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While adolescent-onset schizophrenia (ADO-SCZ) and adolescent-onset bipolar disorder with psychosis (psychotic ADO-BPD) present a more severe clinical course than their adult forms, their pathophysiology is poorly understood. Here, we study potentially state- and trait-related white matter diffusion-weighted magnetic resonance imaging (dMRI) abnormalities along the adolescent-onset psychosis continuum to address this need.
Methods
Forty-eight individuals with ADO-SCZ (20 female/28 male), 15 individuals with psychotic ADO-BPD (7 female/8 male), and 35 healthy controls (HCs, 18 female/17 male) underwent dMRI and clinical assessments. Maps of extracellular free-water (FW) and fractional anisotropy of cellular tissue (FAT) were compared between individuals with psychosis and HCs using tract-based spatial statistics and FSL's Randomise. FAT and FW values were extracted, averaged across all voxels that demonstrated group differences, and then utilized to test for the influence of age, medication, age of onset, duration of illness, symptom severity, and intelligence.
Results
Individuals with adolescent-onset psychosis exhibited pronounced FW and FAT abnormalities compared to HCs. FAT reductions were spatially more widespread in ADO-SCZ. FW increases, however, were only present in psychotic ADO-BPD. In HCs, but not in individuals with adolescent-onset psychosis, FAT was positively related to age.
Conclusions
We observe evidence for cellular (FAT) and extracellular (FW) white matter abnormalities in adolescent-onset psychosis. Although cellular white matter abnormalities were more prominent in ADO-SCZ, such alterations may reflect a shared trait, i.e. neurodevelopmental pathology, present across the psychosis spectrum. Extracellular abnormalities were evident in psychotic ADO-BPD, potentially indicating a more dynamic, state-dependent brain reaction to psychosis.
There is evidence that plant-based diets might be associated with a lower risk of IHD; however, previous studies have not reported on intake of subtypes of fruit and vegetables and sources of dietary fibre. This study aims to assess the associations of major plant foods, their subtypes and dietary fibre with risk of ischaemic heart disease (IHD) in the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD Consortium.
Material and methods
We conducted a prospective analysis of 490,311 men and women in ten European countries without a history of myocardial infarction or stroke at recruitment. Dietary intake was assessed using validated questionnaires and calibrated with 24-hour recall data. Cox regression models, adjusted for IHD risk factors, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).
Results
During a mean of 12.6 years follow-up, we documented 8504 myocardial infarction cases or deaths from IHD. Participants consuming at least eight portions (80 grams each) of fruits and vegetables a day had a 10% lower risk of IHD (HR 0.90, 95% CI: 0.82–0.98) compared with those consuming fewer than three portions a day. The risk of IHD was 6% (95% CI 0.90–0.99; P-trend = 0.009) lower for a 200 g/day higher intake of fruit and vegetables combined, 3% (0.95–1.00; P-trend = 0.021) lower for a 100 g/ day higher fruit intake, and 8% (0.86–0.97; P-trend = 0.006) lower for a 50 g/ day higher intake of bananas. Moreover, risk of IHD was 9% (0.83–0.99; P-trend = 0.032) lower for a 10g/ day higher intake of nuts and seeds, and 10% (0.82–0.98; P-trend = 0.020) lower for a 10g/ day higher intake of total dietary fibre. No associations were observed between legumes, total vegetables and other subtypes of fruit and vegetables and IHD risk.
Discussion
The results from this large prospective study suggest that higher intakes of fruit and vegetables combined, total fruit, bananas, nuts and seeds, and total fibre are associated with a lower risk of IHD. Given the observational design of this study, causality and potential mechanisms should be further investigated.
To describe the development of the Oxford WebQ, a web-based 24 h dietary assessment tool developed for repeated administration in large prospective studies; and to report the preliminary assessment of its performance for estimating nutrient intakes.
