Psychotic-like experiences? Trajectories and typologies of hallucinations and delusions from early adolescence to early adulthood in a population-based sample of Irish youth.

OBJECTIVES: Hallucinations and delusions that occur in the absence of a psychotic disorder are common in children and adolescents. Longitudinal phenomenological studies exploring these experiences are notably lacking. The objective of the current paper was to explore the phenomenology and characteristics of hallucinations and delusions from early adolescence to early adulthood. METHODS: Participants were 17 young people aged 18-21 years from the general population, all of whom had a history of childhood hallucinations and/or delusions. Longitudinal data on the phenomenological characteristics and attributions of reported hallucinatory and delusional phenomena spanning nine years were explored using content analysis. RESULTS: Hallucinatory and delusional phenomena were transient for two-thirds of the sample. The remaining one-third reported reoccurring hallucinatory and delusional phenomena into early adulthood. In those, two typologies were identified: (1) Paranormal typology and (2) Pathological typology. The former was characterised by hallucinatory and delusional phenomena that were exclusively grounded in subcultural paranormal or spiritual belief systems and not a source of distress. The latter was characterised by delusion-like beliefs that were enmeshed with individuals' mood states and a source of distress. The perceived source, the subcultural context and how young people appraised and integrated their experiences differentiated the Paranormal and Pathological typologies. CONCLUSIONS: Not all hallucinatory and delusion-like experiences are psychotic-like in nature. To reliably differentiate between pathological and non-pathological hallucinations and delusions, assessments need to explore factors including the phenomenology of individuals' experiences, how people make sense and appraise them, and the subcultural contexts within which they are experienced.

Prenatal tobacco exposure and psychiatric outcomes in adolescence: is the effect mediated through birth weight?

OBJECTIVE: This study aims to examine the associations between prenatal exposure to maternal smoking, birth weight and persistent offspring psychiatric symptoms. Additionally, we aim to examine whether the relationship between prenatal maternal smoking and persistent offspring psychiatric symptoms is mediated by offspring birth weight. METHODS: This study used the Growing Up in Ireland (GUI) longitudinal cohort. The GUI is a nationally representative longitudinal study of children which consisted of three data collection waves, at ages 9, 13, and 17 years. Logistic regression analysis was used to examine associations between prenatal tobacco exposure, and offspring psychiatric symptoms. Linear regression was used to examine associations between prenatal tobacco exposure and offspring birth weight. We conducted a mediation analysis examining potential etiological pathways linking maternal smoking during pregnancy, offspring birth weight, and later offspring psychiatric symptoms. All analyses were adjusted for confounders including household income, maternal level of education, and family psychiatric history. Additionally, examination of birth weight and subsequent psychiatric symptoms also was controlled for prematurity. RESULTS: We found that the association between prenatal tobacco exposure and later psychiatric symptoms is mediated by birth weight. CONCLUSIONS: This work provides further evidence that maternal smoking during pregnancy is an important modifiable lifestyle factor that has an impact not just on the physical health of offspring but also their mental wellbeing. Supporting women with structured smoking cessation programs at the earliest stages of pregnancy should be a public health priority.

The association between subjective maternal stress during pregnancy and offspring clinically diagnosed psychiatric disorders.

OBJECTIVE: Exposure to prenatal stress is a ubiquitous and non-specific risk factor for adverse outcomes in adulthood. In this study, we examined associations between exposure to subjective maternal stress during pregnancy and subsequent diagnosis of psychiatric disorders in offspring. METHOD: This study used the Helsinki Longitudinal Temperament Cohort, a prospective birth cohort of individuals born between 1 July 1975 and 30 June 1976 in Helsinki, Finland. The sample for this study comprised 3626 infants whose mothers had completed health and well-being assessments during pregnancy which included a measure of self-reported stress. We ran logistic regressions to assess potential associations between prenatal stress and offspring psychiatric disorder in adulthood, identified through the Finnish Hospital Discharge Register. RESULTS: Individuals whose mothers reported stress during pregnancy had significantly greater odds of developing a psychiatric disorder (OR = 1.41, 95% CI = 1.10-1.81) particularly a mood disorder (OR = 1.67, 95% CI = 1.10-2.54). These associations remained after adjusting for parental psychiatric history, and other prenatal factors. CONCLUSIONS: Individuals exposed to prenatal stress had significantly increased risk of developing psychiatric disorders later in life. This finding highlights the importance of supporting the mental health and emotional well-being of women during pregnancy.

