Offspring of older men have impaired cognitive ability as children, but it is unclear if this impairment persists into adulthood. The main objective of this study was to explore the association between paternal age at offspring birth and general cognitive ability as young adults.
Population-based cross-sectional study with prospectively collected data on obstetric factors and parental education.
Nationwide Danish sample.
Male conscripts (n = 169,009).
Primary and secondary outcome measures
General cognitive ability as assessed by the Børge Priens test score, an intelligence test with components related to logical, verbal, numerical and spatial reasoning.
We observed an inverse U-shaped association between paternal age and general cognitive ability (slightly lower test scores in the offspring of fathers aged less than 25 years and older than 40 years, compared with fathers aged 25 to 29 years). However, after adjustment for maternal age, parental education and birth order the shape of the association changed. Offspring of fathers younger than 20 still showed slightly lower cognitive ability (-1.11 (95% CI -1.68 to -0.54)), but no significant impairments were identified in the men whose fathers were older than 29 years at the time of their birth (e.g. the mean difference in test score in the offspring of fathers aged 40 to 44 years were -0.03 [95% CI (-0.27 to 0.20)] compared with fathers aged 25 to 29 years).
We did not find that the offspring of older fathers had impaired cognitive ability as young adults. Whereas, we found a tendency that the offspring of teen fathers have lower cognitive ability. Thus, our results suggest that any potentially deleterious effects of older fathers on general cognitive ability as young adults may be counter-balanced by other potentially beneficial factors.
Previous population-based studies have found that delusional-like experiences (DLEs) are prevalent in the community, and are associated with a wide range of mental health disorders. The aim of the study was to investigate mental health service use by people with DLEs.
Subjects were drawn from the Australian National Survey of Mental Health and Wellbeing 2007 of 8 841community residents aged between 16 and 85 years. The Composite International Diagnostic Interview (CIDI) was used to identify DLEs. Service utilization was assessed using a module that elicited information about hospital admissions, consultations with various health professionals, and prescription medication use. This study focussed on service use for mental health problems. We used logistic regression to examine the association, adjusting for potential confounding factors.
Of 8 773 included participants, 8.4% (n = 776) positively endorsed one or more DLEs. With respect to consultations for mental health needs, individuals who endorsed DLEs were more likely to consult health professionals compared with those who did not endorse DLEs. Individuals with DLEs were also more likely to use prescription medicine. When we repeated the main analysis in a subgroup excluding any CIDI diagnosis of mental health disorders the results remained largely unchanged.
DLEs are common in the general population, and individuals with DLEs have an increased rate of accessing services for their mental health needs. Individuals endorsing both DLEs and increased help-seeking may identify a group of vulnerable people who have increased risk of developing psychotic illnesses later in life. This needs closer scrutiny in longitudinal prospective studies.
Vitamin D deficiency is common in the adult population, and this has been linked to depression and cognitive outcomes in clinical populations. The aim of this study was to investigate the effects of adult vitamin D (AVD) deficiency on behavioural tasks of relevance to neuropsychiatric disorders in male Sprague-Dawley rats.
Ten-week old male Sprague-Dawley rats were fed a control or vitamin D deficient diet for 6 weeks prior to, and during behavioural testing. We first examined a range of behavioural domains including locomotion, exploration, anxiety, social behaviour, learned helplessness, sensorimotor gating, and nociception. We then assessed locomotor response to the psychomimetic drugs, amphetamine and MK-801. Attention and vigilance were assessed using the 5 choice serial reaction time task (5C-SRT) and the 5 choice continuous performance task (5C-CPT) and, in a separate cohort, working memory was assessed using the delay match to sample (DMTS) task. We also examined excitatory and inhibitory neurotransmitters in prefrontal cortex and striatum.
