Comparison of adolescent referred involuntarily or voluntarily to psychiatric hospitalization.

PURPOSE OF THE STUDY: To study in an adolescent clinical inpatient population how clinical, background and psychological factors differ between adolescents referred voluntarily or involuntarily. METHODS: In this prospective cohort study, we compared adolescents (age 13-17 years, n = 206) who had been referred to psychiatric hospitalization for the first time in their life either voluntarily (n = 144) or involuntarily (n = 62). We gathered from clinical records data on the source, mode and reason for referral as well as on whether after referral the subjects were admitted to the hospital voluntarily or not, and whether they were committed to involuntary hospitalization after the observation period. Diagnostics was based on Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL) interview, supplemented by information from clinical records. Structured self-reports provided information on family background, depressive symptoms, substance use, defense styles, self-image and perceived social support. RESULTS: The majority of referrals due to psychotic symptoms were involuntary, whereas self-harm was the primary reason for involuntary and voluntary referrals in comparable extent. After diagnostic evaluation, no significant difference in psychotic disorders was observed between the two groups, but anxiety disorders were more prevalent among inpatients referred voluntarily than involuntarily. Among adolescents referred involuntary, parents were more often unemployed and had mental health problems. In self-assessments, mature defense style and more positive self-image were associated with adolescents referred involuntarily compared with those referred voluntarily. CONCLUSIONS: Not only psychiatric but also psychological and social factors were associated with involuntary referral for psychiatric hospitalization in adolescents.

Adolescent psychiatric outpatient care rapidly switched to remote visits during the COVID-19 pandemic.

BACKGROUND: The COVID-19-pandemic and especially the physical distancing measures drastically changed the conditions for providing outpatient care in adolescent psychiatry. METHODS: We investigated the outpatient services of adolescent psychiatry in the Helsinki University Hospital (HUH) from 1/1/2015 until 12/31/2020. We retrieved data from the in-house data software on the number of visits in total and categorized as in-person or remote visits, and analysed the data on a weekly basis. We further analysed these variables grouped according to the psychiatric diagnoses coded for visits. Data on the number of patients and on referrals from other health care providers were available on a monthly basis. We investigated the data descriptively and with a time-series analysis comparing the pre-pandemic period to the period of the COVID-19 pandemic. RESULTS: The total number of visits decreased slightly at the early stage of the COVID-19 pandemic in Spring 2020. Remote visits sharply increased starting in 3/2020 and remained at a high level compared with previous years. In-person visits decreased in Spring 2020, but gradually increased afterwards. The number of patients transiently fell in Spring 2020. CONCLUSIONS: Rapid switch to remote visits in outpatient care of adolescent psychiatry made it possible to avoid a drastic drop in the number of visits despite the physical distancing measures during the COVID-19 pandemic.

High Beck Depression Inventory 21 scores in adolescents without depression are associated with negative self-image and immature defense style.

Beck Depression Inventory (BDI) is widely used in assessing adolescents' psychological wellbeing, but occasionally the result diverges from diagnostics. Our aim was to identify factors associated with discrepancies between BDI scores and diagnostic assessment in adolescent psychiatric patients and general population. The study comprised 206 inpatients (13-17 years old) and 203 age and gender matched non-referred adolescents. Study subjects filled self-reports on depression symptoms (BDI-21), alcohol use (AUDIT), defense styles (DSQ-40) and self-image (OSIQ-R), and on background information and adverse life events. Diagnostics was based on K-SADS-PL interview, and/or clinical interview and clinical records when available. We compared subjects who scored in BDI-21 either 0-15 points or 16-63 points firstly among subjects without current unipolar depression (n = 284), secondly among those with unipolar depression (n = 105). High BDI-21 scores in subjects without depression diagnosis (n = 48) were associated with female sex, adverse life events, parents' psychiatric problems, higher comorbidity, higher AUDIT scores, worse self-image and more immature defense styles. Low BDI-21 scores among subjects with depression diagnosis (n = 23) were associated with male sex, more positive self-image and less immature defense style. In conclusion, high BDI-21 scores in the absence of depression may reflect a broad range of challenges in an adolescent's psychological development.

Soluble CD14, α-and ß-defensins in breast milk: association with the emergence of allergy in a high-risk population.