Prevalence of Mental Disorder among young adults in Ireland: a population based study.

BACKGROUND: There is a lack of epidemiological research on the mental health of young adults in Ireland. OBJECTIVES: To determine prevalence of psychiatric disorders in a cohort of young Irish adults. METHODS: The Challenging Times study was a landmark study of the prevalence of psychiatric disorders in adolescents in North Dublin, Ireland: 212 school children aged 12-15 years were recruited through schools and interviewed using the K-SADS semi-structured diagnostic instrument. This cohort was traced again at age 19-24 years (mean age 20.8 years) and interviewed using SCID I & II. Main outcome measures were current and lifetime Axis I and Axis II psychiatric disorders. RESULTS: Follow-up rate was 80%. Using a weighted population prevalence analysis 19.8% of the cohort had a current mental disorder, 56.0% had a lifetime mental disorder of whom 28.4% had mood disorders, 27.1% had anxiety disorders, 22.7% had substance use disorders; 25.4% had lifetime multi-morbidity. Cluster A personality disorders were found in 2.3%. Lifetime prevalence of binge-drinking was 75.0%, cannabis use 65% and 17% of young adults had fulfilled criteria for an alcohol use disorder at sometime in their life. Lifetime prevalence of suicidal thoughts/behaviour was 21.1%. CONCLUSIONS: Lifetime prevalence of psychiatric disorder and substance use were high in this sample of young Irish adults. Mental Health service provision for this age group is a priority. Larger studies of nationally representative samples are needed to inform service development.

Facial emotion recognition in adolescents with psychotic-like experiences: a school-based sample from the general population.

BACKGROUND: Psychotic symptoms, also termed psychotic-like experiences (PLEs) in the absence of psychotic disorder, are common in adolescents and are associated with increased risk of schizophrenia-spectrum illness in adulthood. At the same time, schizophrenia is associated with deficits in social cognition, with deficits particularly documented in facial emotion recognition (FER). However, little is known about the relationship between PLEs and FER abilities, with only one previous prospective study examining the association between these abilities in childhood and reported PLEs in adolescence. The current study was a cross-sectional investigation of the association between PLEs and FER in a sample of Irish adolescents. METHOD: The Adolescent Psychotic-Like Symptom Screener (APSS), a self-report measure of PLEs, and the Penn Emotion Recognition-40 Test (Penn ER-40), a measure of facial emotion recognition, were completed by 793 children aged 10-13 years. RESULTS: Children who reported PLEs performed significantly more poorly on FER (ß=-0.03, p=0.035). Recognition of sad faces was the major driver of effects, with children performing particularly poorly when identifying this expression (ß=-0.08, p=0.032). CONCLUSIONS: The current findings show that PLEs are associated with poorer FER. Further work is needed to elucidate causal relationships with implications for the design of future interventions for those at risk of developing psychosis.

Prevalence of psychotic symptoms in childhood and adolescence: a systematic review and meta-analysis of population-based studies.

BACKGROUND: Psychotic symptoms occur more frequently in the general population than psychotic disorder and index risk for psychopathology. Multiple studies have reported on the prevalence of these symptoms using self-report questionnaires or clinical interviews but there is a lack of consensus about the prevalence of psychotic symptoms among children and adolescents. METHOD: We conducted a systematic review of all published literature on psychotic symptom prevalence in two age groups, children aged 9-12 years and adolescents aged 13-18 years, searching through electronic databases PubMed, Ovid Medline, PsycINFO and EMBASE up to June 2011, and extracted prevalence rates. RESULTS: We identified 19 population studies that reported on psychotic symptom prevalence among children and adolescents. The median prevalence of psychotic symptoms was 17% among children aged 9-12 years and 7.5% among adolescents aged 13-18 years. CONCLUSIONS: Psychotic symptoms are relatively common in young people, especially in childhood. Prevalence is higher in younger (9-12 years) compared to older (13-18 years) children.

Implant-related fractures of the femur following hip fracture surgery.

