Search

Introduction: Information about therapeutic serum levels of fluoxetine (FLX) and its major metabolite norfl uoxetine (NORFLX) in children and adolescents is scarce. Methods: Therapeutic drug monitoring (TDM) of FLX was routinely performed in 71 subjects treated for a major depressive disorder (MDD) (10-60 mg/d FLX, median: 20 mg/d). Correlations between serum concentration and dosage, age, gender, smoking habits and adverse events were analysed. Results: Serum concentrations of the active moiety (FLX + NORFLX) ranged from 21 to 613 ng/mL (mean concentration of 213 ± 118 ng/mL, median: 185 ng/mL). High inter-individual variability in serum concentrations of the active moiety of FLX at each dosage level was observed and no relationship between serum concentration and clinical outcome was found. Apart from smoking, none of the factors tested had a significant effect on the serum concentration. Discussion: It was shown that serum concentrations of the active moiety of FLX in children and adolescents seem to be similar to those in adults, with a high level of inter-individual variation. The proportion of patients who showed benefits from treatment with a dose of 20 mg/d FLX was high. [ABSTRACT FROM AUTHOR]

Background: Nonsuicidal self-injury (NSSI) is highly prevalent in adolescents and young adults worldwide. It is linked to a broad variety of mental disorders and an increased suicide risk. Despite its high prevalence, research on the underlying mechanisms and on potential risk and resilience factors for maintaining or quitting NSSI remains scarce. This manuscript presents an overview of the "Self-injury: Treatment-Assessment-Recovery" (STAR) collaboration, which aimed to address these gaps., Methods: We investigated the natural course of NSSI as well as its social, psychological, and neurobiological predictors (observational study; OS). OS data collection occurred at four timepoints (baseline [T0], 4 [post, T1], 12 [follow-up (FU), T2], and 18 [FU, T3] months after baseline) for the NSSI group, which was compared to a healthy control (HC) group at T0 only. Online self-report was used at all timepoints, while semi-structured interviews (face-to-face (f2f)) were conducted at T0 and T3. At T0 only, we conducted ecological momentary assessment and neurobiological investigations. Here, we present the general methodology and sample characteristics of the completed OS including the f2f subprojects, while other subprojects are not within the scope of this paper., Sample Description: The OS sample consists of 343 participants at T0 (180 NSSI, 163 HC). Mean age in the NSSI group (T0) was 18.1 years (SD = 2.09, range: 15-25), gender-related data is available for 166: 156 = female, 7 = male, 3 = transgender, 10 = not disclosed). In the HC group, mean age (T0) was 19.1 years (SD = 2.35, range: 15-25) (142 = female, 21 = male). At T1, 128 (71.11%) of the NSSI participants completed the questionnaires, at T2 125 (69.44%) and at T3 104 (57.78%). In the fMRI subproject, 126 adolescents participated (NSSI = 66, HC = 60, 100% female; mean age (T0): NSSI = 18.10 years, SD = 2.21; HC = 19.08, SD = 2.36)., Conclusion: Understanding predictors is of utmost importance for adequate diagnosis and intervention for NSSI. Our OS applied a multimodal investigation of social, psychological, and neurobiological parameters and is the largest sample of adolescents with NSSI to date including follow-up assessments. As health care providers require specific knowledge to develop new treatments, we believe that our in-depth assessments can potentially enhance care for youths engaging in NSSI., (© 2024. The Author(s).)

Affective dysregulation (AD) in children is characterized by persistent irritability and severe temper outbursts. This study developed and evaluated a screening questionnaire for AD in children. The development included the generation of an initial item pool from existing instruments, a Delphi rating of experts, focus groups with experts and parents, and psychometric analyses of clinical and population-based samples. Based on data of a large community-based study, the final screening questionnaire was developed ( n = 771; 49.7 % female; age M = 10.02 years; SD = 1.34) and evaluated ( n = 8,974; 48.7 % female; age M = 10.00 years; SD = 1.38) with methods from classical test theory and item response theory. The developed DADYS-Screen ( D iagnostic Tool for A ffective Dys regulation in Children- Screen ing Questionnaire) includes 12 items with good psychometric properties and scale characteristics including a good fit to a one-factorial model in comparison to the baseline model, although only a "mediocre" fit according to the root mean square error of approximation (RMSEA). Results could be confirmed using a second and larger data set. Overall, the DADYS-Screen is able to identify children with AD, although it needs further investigation using clinical data.

