Most studies reporting the gender difference in age at onset of schizophrenia show an earlier onset in males, but vary considerably in their estimates of the difference. This may be due to variations ...in study design, setting and diagnostic criteria. In particular, several studies conducted in developing countries have found no difference or a reversed effect whereby females have an earlier onset. The aim of the study was to investigate gender differences in age of onset, and the impact of study design and setting on estimates thereof.
Study methods were a systematic literature search, meta-analysis and meta-regression.
A total of 46 studies with 29,218 males and 19,402 females fulfilled the inclusion criteria and were entered into a meta-analysis. A random-effects model gave a pooled estimate of the gender difference of 1.07 years (95% confidence interval 0.21-1.93) for age at first admission of schizophrenia, with males having earlier onset. The gender difference in age at onset was not significantly different between developed and developing countries. Studies using diagnostic and statistical manual of mental disorders (DSM) criteria showed a significantly greater gender difference in age at onset than studies using International Classification Of Diseases (ICD) criteria, the latter showing no difference.
The gender difference in age of onset in schizophrenia is smaller than previously thought, and appears absent in studies using ICD. There is no evidence that the gender difference differs between developed and developing countries.
We examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized ...that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors.
The study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance.
From the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset.
The striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.
Schizophrenia (SZ) is characterized by a broad global cognitive impairment that precedes the onset of the disease. By contrast, some studies suggest that premorbid deficits are absent, or even ...reversed, in bipolar disorder (BD). However, studies have shown impairments in cognitive functioning after the illness onset in both disorders. The aim of this study was to systematically review and meta-analyze those studies that compared premorbid and/or post-onset global cognitive function between SZ and BD.
We searched Medline (PubMed), EMBASE and PsycINFO for studies where information on cognitive functioning was collected in both SZ and BD within the same study or using the same methods.
Compared to healthy comparison groups, SZ patients showed a significant premorbid cognitive impairment standardized mean difference (SMD) -0.597, 95% confidence interval (CI) -0.707 to -0.487, p < 0.0001 and a large post-onset impairment (SMD -1.369, 95% CI -1.578 to -1.160, p < 0.0001). We found small significant deficits in premorbid intellectual function in the BD group when this was assessed retrospectively (-0.147, 95% CI -0.238 to -0.056, p = 0.001) but not prospectively (-0.029, 95% CI -0.199 to + 0.142, p = 0.744), and moderate cognitive impairment after onset (SMD -0.623, 95% CI -0.717 to -0.529, p < 0.0001).
SZ is characterized by significant deficits in premorbid intellectual function but the evidence regarding premorbid function in BD is equivocal. After illness onset, patients with both disorders seem to suffer a further decline in cognitive function but the magnitude of the impairment remains greater in SZ than in BD.
Clozapine remains the only evidence-based antipsychotic for treatment-resistant schizophrenia (TRS). The ability to predict which patients with their first onset of schizophrenia would subsequently ...meet criteria for treatment resistance (TR) could help to diminish the severe functional disability which may ensue if TR is not recognized and correctly treated.
This is a 5-year longitudinal assessment of clinical outcomes in a cohort of 246 first-episode schizophrenia spectrum patients recruited as part of the NIHR Genetics and Psychosis (GAP) study conducted in South London from 2005 to 2010. We examined the relationship between baseline demographic and clinical measures and the emergence of TR. TR status was determined from a review of electronic case records. We assessed for associations with early-, and late-onset TR, and non-TR, and differences between those TR patients treated with clozapine and those who were not.
Seventy per cent (n = 56) of TR patients, and 23% of the total study population (n = 246) were treatment resistant from illness onset. Those who met criteria for TR during the first 5 years of illness were more likely to have an early age of first contact for psychosis (<20 years) odds ratio (OR) 2.49, 95% confidence interval (CI) 1.25-4.94 compared to those with non-TR. The relationship between an early age of first contact (<20 years) and TR was significant in patients of Black ethnicity (OR 3.71, 95% CI 1.44-9.56); and patients of male gender (OR 3.13 95% CI 1.35-7.23).
For the majority of the TR group, antipsychotic TR is present from illness onset, necessitating increased consideration for the earlier use of clozapine.
The debate endures as to whether schizophrenia and bipolar disorder are separate entities or different manifestations of a single underlying pathological process. Here, we argue that this sterile ...argument obscures the fact that the truth lies somewhere in between. Thus, recent studies support a model whereby, on a background of some shared genetic liability for both disorders, patients with schizophrenia have been subject to additional genetic and/or environmental factors that impair neurodevelopment; for example, copy number variants and obstetric complications are associated with schizophrenia but not with bipolar disorder. As a result, children destined to develop schizophrenia show an excess of neuromotor delays and cognitive difficulties while those who later develop bipolar disorder perform at least as well as the general population. In keeping with this model, cognitive impairments and brain structural abnormalities are present at first onset of schizophrenia but not in the early stages of bipolar disorder. However, with repeated episodes of illness, cognitive and brain structural abnormalities accumulate in both schizophrenia and bipolar disorder, thus clouding the picture.
