A One Year Cost Analysis of Acute Paediatric Mental Health Presentations.

Aim Examine costs associated with acute mental health presentations (AMHP) to a paediatric emergency department (ED) in 2016 and 2018. Methods Case identification and bed costs were calculated. Results In 2018, 163 youths attended the ED with AMHP, 122 (75%) were admitted (average 8 days), representing a yearly cost to the hospital of €1,028,020, average cost per patient €8,426. This marks an increase of €425,320 or €2,686 per patient compared to 2016. Arriving out of hours, presence of self-harm (SH) and discharge to an inpatient psychiatry bed were all associated with greater costs. Conclusion Despite increasing hospital costs associated with out of hours psychiatric emergencies, dedicated funding is not yet in place. All children should have access to urgent MH assessment. Work force planning and creation of pathways of care for young people with MH needs, including dedicated funding from HSE mental health division must be a priority.

Prevention of Depression in At-Risk Adolescents: Moderators of Long-term Response.

In a randomized controlled trial, we found that a cognitive behavioral program (CBP) was significantly more effective than usual care (UC) in preventing the onset of depressive episodes, although not everyone benefitted from the CBP intervention. The present paper explored this heterogeneity of response. Participants were 316 adolescents (M age = 14.8, SD = 1.4) at risk for depression due to having had a prior depressive episode or having current subsyndromal depressive symptoms and having a parent with a history of depression. Using a recursive partitioning approach to baseline characteristics, we (Weersing et al. 2016) previously had identified distinct risk clusters within conditions that predicted depressive episodes through the end of the continuation phase (month 9). The present study used the same risk clusters that had been derived in the CBP group through month 9 to reclassify the UC group and then to examine group differences in depression through month 33. We found that in this overall very high-risk sample, the CBP program was superior to UC among youth in the low-risk cluster (n = 33), characterized by higher functioning, lower anxiety, and parents not depressed at baseline, but not in the middle (n = 95) and high-risk (n = 25) clusters. Across conditions, significantly more depression-free days were found for youth in the low-risk cluster (M = 951.9, SD = 138.8) as compared to youth in the high-risk cluster (M = 800.5, SD = 226.7). Identification of moderators, based on purely prognostic indices, allows for more efficient use of resources and suggests possible prevention targets so as to increase the power of the intervention.

Paediatric Consultation Liaison Psychiatry Services (PCLPS) -what are they actually doing?

Introduction Paediatric Consultation Liaison Psychiatry Services (PCLPS) are specialised services treating mental health difficulties co-morbid with medical problems. Methods Standardised clinical data was retrieved from all case notes (N=108) during the study timeframe (Jan-June 2016). Results The majority of children were female 59 (55%) with a mean age of 13. Presentation was typically via the Emergency Department (ED) (85, 79%), and of those, the majority (53, 62%) were 'out of hours' and for Deliberate Self-harm (44, 52%) Almost half of all cases seen (50, 46%) were previously known, and discharged back (84, 78%), to CAMHS. Discussion The majority of work conducted by the PCLPS involved children with acute or deteriorating psychiatry disorders, previously known to CAMHS, with a much smaller focus on typical liaison presentations. Adequate resourcing of hospital based PCLPS and 'out of hours' CAMHS are necessary to allow PCLPS provide a specialist service to children with combined medical and MH problems. Given the development of the National Children's Hospital, addressing these resourcing deficits is of vital importance.

Methodological considerations in service use assessment for children and youth with mental health conditions; issues for economic evaluation.

Economic evaluations are increasingly used in decision-making. Accurate measurement of service use is critical to economic evaluation. This qualitative study, based on expert interviews, aims to identify best approaches to service use measurement for child mental health conditions, and to identify problems in current methods. Results suggest considerable agreement on strengths (e.g., availability of accurate instruments to measure service use) and weaknesses, (e.g., lack of unit prices for services outside the health sector) or alternative approaches to service use measurement. Experts also identified some unresolved problems, for example the lack of uniform definitions for some mental health services.

General practitioner referrals to a child and adolescent mental health service (CAMHS): pre and post COVID-19 pandemic.

