Thesis advisor: Judith Shindul-Rothschild / Clinical Characteristics Of People In Randomized Clinical Trials Of First Episode Schizophrenia Spectrum Disorders: Attrition Versus Non-Attrition Groups Submitted by Joanne D. Wojcik PhD, RN Dissertation Advisor Judith Shindul-Rothschild, PhD, RN Abstract Background: Early identification of psychosis and intensive treatment has been the focus of the treatment of people with a first episode (FE) schizophrenia spectrum disorder (SSD). Attrition rates in studies of people in the first episode are high, which makes it difficult to understand the meaning of the study outcomes. High attrition rates affect the validity of a study by decreasing its power and the study's ability to detect differences between treatment groups. Additionally, the people who leave a study may be different from those who stay in demographic, illness and treatment characteristics. Method: This study is a secondary analysis of a group of FE SSD participants enrolled in one of three separate double-blind, randomized, drug trials. The variables were first analyzed across the three drug study data sets to determine if the patient populations are comparable across the three studies to allow for the merging of the data. Exploratory and descriptive statistics of study participants were conducted in a comparison of the three studies, for the merged group, and for the attrition and non-attrition groups. Effect sizes (Cohen's d) were calculated for each variable in the individual studies and in the merged dataset for the magnitude of difference between the attrition and non-attrition groups. Results: The three studies were merged after analysis found no consistent difference in demographic and illness characteristics between the three studies. There was no significant difference between the attrition and non-attrition groups in the merged data in demographic and illness characteristics. Treatment characteristics consistently found lack of efficacy and patient withdrawal of consent to be the two most frequent reasons for attrition from the studies. In addition, participants receiving a typical agent were less likely to complete the study. Effect size calculations found attrition group to more likely be Caucasian, with a lower median income. The attrition group had more years of education, but was not in school in the year previous to hospitalization. Conclusion: Historically, attrition is a major problem in clinical trials of people in a first episode of schizophrenia spectrum disorders. People receiving typical antipsychotic medication are more likely to leave a study. Most common reasons for attrition include lack of efficacy and withdrawal of consent / Thesis (PhD) — Boston College, 2009. / Submitted to: Boston College. Connell School of Nursing. / Discipline: Nursing.

No description available.

<p>Tularemia is a zoonosis caused by the small, fastidious, gram-negative rod Francisella tularensis that appears over almost the entire Northern Hemisphere. In Sweden, tularemia has appeared mainly in restricted areas in northern parts of central Sweden.</p><p> The disease can be transmitted through several routes: direct contact with infected animals, by vectors, through contaminated food or water or through inhalation of aerosolized bacteria. Distinct clinical forms of the disease are seen, depending on the route of transmission. During the last years, tularemia has emerged in new areas in central Sweden, south of the endemic area. The emergence of tularemia in the County of Örebro prompted the investigations presented in this thesis.</p><p> We performed a case-control study, using a mailed questionnaire, to identify risk factors for acquiring tularemia in Sweden (Paper I). After multivariate analysis, mosquito bites and cat ownership could be associated with tularemia in all studied areas while farming appeared as a risk factor only in endemic areas.</p><p> In Paper II, we evaluated a PCR analysis, targeting the tul4 gene, used on samples from primary lesions in patients with ulceroglandular tularemia. The method performed well, with a sensitivity of 78% and a specifi city of 96%. The clinical characteristics of tularemia in an emergent area in Sweden were studied Paper III), using case fi les and a questionnaire. Of 278 cases of tularemia reported during the years 2000 to 2004, 234 had been in contact with a doctor from the Department of Infectious Diseases at Örebro University Hospital, and were thus included. The ulceroglandular form of the disease was seen in 89% of the cases, with the primary lesion, in most cases, on the lower leg. An overwhelming majority of cases occurred during late summer and early autumn, further supporting transmission by mosquitoes. Erythemas overlying the affected lymph node areas were seen in 19% of patients with forms of tularemia affecting peripheral lymph nodes. Late skin manifestations, of various appearances, were seen in 30% of the cases, predominantly in women. A raised awareness of tularemia among physicians in the county during the course of the outbreak was found, as documented by the development of shorter doctor’s delay and less prescription of antibiotics inappropriate in tularemia.