J. Welham

Season of birth and schizophrenia: a systematic review and meta-analysis of data from the Southern Hemisphere

AIMSnData from the Northern Hemisphere support an excess of winter-spring births of individuals who later develop schizophrenia when compared with the general population. The data from the Southern Hemisphere have been less consistent. This paper will present a systematic review and meta-analysis of relevant data from the Southern Hemisphere.nnnMETHODSnTo identify relevant studies we searched electronic databases, reviewed citations from target publications and wrote letters to published authors in the field. The counts for observed and expected births were assessed in four planned comparisons. In the absence of significant heterogeneity, the data were combined using Mantel-Haenzel odds ratio in a fixed effect model.nnnRESULTSnTwelve studies were identified. Published and unpublished data from eight of these were able to be included in the analyses. For the two seasonal comparisons (n = 20,017), small but non-significant excesses were found in the first comparison (winter versus other seasons; OR = 1.04, 0.99-1.08) and for the second comparison (winter and spring versus other seasons; OR = 1.03, 0.99-1.07). For the two quarterly comparisons (n = 14,799), there was a small but non-significant excess found in the third comparison (third quarter versus other quarters; OR = 1.03, 0.98-1.09), and a small but non-significant deficit in the fourth comparison (third and fourth quarter versus other quarters OR = 0.99, 0.95-1.04).nnnCONCLUSIONSnAssuming that season of birth acts as a proxy marker for fluctuating non-genetic risk-modifying factors for schizophrenia, this review suggests that in the Southern Hemisphere these factors may be weaker, less prevalent, less regular, and/or may be modified by other confounding or modifying variables.

Seasonality of first admissions for schizophrenia in the Southern Hemisphere

Northern Hemisphere studies of first admissions for schizophrenia have shown an excess of summer admissions (June, July and August) compared to other times of the year. The within-year fluctuations in first admissions could be related to meteorological factors that fluctuate between seasons (e.g. temperature, photoperiod) and/or social factors (e.g. holidays, religious events). If meteorological factors were primarily responsible for the fluctuation, then Southern Hemisphere studies should find excess first admissions in December, January and February. This paper presents the first season of first admission study of schizophrenia in the Southern Hemisphere. The month and year of first admission for schizophrenia (ICD 8/9) for 4487 male and 3252 female, Australian-born individuals were extracted from a Queensland mental health register. Spectral analysis showed a strong annual periodicity of first admissions for males with the peak in August (Southern Hemisphere winter) and a trough in the summer months (December to February). The pattern for females also displayed annual periodicity. These results correspond to the Northern Hemisphere reports of excess of schizophrenia first admissions in terms of the month of the year but not the season of excess. Further work is needed in order to clarify the impact of latitude and meteorological factors on the month of first admission for schizophrenia.

Effects of nifedipine on psychosis and tardive dyskinesia in schizophrenic patients

In an open label study, two fixed doses of nifedipine (30 mg and 60 mg daily) were added to the usual antipsychotic drug treatments of 10 patients suffering from chronic schizophrenia. While no patient experienced significant improvements, statistically significant falls in Brief Psychiatric Rating Scales scores were observed. A significant reduction in Abnormal Involuntary Movement Scale scores was observed in those patients with tardive dyskinesia. After the addition of nifedipine, four of the 10 patients showed large increases in plasma neuroleptic activity (radioreceptor assay) that decreased to baseline levels within two weeks. The possibility that this represents competitive inhibition and subsequent induction of the liver metabolism of the antipsychotic drugs is discussed. Adverse effects encountered are also discussed.

Season of birth effect and latitude: A systematic review and meta-analysis of northern hemisphere schizophrenia studies

The aim of this review was to exmaine if latitude was associated with the magnitude of this seasonal effect in the northern hemisphere. Based on the hypothesis that low prenatal vitamin D is a risk modifying factor for schizophrenia, we hypothesised that higher latitudes would be associated with greater seasonal effect. We undertook a systematic search for all publications related to seasonality in schizophrenia in the northern hemisphere. Inclusion criteria included: ( 1 ) the schizophrenia and general population groups were drawn from the identical time periods and catchment areas; (2) the publication contained data which allowed comparison of winter/spring births versus autumn/summer births. An exact or mean latitude value was given to each site. Data for 62,934 subjects drawn from 20 sites were available. A significant positive correlation was found between the odds ratio for the season of birth comparison and latitude (r=0.48, p=0.03). For the rectaanalysis, we divided the sample into three latitude bands each with roughly equal number of subjects (sample size tertiles).