OBJECTIVES: To compare the characteristics of GP referrals to CAMHS prior to and over the entire pandemic. METHODS: All accepted referrals to a Dublin-based CAMHS between January 1, 2019, and June 30, 2023, were examined. Referral letters were anonymised in batches, and information was extracted directly onto a designated proforma. RESULTS: Before the pandemic (January 2019-February 2020), an average of 17.8 referrals were accepted per month, while during and after the pandemic (March 2020-June 2023), this rose to 18.7 accepted referrals per month. Increases were observed in the clinic's prioritisation of cases during the pandemic period (54.8% v. 41%, p < .001).Referrals post COVID-19 were older (13.1-13.64 years, p = .010) with a higher proportion of females (50.2% v. 62.1%, p < .001). Internalising disorders increased during the pandemic (68.7% v. 78.7%, p = .001), with self-harm referrals also being notably more frequent (18.5% v. 36.3%, p < .001). Referrals for anxiety (43.0% v. 78.2%, p = .004) and eating disorders (0% v.. 6.2%, p < .001) increased significantly. Referrals for psychosis (8.4% v. 4.8%, p = .032) and autism spectrum disorder (ASD) (26.5% v. 18.7%, p = .008) decreased after the onset of the pandemic. CONCLUSIONS: Notable increases in referrals for anxiety, depression, self-harm, and eating disorders underscore the impact of the pandemic on youth mental health. Understanding these shifts is crucial for CAMHS to adapt resources and interventions effectively. Clinicians must remain vigilant in assessing and addressing the evolving mental health needs of youths in the post-COVID era, ensuring timely and appropriate interventions, and resources to mitigate long-term consequences.

Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial.

AIMS/HYPOTHESIS: Type 1 diabetes results from a chronic autoimmune process continuing for years after presentation. We tested whether treatment with teplizumab (a Fc receptor non-binding anti-CD3 monoclonal antibody), after the new-onset period, affects the decline in C-peptide production in individuals with type 1 diabetes. METHODS: In a randomised placebo-controlled trial we treated 58 participants with type 1 diabetes for 4-12 months with teplizumab or placebo at four academic centres in the USA. A central randomisation centre used computer generated tables to allocate treatments. Investigators, patients, and caregivers were blinded to group assignment. The primary outcome was a comparison of C-peptide responses to a mixed meal after 1 year. We explored modification of treatment effects in subgroups of patients. RESULTS: Thirty-four and 29 subjects were randomized to the drug and placebo treated groups, respectively. Thirty-one and 27, respectively, were analysed. Although the primary outcome analysis showed a 21.7% higher C-peptide response in the teplizumab-treated group (0.45 vs 0.371; difference, 0.059 [95% CI 0.006, 0.115] nmol/l) (p = 0.03), when corrected for baseline imbalances in HbA(1c) levels, the C-peptide levels in the teplizumab-treated group were 17.7% higher (0.44 vs 0.378; difference, 0.049 [95% CI 0, 0.108] nmol/l, p = 0.09). A greater proportion of placebo-treated participants lost detectable C-peptide responses at 12 months (p = 0.03). The teplizumab group required less exogenous insulin (p < 0.001) but treatment differences in HbA(1c) levels were not observed. Teplizumab was well tolerated. A subgroup analysis showed that treatment benefits were larger in younger individuals and those with HbA(1c) <6.5% at entry. Clinical responders to teplizumab had an increase in circulating CD8 central memory cells 2 months after enrolment compared with non-responders. CONCLUSIONS/INTERPRETATIONS: This study suggests that deterioration in insulin secretion may be affected by immune therapy with teplizumab after the new-onset period but the magnitude of the effect is less than during the new-onset period. Our studies identify characteristics of patients most likely to respond to this immune therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT00378508 FUNDING: This work was supported by grants 2007-502, 2007-1059 and 2006-351 from the JDRF and grants R01 DK057846, P30 DK20495, UL1 RR024139, UL1RR025780, UL1 RR024131 and UL1 RR024134 from the NIH.

Immunological biomarkers: catalysts for translational advances in autoimmune diabetes.