As innate immunity factors in breast milk (BM) modulate infants' immune responses, we investigated whether soluble CD14 (sCD14) and defensin levels in BM are associated with the emergence of allergy in childhood. The randomly selected group of 260 mother-child pairs belonged to a randomized, double-blind placebo-controlled trial where 1223 mothers with fetuses at high risk for allergy received for the 4 last wk of pregnancy a mixture of probiotics, or placebo; after birth, the child received the treatment for 6 mo. Children were followed for the emergence of sensitization and allergic symptoms for 5 yr. IgE-mediated allergic disorder was diagnosed in 80 children by the age of 5 yr. Levels of sCD14, human neutrophil peptide (HNP) 1-3 and ß-defensin 2 (HBD2) in colostrum and in BM 3 mo post-partum were measured with ELISA. BM sCD14 levels decreased from 0 to 3 mo. HNP1-3 and HBD2 were detected in colostrum, but not in BM 3 mo post-partum. High sCD14 levels in BM 3 mo post-partum were associated with children developing an IgE-mediated allergic disorder by the age of 5 yr. BM HNP1-3, HBD2 or sCD14 levels were not associated with probiotics treatment. Our results suggest that sCD14 in BM influences the emergence of allergy in children with atopic heredity.

Specific antibodies in oral immunotherapy for cow's milk allergy: kinetics and prediction of clinical outcome.

BACKGROUND: METHODS for predicting the clinical outcome of specific oral immunotherapy (OIT) would improve the safety of the therapy. METHODS: We investigated 40 children aged 6-17 years with IgE-mediated cow's milk allergy (CMA) who either successfully completed OIT (n = 32) or discontinued the therapy due to adverse reactions (n = 8). From sera drawn before and after OIT, we analyzed specific IgA, IgG, IgG1 and IgG4 to cow's milk (CM), casein, ß-lactoglobulin and ovalbumin (with enzyme-linked immunosorbent assay) and IgE to CM and hen's egg white [with enzymatic fluoroimmunoassay (Phadia ThermoFisher Scientific CAP system)]. As a reference, we also analyzed serum samples from 8- to 9-year-old children who either had no history of CMA (n = 76) or who had spontaneously recovered from IgE-mediated CMA (n = 56). RESULTS: Levels of specific IgA, IgG, IgG1 and IgG4 to CM and casein, and CM-specific IgE prior to OIT were higher in children who discontinued the therapy than in those who achieved desensitization (p < 0.05). Adverse reactions in the entire population were associated with low IgG and IgG4, but high IgG1 levels to ovalbumin (p < 0.05). Specific IgA, IgG, IgG1 and IgG4 to CM proteins significantly increased and IgE to CM decreased during OIT in children who achieved desensitization (p < 0.01). In those who discontinued OIT, only IgG, IgG1 and IgG4 to CM increased significantly (p < 0.03) and CM IgE remained unchanged. CONCLUSIONS: High specific IgE, IgA and IgG-class antibodies to CM proteins appear to predict failure to achieve desensitization in CM OIT. Specific IgA and IgG-class antibodies to CM increase and CM IgE decreases during desensitization.

Use of IgE and IgG4 epitope binding to predict the outcome of oral immunotherapy in cow's milk allergy.

BACKGROUND: Oral immunotherapy (OIT) with cow's milk (CM) has been reported to induce a number of specific antibody responses, but these remain to be fully characterized. Our objective was to explore whether IgE and IgG4 epitope binding profiles could predict the risk of side effects during CM OIT. METHODS: The study population consisted of 32 children (6-17 yr of age) with CM allergy: 26 children who successfully completed OIT and six children who discontinued therapy due to adverse reactions. We investigated sera drawn before and after OIT. We analyzed specific IgE and IgG4 binding to CM protein-derived peptides with a microarray-based immunoassay. Antibody binding affinity was analyzed with a competition assay where CM proteins in solution competed with peptides printed on the microarray. RESULTS: IgE binding to CM peptides decreased and IgG4 binding increased following the OIT in children who attained desensitization. Compared with children who successfully completed OIT, those who discontinued OIT due to adverse reactions developed increased quantities and affinity of epitope-specific IgE antibodies and a broader diversity of IgE and IgG4 binding, but less overlap in IgE and IgG4 binding to CM peptides. CONCLUSIONS: Detailed analysis of IgE and IgG4 binding to CM peptides may help in predicting whether CM OIT will be tolerated successfully. It may thus improve the safety of the therapy.

Development of natural tolerance and induced desensitization in cow's milk allergy.