AVD-deficient rats were deficient in vitamin D3 (<10 nM) and had normal calcium and phosphate levels after 8–10 weeks on the diet. Overall, AVD deficiency was not associated with an altered phenotype across the range of behavioural domains tested. On the 5C-SRT AVD-deficient rats made more premature responses and more head entries during longer inter-trial intervals (ITI) than control rats. On the 5C-CPT AVD-deficient rats took longer to make false alarm (FA) responses than control rats. AVD-deficient rats had increases in baseline GABA levels and the ratio of DOPAC/HVA within the striatum.
AVD-deficient rats exhibited no major impairments in any of the behavioural domains tested. Impairments in premature responses in AVD-deficient rats may indicate that these animals have specific alterations in striatal systems governing compulsive or reward-seeking behaviour.
Advancing paternal age has been linked to autism.
To further expand knowledge about the relation between paternal age and autism by studying the effect of grandfathers’ age on childhood autism.
Population-based multigenerational case-control study.
Nationwide Multi-Generation and Patient registers in Sweden.
We conducted a study of individuals born in Sweden since 1932. Parental age at birth was obtained for over 90% of the cohort. Grandparental age at the time of birth of the parent was obtained for a smaller subset (5,936 cases and 30,923 controls).
Main Outcome Measures
International Classification of Diseases (ICD) diagnosis of childhood autism in the Patient Registry.
There was a statistically significant monotonic association between advancing grandpaternal age at the time of birth of the parent and risk of autism in grandchildren. Men who had a daughter when they were 50 or older were 1.79 times (95% confidence interval: 1.35-2.37, p<0.001) more likely to have a grandchild with autism, and men who had a son when they were 50 or older were 1.67 times (95% confidence interval: 1.35-2.37, p<0.001) more likely to have a grandchild with autism, compared to men who had children when they were 20-24, after controlling for birth year, sex, age of the spouse, family history of psychiatric disorders, highest family education and residential county. There was also a statistically significant monotonic association between advancing paternal age and risk of autism in the offspring. Sensitivity analyses indicated that these findings were not the result of bias due to missing data on grandparental age.
Advanced grandparental age was associated with increased risk of autism, suggesting that risk for autism could develop over generations. The results are consistent with mutations and/or epigenetic alterations associated with advancing paternal age.
Schizophrenia (SZ) and Bipolar Disorder (BD) are associated with multidimensional disability. This study examined differential predictors of functional deficits between the disorders.
Community dwelling individuals with SZ (N=161) or BD (N=130) were administered neuropsychological tests, symptom measures, performance-based social and adaptive (i.e., everyday-living skills) functional competence measures, and rated on domains of real-world functioning: 1) Community and Household activities, 2) Work skills, and 3) Interpersonal relationships. We used confirmatory path analysis to find the best fitting models to examine the direct and indirect (as mediated by competence) prediction of the three domains of real-world functioning.
In all models for both groups, neurocognition’s relationship with outcomes was largely mediated by competence. Symptoms were negatively associated with outcomes but unassociated with competence, with the exception of depression, which was a direct and mediated (through social competence) predictor in BD. In both groups, neurocognition was related to Activities directly and through a mediated relationship with adaptive competence. Work Skills were directly and indirectly (through mediation with social competence) predicted by neurocognition in SZ and entirely mediated by adaptive and social competence in BD. Neurocognition was associated with Interpersonal Relationships directly in the SZ group, and mediated by social competence in both groups.
Although there was greater disability in SZ, neurocognition predicted worse functioning in all outcome domains in both disorders. Our study supports the shared role of neurocognition in BD and SZ in producing disability, with predictive differences between disorders observed in domain-specific effects of symptoms and social and adaptive competence.
Advanced paternal age has been linked with neurodevelopmental disorders such as schizophrenia. If age-related de novo mutations in the male germ line underlie this association, it would be expected that grandpaternal as well as paternal age may influence the risk of schizophrenia. The aim of the current study was to explore the links between both paternal and grandpaternal age with respect to the risk of schizophrenia in a large, national register-based sample.
