Prevalence and clinical characteristics of body dysmorphic disorder in adolescent inpatient psychiatric patients—a pilot study

Abstract

Background: Body dysmorphic disorder (BDD) is preoccupation with perceived body defects leading to distress and impairment in social functioning. Most of adolescent BDD literature has been done on patients within the outpatient setting with prior versions of DSM with dearth of information about BDD and comorbid psychiatric conditions among adolescents within the inpatient setting.

Aims: This pilot study evaluated the prevalence rate, clinical characteristics in adolescent BDD compared to non-BDD adolescents in a psychiatric in patient setting in addition to their comorbid issues like anxiety, OCD, ADHD and substance abuse.

Methods: Forty-five consecutively admitted adolescent patients participated with 17 meeting the DSM 5 criteria for BDD while 28 did not. Patients were asked four questions designed around the DSM-5 criteria for BDD after which they were asked to complete questionnaires like BDDQ child and adolescent version, BDDM, Multiaxial Anxiety Scale for Children, Children’s Depression Inventory, Y-BOCS and Vanderbilt ADHD rating scales.

Results: Seventeen participants had BDD. Mean age of BDD patients was 13.1 while non-BDD was 12.4. Male patients with BDD were seven (41%) while female BDD patients were 10 (58.8%). Anxiety, depression, OCD and substance use disorders were common comorbid diagnoses. Majority of patients in the BDD group classified their BDD as a severe problem with more BDD, patient’s considering suicide because of their BDD.

Discussion: BDD is present in adolescents admitted in inpatient psychiatric hospital with more female patients endorsing BDD versus their male counterparts. Patients with BDD are more likely to endorse more comorbid psychiatric issues such as anxiety, OCD, ADHD and substance abuse.     

Non-self recognition by monocytes initiates allograft rejection

Maturation of T cell–activating APCs directly links innate and adaptive immunity and is typically triggered by microbial infection. Transplantation of allografts, which are sterile, generates strong T cell responses; however, it is unclear how grafts induce APC maturation in the absence of microbial-derived signals. A widely accepted hypothesis is that dying cells in the graft release “danger” molecules that induce APC maturation and initiate the adaptive alloimmune response. Here, we demonstrated that danger signals associated with dying cells are not sufficient to initiate alloimmunity, but that recognition of allogeneic non-self by the innate immune system is required. In WT as well as in T cell–, B cell–, and innate lymphoid cell–deficient mice, allogeneic grafts elicited persistent differentiation of monocytes into mature DCs that expressed IL-12 and stimulated T cell proliferation and IFN-γ production. In contrast, syngeneic grafts in the same mice elicited transient and less pronounced differentiation of monocytes into DCs, which neither expressed IL-12 nor stimulated IFN-γ production. In a model in which T cell recognition is restricted to a single foreign antigen on the graft, rejection occurred only if the allogeneic non-self signal was also sensed by the host’s innate immune system. These findings underscore the importance of innate recognition of allogeneic non-self by monocytes in initiating graft rejection.     

Detection of homocytotropic antibody associated with a unique immunoglobulin class in the bovine species

Homocytotropic antibodies capable of sensitizing calf skin were demonstrated in serum of cows as early as 7 to 9 days following antigenic stimulation with rabbit serum albumin. In addition, the antibody was present in colostrum of the immunized dam and was taken up by the intestine of the newborn calf as an intact molecule. Skin-sensitizing activity was also detected in calf urine after uptake of colostrum. Evidence is presented for an anamnestic response, suggesting the existence of an immunological memory for the formation of skin-sensitizing antibodies. The homocytotropic antibody was shown to be heat labile and sensitive to treatment with 2-mercaptoethanol. Time course studies revealed that homocytotropic antibodies persist in calf skin for at least 8 weeks. The immunoglobulin class associated with homocytotropic activity was enriched from appropriate antisera by salt precipitation, DEAE-cellulose chromatography and gel filtration on Sephadex G-200 columns. The final preparation was still capable of sensitizing calf skin for positive PCA reactions using a minimum dose of 0.009 μg N. The homocytotropic activity of the vinal fraction could not be removed by antibodies specific for the IgG class, but was completely blocked by antibodies against the fraction enriched in homocytotropic activity. The immunoglobulin class associated with skin-sensitizing activity possesses antigenic determinants which are lacking in μ-, α-, and γ-chains. The results indicate that the homocytotropic activity in the bovine species is associated with a unique immunoglobulin class analogous to human IgE.     

Direct blockade of antigen-reactive B lymphocytes by immune complexes. An ''off'' signal for precursors of IgM-producing cells provided by the linkage of antigen-and Fc-receptors.