</p><p> Finally, we developed a simplifi ed whole-blood lymphocyte stimulation test, as a diagnostic tool in tularemia (Paper IV). The level of IFN-γ, as a proxy for lymphocyte proliferation, was measured after 24-h stimulation. Additionally, a tularemia ELISA with ultra-purifi ed LPS as the antigen was evaluated, showing a high sensitivity. The lymphocyte stimulation test, when performed on consecutive samples from subjects with ongoing tularemia was able to detect the disease earlier in the course of the disease than both the new ELISA and the tube agglutination test. Furthermore, all tularemia cases became positive in the lymphocyte stimulation test within 12 days of disease. In conclusion, this thesis describes risk factors for acquiring tularemia as well as the clinical characteristics of the disease in Sweden. Additionally, a Francisella PCR analysis and a tularemia ELISA based on highly purifi ed LPS is evaluated, and a simplified lymphocyte stimulation test, for early confirmation of the disease, is developed.</p><p>Henrik Eliasson, Department of Infectious Diseases,</p><p>Örebro University Hospital, SE-701 85 Örebro, Sweden,</p><p>henrik.eliasson@orebroll.se</p>

Tularemia is a zoonosis caused by the small, fastidious, gram-negative rod Francisella tularensis that appears over almost the entire Northern Hemisphere. In Sweden, tularemia has appeared mainly in restricted areas in northern parts of central Sweden. The disease can be transmitted through several routes: direct contact with infected animals, by vectors, through contaminated food or water or through inhalation of aerosolized bacteria. Distinct clinical forms of the disease are seen, depending on the route of transmission. During the last years, tularemia has emerged in new areas in central Sweden, south of the endemic area. The emergence of tularemia in the County of Örebro prompted the investigations presented in this thesis. We performed a case-control study, using a mailed questionnaire, to identify risk factors for acquiring tularemia in Sweden (Paper I). After multivariate analysis, mosquito bites and cat ownership could be associated with tularemia in all studied areas while farming appeared as a risk factor only in endemic areas. In Paper II, we evaluated a PCR analysis, targeting the tul4 gene, used on samples from primary lesions in patients with ulceroglandular tularemia. The method performed well, with a sensitivity of 78% and a specifi city of 96%. The clinical characteristics of tularemia in an emergent area in Sweden were studied Paper III), using case fi les and a questionnaire. Of 278 cases of tularemia reported during the years 2000 to 2004, 234 had been in contact with a doctor from the Department of Infectious Diseases at Örebro University Hospital, and were thus included. The ulceroglandular form of the disease was seen in 89% of the cases, with the primary lesion, in most cases, on the lower leg. An overwhelming majority of cases occurred during late summer and early autumn, further supporting transmission by mosquitoes. Erythemas overlying the affected lymph node areas were seen in 19% of patients with forms of tularemia affecting peripheral lymph nodes. Late skin manifestations, of various appearances, were seen in 30% of the cases, predominantly in women. A raised awareness of tularemia among physicians in the county during the course of the outbreak was found, as documented by the development of shorter doctor’s delay and less prescription of antibiotics inappropriate in tularemia. Finally, we developed a simplifi ed whole-blood lymphocyte stimulation test, as a diagnostic tool in tularemia (Paper IV). The level of IFN-γ, as a proxy for lymphocyte proliferation, was measured after 24-h stimulation. Additionally, a tularemia ELISA with ultra-purifi ed LPS as the antigen was evaluated, showing a high sensitivity. The lymphocyte stimulation test, when performed on consecutive samples from subjects with ongoing tularemia was able to detect the disease earlier in the course of the disease than both the new ELISA and the tube agglutination test. Furthermore, all tularemia cases became positive in the lymphocyte stimulation test within 12 days of disease. In conclusion, this thesis describes risk factors for acquiring tularemia as well as the clinical characteristics of the disease in Sweden. Additionally, a Francisella PCR analysis and a tularemia ELISA based on highly purifi ed LPS is evaluated, and a simplified lymphocyte stimulation test, for early confirmation of the disease, is developed.