In a recent workshop organized by the JDRF focused on the 'Identification and Utilization of Robust Biomarkers in Type1 Diabetes', leaders in the field of type 1 diabetes (T1D)/autoimmunity and assay technology came together from academia, government and industry to assess the current state of the field, evaluate available resources/technologies and identify gaps that need to be filled for moving the field of T1D research forward. The highlights of this workshop are discussed in this paper, as well as the proposal for a larger, planned consortium effort, incorporating a JDRF Biomarker Core, to foster collaboration and accelerate progress in this critically needed area of T1D research.

General Practitioner referrals to Child and Adolescent Mental Health Services: Did they differ during Covid-19?

OBJECTIVES: The COVID pandemic has been associated with poorer mental health in youth. This study aimed to evaluate any change in General Practitioner (GP) referral pattern to Child and Adolescent Mental Health (CAMH) services during the first 10 months of Covid-19 and compare with a similar time frame in 2019. METHODS: All accepted referrals to a CAMH Service in Dublin during the study time frame were reviewed. Referral letters were batch anonymised and clinical data extracted using a study specific proforma for analysis. RESULTS: Referral numbers between the two time periods did not statistically differ. Proportionally more females were referred during the pandemic, increasing to 56.9%, n = 99, compared to 43.1%, n = 75 in 2019 (p = 0.01). Referrals were more often designated by the clinician as urgent during the pandemic (61.3%, n = 98) than before (39%, n = 62, p < 0.001). Referrals outlining self-harm or suicidal ideation increased significantly, from 42.1% (n = 67) to 55.9% (n = 90) (p = 0.014). Referrals for externalising problems fell from 2019 rates; ADHD (21.4%, n = 34 vs 11.1%, n = 18; p = 0.013), ASD (26.4%, n = 42 vs 16.1%, n = 26; p = 0.038) and conduct problems (23.3%, n = 37 vs 7.4%, n = 12; p < 0.001). Although numbers for psychosis in 2019 were low (10.7%, n = 17), these also fell significantly in 2020 (2.5%, n = 4; p < 0.001). DISCUSSION: The finding of reduced referrals for ADHD and ASD has not previously been reported. With concerns regarding educational loss linked to online learning, it is crucial that these youth are not doubly disadvantaged by delayed referral and education decline.

Analysis of human biologics with a mouse skin transplant model in humanized mice.

Preclinical testing of human therapeutic monoclonal antibodies has been limited in murine models due to species differences in pharmacokinetics and biologic responses. To overcome these constraints we developed a murine skin transplant model in humanized mice and used it to test human monoclonal antibody therapy. Neonatal NOD/SCID/IL2Rγc(null) mice (NSG) were reconstituted with human CD34(+) hematopoietic stem cells (hNSG). When adult, these mice rejected MHC mismatched murine C57BL/6J skin grafts. Rejection required adequate reconstitution with human cells. There was diffuse infiltration of the epidermis and dermis with hCD8 and hCD4 cells in rejected grafts by immunohistochemistry. Studies with B6/MHC class I and II knockout mice donors indicated that neither is required for rejection. Graft rejection was associated with the development of effector and central memory T cells and an increase in serum immunoglobulins. We also tested the effects of teplizumab (anti-CD3 mAb) and found it could delay skin graft rejection, whereas ipilimumab (anti-CTLA-4 [cytotoxic T-lymphocyte antigen-4] mAb) treatment accelerated rejection. These findings demonstrate that hNSG mice reliably and predictably reject a xenogenic mouse skin graft by a human T cell mediated mechanism. The model can be utilized to investigate the ability of human immunotherapies to enhance or suppress functional human immune responses.

Phenotypic analysis of the inflammatory exudate in murine lymphocytic choriomeningitis.

The massive inflammation of the cerebrospinal fluid (CSF) which occurs in adult mice injected with lymphocytic choriomeningitis virus (LCMV) has been analyzed by flow microfluorometry (FMF). The great majority of the T cells detected by direct examination of freshly obtained CSF were found to be Lyt-2+, with an almost total absence of L3T4+ lymphocytes. The Lyt-2/L3T4 ratio of lymphocytes in blood was within normal limits. Predominance of the Lyt-2+ subset was confirmed by culturing the CSF cells after mitogenic stimulation. In addition, the T lymphocytes in CSF of cyclophosphamide-suppressed, virus-infected recipients that had been injected 4 d previously with LCMV-immune spleen cells were almost entirely donor Lyt-2+ cells, while the nonlymphoid elements were exclusively of host origin. However this pattern of donor and host T cell distribution was reversed when the LCMV-infected recipients were not immunosuppressed. The frequency of LCMV-specific CTL precursors in CSF taken immediately before the development of symptoms was as low as 1:3,000 cells. Thus most of the T lymphocytes extravasating into the CSF of mice with LCM are passive participants recruited as a consequence of the function of relatively few LCMV-specific effector T cells. The dominance of the Lyt-2+ T cell subset in the CSF of mice with LCM is intriguing.

