure in patients with AML.

Acute Disease↗

PubMed1998

Mice deficient for the ecto-nicotinamide adenine dinucleotide glycohydrolase CD38 exhibit altered humoral immune responses.

CD38 is a membrane-associated ecto-nicotinamide adenine dinucleotide (NAD+) glycohydrolase that is expressed on multiple hematopoietic cells. The extracellular domain of CD38 can mediate the catalysis of NAD+ to cyclic adenosine diphosphoribose (cADPR), a Ca2+-mobilizing second messenger, adenosine diphosphoribose (ADPR), and nicotinamide. In addition to its enzymatic properties, murine CD38 has been shown to act as a B-cell coreceptor capable of modulating signals through the B-cell antigen receptor. To investigate the in vivo physiological function(s) of this novel class of ectoenzyme we generated mice carrying a null mutation in the CD38 gene. CD38-/- mice showed a complete loss of tissue-associated NAD+ glycohydrolase activity, showing that the classical NAD+ glycohydrolases and CD38 are likely identical. Although murine CD38 is expressed on hematopoietic stem cells as well as on committed progenitors, we show that CD38 is not required for hematopoiesis or lymphopoiesis. However, CD38-/- mice did exhibit marked deficiencies in antibody responses to T-cell-dependent protein antigens and augmented antibody responses to at least one T-cell-independent type 2 polysaccharide antigen. These data suggest that CD38 may play an important role in vivo in regulating humoral immune responses.

ADP-ribosyl Cyclase↗

PubMed1998

Negative regulation by interleukin-3 (IL-3) of mouse early B-cell progenitors and stem cells in culture: transduction of the negative signals by betac and betaIL-3 proteins of IL-3 receptor and absence of negative regulation by granulocyte-macrophage colony-stimulating factor.

The receptors for interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5 share a common signaling subunit betac. However, in the mouse, there is an additional IL-3 signaling protein, betaIL-3, which is specific for IL-3. We have previously reported that IL-3 abrogates the lymphoid potentials of murine lymphohematopoietic progenitors and the reconstituting ability of hematopoietic stem cells. We used bone marrow cells from betac- and betaIL-3-knock-out mice to examine the relative contributions of the receptor proteins to the negative regulation by IL-3. First, we tested the effects of IL-3 on lymphohematopoietic progenitors by using lineage-negative (Lin-) marrow cells of 5-fluorouracil (5-FU)-treated mice in the two-step methylcellulose culture we reported previously. Addition of IL-3 to the combination of steel factor (SF, c-kit ligand) and IL-11 abrogated the B-lymphoid potential of the marrow cells of both types of knock-out mice as well as wild-type mice. Next, we investigated the effects of IL-3 on in vitro expansion of the hematopoietic stem cells. We cultured Lin-Sca-1-positive, c-kit-positive marrow cells from 5-FU-treated mice in suspension in the presence of SF and IL-11 with or without IL-3 for 7 days and tested the reconstituting ability of the cultured cells by transplanting the cells into lethally irradiated Ly-5 congenic mice together with "compromised" marrow cells. Presence of IL-3 in culture abrogated the reconstituting ability of the cells from both types of knock-out mice and the wild-type mice. In contrast, addition of GM-CSF to the suspension culture abrogated neither B-cell potential nor reconstituting abilities of the cultured cells of wild-type mice. These observations may have implications in the choice of cytokines for use in in vitro expansion of human hematopoietic stem cells and progenitors.

Animals↗

PubMed1998

Case-control, haplotype relative risk and transmission disequilibrium analysis of a dopamine D2 receptor functional promoter polymorphism in schizophrenia.

The dopamine system has long been suspected of aetiological involvement in schizophrenia because of a number of lines of evidence pointing to excess dopaminergic activity in the illness. Recently, negative allelic association was reported between a single base deletion in the promoter region of the DRD2 gene, -141 delta C, and schizophrenia, with an odds ratio of 0.60. This was of particular interest since the deletion, which occurs in about 22% of the Japanese population, is functional in that it results in reduced (20-40% of wild-type) basal levels of receptor expression. We have examined this polymorphism in 229 family trios from SW China, consisting of both parents and a single offspring affected by schizophrenia, and 151 Caucasian cases with schizophrenia and 145 Caucasian normal controls from the UK. Using the haplotype-based haplotype relative risk method (HHRR), the frequency of the -141 delta C allele was 6.9% in the affected Chinese subjects compared to an estimated frequency of 9.0% in this population (chi 2 = 1.21, 1 df, ns), with an odds ratio of 0.76 (95% CI 0.46-1.25). Using the transmission disequilibrium test, we likewise found no evidence for linkage or linkage disequilibrium with this polymorphism (chi 2 = 0.94, 1 df, ns). In the Caucasian cases, the frequency of the -141 delta C was 13% compared to 10% in controls (chi 2 = 1.57, p = 0.21) with an odds ratio of 1.39 (95% CI 0.81-2.40). We thus conclude that the DRD2 -141 delta C polymorphism is less frequent in Chinese and Caucasian populations (9%) than in Japan (22%) and is not a significant risk factor for schizophrenia in our populations. The -141 delta C allele remains a strong candidate for a variety of other traits and diseases, including reward-related behaviours such as drug abuse, which have been associated with the dopamine system.