The study was based on Swedish Multi-Generation and Hospital Discharge Registers. Parents’ ages at offspring birth were compared between 20,582 affected and 100,176 non-affected individuals. Grandparents’ ages at the birth of the parent were compared between 2,511 affected and 15,619 non-affected individuals. The risk of schizophrenia was examined when the predictor variable (parent or grandparent age) was examined in age strata with logistic regression. Planned sensitivity analyses included exploring the variables of interest in males and females separately.
After adjusting for maternal age, birth year and sex of the proband, we confirmed that the offspring of older fathers have an increased risk of schizophrenia (e.g. compared to paternal age 20–24 years, those with fathers > 55 years had a two-fold increased risk). With respect to grandparent age, older maternal (but not paternal) grandfather age was associated with an increased risk of schizophrenia. Compared to maternal grandfather age 20–24 years, those with maternal grandfathers >55 years had a significantly increased risk of schizohrpenia (Adjusted Odds ratio and 95% Confidence intervals; 2.79, 1.71 – 4.56). The pattern of findings were essentially unchanged when we examine male and female probands separately.
This is the first the study to show an association between grandpaternal age and risk of schizophrenia. The selective effect of advanced maternal grandfather age suggests that the biological mechanisms involving the X chromosome may differentially contribute to the association between paternal age and risk of schizophrenia.
schizophrenia; paternal age; grandparental age; mutation
Tremendous progress has been made in the past two decades in molecular genetics of heritable skin diseases, and pathogenic mutations have been identified in as many as 500 distinct human genes. This progress has resulted in improved diagnosis with prognostic implications, refined genetic counseling, and has formed the basis for prenatal and presymptomatic testing as well as preimplantation genetic diagnosis. However, there has been relatively little progress in developing effective and specific treatments for these often devastating diseases. Very recently, however, a number of novel molecular strategies, including gene therapy, cell-based approaches, and protein replacement therapy have been explored for treatment of these conditions. This overview will focus on the prototypic heritable blistering disorders, epidermolysis bullosa and related keratinopathies, in which significant progress has been recently made towards treatment, and illustrate how some of the translational research therapies have already entered the clinical arena.
The Department of Health's Enhanced Recovery Partnership Programme (ERPP) started a spread and adoption scheme of Enhanced Recovery After Surgery (ERAS) throughout England. In preparation for widespread adoption the ERPP wished to obtain expert consensus on appropriate outcome measures for ERAS, emerging techniques being widely adopted and proposed methods for the continued development and sustainability of ERAS in the National Health Service. The aim of this study was to interrogate expert opinion and define areas of consensus on these issues.
A Delphi technique using three rounds of reiterative questionnaires was used to obtain consensus.
Experts were chosen from teams with experience of delivering a successful ERAS programme across different surgical specialties and across various disciplines.
The first two rounds of the questionnaire were completed online and a final, third round was undertaken in a meeting using interactive voting.
86 experts took part in this study. Consensus statements agreed that patient experience data should be recorded, analysed and reviewed at regular ERAS meetings. Recent developments in regional analgesia, the increased use of intraoperative monitoring for fluid management and cardio-pulmonary exercise testing were the main emerging techniques identified. National standards for those outcome measures would be welcomed. To sustain success in ERAS, the experts highlighted clinical champions and the presence of a dedicated ERAS facilitator as essential elements. For future networking, a unanimous agreement was achieved on the formation a national network to facilitate spread and adoption of ERAS and to promote research and education across surgery.
Consensus was achieved on regular measurement and review of patient experience in ERAS. Agreement was reached on the role of regional analgesia and the use of oesophageal Doppler for intraoperative goal-directed fluid therapy. In order to facilitate the further spread and adoption of best practices and to promote research and education, an ERAS-UK network was recommended.