Introduction: Sleep, circadian rhythms, (mental) health, and development are assumed to be intertwined. However, differentiated and reliable parameters of sleep and circadian rhythms are particularly difficult to assess for Fragile X (FXS) individuals. As those parameters need to be observed in complex settings, the feasibility of measurements for people with FXS was to be proven. Findings from this pilot study can inform further research and help to estimate sample sizes for future studies on FXS patients., Methods and Sample: Nine individuals (male and female) with full mutation of the FMR1 gene were integrated in the study and underwent a complex measurement including actigraphy, sleep log, and 24-h saliva sampling in order to examine profiles of melatonin and cortisol, and a polysomnography., Results: Seven actigraphy profiles, eight sleep logs, eight saliva profiles and seven polysomnographic data sets were collected. Complete data were analyzed for six individuals [mean age 14.87 years (SD 4.12), mean BMI 25.90 (SD 4.44)] were collected. No drop outs due to the constraints of the assessment were registered., Discussion: All assessments and the setting in total were tolerated well by participants and caregivers. Procedures were adapted to individual needs of the participants., Conclusion: All its components and the setting in total are absolutely feasible in the specific population of FXS individuals. Losses during consenting and recruiting have to be planned as well as high amounts of interindividual variances have to be taken into account., (Copyright © 2020 Dueck, Reis, Bastian, van Treeck, Weirich, Haessler, Fiedler, Koelch and Berger.)

Development of an Online Intervention for Adolescents and Young Adults Engaging in Nonsuicidal Self-injury Nonsuicidal self-injury (NSSI) is a prevalent phenomenon in adolescence. Despite the existence of effective psychotherapeutic interventions, the majority of affected adolescents and young adults do not receive any treatment. Structural (e. g., no specific interventions, limited resources, limited accessibility) as well as individual factors (e. g., low help-seeking behavior) impede access to adequate clinical care for adolescent NSSI. Online interventions offer the possibility to provide specific interventions independent of one's location or local healthcare structures. Because of its high confidentiality and accessibility, the Internet also reaches adolescents with low help-seeking behavior. There is already evidence for online interventions concerning different mental health issues, like depression and anxiety. However, regarding NSSI, there are no effective, online interventions. Thus, we developed an online intervention based on an already evaluated short term program specific for adolescents and young adults with NSSI within the German STAR consortium (STAR: Self-Injury - Treatment, Assessment, Recovery). Within a randomised controlled trial, the intervention will be evaluated regarding its efficacy.

Background: Non-suicidal self-injury (NSSI) is a clinically significant behavior affecting approximately 18% of adolescents and young adults worldwide. The importance of NSSI is supported by its association with a broad spectrum of mental disorders. Despite its high relevance, evidence-based, specific, time-, and cost-effective treatment approaches are scarce. Cognitive behavioral therapy (CBT) seems effective in reducing the frequency of NSSI in adolescents and young adults. However, young people are often reluctant to seek professional help and effective interventions adressing NSSI are not sufficiently available across all regions of Germany. Research indicates that the majority of youth with risk behavior (including NSSI) prefer technology-based interventions. To date, effective interventions for adolescents and young adults with NSSI that are deliverd online are not available., Methods: The present project aims to develop and evaluate an online intervention for adolescents and young adults with NSSI based on the content of a recently evaluated face-to-face short-term program that includes elements of CBT and dialectical behavior therapy (DBT): "The Cutting Down Programme" (CDP). The efficacy of the new online CDP intervention will be tested in a randomized controlled trial (RCT) in which n = 700 youths engaging in repetitive NSSI will participate in either an online psychoeducation (n = 350) or online CDP (n = 350). Within a postline assessment four months after baseline (end of treatment; T1), and follow-up evaluations 12 and 18 months after baseline (follow-ups; T2 and T3), NSSI and comorbid symptoms as well as quality of life will be assessed. It is hypothesized that participants receiving online CDP report a greater reduction in the frequency of NSSI within the last three months at T2 (primary endpoint) compared to those receiving online psychoeducation. Exploratory analyses will focus on predictors of treatment outcome., Discussion: We report on the development and evaluation of an online intervention for adolescents and young adults engaging in NSSI based on the CDP. If supported by empirical evidence, an online-based intervention for NSSI might help to overcome the limited availability of adequate interventions for youth., Trial Registration: German Clinical Trials Register, DRKS00014623 . Registered on 22 May 2018.