Adolescent↗

PubMed1998

The role of IL-7 in thymic and extrathymic development of TCR gamma delta cells.

IL-7-deficient (IL-7(-/-)) mice have reduced numbers of B and TCR alpha beta cells, but lack mature TCR gamma delta cells. Although most T cell development occurs in the thymus, some intestinal intraepithelial lymphocytes (IEL), including TCR gamma delta cells, can develop extrathymically. Epithelial cells in both thymus and intestine synthesize IL-7, suggesting that TCR gamma delta cell development could occur in either site. To evaluate the role of thymic IL-7 in development of TCR gamma delta cells, newborn TCR beta-deficient (TCR beta(-/-)) thymi were grafted to IL-7(-/-) mice. Donor- and host-derived TCR gamma delta cells were recovered from thymus grafts, spleen, and IEL. However, when IL-7(-/-) thymi were grafted to TCR beta(-/-) mice, no development of graft-derived TCR gamma delta cells occurred, indicating that extrathymic IL-7 did not support TCR gamma delta IEL generation from newborn thymic precursors. In contrast, TCR gamma delta IEL development occurred efficiently in adult, thymectomized, irradiated C57BL/6J mice reconstituted with IL-7(-/-) bone marrow. This demonstrated that extrathymic development of TCR gamma delta IEL required extrathymic IL-7 production. Thus, intrathymic IL-7 was required for development of thymic TCR gamma delta cells, while peripheral IL-7 was sufficient for development of extrathymic TCR gamma delta IEL.

Animals↗

PubMed1998

Testosterone and IL-6 requirements for human C-reactive protein gene expression in transgenic mice.

In vitro, IL-6 is the main inducer of the human C-reactive protein (CRP) gene, and IL-1 and steroids can enhance this effect. However, in mice, IL-6 is necessary but not sufficient for induction of the human CRP transgene, and testosterone is required for its constitutive expression by males. To examine the relative contributions of testosterone and IL-6 in the regulation of CRP gene expression, we produced CRP-transgenic (CRPtg), IL-6-deficient (IL-6-/-) mice. Male CRPtg/IL-6-/- mice expressed CRP constitutively, but CRP levels were not increased after injection of LPS. However, acute-phase CRP levels were attained after injection of IL-6. In contrast, female CRPtg/IL-6-/- mice did not express CRP constitutively or after administration of LPS, IL-6, IL-1, or IL-6 plus IL-1. Like males, testosterone-treated CRPtg/IL-6-/- females expressed CRP constitutively, and their transgene responded to injection of IL-6. The endogenous acute-phase protein serum amyloid P (SAP) was expressed constitutively equally by male and female IL-6-/- mice, responded minimally to LPS, and did not respond to either IL-6 or IL-1 alone. Acute-phase levels of SAP were induced in IL-6-/- mice by injection of IL-6 together with IL-1 or LPS. We conclude that in vivo, both constitutive and IL-6-dependent acute-phase expression of the CRP transgene require testosterone. In contrast, testosterone is not required for expression of the SAP gene, which requires IL-1 plus IL-6 for acute-phase induction.

Age Factors↗

PubMed1998

Obstetric complications and familial morbid risk of psychiatric disorders.

Obstetric complications (OCs) have been found to occur in higher frequency in patients with schizophrenia. One explanation for this finding is that the genes that contribute to the schizophrenia phenotype also influence the likelihood to experience OCs. If this were true, morbid risk of psychiatric illness should be higher in the first-degree relatives of both schizophrenic and control probands exposed to OCs, compared to probands not exposed to OCs. We set out to test this hypothesis. Information on OCs, blind to family history of psychiatric disorder, was collected retrospectively through maternal interview in 151 psychotic patients and 100 controls. Family history (FH) in relatives of cases (n = 600) and controls (n = 461) was assessed with the FH-RDC and through personal interviews. Tests for associations between family history and OCs were conducted using Cox proportional hazard regression. In the cases, familial morbid risk of affective disorder was greater in those with a history of OCs (hazard ratio (HR) = 1.9, P = 0.007). Analyses examining individual complications revealed associations between FH of affective disorder and pre-eclampsia (HR = 2.9, P = 0.003) and FH of affective disorder and breech presentation (HR = 2.8, P = 0.02), especially when family history in the relatives was confined to affective illness in the mother (HR pre-eclampsia = 4.4, P = 0.009; HR breech-presentation = 4.2, P = 0.008). In controls, affective illness in the mother was not only associated with breech presentation (HR = 7.0, P = 0.01) and pre-eclampsia (HR = 4.4, P = 0.03) but also with other complications. Familial morbid risk of schizophrenia and related psychoses was not associated with OCs. The positive associations between OCs and familial morbid risk of affective disorder suggest that the factors that contribute to familial aggregation of affective symptoms in psychotic patients also influence the likelihood to experience OCs. Although the proportion of OCs that could be attributed to these factors was very small, part of the relationship between family history of affective disorder and psychosis may be mediated by OCs.