Enhanced Recovery After Surgery; Consensus Views; Perioperative care; Patient feedback; Oesophageal doppler; CPEX testing
The complete sequence of the 46,267 bp genome of the lytic bacteriophage tf specific to Pseudomonas putida PpG1 has been determined. The phage genome has two sets of convergently transcribed genes and 186 bp long direct terminal repeats. The overall genomic architecture of the tf phage is similar to that of the previously described Pseudomonas aeruginosa phages PaP3, LUZ24 and phiMR299-2, and 39 out of the 72 products of predicted tf open reading frames have orthologs in these phages. Accordingly, tf was classified as belonging to the LUZ24-like bacteriophage group. However, taking into account very low homology levels between tf DNA and that of the other phages, tf should be considered as an evolutionary divergent member of the group. Two distinguishing features not reported for other members of the group were found in the tf genome. Firstly, a unique end structure – a blunt right end and a 4-nucleotide 3′-protruding left end – was observed. Secondly, 14 single-chain interruptions (nicks) were found in the top strand of the tf DNA. All nicks were mapped within a consensus sequence 5′-TACT/RTGMC-3′. Two nicks were analyzed in detail and were shown to be present in more than 90% of the phage population. Although localized nicks were previously found only in the DNA of T5-like and phiKMV-like phages, it seems increasingly likely that this enigmatic structural feature is common to various other bacteriophages.
Dopamine β-hydroxylase (DβH) catalyzes the conversion of dopamine to norepinephrine. DβH enters the plasma after vesicular release from sympathetic neurons and the adrenal medulla. Plasma DβH activity (pDβH) varies widely among individuals, and genetic inheritance regulates that variation. Linkage studies suggested strong linkage of pDβH to ABO on 9q34, and positive evidence for linkage to the complement fixation locus on 19p13.2-13.3. Subsequent association studies strongly supported DBH, which maps adjacent to ABO, as the locus regulating a large proportion of the heritable variation in pDβH. Prior studies have suggested that variation in pDβH, or genetic variants at DβH, associate with differences in expression of psychotic symptoms in patients with schizophrenia and other idiopathic or drug-induced brain disorders, suggesting that DBH might be a genetic modifier of psychotic symptoms. As a first step toward investigating that hypothesis, we performed linkage analysis on pDβH in patients with schizophrenia and their relatives. The results strongly confirm linkage of markers at DBH to pDβH under several models (maximum multipoint LOD score, 6.33), but find no evidence to support linkage anywhere on chromosome 19. Accounting for the contributions to the linkage signal of three SNPs at DBH, rs1611115, rs1611122, and rs6271 reduced but did not eliminate the linkage peak, whereas accounting for all SNPs near DBH eliminated the signal entirely. Analysis of markers genome-wide uncovered positive evidence for linkage between markers at chromosome 20p12 (multi-point LOD = 3.1 at 27.2 cM). The present results provide the first direct evidence for linkage between DBH and pDβH, suggest that rs1611115, rs1611122, rs6271 and additional unidentified variants at or near DBH contribute to the genetic regulation of pDβH, and suggest that a locus near 20p12 also influences pDβH.
Schizophrenia is a highly debilitating illness that often results in disruption to independent living and employment. However, “gold standard” methods of assessing functional abilities to achieve these milestones are still lacking. In a sample of 367 individuals with schizophrenia, we examined the sensitivity and specificity of the Brief UCSD Performance-based Skills Assessment (UPSA-B) to predict both residential and employment status. Of all individuals residing independently, 75.9% scored 78 or above on the UPSA-B, and of all individuals not residing independently, 59% scored below 78 on the UPSA-B. Of individuals who were employed, 73.9% scored above 82 on the UPSA-B, and of those not employed, 57.8% scored below 82. These results expand upon both the population base and functional milestones with which the UPSA-B is validated, although future work should examine whether the UPSA-B can be used as a decision aid in the likelihood of success in a longitudinal study, such as at critical transitions (post-hospitalization, cessation of supported housing).