Placebo controlled double blind study of the effects of proglumide in the treatment of schizophrenia

A double-blind, placebo-controlled, randomized study was performed to determine whether proglumide added to ongoing neuroleptic medication was efficacious in the treatment of 32 patients with persistent positive and negative schizophrenic symptoms. Patients treated with both proglumide and placebo showed a significant improvement over the 8 weeks of the study, but no significant difference between the patients taking proglumide and those taking placebo could be demonstrated. In addition, proglumide had no effect on plasma homovanillic acid concentrations or neuroleptic drug activity. The results suggest that, at least for the dose of proglumide used in this study (15 mg/day), the addition of this particular cholecystokinin antagonist does not potentiate the antipsychotic efficacy of neuroleptic medication in patients with persistent schizophrenic symptoms.

Heterogeneity in schizophrenia; mixture modelling of age-at-first-admission, gender and diagnosis

Welham J, McLachlan G, Davies G, McGrath J. Heterogeneity in schizophrenia; mixture modelling of age‐at‐first‐admission, gender and diagnosis.

A systematic review of the incidence of schizophrenia: The distribution of rate items and the influence of methodology, urbanicity, sex and migrant status

Background: A single-blind, multicentre RCT compared the class of new (non-clozapine) atypical drugs with clozapine in patients in the NHS whose medication was being changed because of poor clinical response to two or more antipsychoticdrugs.Methods: The primary outcome was the Quality of Life Scale. Secondary clinical outcomes included symptoms (PANSS), side effects and participant satisfaction. Economic outcomes were costs of health and social care and a utility measure. A total of 136 (98% of the planned sample) participants were randomised. Followup at 52 weeks, blind to treatment allocation, was complete in 87%.Results: The intent to treat comparison of new atypicals compared with clozapine in people with more narrowly defined treatment resistance showed an advantage for commencing clozapine in quality of life (QLS) at trend level ( p = 0.08) and insymptoms (PANSS), that was statistically significant ( p = 0.01), at 1 year. Clozapine showed approximately a 4-point advantage (not statistically significant) on QLS score at 52 weeks, against the predicted 10 points, and approximately a 5-point advantage on PANSS total score. Clozapine showed a trend towards having less total extrapyramidal side effects ( p = 0.1). Participants reported at 12 weeks that their mental health was significantly better with clozapine than with new atypicals ( p < 0.05). Net costs of care varied widely, with a mean of �33,588 in the clozapine group and �28,122 in the new atypical group, not a statistically significant difference. Of these costs, 4.0% and 3.3%, respectively, were dueto antipsychotic drug costs.Background/objective: Despite the high comorbidity of substance misuse and schizophrenia, few large scale British studies have looked at symptom profile and outcome in this population. The aim of this study was to use data on substance use among subjects with schizophrenia collected in a randomised controlled trial,nvalidated for the purpose of this study, to see if there are differences between substance users and non users on a variety of outcome measures.nMethod: 1. A sample of subjects in the CUtLASS study were interviewed using the SCID to determine whether SCID-diagnosed substance misuse disorders corresponded to substance misuse categories generated in the CUtLASS study from casenote review. 2. Substance users were compared with non users on a variety of outcome measures.nResults: 1. Two CUtLASS categories, no substance use and major substance use, could be validated against SCID diagnoses; the third category, minor use, could not be validated. 2. Substance misusers were more likely to be young men. There were no significant differences between users and non users for positivenand negative symptoms, quality of life, number of previous hospitalisations, extrapyramidal side effects or medication compliance. Drug users were younger at age of first treatment than non users. Alcohol users had more depressive symptoms than non users. Substance users had more negative attitudes towardsnprescribed medication, although this effect disappeared when age and gender were controlled for. Non compliance was associated with more severe psychopathology, and a worse quality of life.nConclusion: Substance misuse did not seem to confer the adverse outcomes that previous studies suggest.Background/objective: There is accumulating evidence for an important role for vitamin D in brain function, including our recent observations that animals deprived of vitamin D in utero had brains that were altered in shape at birth, with increased cell proliferation and reduced levels of NGF and GDNF. In the current study we examined the hypothesis that vitamin D deficiency during two separate developmental periods alters adult behaviour. Methods: Rats were conceived and born to mothers receiving a vitamin D-deficient diet and housed without UV light. At birth, the litters were reduced to three males and three females and half the mothers were placed under normal vitamin D conditions whilst half remained under vitamin D deplete conditions. At weaning, all animals were fed the normal diet. Mothers, and all animals at weaning, were rendered normocalcaemic with calcium supplemented water (2 mM). Control animals were born to mothers fed a normal diet but subject to similar litter size and calcium supplementation. At 10 weeks, all animals were subject to the holeboard test, elevated plus maze test, social interaction, prepulse inhibition of the acoustic startle response and a forced swim test. Results: Early vitamin D deficiency selectively enhanced locomotion in the holeboard test and increased activity in the elevated plus maze. Thus, early vitamin D deficiency appeared to induce quite specific behavioural deficits in adulthood, without inducing severe learning or motor abnormalities. Conclusion: These observations are consistent with an increase in dopaminergic tone, a finding previously reported in vitamin D depleted animals.Background/objective: There is accumulating evidence for an important role for vitamin D in brain function, including our recent observations that animals deprived of vitamin D in utero had brains that were altered in shape at birth, with increased cell proliferation and reduced levels of NGF and GDNF. In the current study we examined the hypothesis that vitamin D deficiency during two separate developmental periods alters adult behaviour. Methods: Rats were conceived and born to mothers receiving a vitamin D-deficient diet