Purpose: The relation between the causal attributions of individuals with panic disorder (PD) and their health outcomes remains relatively unexplored. Therefore we examined 1) the relationship between participants’ etiological beliefs about PD and baseline demographic and clinical characteristics and 2) whether participants’ etiological beliefs about PD predicted compliance, clinical response, and side effect profiles with the treatments they were assigned. Method: The study included 251 participants. A series of multiple linear regressions were used to evaluate the relationship between participants’ causal attributions, measured by the Etiological Model Questionnaire, and their baseline characteristics. To determine whether these beliefs predicted treatment outcome, logistic and linear regressions were conducted. Results: Our results revealed that participants with a family history of psychiatric illnesses were more likely to endorse biological etiological beliefs whereas those with a younger age, comorbid psychiatric disorders, and a history of suicide attempts were more likely to attribute their illness to psychological causes. Participants experiencing impairment in family life endorsed both psychological and environmental causal beliefs, while those reporting higher fear of body sensations and agoraphobic cognitions were more likely to attribute their illness to biological and psychological causes. With regards to treatment outcome, results indicated that participants who endorsed psychological and environmental etiological beliefs experienced more severe symptoms 12 weeks following treatment; irrespective of the type of treatment they received. Implications: The consideration of individuals’ causal attributions might help health-care professionals better assist clients by communicating a more balanced perspective of the causes of PD and deliver interventions that are in line with clients’ individual beliefs.

Background: Specific features of university student rugby players and the tournaments they compete in may involve epidemiology, clinical characteristics, and associated risk factors that differ from other populations. To date, this has not been studied. Aim of the study: To determine the epidemiology, clinical characteristics of and the associated risk factors for rugby-related injuries in university student rugby players. Design: Prospective cohort study Setting: Rugby teams (Young Guns [YG] and Varsity Cup [VC] representing the University of Pretoria (UP) in the Varsity Rugby tournament. Participants: 171 male university student rugby players. Methods: A prospective cohort study was conducted over two consecutive rugby seasons (2018/19 and 2019/20). Male student rugby players at UP that were included in the YG and VC squads, were followed over a total period of 35 weeks (2018/19: 18 weeks, 2019/20: 17 weeks). The two squads were comprised of a total of 179 players over the two-year period, where 171 players gave consent for study participation. Baseline data were collected at the beginning of pre-season preparations. These included player’s age, playing position and highest level of representation, and completion of injury history and medical history questionnaires. Medical staff affiliated with the teams recorded all training and match time-loss injuries during preseason and in-competition period. Data are reported as the incidence (injuries per 1 000 player-hours: 95% CI) of time-loss rugby-related injuries, injured player proportion (%), frequency (% of injuries) of injury characteristics and injury severity grade (time loss) for training and match injuries. These outcome measures are reported for anatomical region, body area, tissue type, pathology type, and mechanism of injury. The relative risk (RR) of injury was calculated for potential risk factors (participant demographics [age groups], rugby specific information [level of competition, playing position, highest level of play], medical history of disease [medical risk category], and injury history [acute or chronic injury 12 months prior, severe injury in entire sporting career]) by means of univariate analysis. Results: The primary findings with regards to epidemiology and clinical characteristics are as follows: 1) 60% of players sustained an injury during each season, 2) 64% of all injuries occurred during matches and the overall injury incidence (per 1 000 player hours) was significantly higher in matches (131.1) compared with training (2.4), 3) 84% of injuries were new injuries, 4) during training, most injuries (65%) affected the lower limb, while in matches upper limb (37%) and lower limb injuries (36%) were equally common, 5) training injuries mostly affected the ankle (16%) body area, whereas match injuries more frequently affected the shoulder (20%), 6) the majority of injuries involved muscle/tendon (57%) as the tissue type, of which approximately half were muscle injuries and a third were muscle contusions, 7) the