BACKGROUND: Most hip fractures are treated surgically, with use of either internal fixation or prosthetic replacement of the femoral head. The presence of these implants increases the risk of a later femoral fracture in susceptible osteoporotic patients. The purpose of this study was to analyze the incidence of and risk factors for implant-related fractures of the femur after previous hip fracture surgery. METHODS: Over a ten-year period from January 1988 to December 1997, 6230 patients (median age, eighty-two years; male:female ratio, 1247:4983) who sustained a total of 6696 hip fractures were admitted to the Edinburgh Orthopaedic Trauma Unit. Demographic information on the patients and details of the original treatment of the hip fracture were prospectively coded and entered into a trauma database. All subsequent readmissions due to a femoral fracture related to the implant were prospectively audited and extracted for the purposes of this study. RESULTS: One hundred and forty-one patients sustained an ipsilateral fracture of the femur at a median of twenty-four weeks following the original hip fracture surgery. Survivorship analysis of the hip fracture population revealed an overall rate of subsequent femoral fracture of 2.9% at five years, which increased to 5.1% at ten years. The median age and gender distribution of the patients who sustained a subsequent femoral fracture were similar to those of the hip fracture population as a whole. Two-thirds of the fractures propagated from the tip of the implant. Analysis of the subsequent fractures according to the type of implant used to treat the original fracture revealed considerable differences in incidence. The incidence was relatively high in the patients initially treated with a Gamma nail (18.74 fractures per 1000 person-years) or a cementless hemiarthroplasty (11.72 per 1000 person-years) and was relatively low in those treated with a compression hip screw (4.46 per 1000 person-years), cannulated screws (4.50 per 1000 person-years), or a primary arthroplasty with cement (6.2 per 1000 person-years). The highest incidence of fracture was seen in the patients who had required an arthroplasty with cement as a revision procedure following failure of a primary implant (22.39 per 1000 person-years). CONCLUSIONS: Implant-related fractures following hip fracture surgery are more common than has previously been appreciated. The risk of later ipsilateral femoral fracture is increased by the use of a Gamma nail or a cementless hemiarthroplasty to treat the original hip fracture.

Modulation of sex hormone secretion in cows by acute infection with bovine viral diarrhoea virus.

Bovine viral diarrhoea virus (BVDV) is a major pathogen of cattle and is responsible for considerable reproductive loss. In this study, the in vivo responses in six multiparous cows were investigated after a non-cytopathogenic BVDV challenge (strain Pe 515; 5 x 10(6) tissue culture infective dose 50) given 9 days before a synchronized ovulation. Six similar cows challenged with non-infectious culture medium served as controls. The experimental noncytopathogenic BVDV infection was followed by a viraemia and leucopenia at days 5-9 after challenge, but no other clinical signs of infection were detected. However, the BVDV infection altered endocrine function. Mean LH pulse frequency immediately before CIDR withdrawal was lower (P < or = 0.05) in the BVDV-infected (2.17 +/- 0.34 pulses per 8 h) compared with the sham-infected (4.83 +/- 1.04 pulses per 8 h) animals. At day 3 after CIDR withdrawal, plasma oestradiol concentrations remained high (P < 0.05) in the infected cows (2.19 +/- 0.51 pg ml(-1)) compared with the sham-infected controls (0.72 +/- 0.29 pg ml(-1)). However, there was no difference in the peak oestradiol concentration (BVDV: 2.31 +/- 0.29 versus sham: 2.34 +/- 0.41 pg ml(-1)). In addition, non-cytopathogenic BVDV significantly (P < 0.05) increased the duration of the interval between ovulation and onset of the postovulatory progesterone increase (values 1.0 ng ml(-1)) (BVDV: 3.0 +/- 0.26 versus sham: 4.0 +/- 0.26 days). The viral infection also significantly (P < 0.01) decreased mean plasma progesterone concentrations between day 3 and day 11 after ovulation (BVDV: 2.59 +/- 0.32 versus sham: 4.13 +/- 0.27 ng ml(-1)). These data show that non-cytopathogenic BVDV viraemias during the follicular phase can modulate the secretion of gonadotrophins and sex steroids, in particular progesterone, during a synchronized oestrous cycle. Therefore, viraemias during the follicular phase may reduce the fertility of cattle by disrupting the capacity of the ovulatory follicle to form a competent corpus luteum, thereby compromising early embryo development and maternal recognition of pregnancy.