Antigen-antibody complexes efficiently inhibit the induction of antibody formation. Using Mishell-Dutton cultures, it can be demonstrated that neither T cells nor their products are required for this inhibition of IgM PFC formation. The blockade is at the level of B cells and cannot be overcome by LPS or TRF. The data demonstrate that cross-linking of antigen- and Fc-receptors by antigen-antibody complexes is a blocking signal for B cells.     

Tertiary Lymphoid Tissues Generate Effector and Memory T Cells That Lead to Allograft Rejection

Tertiary lymphoid tissues are lymph node‐like cell aggregates that arise at sites of chronic inflammation. They have been observed in transplanted organs undergoing chronic rejection, but it is not known whether they contribute to the rejection process by supporting local activation of naïve lymphocytes. To answer this question, we established a murine transplantation model in which the donor skin contains tertiary lymphoid tissues due to transgenic expression of lymphotoxin‐α(RIP‐LTα), whereas the recipient lacks all secondary lymphoid organs and does not mount primary alloimmune responses. We demonstrate in this model that RIP‐LTα allografts that harbor tertiary lymphoid tissues are rejected, while wild‐type allografts that lack tertiary lymphoid tissues are accepted. Wild‐type allografts transplanted at the same time as RIP‐LTα skin or 60 days later were also rejected, suggesting that tertiary lymphoid tissues, similar to secondary lymphoid organs, generate both effector and memory immune responses. Consistent with this observation, naive T cells transferred to RIP‐LTα skin allograft but not syngeneic graft recipients proliferated and differentiated into effector and memory T cells. These findings provide direct evidence that tertiary lymphoid structures perpetuate the rejection process by supporting naïve T‐cell activation.     

Cognate antigen directs CD8+ T cell migration to vascularized transplants

The migration of effector or memory T cells to the graft is a critical event in the rejection of transplanted organs. The prevailing view is that the key steps involved in T cell migration — integrin-mediated firm adhesion followed by transendothelial migration — are dependent on the activation of Gα_i-coupled chemokine receptors on T cells. In contrast to this view, we demonstrated in vivo that cognate antigen was necessary for the firm adhesion and transendothelial migration of CD8⁺ effector T cells specific to graft antigens and that both steps occurred independent of Gα_i signaling. Presentation of cognate antigen by either graft endothelial cells or bone marrow–derived APCs that extend into the capillary lumen was sufficient for T cell migration. The adhesion and transmigration of antigen-nonspecific (bystander) effector T cells, on the other hand, remained dependent on Gα_i, but required the presence of antigen-specific effector T cells. These findings underscore the primary role of cognate antigen presented by either endothelial cells or bone marrow–derived APCs in the migration of T cells across endothelial barriers and have important implications for the prevention and treatment of graft rejection.     

Type I Interferons Are Not Critical for Skin Allograft Rejection or the Generation of Donor-Specific CD8+ Memory T Cells

Type I interferons (IFN-I) link innate to adaptive immunity in microbial infection, autoimmune disease and tumor immunity. It is not known whether IFN-I have an equally central role in alloimmunity. Here we tested this possibility by studying skin allograft survival and donor-specific CD8⁺ T-cell responses in mice that lack the IFN-I receptor (IFN-IR^−/−). We found that IFN-IR^−/− mice reject fully allogeneic wild-type skin grafts at the same rate as wild-type recipients. Similarly, allograft rejection was not delayed if IFN-IR^−/− male skin was transplanted to syngeneic IFN-IR^−/− female mice. Quantitation of the male (H-Y)-specific CD8⁺ T-cell response in these mice revealed normal generation of donor-specific CD8⁺ effector T cells but fourfold reduction in CD8⁺ memory T cells. Memory CD8⁺ T cells generated in the absence of IFN-IR had normal phenotype and recall function, assessed by ex vivo cytokine production and the ability of IFN-IR^−/− mice to mount second set rejection. Finally, these memory T cells were maintained at a constant number despite their inability to respond to IFN-1. Our findings indicate that IFN-I cytokines are not critical for acute allograft rejection or for the expansion and differentiation of donor-specific CD8⁺ T cells into long-lived, functional memory T cells.     

The innate immune system in transplantation

The vertebrate innate immune system consists of inflammatory cells and soluble mediators that comprise the first line of defense against microbial infection and, importantly, trigger antigen-specific T and B cell responses that lead to lasting immunity. The molecular mechanisms responsible for microbial non-self recognition by the innate immune system have been elucidated for a large number of pathogens. How the innate immune system recognizes non-microbial non-self, such as organ transplants, is less clear. In this review, we approach this question by describing the principal mechanisms of non-self, or ‘damaged’ self, recognition by the innate immune system (pattern recognition receptors, the missing self theory, and the danger hypothesis) and discussing whether and how these mechanisms apply to allograft rejection.