and housed without UV light. At birth, the litters were reduced to three males and three females and half the mothers were placed under normal vitamin D conditions whilst half remained under vitamin D deplete conditions. At weaning, all animals were fed the normal diet. Mothers, and all animals at weaning, were rendered normocalcaemic with calcium supplemented water (2 mM). Control animals were born to mothers fed a normal diet but subject to similar litter size and calcium supplementation. At 10 weeks, all animals were subject to the holeboard test, elevated plus maze test, social interaction, prepulse inhibition of the acoustic startle response and a forced swim test. Results: Early vitamin D deficiency selectively enhanced locomotion in the holeboard test and increased activity in the elevated plus maze. Thus, early vitamin D deficiency appeared to induce quite specific behavioural deficits in adulthood, without inducing severe learning or motor abnormalities. Conclusion: These observations are consistent with an increase in dopaminergic tone, a finding previously reported in vitamin D depleted animals.Background: The subjective experience of patients with schizophrenia, receiving antipsychotic medication has been a neglected research area.Methods: In a randomised controlled trial comparing the impact of new atypical antipsychotic drugs versus clozapine, 67 out of 136 patients with schizophrenia were randomised to receive clozapine. Baseline and 12 week assessments included the PANSS, DAI, and the Kemp Compliance scale.Results: The greater percentage improvement in total PANSS scores in patients randomised to clozapine was statistically significant when compared to the atypical group at 12 weeks (p < 0.05). Patients? subjective rating of their mental health improvement since commencing clozapine treatment correlated significantly with actual percentage improvement in PANSS scores from baseline to week 12 (p < 0.01). Significant correlations were also observed between the patients? subjective rating of their mental health improvement and both DAI score and theg12 PANSS insight item (p < 0.05). In a regression analysis, DAI score at week 12 explained 26% of the variance in patients? subjective rating of mental health improvement with clozapine. Percentage PANSS improvement explained a further 8% of the variance.Conclusion: Patients in an RCT of clozapine versus atypicals were able to subjectively rate their own improved mental health status, validated by objective improvement on the PANSS. This was predicted by drug attitude as measured by the DAI. Subjective reports are a useful and valid outcome measure in drug treatment trials.Background: Conceptually quality of life is a broad term and consists of a sense of well-being, life satisfaction and access to resources and opportunities.Methods: A subjective quality of life measure, the Lancashire quality of life scale(Oliver, 1991) was compared with an objective measure, the Heinrichs quality of life scale (Heinrichs et al,1884) in 75 subjects entering a randomised controlled trial comparing conventional and new atypical antipsychotics and clozapine.Results: A significant correlation was found between the two scales (r = 0.386 p < 0.01). Determinants of subjective and objective quality of life were explored using multiple regression analyses. The main determinants of subjective quality of life were depression measured on the Calgary Scale, insight(Birchwood Scale) and nonneurological side-effects, which together explained 44% of the variance p < 0.01. Depression was responsible for 34% of this variance. In contrast, the main determinant of objective QLS were PANSS negative score and PANSS total score. These two together explained 51% of the variance with PANSS negative accounting for most 46% of this p < 0.01.Conclusion: The choice of subjective or objective quality of life measures is likely to reflect different dimensions of outcome,reflecting the underlying psychopathology of schizophrenia as opposed to measuring a discrete construct. A value judgement must therefore be made as to which of these measures best encapsulates what is meant by quality of life in schizophrenic illnesses.Edited by Glen Van Brummelen The purpose of this department is to give sufficient information about the subject matter of each publication to enable users to decide whether to read it. It is our intention to cover all books, articles, and other materials in the field. Books for abstracting and eventual review should be sent to this department. Materials should be sent to Glen Van Brummelen, Bennington College, Bennington, VT 05201, U.S.A. (E-mail: gvanbrum@bennington.edu) Readers are invited to send reprints, autoabstracts, corrections, additions, and notices of publications that have been overlooked. Be sure to include complete bibliographic information, as well as transliteration and translation for non-European languages. We need volunteers willing to cover one or more journals for this department. In order to facilitate reference and indexing, entries are given abstract numbers which appear at the end following the symbol #. A triple numbering system is used: the first number indicates the volume, the second the issue number, and the third the sequential number within that issue. For example, the abstracts for Volume 20, Number 1, are numbered: 20.1.1, 20.1.2, 20.1.3, etc. For reviews and abstracts published in Volumes 1 through 13 there are an author index in Volume 13, Number 4, and a subject index in Volume 14, Number 1. The initials in parentheses at the end of an entry indicate the abstractor. In this issue there are abstracts by Francine Abeles (Kean, NJ), Peter Bernhard (Erlangen, Germany), Herbert Kasube (Peoria, IL), Gary S. Stoudt (Indiana, PA), Kevin VanderMeulen (Hamilton, Canada), David Wallace (Glasgow, UK), and Glen Van Brummelen. Abgrall, Philippe. La Géométrie de l’Astrolabe au Xe Siècle, Arabic Sciences and Philosophy 10(1) (2000), 7–77. An analysis of treatises of al-Saganı̄, al-Qūhı̄, and Ibn Sahl dealing with the projection of the sphere on a plane applied to the construction of the astrolabe. See the review by Emilia Calvo in Mathematical Reviews 2001d:01005. (GSS) #28.4.1 Abraham, George. See #28.4.58. Abramovich, Y. A.; and Veksler, A. I. G. Ya. Lozanovsky: His Contributions to the Theory of Banach Lattices, in Henryk Hudzik and Leszek Skrzypczak, eds., Function Spaces, New York: Dekker, 2000, pp. 5–21. This description of Lozanovsky’s main results in the theory of Banach lattices also contains reflections on his personality and mathematical legacy, as well as a supplement to the papers listed in his obituary. (GVB) #28.4.2 Almgren, Frederick J., Jr. Selected Works of Frederick J. Almgren, Jr., edited by Jean E. Taylor, Providence, RI: American Mathematical Society, 1999, xlvi+586 pp.,