Scrapie strains maintain biological phenotypes on propagation in a cell line in culture.

Bovine spongiform encephalopathy (BSE) and its human equivalent, variant Creutzfeldt-Jakob disease (vCJD), are caused by the same strain of infectious agent, which is similar to, but distinct from, >20 strains of their sheep scrapie homologue. A better understanding of the molecular strain determinants could be obtained from cells in monoculture than from whole animal studies where different cell targeting is commonly a strain-related feature. Although a few cell types can be infected with different strains, the phenotypes of the emergent strains have not been studied. We have cured the scrapie-infected, clonal SMB cell line with pentosan sulfate, stably re-infected it with a different strain of scrapie and shown that biological properties and prion protein profiles characteristic of each original strain are propagated faithfully in this single non-neuronal cell type. These findings attest to the fact that scrapie strain determinants are stable and host-independent in isolated cells.

Bovine viral diarrhoea virus: its effects on ovarian function in the cow.

Bovine viral diarrhoea virus (BVDV) is a major cattle pathogen responsible for a spectrum of symptoms, including reproductive failure. In this paper we investigate how BVDV interacts with the ovary. The viruses' tropism for the pre-ovulatory oocyte was studied by indirect immunohistochemistry. Two monoclonal antibodies, raised against the non-structural protein NS3 and the envelope glycoprotein E2 were used to probe cryo-sections cut from the ovaries of three persistently infected heifers. NS3 and E2 antigens were widely distributed within the ovarian stroma and follicular cells. NS3 was also localised within the proportion of oocytes. Overall 18.7% of the oocyte population had detectable levels of NS3. What is more, the proportion of antigen positive oocytes remained constant (P>0. 05) throughout the different stages of oocyte maturation. In a subsequent study seven cows were challenged with non-cytopathogenic BVDV (strain Pe515: 5x10(6) TCID(50)) to determine the oestradiol and progesterone responses to an acute infection. The sensitivity of the endogenous luteolytic mechanism was also established by analysing plasma prostaglandin F2alpha metabolite (PGFM) levels following an exogenous oxytocin (50 IU) challenge. The inoculation was given 2 days before a synchronised oestrus and was timed to ensure that viraemia occurred during the initial stage of corpora luteal development. Seven cows inoculated with non-infectious culture medium served as control animals and remained BVDV naive throughout the study. The BVDV challenge was followed by leucopenia, viraemia and sero-conversion. The virus also significantly (P<0.01) reduced plasma oestradiol levels between day 6 and day 11 post-inoculation (i.e. between day 4 and day 9 post-oestrus). However, the infection did not alter (P>0.05) progesterone secretion throughout the oestrous cycle or the plasma concentration of PGFM. These data indicate that bovine follicular cells and oocytes are permissive to BVDV at all stages of follicular development. They also show that a transient fall in oestradiol secretion may accompany an acute infection. In conclusion, this work has identified two potential routes through which BVDV can reduce fertility in the cow, namely impairment of oocyte quality and disruption of gonadal steroidogenesis.

Constitutive death of platelets leading to scavenger receptor-mediated phagocytosis. A caspase-independent cell clearance program.

Apoptosis is a physiological program for the deletion of cells in which caspases govern events leading to safe clearance by phagocytes. However, a growing weight of evidence now suggests that not all forms of programmed cell death are caspase-dependent. We now report a complete and constitutive but caspase-independent program for the specific phagocytic clearance of intact effete platelets, anucleated blood cells of critical importance in health and disease. Platelets aged in vitro not only exhibited increased expression of proapoptotic Bak and Bax but also evidenced constitutive diminution of function such as decreased aggregation to ADP, which was accelerated by culture in the absence of plasma. This abrogation of cell function in plasma-deprived platelets was associated with morphological and biochemical features similar to those of granulocyte apoptosis, that is, cytoplasmic condensation, plasma membrane changes including exposure of phosphatidylserine and the granule protein P-selectin, and recognition by phagocyte scavenger receptors. However, and in contrast with constitutive death of other inflammatory blood cells by apoptosis, these events were not affected by caspase inhibitors, nor was there evidence of caspase-3 activation either by hydrolysis of analog peptide substrates or Western blot analysis, serving to emphasize that neither programmed cell death nor clearance by phagocytes need involve caspases.