Age of Onset↗

PubMed1998

Liarozole--a novel treatment approach for advanced prostate cancer: results of a large randomized trial versus cyproterone acetate. Liarozole Study Group.

OBJECTIVES: To compare the efficacy of oral liarozole, the first retinoic acid metabolism-blocking agent (RAMBA) to be developed as differentiation therapy for human solid tumors, with that of cyproterone acetate (CPA), an antiandrogen for the treatment of metastatic prostate cancer. Liarozole promotes differentiation of cancer cells by increasing the intratumoral levels of retinoic acid. METHODS: A total of 321 patients with metastatic prostate cancer in relapse after first-line endocrine therapy entered a Phase III international multicenter study (recruitment from February 1992 to August 1994) comparing liarozole (300 mg two times daily) with CPA (100 mg two times daily). RESULTS: Accounting for differences in baseline prognostic factors, the adjusted hazard ratio for survival was 0.74 in favor of liarozole (P = 0.039), indicating a 26% lower risk of death than in patients treated with CPA. Median crude (unadjusted) survival time was the same in the liarozole group as in the CPA group (10.3 months). More patients showed a PSA response (at least 50% reduction in PSA from baseline) when treated with liarozole (20%) than with CPA (4%) (P < 0.001). Prostate-specific antigen (PSA) responders had a median survival benefit of 10 months over nonresponders, irrespective of treatment (hazard ratio 0.43; P = 0.0018). PSA response was apparent within 3 months in approximately 90% of patients who responded. Pain improved more in the liarozole group than in the CPA group (P = 0.03). PSA responders had lower median pain scores than nonresponders (1.7 versus 2.5) and better quality of life (median Functional Living Index-Cancer score 108 versus 98) at end point, ie, treatment discontinuation, as well as throughout the treatment period. Among the most frequently occurring adverse events in the liarozole group were dry skin (51% of patients), pruritus (25%), rash (16%), nail disorders (16%), and hair loss (15%). These adverse events were generally mild to moderate in severity and did not affect the overall quality of life score. There were no detectable effects of either treatment on vital signs such as blood pressure, heart rate, electrocardiogram, and body weight. CONCLUSIONS: Liarozole is superior to CPA in terms of PSA response, PSA progression, and survival, and is capable of maintaining patients' quality of life. The observed adverse events were mild to moderate in nature. These results show that liarozole is a possible treatment option after first-line endocrine therapy has failed.

Aged↗

PubMed1998

Does the method of data collection affect the reporting of depression in the relatives of depressed probands?

BACKGROUND: Data is usually collected from different sources in family studies in depression. We sought to determine what effect different methods of data collection had on the reporting of the lifetime prevalence of depression in the relatives of depressed probands. METHOD: We examined the psychiatric histories of 519 first-degree relatives of a consecutive series of 89 hospitalised depressed probands to ascertain their lifetime prevalence of RDC Major Depression. These data on relatives were obtained either directly with the SADS-L (n = 116), indirectly with the Family History RDC (FH-RDC) (n = 283) or by examining the casenotes of the probands (n = 120). RESULTS: The method of data collection had a marked effect on the reported prevalence of depression, with direct interview being much more sensitive in detecting the less severe forms of the illness. The lifetime prevalence of hospitalised depression in relatives, however, was unaffected by the method of the data collection. Variation in lifetime prevalence of depression between the SADS-L and FH-RDC appeared to be due mainly to differences in the sensitivity of the instrumentation rather than to biases in sampling. CONCLUSION: We confirm that indirect sources of family information have reduced sensitivity for the detection of depression in relatives compared with direct interview. LIMITATIONS: The numbers of relatives directly interviewed were small and the probands represented a severely affected sample which limits the generalisability of the findings. CLINICAL RELEVANCE: Combining data from different methods of collection in family studies is therefore problematic unless a narrow definition of caseness is used (e.g. depression requiring hospitalisation).

Bias↗

PubMed1998

Primary sensory neurons migrate in response to the chemokine RANTES.