High bone turnover in Irish professional jockeys.

SUMMARY: Professional jockeys are routinely exposed to high impact trauma and sustain fractures frequently. We found that jockeys restrict their caloric intake in order to maintain regulation weights, and that bone turnover is high. There are significant health and safety implications for the racing industry. INTRODUCTION: Professional jockeys routinely sustain fractures from high impact falls. Jockeys maintain a low percentage body fat and a low body mass index (BMI) to achieve low weight targets in order to race. We evaluated dietary habits and bone metabolism in jockeys. METHODS: Bone mineral density (BMD) was measured in 27 male jockeys of the 144 jockeys licensed in Ireland. Fourteen (52%) had BMD T score below -1.0, of whom 12 consented to clinical review, nutritional survey, endocrine studies, and bone turnover markers (BTM). BTM were compared to age- and sex-matched controls (n = 16). RESULTS: BMI was 20.6 +/- 1.7 kg/m(2); previous fracture frequency was 3.2 +/- 2.0 per rider. All had normal endocrine axes. The jockeys' diet as determined by a 7-day dietary recall was deficient in energy, calcium, and vitamin D intake. Compared with the control group, the jockey group had evidence of increased bone turnover. CONCLUSIONS: A substantial proportion of the professional jockeys in Ireland have low-normal BMD, low BMI, and high bone turnover that may result from weight and dietary restrictions. These factors seem to have a deleterious effect on their bone health and predispose the jockeys to a high fracture risk that should be remediated.

Cannabis use and childhood trauma interact additively to increase the risk of psychotic symptoms in adolescence.

BACKGROUND: Adolescent cannabis use has been shown in many studies to increase the risk of later psychosis. Childhood trauma is associated with both substance misuse and risk for psychosis. In this study our aim was to investigate whether there is a significant interaction between cannabis use and childhood trauma in increasing the risk for experiencing psychotic symptoms during adolescence. METHOD: Psychiatric interviews using the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) semi-structured instrument were carried out with 211 adolescents aged between 12 and 15 years and their parents as part of a population-based study. The interview enquired about early traumatic events, cannabis use and psychiatric symptoms in adolescence. RESULTS: In separate analyses both cannabis use and childhood trauma were significantly associated with risk of experiencing psychotic symptoms. However, the presence of both childhood trauma and early cannabis use significantly increased the risk for psychotic symptoms beyond the risk posed by either risk factor alone, indicating that there was a greater than additive interaction between childhood trauma and cannabis use. CONCLUSION: Our finding of a greater than additive interaction between childhood trauma and cannabis use may have implications for the identification of individuals at high risk of experiencing psychotic symptoms. For example, measures to actively discourage or intensively treat cannabis use in children and adolescents who have experienced abuse may help to prevent the development of psychosis in this vulnerable group. Our findings require replication in larger samples to confirm this interaction effect.

Dress and address: patient preferences regarding doctor's style of dress and patient interaction.

We sought to determine patient preferences regarding doctor's dress styles and mode of doctors introducing themselves to patients and addressing patients. A survey of patients attending a general medical/endocrinology outpatient clinic in a tertiary referral hospital over a 6 week period was performed. 124 people completed the survey (62 male, 62 female). Mean age was 52.3 years (Range 19-84). Patients preferred to be addressed by their first name while they prefer doctors to introduce themselves by their first and last name. However the majority of patients found all forms of doctors introducing themselves acceptable. Patients preferred formal attire for both male and female doctors, with a white coat being the most preferred option. 84.5% of patients felt that doctors should wear name badges in a clearly visible place although only 26% of patients saw name badges always or almost always during a consultation. This study raises important points regarding the doctor patient interaction.