Bovine viral diarrhea virus: its effects on estradiol, progesterone and prostaglandin secretion in the cow.

Bovine viral diarrhea virus (BVDV) is a major cattle pathogen responsible for a spectrum of symptoms, including reproductive failure. This study was designed to establish the effects of BVDV infection on estradiol, progesterone and PGF2alpha secretion in the cow. Seven BVDV-free cows were challenged with non-cytopathogenic BVDV (strain Pe 515: 5x10(6) tissue culture infected dose50) so that peak viremia occurred during the initial phase of luteal development in a synchronized estrous cycle. Ovulation was also synchronized in 7 sham-infected animals. Within 2 wk of inoculation, viremia, leukopenia and serum neutralizing antibodies were recorded in all of the BVDV-infected cows but not the sham-infected animals. Between Day 4 and Day 9 post estrus the BVDV-infected cows had significantly (P<0.01) lower plasma estradiol levels than the sham-infected animals. However, the BVDV infection did not alter rectal temperatures, plasma progesterone concentrations or PGF2alpha secretion 17, 18 and 19 d post estrus. These data highlight a potential causal link between BVDV viremia, endocrine dysfunction and poor fertility in the cow.

Serological characteristics of peanut allergy.

BACKGROUND: Peanut is the most common cause of severe or fatal food-associated anaphylaxis. Studies indicate that peanut extracts contain many allergenic proteins. The identification of major and minor allergenic components is necessary for standardization of experimental and diagnostic extracts. OBJECTIVE: To identify further major and minor allergenic components of peanut extract using a large population of peanut allergics, and to relate serological findings to clinical parameters. METHODS: The crude peanut extract was fractionated by fast protein liquid chromatography and the IgE binding proteins identified by sodium dodecyl sulphate polyacrylamide gel electrophoresis followed by western blotting. Serum from 89 peanut allergics with a positive history of peanut allergy and elevated specific IgE and control serum from four atopic and four non-atopic, non-peanut allergics were used. RESULTS: Nineteen peanut proteins were found to bind IgE from peanut allergic sera. Over 70% of subjects reacted to protein bands of 63 and 17 kDa (consistent with Ara h 1 and Ara h 2, respectively), confirming the importance of these two proteins as major allergens. A high proportion of patient sera also bound proteins at 15, 10, 30, 18 and 51 kDa in decreasing order. The percentage of cases with sensitivity to a 15 kDa protein was found to be higher in patient groups with severe reactions to peanut. CONCLUSION: This study highlights the diversity of peanut allergens. Diagnostic extracts containing a high proportion of the 15 kDa component may aid in diagnosis.

Immunohistochemical evidence for the localization of bovine viral diarrhea virus, a single-stranded RNA virus, in ovarian oocytes in the cow.

Bovine viral diarrhea virus (BVDV) is a single-stranded RNA virus responsible for enteric disease and reproductive failure in cattle. The virus can pass vertically from cow to fetus, causing abortion, birth of malformed calves, and calves born with persistent and life-long infections. In this study, we investigated the tropism of BVDV in ovarian tissue from persistently infected animals. Three heifers persistently infected with BVDV were euthanatized and their ovaries were recovered. A specimen of each ovary was taken (n = 6) for virus isolation, and the remaining ovarian tissue was stored at -70 C. Cryosections (6 microm) cut from each ovary were analyzed for the presence of BVDV antigens by indirect immunofluorescence. The immunofluorescent analysis employed two monoclonal antibodies, WB103 and WB162, previously raised against the nonstructural protein NS3 and the envelop glycoprotein E2, respectively. High titers (6.97 +/- 0.17 log10 tissue culture infective dose50/ml) of BVDV were recovered from 6/6 ovarian samples; NS3 and E2 were widely distributed within the ovarian stroma, the cumulus cell population, and the oocytes maturing in primordial, primary, and secondary follicles. Overall, 362/1,939 (18.7%) of the oocytes contained BVDV antigens, and there was no significant (P > 0.05) difference in the proportion of BVDV-infected oocytes recorded within the primordial (227/1,247, 18.2%), primary (122/630, 19.4%), and secondary (13/62, 21.0%) follicle populations. Although the developmental potential of the infected oocytes could not be established in the present study, we conclude that bovine oocyte and the cumulus cells are susceptible to BVDV infection.