Psychosis; Functional Capacity; Functioning; Employment; Independence; Well-being
Hemidesmosomes are composed of intricate networks of proteins, that are an essential attachment apparatus for the integrity of epithelial tissue. Disruption leads to blistering diseases such as epidermolysis bullosa. Members of the Sox gene family show dynamic and diverse expression patterns during development and mutation analyses in humans and mice provide evidence that they play a remarkable variety of roles in development and human disease. Previous studies have established that the mouse mutant ragged-opossum (Raop) expresses a dominant-negative form of the SOX18 transcription factor that interferes with the function of wild type SOX18 and of the related SOXF-subgroup proteins SOX7 and −17. Here we show that skin and oral mucosa in homozygous Raop mice display extensive detachment of epithelium from the underlying mesenchymal tissue, caused by tearing of epithelial cells just above the plasma membrane due to hemidesmosome disruption. In addition, several hemidesmosome proteins expression were found to be dysregulated in the Raop mice. Our data suggest that SOXF transcription factors play a role in regulating formation of cytoplasmic plaque protein assembly, and that disrupted SOXF function results in epidermolysis bullosa-like skin phenotypes.
A comprehensive revision of the Global Burden of Disease (GBD) study is expected to be completed in 2012. This study utilizes a broad range of improved methods for assessing burden, including closer attention to empirically derived estimates of disability. The aim of this paper is to describe how GBD health states were derived for schizophrenia and bipolar disorder. These will be used in deriving health state-specific disability estimates. A literature review was first conducted to settle on a parsimonious set of health states for schizophrenia and bipolar disorder. A second review was conducted to investigate the proportion of schizophrenia and bipolar disorder cases experiencing these health states. These were pooled using a quality-effects model to estimate the overall proportion of cases in each state. The two schizophrenia health states were acute (predominantly positive symptoms) and residual (predominantly negative symptoms). The three bipolar disorder health states were depressive, manic, and residual. Based on estimates from six studies, 63% (38%-82%) of schizophrenia cases were in an acute state and 37% (18%-62%) were in a residual state. Another six studies were identified from which 23% (10%-39%) of bipolar disorder cases were in a manic state, 27% (11%-47%) were in a depressive state, and 50% (30%-70%) were in a residual state. This literature review revealed salient gaps in the literature that need to be addressed in future research. The pooled estimates are indicative only and more data are required to generate more definitive estimates. That said, rather than deriving burden estimates that fail to capture the changes in disability within schizophrenia and bipolar disorder, the derived proportions and their wide uncertainty intervals will be used in deriving disability estimates.
Global Burden of Disease; Health States; Schizophrenia; Bipolar Disorder
Non-clinical psychotic experiences are common and distressing. It has been hypothesized that early life vitamin D deficiency may be a risk factor for psychosis-related outcomes, but it is not known if circulating concentrations of 25-hydroxyvitamin D (25(OH)D) during childhood are associated with psychosis-related outcomes or whether the two different forms of 25(OH)D, (25(OH)D3 and 25(OH)D2, have similar associations with psychosis-related outcomes.
We investigated the association between serum 25(OH)D3 and 25(OH)D2 concentrations and psychotic experiences in a prospective birth cohort study. Serum 25(OH)D3 and 25(OH)D2 concentrations were measured at mean age 9.8 years and psychotic experiences assessed at mean age 12.8 years by a psychologist (N = 3182).
Higher 25(OH)D3 concentrations were associated with lower risk of definite psychotic experiences (adjusted odds ratio: OR (95% confidence interval: CI) 0.85 (0.75–0.95)). Higher concentrations of 25(OH)D2 were associated with higher risk of suspected and definite psychotic experiences (adjusted odds ratio: OR (95% confidence interval: CI) 1.26 (1.11, 1.43)). Higher 25(OD)D2 concentrations were also weakly associated with definite psychotic experiences (adjusted OR (95% CI) 1.17 (0.96, 1.43), though with wide confidence intervals including the null value.
Our findings of an inverse association of 25(OH)D3 with definite psychotic experiences is consistent with the hypothesis that vitamin D may protect against psychosis-related outcomes.
There is growing evidence that delusional-like experiences (DLE) are associated with common mental disorders. In particular, a National Mental Health Survey conducted in Australia during 2007 reported an association between DLE and both anxiety disorder and major depressive disorder (MDD). However, the previous study did not examine this association with respect to subtypes of anxiety disorder nor with severity of MDD. The aim of this study was to examine the associations between DLE and both anxiety disorder and MDD in more detail based on an independent population sample.