Cow's milk allergy (CMA) affects 2-3% of infants. It resolves in the great majority spontaneously during childhood. CMA encompasses a spectrum of clinical and immunologic characteristics. Non-IgE-mediated allergy typically resolves earlier than IgE-mediated allergy. The most documented prognostic characteristic is that intense-specific IgE response predicts persistence of CMA. Low serum levels of cow's milk (CM)-specific IgG4 are also associated with persistent CMA. Natural development of tolerance involves an immunologic shift where Th2 responses diminish, and Th1 as well as T regulatory cell responses strengthen. Accordingly, specific IgE levels decrease and specific IgG4, possibly also IgA, levels increase in serum. Specific oral immunotherapy (OIT) with CM induces desensitization in most cases where spontaneous recovery has not yet occurred. Data on long-term tolerance induction are still scarce. According to current research data, the immunologic changes induced by OIT resemble those seen during natural development of tolerance.

Cow's milk and ovalbumin-specific IgG and IgA in children with eczema: low ß-lactoglobulin-specific IgG4 levels are associated with cow's milk allergy.

Tolerance to allergens may partly depend on allergen-specific IgG and IgG subclasses and IgA antibodies. We investigated whether specific IgG and IgG subclasses and IgA antibodies to ß-lactoglobulin, α-casein, and ovalbumin differed between infants who had verified cow's milk allergy (CMA) and infants with cow's milk (CM)-associated eczema, but negative CM oral challenge. The study population comprised 95 infants with clinical eczema that was by history associated with the consumption of CM. After an elimination period, a double-blind, placebo-controlled (DBPC) CM oral challenge confirmed CMA in 45 infants. Skin prick tests (SPT) were performed with CM and hen's egg. Serum levels of IgE antibodies to CM and hen's egg were measured with UniCAP (Phadia, Uppsala, Sweden), and levels of IgA, IgG, IgG1, and IgG4 antibodies to ß-lactoglobulin, α-casein, and ovalbumin were measured with enzyme-linked immunosorbent assay. We observed that infants with CMA had lower IgG4 levels to ß-lactoglobulin than infants with negative DBPC CM challenge (p = 0.004). Positive CM SPT was associated with lower IgG4 levels to α-casein (p = 0.04). The relation of CM IgE to ß-lactoglobulin and α-casein IgG4 was higher in CMA than in infants with negative challenge (p < 0.002 and 0.0001). Positive egg SPT was associated with elevated levels of specific IgG to ovalbumin, ß-lactoglobulin, and α-casein as well as IgA to α-casein (p < 0.04). Our study thus shows that low ß-lactoglobulin-specific serum IgG4 levels may differentiate eczematous infants with CMA from infants who have eczema with only suspected association with CM.

Early recovery from cow's milk allergy is associated with decreasing IgE and increasing IgG4 binding to cow's milk epitopes.

BACKGROUND: The dynamics and balance of allergen-specific IgE, IgG4, and IgA binding might contribute to the development of tolerance in patients with cow's milk allergy (CMA). Profiling of antibody binding to cow's milk (CM) protein epitopes might help in predicting the natural history of allergy. OBJECTIVE: We sought to investigate differences in IgE, IgG4, and IgA binding to CM epitopes over time between patients with early recovery or with persisting CMA. METHODS: We studied serum samples at the time of diagnosis (mean age, 7 months), 1 year later, and at follow-up (mean age, 8.6 years) from 11 patients with persisting IgE-mediated CMA at age 8 to 9 years and 12 patients who recovered by age 3 years. We measured the binding of IgE, IgG4, and IgA antibodies to sequential epitopes derived from 5 major CM proteins with a peptide microarray-based immunoassay. We analyzed the data with a novel image-processing method together with machine learning prediction. RESULTS: IgE epitope-binding patterns were stable over time in patients with persisting CMA, whereas binding decreased in patients who recovered early. Binding patterns of IgE and IgG4 overlapped. Among patients who recovered early, the signal of IgG4 binding increased and that of IgE decreased over time. IgE and IgG4 binding to a panel of alpha(s1)-, alpha(s2)-, beta-, and kappa-casein regions predicted outcome with significant accuracy. CONCLUSIONS: Attaining tolerance to CM is associated with decreased epitope binding by IgE and a concurrent increase in corresponding epitope binding by IgG4.

Combined T regulatory cell and Th2 expression profile identifies children with cow's milk allergy.