Design
We developed the Oxford WebQ by repeated testing until it was sufficiently comprehensive and easy to use. For the latest version, we compared nutrient intakes from volunteers who completed both the Oxford WebQ and an interviewer-administered 24 h dietary recall on the same day.
Setting
Oxford, UK.
Subjects
A total of 116 men and women.
Results
The WebQ took a median of 12·5 (interquartile range: 10·8–16·3) min to self-complete and nutrient intakes were estimated automatically. By contrast, the interviewer-administered 24 h dietary recall took 30 min to complete and 30 min to code. Compared with the 24 h dietary recall, the mean Spearman's correlation for the 21 nutrients obtained from the WebQ was 0·6, with the majority between 0·5 and 0·9. The mean differences in intake were less than ±10 % for all nutrients except for carotene and vitamins B12 and D. On rare occasions a food item was reported in only one assessment method, but this was not more frequent or systematically different between the methods.
Conclusions
Compared with an interviewer-based 24 h dietary recall, the WebQ captures similar food items and estimates similar nutrient intakes for a single day's dietary intake. The WebQ is self-administered and nutrients are estimated automatically, providing a low-cost method for measuring dietary intake in large-scale studies.
Vegetarians and vegans exclude certain food sources of vitamin D from their diet, but it is not clear to what extent this affects plasma concentrations of 25-hydroxyvitamin D (25(OH)D). The objective was to investigate differences in vitamin D intake and plasma concentrations of 25(OH)D among meat eaters, fish eaters, vegetarians and vegans.
Design
A cross-sectional analysis.
Setting
United Kingdom.
Subjects
Plasma 25(OH)D concentrations were measured in 2107 white men and women (1388 meat eaters, 210 fish eaters, 420 vegetarians and eighty-nine vegans) aged 20–76 years from the European Prospective Investigation into Cancer and Nutrition (EPIC)–Oxford cohort.
Results
Plasma 25(OH)D concentrations reflected the degree of animal product exclusion and, hence, dietary intake of vitamin D; meat eaters had the highest mean intake of vitamin D (3·1 (95 % CI 3·0, 3·2) μg/d) and mean plasma 25(OH)D concentrations (77·0 (95 % CI 75·4, 78·8) nmol/l) and vegans the lowest (0·7 (95 % CI 0·6, 0·8) μg/d and 55·8 (95 % CI 51·0, 61·0) nmol/l, respectively). The magnitude of difference in 25(OH)D concentrations between meat eaters and vegans was smaller (20 %) among those participants who had a blood sample collected during the summer months (July–September) compared with the winter months (38 %; January–March). The prevalence of low plasma concentrations of 25(OH)D (<25 nmol/l) during the winter and spring ranged from <1 % to 8 % across the diet groups.
Conclusions
Plasma 25(OH)D concentrations were lower in vegetarians and vegans than in meat and fish eaters; diet is an important determinant of plasma 25(OH)D in this British population.
The nature of the relationship between duration of the pre-diagnostic
interval in schizophrenia and better outcomes remains unclear.
Aims
To re-examine data from one of the earliest studies suggesting an
association between long pre-treatment interval and compromised outcome,
assessing the relationship between symptomatic and social variables and
increased relapse risk at 1 year.
Method
Symptomatic, social and demographic data from participants in the
Northwick Park Study of First Episodes who completed 12-month follow-up
(n = 101) were re-analysed in the context of duration
of untreated illness (DUI).
Results
At admission, those with long DUI were more likely to have lower scores
on tension derived from the Present State Examination, exhibited more
behaviour threatening to others and more bizarre behaviour, were more
likely to be single, to live alone or dependently, to be unemployed and
to have experienced more adverse life events prior to admission. Logistic
regression showed that diminished tension, bizarre behaviour and
unemployed status independently increased the risk of relapse, bizarre
behaviour making the single biggest contribution. Tension did not remain
significant with log-transformation of data.
Conclusions
Findings are consistent with the conclusion that long DUI can reflect
characteristics of the psychosis itself rather than delay in
treatment.