Subjects were drawn from the Australian Survey of Mental Health and Wellbeing 1997 using a stratified multistage area sampling of persons living in private dwellings in all States and Territories of Australia.
Approximately 13 600 private dwellings were initially selected with one person aged 18 years or older from each dwelling invited to participate. In total, 10 641 individuals participated in the survey.
Primary and secondary outcome measures
The Composite International Diagnostic Interview was used to identify individuals with DLE and Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition (DSM IV) lifetime diagnoses of anxiety disorders and MDD. The influence of various anxiety disorders and MDD on DLE was assessed with logistic regression.
Having a lifetime diagnosis of either any anxiety disorder or MDD was significantly associated with the endorsement of DLE. The association was found for each of the main anxiety disorders when examined separately. There was a dose–response relationship between increasing severity of MDD and higher odds of DLE endorsement.
DLE are associated with a wide range of anxiety disorders and are more prevalent in those with MDD. Understanding the relationship between DLE, anxiety disorders and depression may provide insights into shared pathways that underpin both psychotic disorders and common mental disorders.
The study was undertaken in order (1) to examine the association between DLE and (a) broadly defined anxiety disorders and (b) MDDs; (2) to explore the association between DLE and a range of specific anxiety disorders and (3) to examine if severity of MDD influenced the risk of endorsement of DLE.
Having a lifetime diagnosis of either any anxiety disorder or MDDs was significantly associated with the endorsement of DLE.
The association was found for each of the main anxiety disorders when examined separately.
There was a dose–response relationship between increasing severity of MDD and higher odds of DLE endorsement.
Strengths and limitations of this study
The data were drawn from the nationally representative sample from the Australia general population.
Epidemiological evidence suggests that Developmental Vitamin D (DVD) deficiency is associated with an increased risk of schizophrenia. DVD deficiency in mice is associated with altered behaviour, however there has been no detailed investigation of cognitive behaviours in DVD-deficient mice. The aim of this study was to determine the effect of DVD deficiency on a range of cognitive tasks assessing attentional processing in C57BL/6J mice. DVD deficiency was established by feeding female C57BL/6J mice a vitamin D-deficient diet from four weeks of age. After six weeks on the diet, vitamin D-deficient and control females were mated with vitamin D-normal males and upon birth of the pups, all dams were returned to a diet containing vitamin D. The adult offspring were tested on a range of cognitive behavioural tests, including the five-choice serial reaction task (5C-SRT) and five-choice continuous performance test (5C-CPT), as well as latent inhibition using a fear conditioning paradigm. DVD deficiency was not associated with altered attentional performance on the 5C-SRT. In the 5C-CPT DVD-deficient male mice exhibited an impairment in inhibiting repetitive responses by making more perseverative responses, with no changes in premature or false alarm responding. DVD deficiency did not affect the acquisition or retention of cued fear conditioning, nor did it affect the expression of latent inhibition using a fear conditioning paradigm. DVD-deficient mice exhibited no major impairments in any of the cognitive domains tested. However, impairments in perseverative responding in DVD-deficient mice may indicate that these animals have specific alterations in systems governing compulsive or reward-seeking behaviour.
Recent studies suggest that anhedonia, an inability to experience pleasure, can be measured as an enduring trait in non-clinical samples. In order to examine trait anhedonia in a non-clinical sample, we examined the properties of a range of widely used questionnaires capturing anhedonia.
887 young adults were recruited from colleges. All of them were administered a set of checklists, including Chapman Scale for Social Anhedonia (CRSAS) and the Chapman Scale for Physical Anhedonia Scale (CPAS), The Temporal Experience of Pleasure Scale(TEPS), and The Schizotypal Personality Questionnaire (SPQ).