Debut de diabetes tipo 1 en niños durante la pandemia Covid-19 en el Hospital de Pediatría Juan P. Garrahan / Debut of type-1 diabetes in children during the COVID-19 pandemic at Hospital de Pediatría Juan P. Garrahan

Introducción: Según numerosos reportes, la pandemia por COVID­19 aumentó la incidencia de diabetes tipo 1 (DBT1) y cetoacidosis (CAD). Nuestro objetivo fue describir la frecuencia de nuevos casos de DBT1 y su severidad al ingreso en el Hospital J. P. Garrahan durante la pandemia, comparando con el periodo anterior. Material y métodos: Se realizó un estudio descriptivo, observacional, con análisis retrospectivo. Se incluyeron todos los nuevos casos entre 19/03/20- 31/12/21, comparados con el período 19/03/18-31/12/19. El diagnóstico de DBT1, CAD y su severidad se realizó según la International Society for Pediatric and Adolescent Diabetes. Se analizó el requerimiento de cuidados intensivos (UCI), presencia de COVID-19, hemoglobina glicosilada A1C (HbA1C) y autoanticuerpos (GADA, IAA, IA2, ZNT8). Se consideró significativa una p < 0,05. Resultados: En el período 2020-2021 se observó un incremento del 107% de nuevos casos, ingresando 56 pacientes con DBT1. La media y mediana de edad disminuyeron (8 vs 9,1 y 7,7 vs 10,4, respectivamente), con un incremento del 35% de menores de 5 años. Aumentó la frecuencia de CAD severa (41.1% vs 25.9%) y de requerimiento de UCI (17.9% vs 11.1%). La Hb A1C y la glucemia de ingreso mostraron incremento significativo (10.1% vs 12.32%, p<0.003 y 580 mg/dl ± 220 vs 490 mg/dl ± 188; p<0.05, respectivamente). Conclusión: En 2020-2021 se incrementó el número de nuevos casos de DBT1 en nuestra institución. Al ingreso hubo mayor proporción de niños pequeños y casos severos. Las dificultades de acceso a la consulta de atención primaria podrían relacionarse con nuestro hallazgo (AU)

Introduction: Numerous reports have shown that during the COVID-19 pandemic the incidence of type-1 diabetes (T1DB) and ketoacidosis (DKA) increased. The aim of this study was to describe the frequency of new cases and their severity on admission of T1DB at Hospital J. P. Garrahan during the pandemic, compared with the previous period. Material and methods: A descriptive, observational study with a retrospective analysis was conducted. All new cases seen between 19/03/20-31/12/21 were included and compared with the period 19/03/18-31/12/19. The diagnosis of T1DB, DKA, and its severity was made according to the International Society for Pediatric and Adolescent Diabetes. Intensive care (ICU) requirement, presence of COVID-19, glycosylated hemoglobin A1C (HbA1C), and autoantibodies (GADA, IAA, IA2, ZNT8) were analyzed. A p < 0.05 was considered significant. Results: In the period 2020-2021, a 107% increase in new cases was observed including 56 patients with T1DB. Mean and median age decreased (8 vs 9.1 and 7.7 vs 10.4, respectively), with a 35% increase in children under 5 years of age. The frequency of severe DKA (41.1% vs 25.9%) and ICU requirement (17.9% vs 11.1%) increased. Hb A1C and glycemia on admission also showed a significant increase (10.1% vs 12.32%, p<0.003 and 580 mg/dl ± 220 vs 490 mg/dl ± 188; p<0.05, respectively). Conclusion: In 2020-2021 an increase in the number of new cases of T1DB was observed at our institution. On admission, a higher rate of young children and severe cases was found. Difficulties to access primary care may have been related to our finding (AU)

When a stroke is not a stroke; posterior leukoencephalopathy syndrome mimicking posterior circulation stroke.