In a sample of 268 cases of first-episode schizophrenia, 15 patients were found to have organic disease which appeared relevant to the mental state. There were three cases of syphilis, two cases of sarcoidosis, three of alcohol excess and two of drug abuse. There was one case each of carcinoma of the lung, autoimmune multisystem disease, cerebral cysticercosis, thyroid disease and previous head injury. In this series, identified organic disease was associated with less than 6% of cases of schizophrenia.
In a series of 36 patients with acute schizophrenia flupenthixol dosage was blindly adjusted to give a fixed level of sedation. Patients were then randomly allocated to procyclidine or placebo. The patients receiving procyclidine experienced more positive schizophrenic symptoms and less severe extrapyramidal features by comparison with placebo patients. Blood levels of prolactin and flupenthixol estimated by radloimmunoassay were not significantly changed by the addition of procyclidine. Flupenthixol dosage and levels and prolactin levels were significantly related. There was no significant association between clinical and laboratory measures, with the exception that a curvilinear (inverted U) relationship was demonstrated between flupenthixol levels and antipsychotic and extrapyramidal effects. This relationship may be due to the fact that, in a study of this design, patients resistant to the effects of neuroleptic medication are likely to be given the highest doses. The findings support earlier claims that anticholinergic medication has adverse effects on schizophrenic symptoms.
A higher proportion of n-3 long-chain PUFA in tissue lipids has been associated with a lower risk of CVD and some cancers. Diet is an important predictor of n-3 long-chain PUFA composition; however, the importance of non-dietary factors such as sex and age is unclear. We measured the proportion of n-3 long-chain PUFA in serum phospholipid, cholesterol ester and TAG of 2793 New Zealanders 15 years or older who participated in the 1997 National Nutrition Survey to determine differences by sex and age. Women had lower proportions of EPA and docosapentaenoic acid in phospholipid, by 0·07 (P = 0·004) and 0·10 (P < 0·001) mol%, respectively, and a higher proportion of DHA by 0·16 mol% (P = 0·001) compared with men. Intake of fish fat did not differ between men and women. There was a positive association between age and the proportion of EPA and DHA in phospholipid (P < 0·001). The sex differences in EPA and DHA were similar at all ages. Similar sex and age differences in serum cholesterol ester n-3 long-chain PUFA were found; only age differences were found in serum TAG. Sex and age differences in n-3 long-chain PUFA occur in the general population. Men and women may need to be considered separately when examining the association between disease risk and biomarkers of n-3 fatty acids.
To test the hypothesis that many foods with reduced-fat (RF) claims are relatively energy-dense and that high-fat (HF) vegetable-based dishes are relatively energy-dilute.
Design:
Nutrient data were collected from available foods in Melbourne supermarkets that had an RF claim and a full-fat (FF) equivalent. Nutrient analyses were also conducted on recipes for HF vegetable-based dishes that had more than 30% energy from fat but less than 10% from saturated fat. The dietary intake data (beverages removed) from the 1995 National Nutrition Survey were used for the reference relationships between energy density (ED) and percentage energy as fat and carbohydrate and percentage of water by weight.
Statistics:
Linear regression modelled relationships of macronutrients and ED. Paired t-tests compared observed and predicted reductions in the ED of RF foods compared with FF equivalents.
Results:
Both FF and RF foods were more energy-dense than the Australian diet and the HF vegetable-based dishes were less energy-dense. The Australian diet showed significant relationships with ED, which were positive for percentage energy as fat and negative for percentage energy as carbohydrate. There were no such relationships for the products with RF claims or for the HF vegetable-based dishes.
Conclusion:
While, overall, a reduced-fat diet is relatively energy-dilute and is likely to protect against weight gain, there appear to be two important exceptions. A high intake of products with RF claims could lead to a relatively energy-dense diet and thus promote weight gain. Alternatively, a high intake of vegetable-based foods, even with substantial added fat, could reduce ED and protect against weight gain.