injury severity profile was similar between match and training injuries and more than a quarter of all injuries resulted in time-loss of more than 28 days, 8) contact mechanisms of injury lead to most injuries in matches, whereas non-contact mechanisms accounted for a larger proportion of training injuries, 9) almost half of match injuries occur during the tackle phase (49%), and 10) a high percentage of players could not recall the match period where the injury occurred (24%). The following risk factors associated with incurring an injury during a season were identified: 1) the older age group within the student cohort, 2) higher level of tournament, and 3) any recent injury (past 12 months), 4) a recent injury (past 12 months) to the lower limb. Conclusion: The injured player proportion and match injury incidence were higher in university student rugby players participating in the VC and YG tournaments than has been previously reported in elite professional rugby. The number and severity profiles of training and match injuries were similar. Training injuries mostly occurred in non-contact situations and affected the lower limb, whereas contact injuries were more common in matches and the upper and lower limb were affected at equal frequencies. We show an association between injury risk and age, level of competition, previous acute and/or chronic injury during the past 12 months and specifically a lower limb injury in the past 12 months. The study findings can add to the collective knowledge of injuries and associated risk for injury among student rugby players which in turn may assist medical team members to plan and implement effective injury prevention strategies for this specific population in future. / Dissertation (MPhysiotherapy)--University of Pretoria, 2020. / Physiotherapy / MPhysiotherapy / Restricted

O espasmo hemifacial (EHF) é um distúrbio de movimento caracterizado por contrações tônico ou clônicas involuntárias, unilaterais, intermitentes e irregulares dos músculos inervados pelo nervo facial ipsilateral. Apesar de considerado como um transtorno benígno, promove influência significativa na qualidade de vida dos portadores através do comprometimento funcional físico e emocional que promove, englobando, desde o prejuízo na leitura e outras funções visuais, até o constrangimento social e distúrbios psiquiátricos associados, como depressão e ansiedade. Objetivo.: Descrever as características clínicas e demográficas, assim como a frequência de sintomas psiquiátricos de ansiedade generalizada, social e depressão, e a relação destes sintomas com a qualidade de vida nesta amostra de pacientes. Métodos.: 111 pacientes portadores de EHF primário foram avaliados. Foi aplicado questionário geral para coleta de dados demográficos e clínicos associados a evolução e tratamento do distúrbio de movimento com toxina botulínica. Os sintomas psiquiátricos foram avaliados através de escalas validadas para a população brasileira. A avaliação de qualidade de vida foi através de escala específica validada para avaliação funcional nos portadores de EHF. Resultados.: A idade média de início foi de 49±13,1 (intervalo: 12 -77) e tempo de evolução até o diagnóstico de 3±1,5 anos, com predomínio no sexo feminino (2,08:1). O lado esquerdo foi afetado em 61 (54,9%) pacientes e o músculo orbicular dos olhos foi o primeiro acometido na maioria dos casos (85,5%). Grande parte (n=87) referiu início insidioso e evolução gradual. Nervosismo, estresse e ansiedade são importantes contribuintes de piora do espasmo, relatado por mais de 82% (n=92) dos portadores de EHF, e momentos de relaxamento, tranquilidade, descanso e atividades de lazer foram responsáveis por aliviar o espasmo em 57 entrevistados. Mais de 90% (n=96) perceberam melhora importante do espasmo após aplicação de TXB, e 24,5% (n=26) relataram algum efeito adverso em última aplicação, sendo assimetria labial e ressecamento ocular os mais frequentes. Sobre os sintomas psiquiátricos, 41,7% (n=45) apresentavam pontuações que sugerem algum grau de depressão, até 56,4% (n=57) ansiedade generalizada e 34,2% (n=38) ansiedade ou fobia social. A leitura como domínio funcional físico e a vergonha, a tristeza e a preocupação com reação de outras pessoas foram os maiores prejuízos funcionais descritos nesses pacientes. Conclusão.: As características clínicas e demográficas nos pacientes com EHF se assemelham a outras evidências descritas na literatura, assim como uma maior frequência de sintomas de depressão, ansiedade generalizada e fobia social nesta população. Os sintomas psiquiátricos, mais do que a gravidade do espasmo, apresentaram uma maior correlação com a qualidade de vida nesta amostra de pacientes. / Hemifacial spasm (HFS) is a movement disorder characterized by involuntary, unilateral, intermittent, tonic or clonic contractions of muscles innervated by the ipsilateral facial nerve. Although considered as a benign disorder, it promotes a significant influence