Background: Most psychiatric disorders in childhood and adolescence cause impairment in academic performance. Early interventions in school are thought to reduce the burden of disorder and prevent chronicity of disorder, while a delay in reachable help may result in more severe symptoms upon first time presentation, often then causing upon first-time presentation immediate need of inpatient care., Methods: The study aims at reducing hospitalization rates and increasing social participation and quality of life among children and adolescents by establishing collaborations between schools, mental health care services and youth welfare services. CCSchool offers children and adolescents, aged six to 18 years, who present with psychiatric problems associated to school problems, a standardized screening and diagnostic procedure as well as treatment in school if necessary. Students can participate in CCSchool in three federal states of Germany if they a) show symptoms vindicating a mental health diagnosis, b) present with confirmed school problems and c) have a level of general functioning below 70 on the children global assessment of Functioning (C-GAF). Intervention takes place in three steps: module A (expected n = 901, according to power calculation) with standardized diagnostic procedures; module B (expected n = 428) implies a school-based assessment followed by a first intervention; module C (expected n = 103) offering school-based interventions with either four to six sessions (basic, 80% of patients) or eight to 12 sessions (intensive, 20% of patients). Primary aim is to evaluate the effectiveness of CCSchool, in reducing the need of hospitalization in children with mental health problems. The analyses will be conducted by an independent institute using mainly data collected from patients and their caregivers during study participation. Additionally, claims data from statutory health insurances will be analysed. Relevant confounders will be controlled in all analyses., Discussion: Evaluation may show if CCSchool can prevent hospitalizations, enhance social participation and improve quality of life of children and adolescents with mental health problems by providing early accessible interventions in the school setting., Trial Registration: Deutsches Register Klinischer Studien, Trial registration number: DRKS00014838 , registered on 6th of June 2018.