Studies suggest that neuronal density in left dorsolateral prefrontal
cortex is increased in schizophrenia.
Aims
To replicate these findings and extend them to both hemispheres.
Method
Neuronal density, size and shape were estimated in the prefrontal cortex
(Brodmann area 9) of the left and right hemispheres of brains taken
postmortem from 10 people with schizophrenia and 10 without mental
illness (6 men, 4 women in both groups).
Results
Overall neuronal density (individually corrected for shrinkage) did not
differ between the groups. In the control brains, density was generally
greater in the left than the right hemisphere, the reverse was seen in
the schizophrenia brains; this loss or reversal of asymmetry was most
significant in cortical layer 3. Pyramidal neurons in this cell layer
were significantly larger on the left and more spherical in shape than on
the right side in control brains, but size and shape did not differ
between the two sides in schizophrenia. Non-pyramidal and glial cell
densities were unchanged.
Conclusions
We failed to find an increase in neuronal density, but found evidence at
a cellular level of loss or reversal of asymmetry, consistent with the
hypothesis of a primary change in the relative development of areas of
heteromodal association cortex in the two hemispheres.
the claim of consistent hemispheric specialisations across classes of chordates is undermined by the absence of population-based directional asymmetry of paw/hand use in rodents and primates. no homologue of the cerebral torque from right frontal to left occipital has been established in a nonhuman species. the null hypothesis that the torque is the sapiens-specific neural basis of language has not been disproved.
In December 1999, as part of its tricentenary celebrations, the Berlin Academy of Sciences invited eleven speakers to discuss the Origin of Language (cf. the Trabant & Ward volume, henceforth T&W). In March 2000 a workshop (Crow 2002a) under the auspices of the British Academy and the UK Academy of Medical Sciences, ‘The speciation of modern Homo sapiens’, addressed the same problem. The speciation of Homo sapiens and the origins of language are surely two sides of the same coin. At about the same time, the Christiansen & Kirby volume on Language Evolution (henceforth C&K) was conceived at the Fifth Australasian Cognitive Science Conference. Together the contributions of these volumes constitute a substantial contemporary archive on the origin of language. Their publication provides an opportunity to review the status of attempts to account for the evolution of language. Do the contributions converge on a solution?
Accumulating evidence suggests that early-onset schizophrenia arises from a disturbance in the normal trajectory of cerebral development.
Aims
To investigate brain structure, asymmetry and IQ in early-onset schizophrenia.
Method
Volumes of left and right cerebral hemispheres and IQ were assessed in 33 participants with early-onset DSM – IV schizophrenia and 30 members of a matched, normal control group.
Results
Total brain volume was significantly smaller in the group with early-onset disease (‘cases’) relative to the control group (4.5%), especially for the left hemisphere in males (6.0%). A significant sex x diagnosis interaction in hemisphere asymmetry revealed that the female cases group had significantly reduced rightward asymmetry relative to the female control group and that the male cases tended to have reduced leftward asymmetry relative to the male control group. Decreased left hemisphere volume in males and decreased rightward hemispheric asymmetry in females correlated with reduced IQ.
Conclusions
Sexually dimorphic alterations in asymmetry correlate with degree of intellectual impairment in early-onset schizophrenia.
The 20th century ended without a resolution of the debate about the supremacy of Schneider's psychopathological conceptualisation of schizophrenia (the first-rank symptoms) over Bleuler's ‘four As' (disorders of association and affect, ambivalence and autism).
Aims
To examine the relationships between linguistic deviations and symptoms in patients with acute psychosis.
Method
We assessed language disturbances and first-rank symptoms with the Clinical Language Disorder Rating Scale (CLANG) in 30 consecutive patients with acute psychosis, selected for the presence of at least one active first-rank symptom, and 15 control participants with depression but no psychotic symptoms.
Results
Strong positive correlations were found between the CLANG factor ‘poverty’ (of speech) and first-rank delusions of control and (‘delusional perceptions’) between semantic/phonemic paraphasias and verbal auditory hallucinations. Language disturbances were superior to nuclear symptoms in discriminating ICD–10 schizophrenia from other psychoses.