Prolonged nasal shedding and viraemia of cytopathogenic bovine virus diarrhoea virus in experimental late-onset mucosal disease.

A calf persistently infected with bovine virus diarrhoea virus (BVDV) was super-infected with a heterologous BVDV strain, C874, which contained non-cytopathogenic and cytopathogenic viruses. High titres of cytopathogenic BVDV were recovered in the three to four weeks after the challenge. Thereafter low titres of cytopathogenic virus were recovered repeatedly from the blood and the nose, with the titres in nasal secretions increasing in the four weeks before the onset of clinical signs. Neutralising antibodies against the challenge cytopathic virus (C874cp) were first detected 21 days after the super-infection, but these antibodies failed to neutralise the persisting non-cytopathogenic and cytopathogenic viruses isolated from the animal during the course of the infection. Serum collected from 105 days after the super-infection neutralised the cytopathogenic viruses isolated on day 105 and postmortem. These data indicate that unaltered wild-type C874cp was not directly responsible for the late-onset mucosal disease.

Application of an electrophoretic methodology for the identification of low molecular weight proteins in foods.

Identification and characterisation of food proteins are core features of food allergy research. Current methods used to identify allergenic proteins in food have insufficient resolution and are unable to detect low molecular weight proteins. In this study we report the use of a simple SDS-PAGE method which allows resolution of small proteins. We have subsequently applied this method and reported presence of low molecular weight proteins in a range of hydrolysed milk formulae (Nutramigen, Pregistimil, Alfare, Pepti-Junior and Pregomin), and crude peanut protein extract. The molecular weight distribution for the peanut extract and the hydrolysates ranged between 5-200kDa and 2-17kDa respectively.

Cell death induced by cytopathic bovine viral diarrhoea virus is mediated by apoptosis.

Cells infected with two closely related isolates of bovine viral diarrhoea virus (BVDV), one cytopathic (CP) and one non-cytopathic (NCP), were examined for signs of apoptosis. The results from labelling DNA using terminal transferase and biotinylated dUTP and by observing oligonucleosomal-sized DNA fragmentation indicated that the CP strain of BVDV induced apoptosis in cell culture but the NCP strain did not. Induction of apoptosis correlated with infected cells undergoing apoptosis rather than interactions between infected and uninfected cells and the induction of apoptosis by CP BVDV was a dominant trait in cells co-infected with both types of virus.

Image Analysis of the Growth of Globodera pallida and Meloidogyne incognita on Transgenic Tomato Roots Expressing Cystatins.

An approach based on image analysis that enables rapid collection and analysis of nematode size and shape during growth is reported. This technique has been applied to assess Meloidogyne incognita and Globodera pallida during their development over 35 and 42 days, respectively, on transgenic tomato roots expressing the wild-type rice cystatin Oc-I or an engineered variant, Oc-IAD86. Morphometric values were established that subdivided enlarged saccate females from other life stages. Analysis of this data subset indicates that the size of females and the frequency with which they parasitize roots expressing a cystatin are reduced. Results also demonstrate that cystatins can influence the growth of G. pallida prior to the adult stage. Similar image analysis procedures should be generally applicable to the study of host status or erivironmental factors that influence growth rates of plant-parasitic nematodes.

Protection of the bovine fetus from bovine viral diarrhoea virus by means of a new inactivated vaccine.

A model is described for the validation of vaccines designed to protect the bovine fetus from bovine viral diarrhoea virus (BVDV). The fetopathic nature of the challenge strain of virus was confirmed and the method used to test a commercial vaccine (Bovidec) developed from a Compton prototype. Heifers were vaccinated two or three times about the time of impregnation and challenged when they were between 25 and 80 days of gestation. There was no evidence of a viraemia in the heifers after the challenge, or of infection with BVDV of 13 liveborn calves or two aborted fetuses.