Posterior leukoencephalopathy syndrome (PLS) is a potentially reversible syndrome that may mimic the clinical and radiological features of posterior circulation cerebral infarction. Three cases of PLS are presented which were erroneously diagnosed as strokes and treated in accordance with recent evidence based guidelines; none of the cases fulfilled the current criteria requiring treatment for hypertension in the acute stroke setting. Once the diagnosis of PLS was made, and the patients blood pressure treated aggressively, all patients had rapid and full clinical resolution of their symptoms. Given the important differences in management and prognosis, rapid and accurate diagnosis is essential. Posterior leukoencephalopathy syndrome needs to be considered in patients presenting with clinical and/or radiological findings that predominantly affect the occipital lobes.

dUTP nucleotidohydrolase isoform expression in normal and neoplastic tissues: association with survival and response to 5-fluorouracil in colorectal cancer.

Aberrant dUTP metabolism plays a significant role in the underlying molecular mechanisms of cell killing mediated by inhibitors of thymidylate biosynthesis. dUTP nucleotidohydrolase (dUTPase) is the key regulator of dUTP pools, and significant evidence exists suggesting that the expression of this enzyme may be an important determinant of cytotoxicity mediated by inhibitors of thymidylate synthase (TS). In this study, we have determined the expression patterns of dUTPase in normal and neoplastic tissues and examined the association between dUTPase expression and response to 5-fluorouracil (5-FU)-based chemotherapy and overall survival in colorectal cancer. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue sections using a monoclonal antibody (MAb), DUT415, that cross-reacts with both nuclear and mitochondrial isoforms of human dUTPase. Nuclear and cytoplasmic staining was observed in both normal and neoplastic tissues. In normal tissues, nuclear dUTPase staining was observed exclusively in replicating cell types. This observation is in agreement with cell culture studies where expression of the nuclear isoform (DUT-N) is proliferation dependent In contrast, cytoplasmic expression of dUTPase does not correlate with proliferation status and was observed in tissues rich in mitochondria. Consistent with this observation, cell culture studies reveal that the mitochondrial isoform (DUT-M) is expressed constitutively, independent of cell cycle status. These data suggest that in normal tissues, nuclear staining with the DUT415 antibody represents the DUT-N isoform, whereas cytoplasmic staining represents the DUT-M isoform. In colon cancer tumor specimens, expression of dUTPase was shown to be highly variable in both amount and intracellular localization. Patterns of dUTPase protein expression observed included exclusive nuclear, exclusive cytoplasmic, and combined nuclear and cytoplasmic staining. Thus, immunohistochemical detection of dUTPase in colon cancers provides distinct intracellular phenotypes of expression that may be of significant prognostic value. To examine the association between dUTPase expression and response to 5-FU-based chemotherapy and overall survival, we initiated a retrospective study including tumor specimens from 20 patients who had received protracted infusion of 5-FU and leucovorin for treatment of metastatic colon cancer. Positive nuclear staining was found in 8 patients, whereas 12 lacked nuclear expression. Of the patients lacking nuclear dUTPase expression, 6 responded to 5-FU-based chemotherapy, 4 had stable disease, and 2 had progressive disease. Of the patients presenting positive nuclear dUTPase expression, 0 responded to chemotherapy, 1 had stable disease, and 7 had progressive disease (P = 0.005). The median survival for patients with tumors lacking nuclear staining was 8.5 months and 6.9 months for patients with tumors demonstrating positive nuclear dUTPase expression (P = 0.09). Time to progression was significantly longer for patients with tumors lacking nuclear staining (P = 0.017). Variable cytoplasmic dUTPase expression was observed in these tumors; however, there was no apparent association with clinical response or survival in this limited study. Nuclear dUTPase staining within these tumors was also associated with TS gene expression (P = 0.06). This study demonstrates that low intratumoral levels of nuclear dUTPase protein expression is associated with response to 5-FU-based chemotherapy, greater time to progression, and greater overall survival in colorectal cancer. Conversely, high levels of nuclear dUTPase protein expression predict for tumor resistance to chemotherapy, shorter time to progression, and shorter overall survival. This report represents the first clinical study implicating dUTPase overexpression as a mechanism of resistance to TS inhibitor-based chemotherapy.

A randomized trial of a group cognitive intervention for preventing depression in adolescent offspring of depressed parents.