Conclusions
Evaluating the features of psychosis as deviations in the cerebral organisation of language paves the way to a concept of psychosis that supersedes these traditional but competing categorical concepts.
Neurological soft signs preceding adult-onset schizophrenia suggest a neurodevelopmental origin and could reflect physical illness in childhood.
Aims
To investigate possible associations of adult-onset psychosis with neurological soft signs and common infectious illnesses in childhood.
Method
Using data from the UK National Child Development Study, a longitudinal general population sample, odds ratios were calculated for clinical diagnoses of common childhood viral illnesses and later adult psychotic illness, childhood epilepsy and a range of neurological soft signs.
Results
The number of illnesses per individual did not relate either to the number of soft signs, or to any particular adult outcome. Schizophrenia, affective psychosis and epilepsy were not associated with common childhood illness but were associated with neurological soft signs and an increased, but small, frequency of previous meningitis and tuberculosis.
Conclusions
Overall the data support the notion of neurological soft signs as markers of disordered neurodevelopment in schizophrenia (but the early neurological abnormalities are not caused by infectious illness) and an association between meningitis or tuberculosis in childhood and a small proportion of cases of epilepsy, affective psychosis and schizophrenia.
Claims that schizophrenia is a disease of the limbic system have been strengthened by meta-analyses of magnetic resonance imaging (MRI) studies finding reduced hippocampus and amygdala volumes. Some post-mortem studies do not find these abnormalities.
Aims
To assess the volume of the amygdala in a series of brains post-mortem.
Method
Amygdala volume was estimated using point-counting in both hemispheres of the brains of 10 male and 8 female patients with schizophrenia, and a comparison group of 9 males and 9 females.
Results
No significant reduction of amygdala volume was found.
Conclusions
Significant volume reduction of the amygdala is not a consistent feature of schizophrenia; findings from early MRI studies using coarse delineation methods may introduce bias to subsequent meta-analyses.
It has been suggested that there is frontal lobe involvement in schizophrenia, and that it may be lateralised and gender-specific.
Aims
To clarify the structure of the frontal lobes in schizophrenia in a postmortem series.
Method
The volume of white matter and cortical components of the frontal lobes was measured in brains of controls and patients with schizophrenia using planimetry and the Cavalieri principle. The components measured were: superior frontal gyrus, middle frontal gyrus, a composite of inferior frontal gyrus and orbito-frontal cortex, as well as total frontal lobe cortex and white matter. In addition, the anterior cingulate gyrus was measured.
Results
No diagnosis, gender, diagnosis × side, diagnosis × gender or diagnosis × gender × side interactions were observed in the volume of any of the components, the grey matter as a whole or the white matter. No evidence for volumetric inter-group differences was found for the anterior cingulate gyrus.
Conclusions
Such structural abnormalities as are present in the frontal lobes are more subtle than straightforward alterations in tissue volume; they may include changes in shape and the pattern of gyral folding.
Since their introduction as diagnostic criteria by Schneider in 1937, nuclear symptoms have played a key role in concepts of schizophrenia, but their relationship to each other and to genetic predisposition has been unclear.
Aims
To ascertain the factor structure and familiality of nuclear symptoms.
Methods
Nuclear (Schneiderian) symptoms were extracted from case notes and interviews in a study of 103 sibling pairs with DSM–III–R schizophrenia or schizoaffective disorder.
Results
Principal components analysis demonstrated two major factors: one, accounting for about 50% of the variance, groups thought withdrawal, insertion and broadcasting, with delusions of control; and the second, accounting for <20% of the variance, groups together third-person voices, thought echo and running commentary. Factor I was significantly correlated within sibling pairs.
Conclusions
The correlation within sibling pairs suggests that, contrary to the conclusion of some previous studies, some nuclear symptoms do show a degree of familiality and therefore perhaps heritability.