Background: Current resting state imaging findings support suggestions that the neural signature of depression and therefore also its therapy should be conceptualized as a network disorder rather than a dysfunction of specific brain regions. In this study, we compared neural connectivity of adolescent patients with depression (PAT) and matched healthy controls (HC) and analysed pre-to-post changes of seed-based network connectivities in PAT after participation in a cognitive behavioral group psychotherapy (CBT)., Methods: 38 adolescents (30 female; 19 patients; 13-18 years) underwent an eyes-closed resting-state scan. PAT were scanned before (pre) and after (post) five sessions of CBT. Resting-state functional connectivity was analysed in a seed-based approach for right-sided amygdala and subgenual anterior cingulate cortex (sgACC). Symptom severity was assessed using the Beck Depression Inventory Revision (BDI-II)., Results: Prior to group CBT, between groups amygdala and sgACC connectivity with regions of the default mode network was stronger in the patients group relative to controls. Within the PAT group, a similar pattern significantly decreased after successful CBT. Conversely, seed-based connectivity with affective regions and regions processing cognition and salient stimuli was stronger in HC relative to PAT before CBT. Within the PAT group, a similar pattern changed with CBT. Changes in connectivity correlated with the significant pre-to-post symptom improvement, and pre-treatment amygdala connectivity predicted treatment response in depressed adolescents., Limitations: Sample size and missing long-term follow-up limit the interpretability., Conclusions: Successful group psychotherapy of depression in adolescents involved connectivity changes in resting state networks to that of healthy controls., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: While major effort has been put in investigating neural correlates of depression and its treatment in adults, less is known about the effects of psychotherapy in adolescents. Given the concordance of the ventral striatum, amygdala, hippocampus and the subgenual anterior cingulate cortex (sgACC) as correlates of depression and their involvement in reward processing, we used functional magnetic resonance imaging (fMRI) during performance of a monetary reward task in an intervention versus waitlist-control design to investigate the clinical and neural effects of cognitive behavioral group therapy (CBT-G)., Methods: 22 medication naïve adolescents with major depressive disorder were scanned before and after five sessions of CBT-G (PAT-I), or before and after five weeks of waiting (PAT-W). Changes in symptom scales were analyzed along with neural activation changes within the amygdala, hippocampus, sgACC and ventral striatum regions of interest (ROI)., Results: Psychometric assessments and ROI activation remained unchanged in PAT-W. In PAT-I, significant reduction in clinical symptoms accompanied significant changes in brain activation within the left amygdala, left hippocampus and bilateral sgACC. In line with previous findings in adults, pre-to-post-activation changes in the bilateral sgACC correlated with pre-to-post and pre-to-follow-up symptom improvement, and individual expressions of sgACC activation before treatment were related to pre-to-follow-up therapeutic success., Limitations: Future studies should include larger sample sizes., Conclusions: Successful group psychotherapy of depression in adolescents was related to signal changes in brain regions previously demonstrated to be reliably linked with successful, particularly pharmacological treatment in adults., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Non-suicidal self-injury (NSSI) and suicidal behaviors frequently occur among adolescent psychiatric patients. Although those behaviors are distinct with regards to intent, NSSI has been shown to be an important risk-factor for suicide attempts. However, the association of NSSI and Suicidal Behavior Disorder (SBD) according to DSM-5 criteria has not yet been investigated. For investigating distinctive features and mutual risk-factors of NSSI-disorder and SBD, adolescent psychiatric inpatients (N=111, aged 12-19 years; 65.8% females) were interviewed using the Self-Injurious-Thoughts-And-Behaviors-Interview-German (SITBI-G). NSSI started significantly earlier in life (M=12.5 years, SD=2.2) than first suicide attempts (M=14.1 years, SD=2.0). Patients meeting NSSI-disorder and/or SBD were significantly more likely to be female and to be diagnosed with an affective disorder. NSSI-disorder and SBD seem to have several distinctive features (i.e. age of onset or frequency), but also seem to share certain mutual risk-factors (i.e. affective disorders, female gender). While both NSSI and SBD seem to be maintained by mainly automatic negative reinforcement, positive automatic and social functions were rated significantly higher for NSSI. Most importantly, NSSI seems to be a strong risk factor for the occurrence of SBD (even when controlling for suicidal ideation) and should therefore always be assessed when dealing with psychiatric adolescent patients., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Preceding studies demonstrated a high agreement between self-report and clinician's assessment of depression. The concordance on the level of sum scores, subscales, and single items, however, has yet to be investigated in a psychiatric adolescent sample. Also, the influence of additional variables such as age, sex, and IQ has been insufficiently studied in adolescents., Methods: Scores on the BDI-II and CDRS-R, assessed within 1 week, were collected from 105 adolescents (mean age = 15.94 years). Analyses of correlation were done on levels of sum scores, subscales, and single items., Results: There was a high correlation between self-report and clinician's assessment (r = .67). At the level of subscales, items assessing somatic contents demonstrated no higher agreement than did items assessing cognitive and affective contents. The highest agreement at the symptom level was shown for the item assessing suicidal ideations. Additional variables had no significant influence on concordance. Adolescents with a high IQ and outpatient adolescents tended to overestimate their symptoms., Conclusions: The overall correlation was high and did not differ from results of comparable studies of correlations. The highest congruence was shown for the item assessing suicidal ideations, which underlines the accurate assessment of suicidality by clinicians as well. In summary, questionnaires can provide information about the existence of a depressive disorder, although one diagnostic instrument should not be replaced by the other despite a high correlation.

Background: Group therapy is an economic intervention, allowing for fast access, for the treatment of several depressed adolescents simultaneously; evaluated manualised programs, however, are scarce., Method: Nine depressive adolescent inpatients (M = 16.33 years; SD  = 1.92) participated between October 2009 and March 2010 in a brief manualised group therapy programme (MICHI), which was evaluated with respect to feasibility and trends of efficacy., Results: MICHI demonstrated good feasibility, was positively evaluated by the participants by means of an evaluation questionnaire ranging from 1 (very bad) to 10 (very good) (M = 7.22; SD  = 1.79), and showed significant reduction of depressive symptoms (z = -2.66, p = .008) assessed by means of a clinical interview., Conclusions: Feasibility of MICHI was demonstrated and larger trials for efficacy will follow., (© 2012 The Authors. Child and Adolescent Mental Health. © 2012 Association for Child and Adolescent Mental Health.)