Males showed significantly higher level of physical (F = 5.09, p<0.001) and social (F = 4.38, p<0.005) anhedonia than females. As expected, individuals with schizotypal personality features also demonstrated significantly higher scores of physical (t = 3.81, p<0.001) and social (t = 7.33, p<0.001) trait anhedonia than individuals without SPD features, but no difference on self-report anticipatory and consummatory pleasure experience.
Concerning the comparison on each item of physical and social anhedonia, the results indicated that individuals with SPD feature exhibited higher than individuals without SPD features on more items of social anhedonia than physical anhedonia scale. These preliminary findings suggested that trait anhedonia can be identified a non-clinical sample. Exploring the demographic and clinical correlates of trait anhedonia in the general population may provide clues to the pathogenesis of psychotic disorder.
Objective: Population-based surveys have confirmed that psychotic-like experiences are prevalent in the community. However, it is unclear if these experiences are associated with common mental disorders. The aim of this study was to examine the prevalence of psychotic-like experiences in those with affective and anxiety disorders. Methods: Subjects were drawn from the Mater-University of Queensland Study of Pregnancy. Delusion-like experiences were assessed with the Peters Delusional Inventory (PDI). The Composite International Diagnostic Interview (CIDI) was used to identify individuals with Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) lifetime diagnoses of major depression, anxiety disorder, substance use/dependence, and psychotic disorders. The influence of affective and anxiety disorders on PDI and CIDI psychosis-related items’ scores were assessed with logistic regression, with adjustments for age, sex, and the presence of the other comorbid psychiatric diagnoses. Results: Having either a lifetime diagnosis of major depressive disorder or an anxiety disorder was associated with significantly higher PDI total scores (highest vs lowest quartile adjusted odds ratios [ORs] and 95% confidence intervals [CIs] = 4.43, 3.09–6.36; 3.08, 2.26–4.20, respectively). The odds of endorsing any CIDI hallucination or delusion item was increased in those with a major depressive or anxiety disorder. The presence of current anxiety disorder symptoms was significantly associated with PDI score (OR = 5.81, 95% CI = 3.68–9.16). Conclusion: While psychotic-like experiences are usually associated with psychotic disorders, individuals with depression and anxiety are also more likely to report these symptoms compared with well individuals. Psychotic-like experiences are associated with a range of common mental disorders.
psychotic-like experience; depression; anxiety; epidemiology; birth cohort
Adequate prenatal nutrition is essential for optimal brain development. There is a growing body of evidence from epidemiology linking exposure to nutritional deprivation and increased risk of schizophrenia. Based on studies from the Netherlands and China, those exposed to macronutrient deficiencies during famine have an increased risk of schizophrenia. With respect to micronutrients, we focus on 3 candidates where there is biological plausibility for a role in this disorder and at least 1 study of an association with schizophrenia. These nutrients include vitamin D, folic acid, and iron. While the current evidence is incomplete, we discuss the potential implications of these findings for the prevention of schizophrenia. We argue that schizophrenia can draw inspiration from public health interventions related to prenatal nutrition and other outcomes and speculate on relevant factors that bear on the nature, risks, impact, and logistics of various nutritional strategies that may be employed to prevent this disorder.
nutrition; epidemiology; prevention; schizophrenia
Revertant mosaicism is a naturally occurring phenomenon involving spontaneous correction of a pathogenic mutation in a somatic cell. Recent studies suggest that it is not a rare event and that it could be clinically relevant to phenotypic expression and patient treatment. Indeed, revertant cell therapy represents a potential “natural gene therapy” because in vivo reversion obviates the need for further genetic correction. Revertant mosaicism has been observed in several inherited conditions, including epidermolysis bullosa, a heterogeneous group of blistering skin disorders. These diseases provide a useful model for studying revertant mosaicism because of the visual and accessible nature of skin. This overview highlights the latest developments in revertant mosaicism and the translational implications germane to heritable skin disorders.