CONTEXT It is unknown how genetic variants conferring liability to psychiatric disorders survive in the population despite strong negative selection. However, this is key to understanding their ...etiology and designing studies to identify risk variants. OBJECTIVES To examine the reproductive fitness of patients with schizophrenia and other psychiatric disorders vs their unaffected siblings and to evaluate the level of selection on causal genetic variants. DESIGN We measured the fecundity of patients with schizophrenia, autism, bipolar disorder, depression, anorexia nervosa, or substance abuse and their unaffected siblings compared with the general population. SETTING Population databases in Sweden, including the Multi-Generation Register and the Swedish Hospital Discharge Register. PARTICIPANTS In total, 2.3 million individuals among the 1950 to 1970 birth cohort in Sweden. MAIN OUTCOME MEASURES Fertility ratio (FR), reflecting the mean number of children compared with that of the general population, accounting for age, sex, family size, and affected status. RESULTS Except for women with depression, affected patients had significantly fewer children (FR range for those with psychiatric disorder, 0.23-0.93; P < 10−10). This reduction was consistently greater among men than women, suggesting that male fitness was particularly sensitive. Although sisters of patients with schizophrenia and bipolar disorder had increased fecundity (FR range, 1.02-1.03; P < .01), this was too small on its own to counterbalance the reduced fitness of affected patients. Brothers of patients with schizophrenia and autism showed reduced fecundity (FR range, 0.94-0.97; P < .001). Siblings of patients with depression and substance abuse had significantly increased fecundity (FR range, 1.01-1.05; P < 10−10). In the case of depression, this more than compensated for the lower fecundity of affected individuals. CONCLUSIONS Our results suggest that strong selection exists against schizophrenia, autism, and anorexia nervosa and that these variants may be maintained by new mutations or an as-yet unknown mechanism. Bipolar disorder did not seem to be under strong negative selection. Vulnerability to depression, and perhaps substance abuse, may be preserved by balancing selection, suggesting the involvement of common genetic variants in ways that depend on other genes and on environment.
Background
Clozapine is the most effective medication for the positive symptoms of treatment-refractory schizophrenia. Although clozapine use is associated with fewer admissions, less is known about ...the impact of clozapine cessation on hospitalisation.
Aims
The aims of this study were to investigate whether clozapine-reduced psychiatric inpatient admissions and bed days, and investigate patient factors associated with these changes from a sample of 1906 people commenced on clozapine.
Methods
All people commencing clozapine during an acute hospitalisation over a 10-year period in Queensland, Australia, were included in this retrospective cohort study. A mirror image design was used to compare psychiatric bed days and hospitalisations 2 years before and after clozapine treatment, and the impact of clozapine continuation or early cessation. Changes in psychiatric bed days and hospitalisations were analysed using linear regression, adjusting for the duration on clozapine, sex, age, indigenous status, country of origin and time to clozapine commencement.
Results/outcomes
There was a significant reduction in bed days (29.55 days vs 24.46 days,
p
< 0.001) and admissions (2.27 vs 1.87 < 0.001) associated with clozapine commencement. This remained significant among clozapine continuers, but not among those with early cessation. Longer duration on clozapine was associated with greater reductions in psychiatric bed days and admissions. Age, sex and time to clozapine commencement, indigeneity and country of origin did not impact outcomes.
Conclusion/interpretation
Longer clozapine therapy led to a greater reduction in psychiatric bed days and hospitalisations. Early cessation was associated with a return to pre-clozapine levels of bed days and admissions.
Many studies have addressed the question of whether mental disorder is associated with creativity, but high-quality epidemiological evidence has been lacking.AimsTo test for an association between ...studying a creative subject at high school or university and later mental disorder.
In a case-control study using linked population-based registries in Sweden (N = 4 454 763), we tested for associations between tertiary education in an artistic field and hospital admission with schizophrenia (N = 20 333), bipolar disorder (N = 28 293) or unipolar depression (N = 148 365).
Compared with the general population, individuals with an artistic education had increased odds of developing schizophrenia (odds ratio = 1.90, 95% CI = 1.69; 2.12) bipolar disorder (odds ratio = 1.62 1.50; 1.75) and unipolar depression (odds ratio = 1.39 1.34; 1.44. The results remained after adjustment for IQ and other potential confounders.
Students of artistic subjects at university are at increased risk of developing schizophrenia, bipolar disorder and unipolar depression in adulthood.Declaration of interestNone.
A bidirectional association between type 2 diabetes (T2DM) and depression has been consistently reported. Depression is associated with worse biomedical outcomes and increased mortality. The ...mechanisms underlying the association of T2DM with depression remain unclear. One possible question we can address is the extent to which the co-occurrence of diabetes and depression is due to correlated genetic and/or environmental risk factors. In this study, we performed structural equation model fitting to population-level data from the Swedish (n=68 606) and Danish (n=95 403) twin registries. The primary outcomes were clinical diagnosis of T2DM and depression using national hospital discharge registries. The phenotypic correlation between T2DM and depression is modest in both samples. In the Swedish sample, unique environmental effects explain a greater proportion of the covariance in males, whereas the association is primarily attributed to genetic effects in females. In the Danish sample, genetic effects account for the majority of the covariance in both males and females. Qualitative genetic sex differences are observed in both samples. We believe this is the first study to demonstrate significant genetic overlap between T2DM and depression.
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