Between-year fluctuations in schizophrenia birth rate and associations with the Southern Oscillation Index, cloud cover and sunshine

105. This book contains a collection of the most significant “short” papers and expository and survey articles written by Frederick J. Almgren, Jr. See the review by Giandomenico Orlandi in Mathematical Reviews 2001f:01053. (HEK) #28.4.3 Amunategui, Godofredo Iommi. See #28.4.87. Andreozzi, Luciano. Vito Volterra as Scientific Organizer and the Origins of Mathematical Biology in Italy [in Italian], Nuncius 15(1) (2000), 79–109. Discusses Volterra’s organizational role in oceanographic studies from 1910 to 1925. (GVB) #28.4.4 Aouad, Maroun. See #28.4.61. Apostol, Tom M. A Centennial History of the Prime Number Theorem, in R. P. Bambah, V. C. Dumir, and R. J. Hans-Gill, eds., Number Theory, Basel: Birkhäuser, 2000, pp. 1–14. A survey article on the prime number 315 0315-0860/01

The incidence and prevalence of schizophrenia: Preliminary results from a systematic review

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The incidence of schizophrenia: A systematic review

Our group have recently proposed that low prenatal vitamin D may be a risk-modifying factor for schizophrenia. Climate variability impacts on vitamin D levels in a population via fluctuations in the amount of available UV radiation. In order to explore this hypothesis, we examined fluctuations in the birthrates for people with schizophrenia born between 1920 and 1967 and three sets of variables strongly associated with UV radiation. These included: (a) the Southern Oscillation Index (SOI), a marker of El Nino which is the most prominent meteorological factor that influences Queensland weather: (b) measures of cloud cover and (c) measures of sunshine. Schizophrenia births were extracted from the Queensland Mental Health register and corrected for background population birth rates. Schizophrenia birth rates had several apparently non-random features in common with the SO1. The prominent SO1 fluctuation event that occurred between 1937 and 1943 is congruent with the most prominent fluctuation in schizophrenia birth rates. The relatively flat profile of SOI activity between 1927 and 1936 also corresponds to the flattest period in the schizophrenia time series. Both time series have prominent oscillations in the 3 ~, year range between 1946 and 1960. Significant associations between schizophrenia birth rates and measures of both sunshine and cloud cover were identified,and all three time series shared periodicity in the 3-4 year range. The analyses suggest that the risk of schizophrenia is higher for those born during times of increased cloud cover,reduced sunshine and positive SO1. These ecological analyses provide initial support for the vitamin D hypothesis, however alternative non-genetic candidate exposures also need to be considered. Other sites with year-to-year fluctuations in cloud cover and sunshine should examine patterns of association between these climate variables and schizophrenia birth rates. The Stanley Foundation supported this project.