BACKGROUND: Adolescent offspring of depressed parents are at high risk for development of depression. Cognitive restructuring therapy holds promise for preventing progression to depressive episodes. METHODS: A randomized, controlled trial was conducted to prevent depressive episodes in at-risk offspring (aged 13-18 years) of adults treated for depression in a health maintenance organization (HMO). Potential adult cases were found by reviewing the HMO pharmacy records for dispensation of antidepressant medication and the mental health appointment system. Medical charts were reviewed for a depression diagnosis. Recruitment letters signed by treating physicians were mailed to adults. Eligible offspring had subdiagnostic depressive symptoms insufficient to meet full DSM-III-R criteria for affective disorder and/or a past mood disorder. These youth were randomized to usual HMO care (n = 49) or usual care plus a 15-session group cognitive therapy prevention program (n = 45). RESULTS: We detected significant treatment-by-time (program) effects for the Center for Epidemiological Studies Depression Scale (P=.005) and the Global Assessment of Functioning scores (P =.04). Survival analysis of incident major depressive episodes during a median 15-month follow-up found a significant advantage (P =.003) for the experimental condition (9.3% cumulative major depression incidence) compared with the usual-care control condition (28.8%). CONCLUSION: A brief, group cognitive therapy prevention program can reduce the risk for depression in the adolescent offspring of parents with a history of depression.

The association between economic inactivity and mental health among young people: a longitudinal study of young adults who are not in employment, education or training.

OBJECTIVES: Increasing rates of young people not in education, employment or training (NEETs) are a cause of concern both in Ireland and internationally, but little longitudinal research has examined the link between psychiatric disorder in young people and NEET status. METHODS: The Challenging Times (CT) Study is a longitudinal, population-based study of psychopathology among 212 young Irish people. Clinical interviews were performed at two time points: 12-15 years and 19-24 years. RESULTS: NEET status in young adulthood was associated with a sevenfold increased risk of current suicidal ideation. This result was independent of prior adolescent mental disorder. NEET young people had a fourfold increased odds of being diagnosed with a mental disorder in childhood or early adolescence compared with their economically active peers. NEET young people were at an almost threefold increased risk of any mental health disorder a twofold increased risk of anxiety disorder and threefold increased odds of suicide attempts over their lifetime compared with economically active peers. CONCLUSIONS: NEET young people are at increased risk for mental disorder and suicidal ideation. The association is bidirectional, as prior mental disorder in adolescence appeared to account for much of the association between NEET status and current mental health problems. However, economic inactivity conveys an increased risk for suicidal ideation over and above that due to prior disorder. Our findings provide a compelling economic and societal argument for early intervention and treatment of mental disorder and the importance of vocational interventions for reducing suicide risk in young adults.

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.

Split tolerance to the MHC class I molecule H-2Dd in animals transgenic for its soluble analog.

To determine whether the function of MHC molecules in tolerance and education is related to cell surface expression, we have produced two strains of transgenic mice in the C57Bl/6 background that express soluble analogs of the H-2D(d) class I protein. The transgenes were stably integrated and genetically transmitted in a Mendelian fashion. Messenger RNA for the hybrid genes was detected in all tissues analyzed in a class I-like pattern of expression, with the highest levels in lymphoid tissues. All mice bearing the transgenes expressed relatively high levels (0.1 mg/ml) of the encoded protein in their serum as assessed by Western blotting and enzyme-linked immunosorbent assay (ELISA). Gel filtration chromatography showed that the soluble H-2D(d) protein exists as a heterodimer with beta2-microglobulin and as higher order multimers in serum. Lymphoid cells from the transgenic mice showed no cell surface expression of the soluble class I protein in indirect immunofluorescence assays. Splenocytes from two independently derived transgenic lines generated primary cytotoxic and proliferative responses directed against membrane H-2D(d) antigens. Mice of both strains rejected tail skin from donors that differed from the B6 background at the H-2D(d) locus only, but with delayed kinetics compared to nontransgenic littermate controls. Mice expressing the transgenic protein on immunization did not produce antibodies that recognized soluble H-2D(d) in ELISA, whereas B6 mice generated strong antibody responses to challenge with splenocytes bearing cell surface H-2D(d). Thus, transgenic mice expressing soluble H-2D(d) were partially tolerant to stimulation by membrane-bound H-2D(d). As with the activation of T-cells, the induction and maintenance of immunologic tolerance apparently displayed different requirements depending upon the T-cell subpopulation involved.