We examined the potential for the C-C chemokine RANTES to stimulate dorsal root ganglia (DRG) cell migration. Embryonic day 12 (E12.5) mouse DRG cells migrated in response to RANTES, in vitro, differentiating to the nociceptive phenotype within 18 h. In addition, RANTES stimulated intracellular calcium mobilization in DRG cells. RANTES expression was demonstrated by polymerase chain reaction analysis to be present in E10.5 limb bud, E12.5 DRG, Schwann cells, spinal cord and skin. RANTES protein was detected immunohistochemically in E12.5 DRG and the cutaneous layers of the developing hind limb. Thus, RANTES expression is spatially and temporally consistent with an effector molecule in sensory neuropoiesis, potentially expanding the role of this chemokine to include neurotropism.

Animals↗

PubMed1998

The general approach to the difficult patient.

Difficult patients are familiar to emergency physicians. This article explores characteristics of the difficult patient, recognized emergency department processes, and physician characteristics that can contribute to difficulties. These difficulties can be minimized by caregivers who are skilled in managing the therapeutic relationship. This relationship is characterized by firm boundaries, good communication, patient trust, wisdom, and an effective system that supports both patients and caregivers.

Attitude of Health Personnel↗

PubMed1998

Impaired development of Th2 cells in IL-13-deficient mice.

We report that Th2 cell cultures generated using T cells or splenocytes from IL-13-deficient mice produce significantly reduced levels of IL-4, IL-5, and IL-10 compared with wild-type. In contrast, IL-4 and IL-5 production by mast cells stimulated in vitro with PMA, ionomycin, or IgE cross-linking are unaffected. In vitro Th2 cell differentiation cannot be rescued by the addition of exogenous factors, but in vivo antigen challenge and administration of IL-13 can increase Th2-like cytokine responses as can infection with the parasitic nematode Nippostrongylus brasiliensis. IL-13-deficient mice also have lower basal levels of serum IgE and biased antigen-specific immunoglobulin responses. Thus, IL-13 is an important regulator of Th2 commitment and may therefore play a central role in atopy and infectious diseases.

Animals↗

PubMed1998

Quality of parenting and vulnerability to depression: results from a family study.

BACKGROUND: We examined a group of subjects at familial risk of depression and explored the relationship between the perceptions of parents and a history of depression. We also investigated: (a) whether any difference in perceived parenting found between those with and without a past history of depression was an artefact of the depression; and (b) whether the relationship between parenting and depression was explained by neuroticism. METHOD: We took a sample of first-degree relatives selected from a family study in depression and subdivided them by their history of mental illness on the SADS-L, into those: (a) without a history of mental illness (N = 43); and (b) those who had fully recovered from an episode of RDC major depression (N = 34). We compared the perceptions of parenting, as measured by the Parental Bonding Instrument (PBI), in these two groups having adjusted for the effect of neuroticism and subsyndromal depressive symptoms. We also had informants report on parenting of their siblings, the latter being subdivided into those with and without a past history of depression. RESULTS: Relatives with a past history of depression showed lower care scores for both mother and father combined compared with the never ill relatives. The presence of a history of depression was associated with a non-significant reduction in the self-report care scores compared to the siblings report. Vulnerable personality (as measured by high neuroticism) and low perceived care were both found to exert independent effects in discriminating between the scores of relatives with and without a history of depression and there was no interaction between them. CONCLUSION: This study confirmed that low perceived parental care was associated with a past history of depression, that it was not entirely an artefact of having been depressed, and suggested that this association was partially independent of neuroticism.

Adult↗

PubMed1998

Urbanization and psychosis: a study of 1942-1978 birth cohorts in The Netherlands.

BACKGROUND: Urban birth is associated with later schizophrenia. This study examined whether this finding is diagnosis-specific and which individuals are most at risk. METHODS: All live births recorded between 1942 and 1978 in any of the 646 Dutch municipalities were followed-up through the National Psychiatric Case Register for first psychiatric admission for psychosis between 1970 and 1992 (N = 42115). RESULTS: Urban birth was linearly associated with later schizophrenia (incidence rate ratio linear trend (IRR), 1.39; 95% confidence interval (95% CI), 1.36-1.42), affective psychosis (IRR, 1.18; 95% CI, 1.15-1.21) and other psychosis (IRR, 1.27; 95% CI, 1.24-1.30). Individuals born in the highest category of the three-level urban exposure were around twice as likely to develop schizophrenia. Associations were stronger for men and for individuals with early age of onset. The effect of urban birth was also stronger in the more recent birth cohorts. CONCLUSIONS: There are quantitative differences between diagnostic categories in the strength of the association between urban birth and later psychiatric disorder. High rates of psychosis in urban areas may be the result of environmental factors associated with urbanization, the effect of which appears to be increasing over successive generations.

Adult↗