Objectives: Recent studies indicate that the selective serotonin reuptake inhibitor (SSRI) fluoxetine is not solely effective by the instant inhibition of the serotonin transporter (SERT) but also by its influence on mitotic and/or apoptotic processes., Methods: To investigate the effects of the compound in vitro, we treated neurons from different brain areas with increasing concentrations of fluoxetine. Additionally, human embryonic kidney (HEK-293) cells and HEK-293 cells stably expressing the SERT were used. Cell viability was quantified by MTT-assay and apoptosis via fluorescence-activated cell-sorting analyses. Fluoxetine's effect on the γ-aminobutyric acid (GABA) receptor was electrophysiologically investigated to test the hypothesis if a GABA-mimetic effect exists that might lead - additionally to the well-known N-methyl-D-aspartate (NMDA)-antagonism - to increased apoptosis in immature neurons., Results: In hippocampal, cortical, and both types of HEK-293 cells, viability decreased and apoptosis increased in a dose-dependent manner (0.5-75 μM). In contrast, in mesencephalic and striatal cells the viability was unchanged or even slightly stimulated up to 20 μM fluoxetine. An anti-apoptotic effect of concentrations below 10 μM was observed in these cells. The GABA(A) receptor was directly activated by fluoxetine., Conclusions: We conclude that fluoxetine affects apoptotic processes independently from SERT expression. Since especially the combined GABA-mimetic and NMDA-antagonistic effects increase apoptosis in developing neuronal cells, whereas both effects are neuroprotective in adult neurons we hypothesise that these mechanisms explain the discrepancy of in vitro and in vivo studies.

Introduction: The MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) was used in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and co-morbid oppositional defiant disorder (ODD) and in their parents. The aims were to test feasibility and to determine children's understanding of the elements of disclosure for a clinical drug trial and their competence to assent., Method: The contents and language of MacCAT-CR were adapted to be age appropriate for the children. Twelve children (mean age, 9.87 [7.7-12.2]; mean intelligence quotient [IQ], 97 [72-122]) and either the mother or father of each child were interviewed. Psychologists rated the interviews and, in addition to MacCAT-CR, competence was assessed by trained clinicians., Results: The MacCAT-CR was practicable, and the time required was acceptable. Interrater reliability was excellent in children. Children performed less well than parents on this test (children;s vs. parents' scores: Understanding 5.86 vs. 9.08, appreciation 2.64 vs. 4.96, reasoning 3.05 vs. 4.63, respectively). Whereas clinicians assessed all children as competent, lack of competence became apparent in the MacCAT-CR., Conclusions: The practicability and the interrater reliability suggest that the MacCAT-CR is feasible in children, but the question of whether competence is assessed validly remains unsolved in the absence of external validation. The differences between assessment by clinicians and the low scores obtained in the MacCAT-CR suggest that children may give assent even if they do not understand completely. The results of this initial pilot study may help in the planning of further investigations intended to improve information about studies and assessment of assent/consent.

In the treatment of children with psychiatric disorders as a vulnerable population, ethical issues arise that seldom come into play with adults. The UN Conventions on the Rights of the Child and the Rights of Persons with Disabilities set out rights to be respected in child and adolescent psychiatric treatment. Rights of participation and inclusion (minimizing of barriers to the involvement of disabled people) can create complex problems in cases of restraint or deprivation of liberty. This paper analyses the consequences of these conventions and other ethics guidelines on child and adolescent psychiatric treatment and research. Beneficence, justice and autonomy are core principles that are mirrored in the problems of inclusion and protection, confidentiality, and the safety of psychopharmacological interventions. Factors of inclusion are involved in the areas of availability of care, participation in best evidence-based treatment, and research. The right of the child to protection, the right of inclusion, and parents' rights and duties to safeguard their child's wellbeing form a triangle. National laws to regulate the treatment of psychiatrically ill children should be created and implemented and these should be non-discriminatory but at the same time safeguard the developing human being.