Phosphonates are compounds that contain the chemically stable carbon–phosphorus (C–P) bond. They are widely distributed amongst more primitive life forms including many marine invertebrates and constitute a significant component of the dissolved organic phosphorus reservoir in the oceans. Virtually all biogenic C–P compounds are synthesized by a pathway in which the key step is the intramolecular rearrangement of phosphoenolpyruvate to phosphonopyruvate. However C–P bond cleavage by degradative microorganisms is catalyzed by a number of enzymes – C–P lyases, C–P hydrolases, and others of as-yet-uncharacterized mechanism. Expression of some of the pathways of phosphonate catabolism is controlled by ambient levels of inorganic P (Pi) but for others it is Pi-independent. In this report we review the enzymology of C–P bond metabolism in bacteria, and also present the results of an in silico investigation of the distribution of the genes that encode the pathways responsible, in both bacterial genomes and in marine metagenomic libraries, and their likely modes of regulation. Interrogation of currently available whole-genome bacterial sequences indicates that some 10% contain genes encoding putative pathways of phosphonate biosynthesis while ∼40% encode one or more pathways of phosphonate catabolism. Analysis of metagenomic data from the global ocean survey suggests that some 10 and 30%, respectively, of bacterial genomes across the sites sampled encode these pathways. Catabolic routes involving phosphonoacetate hydrolase, C–P lyase(s), and an uncharacterized 2-aminoethylphosphonate degradative sequence were predominant, and it is likely that both substrate-inducible and Pi-repressible mechanisms are involved in their regulation. The data we present indicate the likely importance of phosphonate-P in global biogeochemical P cycling, and by extension its role in marine productivity and in carbon and nitrogen dynamics in the oceans.
phosphonate; C–P bond; marine bacteria; phosphorus cycling
In a previous study, we demonstrated that mouse adult F1 offspring, exposed to a vitamin D deficiency during pregnancy, developed a less severe and delayed Experimental Autoimmune Encephalomyelitis (EAE), when compared with control offspring. We then wondered whether a similar response was observed in the subsequent generation. To answer this question, we assessed F2 females whose F1 parents (males or females) were vitamin D-deprived when developing in the uterus of F0 females. Unexpectedly, we observed that the vitamin D deficiency affecting the F0 pregnant mice induced a precocious and more severe EAE in the F2 generation. This paradoxical finding led us to assess its implications for the epidemiology of Multiple Sclerosis (MS) in humans. Using the REFGENSEP database for MS trios (the patient and his/her parents), we collected the parents’ dates of birth and assessed a potential season of birth effect that could potentially be indicative of the vitamin D status of the pregnant grandmothers. A trend for a reduced number of births in the Fall for the parents of MS patients was observed but statistical significance was not reached. Further well powered studies are warranted to validate the latter finding.
vitamin D experimental autoimmune encephalomyelitis; multiple sclerosis; deficiency; season of birth; transgenerational
Previous population-based studies have found that delusional-like experiences (DLE) are prevalent in the community, and are associated with a wide range of mental health disorders including substance use. The aim of the study was to explore the association between DLE and three commonly used substances - tobacco, alcohol and cannabis.
Subjects were drawn from the Australian National Survey of Mental Health and Wellbeing 2007. The Composite International Diagnostic Interview was used to identify DLE, common psychiatric disorders, and substance use. We examined the relationship between the variables of interest using logistic regression, adjusting for potential confounding factors.
Of 8 773 participants, 8.4% (n = 776) subjects endorsed one or more DLE. With respect to tobacco use, compared to nonusers, DLE were more common in those who (a) had daily use, (b) commenced usage aged 15 years or less, and (c) those who smoked heavily (23 or more cigarettes per day). Participants with cannabis use disorders were more likely to endorse DLE; this association was most prominent in those with an onset of 16 years or younger. In contrast, the pattern of association between DLE versus alcohol use or dependence was less consistent, however those with early onset alcohol use disorders were more likely to endorse DLE probe items.
While cannabis use disorders have been previously linked with DLE, our findings linking alcohol and tobacco use and DLE suggest that the influence of these substances on psychosis-related outcomes warrants closer scrutiny in longitudinal prospective studies.
Delusional-like experiences; smoking; cannabis; alcohol use or dependence