The role of T regulatory cells in spontaneous recovery from cow's milk allergy (CMA) is unclear. We investigated the mRNA expression of 12 T-cell markers and the protein expression of CD4, CD25, CD127, FoxP3 after in vitro beta-lactoglobulin stimulation of peripheral blood mononuclear cells from children with persisting CMA (n=16), early recovery (n=20) or no atopy (n=21). Artificial neural networks with exhaustive search for all marker combinations revealed that markers FoxP3, Nfat-C2, IL-16 and GATA-3 distinguished patients with persisting CMA most accurately from other study groups. FoxP3 mRNA expression following beta-lactoglobulin stimulation was highest in children with persisting CMA. Also the FoxP3 intensity in CD4(+) CD25(high)CD127(low) cells was higher in children with CMA compared with non-atopic children. The expression profile of both Th2- and T regulatory cell-related genes thus reflects the clinical activity of CMA. Tolerance, in contrast, is not characterized by activation of circulating T regulatory cells.

Human leukocyte antigen (DR1)-DQB1*0501 and (DR15)-DQB1*0602 haplotypes are associated with humoral responses to early food allergens in children.

BACKGROUND: Infants' immunological responses to cow's milk (CM) proteins, which in 2-3% result in allergy, may partially depend on genetic factors. We evaluated whether genes with immunological functions, i.e. human leukocyte antigen (HLA) II, the protein tyrosine phosphatase, non-receptor type 22 (PTPN22) and filaggrin, modulate immune responses to dietary antigens. METHODS: We analyzed 14 HLA class II haplotypes, the PTPN22 1858 SNP (R620W allele) and 5 known filaggrin null mutations from blood samples of 87 patients with CM allergy (CMA) and 76 control subjects (age 8.0-9.3 years). Serum levels of IgA, IgG, IgG1 and IgG4 antibodies to beta-lactoglobulin, alpha-casein and ovalbumin were measured with enzyme-linked immunosorbent assay, levels of IgE antibodies to CM, ovalbumin and birch with UniCap (Phadia, Uppsala, Sweden). RESULTS: In children with CMA, the HLA (DR15)-DQB1*0602 haplotype was associated with high levels of beta-lactoglobulin-specific total IgG (p < 0.001) and IgG4 (p < 0.001) and alpha-casein-specific total IgG (p = 0.003) and IgG4 (p = 0.002), but not among control subjects. (DR1/10)-DQB1*0501 was associated with lower levels of beta-lactoglobulin-specific total IgG (p < 0.001) and IgG4 (p < 0.001), ovalbumin-specific total IgG (p = 0.002) and IgG4 (p < 0.001), particularly in control subjects (p < 0.001). Six children with eczema (3 with CMA) had the filaggrin mutation del22824. PTPN22 was not associated with specific antibody responses or CMA. CONCLUSION: The HLA II, but not PTPN22 or filaggrin, genotype modulates humoral responses to early food allergens, whereas none of these genes was associated with CMA.

IgG and IgA antibody levels to cow's milk are low at age 10 years in children born preterm.

BACKGROUND: Both innate and specific defenses of the preterm infant are even less developed than those of term infants, and the immune systems of preterm infants might be skewed differently at birth. Their immune responses to food antigens started early in life might therefore differ from those of term infants. OBJECTIVE: We sought to compare antibody levels to cow's milk, ovalbumin, and gliadin at age 10 years in children who had been born either preterm or at term. METHODS: IgG and IgA isotype antibodies to whole cow's milk, beta-lactoglobulin, alpha-casein, and ovalbumin, as well as IgG antibody levels to gliadin and to tetanus and diphtheria toxoids, were measured for a group of 62 children born preterm and 61 control subjects born at term. These children were studied at the same time for atopy. RESULTS: Children born preterm had markedly lower levels of antibodies to cow's milk and to its protein fractions (P <.0001 for IgA and IgG antibodies to cow's milk and alpha-casein and IgG beta-lactoglobulin antibodies). IgG gliadin antibodies were also significantly lower in the preterm group (P =.03), although the difference was not significant for IgG ovalbumin antibodies. In the preterm group both those born before gestational week 30 and those given cow's milk-based formula early (before day 50) had the lowest levels of cow's milk antibodies. In the preterm group atopy was associated with low levels of IgG cow's milk antibodies but with high levels of IgG ovalbumin antibodies. CONCLUSIONS: Early introduction of food antigens into the immature gastrointestinal tract of preterm infants might result in tolerance. The presence of less atopy in these children might also be a result of tolerance development.