Attention-deficit hyperactivity disorder (ADHD) is the most common neurobehavioral disorder in youth. About a third to one-half of the affected subjects continue to have symptoms in adulthood. Remarkably, the prevalence numbers published for adult females are higher than for girls. The differences in the epidemiological data between the age groups clearly point to underdiagnosed ADHD in girls. Major depression, the most frequent psychiatric condition worldwide in adulthood, is twice as common in female as in male adults. Anxiety and depression are also among the most common comorbidities in adults with ADHD. Therefore, an undiagnosed ADHD may often underlie the psychopathology in depressive women. Another possibly associated phenomenon is the increased frequency of smoking in adult females. Since nicotine indirectly enhances the intrasynaptic dopamine level which presumably is too low both in ADHD and in depression, smoking might be used as a self-medication in women with untreated ADHD and consecutive depression. Furthermore, smoking during pregnancy is a major risk factor for ADHD in the offspring, so the vicious circle is complete. Depression in mothers of children with ADHD is associated with a higher rate of comorbidity in the children. Improved screening for ADHD in girls and treatment in childhood might thus reduce the rate of depression and smoking in adult females. We hypothesize that earlier identification and interventions might not only improve the lives of millions of girls and women but might also reduce the prevalence rates in future generations or at least moderate the deviant behaviour in this highly heritable disorder in which the development and severity of symptoms and the functional impairment depend to a high degree on epigenetic factors.

Background: The aim of this study is to assess and evaluate the capacities for understanding, appreciation and reasoning of legal minors with psychiatric disorders and their parents and their competence to consent or assent to participation in clinical trials. The beliefs, fears, motivation and influencing factors for decision-making of legal minors and parents were also examined., Methods: Using the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), an instrument developed for adults whose capacities to consent are unclear, we provided information about clinical trials and assessed understanding, appreciation and reasoning. We adapted this tool for legal minors and examined 19 children and adolescents between the ages of 7 and 15 with attention deficit/hyperactivity disorder (ADHD) or ADHD combined with oppositional defiant disorder (DSM-IV 314.00/314.01/312.8) enrolled in clinical trials. Parents were also examined using the MacCAT-CR., Results: Facts such as the procedures involved in trials or their duration were well understood by legal minors, but more abstract issues like the primary purpose of the trial were not understood by children and adolescents or by many parents. Legal minors also had difficulties understanding the nature of placebo and the probability of receiving placebo. Children's and adolescents' decisions were influenced by fears about their disorder worsening and by problems in their relationship with their parents. Parents wanted the best therapy for their children in order to minimize problems in school., Conclusion: Legal minors and parents need to be informed more precisely about specific issues like placebo and the primary purpose of trials. In general, the reasoning of children and adolescents was influenced by their experience with their disorder and decision making was based on reasonable arguments. Their fears were based on everyday experiences such as school performance or family relationships.

Research in psychopharmacology for children and adolescents is fraught with ethical problems and tensions. This has practical consequences as it leads to a paucity of the research that is essential to support the treatment of this vulnerable group. In this article, we will discuss some of the ethical issues which are relevant to such research, and explore their implications for both research and standard care. We suggest that finding a way forward requires a willingness to acknowledge and discuss the inherent conflicts between the ethical principles involved. Furthermore, in order to facilitate more, ethically sound psychopharmacology research in children and adolescents, we suggest more ethical analysis, empirical ethics research and ethics input built into psychopharmacological research design.

Purpose of Review: This summary of the literature published over recent years focuses on the ethical aspects of interventions with psychotropic medication in child and adolescent psychiatry. Ethical issues of pharmacotherapy concern aspects of research, safety, indicated use, enhancement, information and evidence-based practice., Recent Findings: The literature on pharmacological interventions suggests changes in prescribing patterns for some substance classes owing to regulatory authorities' warnings. For most of the commonly used medications in children and adolescents no sound database about efficacy and safety is available and knowledge about adverse events and long-term safety remains poor. This is due to a general lack of clinical trials in this population. Legislative efforts have tried to improve safety and labelling of medicines for children. Ethical issues of enhancement in minors have been increasingly discussed over recent years., Summary: The ethical aspects of psychopharmacotherapy in minors are still rarely discussed in the literature. Practical questions of research and treatment ethics such as a need for information for children and parents are pointed out; conflicts of evocation and access to care for special populations in need are identified in a field lacking adequate ethical and clinical research.