on the quality of life of the patients through the physical and emotional impairment it promotes, ranging from impairment in reading and other visual functions to social embarrassment, and associated psychiatric disorders, such as depression and anxiety. Objective.: To describe the clinical and demographic characteristics, as well as the frequency of psychiatric symptoms of generalized anxiety, social anxiety and depression, and the relation of these symptoms with quality of life in this sample of patients. Methods.: 111 patients with primary HFS were evaluated. A general questionnaire was used to collect demographic and clinical data associated with the evolution and treatment of the movement disorder with botulinum toxin (BTX). The psychiatric symptoms were evaluated through scales validated for the Brazilian population. The quality of life assessment was based on a specific validated scale for functional evaluation in patients with HFS. Results.: The mean age at onset was 49 ± 13.1 (range: 12-77) and time to diagnosis of 3 ± 1.5 years, with a predominance of females (2.08 :1). The left side was affected in 61 (54.9%) patients and the orbicularis oculi muscles were the first affected in the majority of cases (85.5%). A large part (n = 87) reported insidious onset and gradual evolution. Nervousness, stress, and anxiety are important contributors to worsening spasm, reported by more than 82% (n = 92) of HFS patients, and moments of relaxation, tranquility, rest, and leisure activities were responsible for relieving spasm in 57 interviewees. More than 90% (n = 96) reported significant improvement of spasm after BTX application, and 24.5% (n = 26) reported some adverse effects in the last application, with lip asymmetry and ocular dryness being the most frequent. On the psychiatric symptoms, 41,7% (n = 45) presented scores that suggest some degree of depression, up to 56.4% (n = 57) generalized anxiety and 34.2% (n = 38) anxiety or social phobia. Reading as a physical functional domain and shame, sadness and concern for other people\'s reactions were the major functional losses described in these patients

O espasmo hemifacial (EHF) é um distúrbio de movimento caracterizado por contrações tônico ou clônicas involuntárias, unilaterais, intermitentes e irregulares dos músculos inervados pelo nervo facial ipsilateral. Apesar de considerado como um transtorno benígno, promove influência significativa na qualidade de vida dos portadores através do comprometimento funcional físico e emocional que promove, englobando, desde o prejuízo na leitura e outras funções visuais, até o constrangimento social e distúrbios psiquiátricos associados, como depressão e ansiedade. Objetivo.: Descrever as características clínicas e demográficas, assim como a frequência de sintomas psiquiátricos de ansiedade generalizada, social e depressão, e a relação destes sintomas com a qualidade de vida nesta amostra de pacientes. Métodos.: 111 pacientes portadores de EHF primário foram avaliados. Foi aplicado questionário geral para coleta de dados demográficos e clínicos associados a evolução e tratamento do distúrbio de movimento com toxina botulínica. Os sintomas psiquiátricos foram avaliados através de escalas validadas para a população brasileira. A avaliação de qualidade de vida foi através de escala específica validada para avaliação funcional nos portadores de EHF. Resultados.: A idade média de início foi de 49±13,1 (intervalo: 12 -77) e tempo de evolução até o diagnóstico de 3±1,5 anos, com predomínio no sexo feminino (2,08:1). O lado esquerdo foi afetado em 61 (54,9%) pacientes e o músculo orbicular dos olhos foi o primeiro acometido na maioria dos casos (85,5%). Grande parte (n=87) referiu início insidioso e evolução gradual. Nervosismo, estresse e ansiedade são importantes contribuintes de piora do espasmo, relatado por mais de 82% (n=92) dos portadores de EHF, e momentos de relaxamento, tranquilidade, descanso e atividades de lazer foram responsáveis por aliviar o espasmo em 57 entrevistados. Mais de 90% (n=96) perceberam melhora importante do espasmo após aplicação de TXB, e 24,5% (n=26) relataram algum efeito adverso em última aplicação, sendo assimetria labial e ressecamento ocular os mais frequentes. Sobre os sintomas psiquiátricos, 41,7% (n=45) apresentavam pontuações que sugerem algum grau de depressão, até 56,4% (n=57) ansiedade generalizada e 34,2% (n=38) ansiedade ou fobia social. A leitura como domínio funcional físico e a vergonha, a tristeza e a preocupação com reação de outras pessoas foram os maiores prejuízos funcionais descritos nesses pacientes. Conclusão.: As características clínicas e demográficas nos pacientes com EHF se assemelham a outras evidências descritas na literatura, assim como uma maior frequência de sintomas de depressão, ansiedade generalizada e fobia social nesta população. Os sintomas psiquiátricos, mais do que a gravidade do espasmo, apresentaram uma maior correlação com a qualidade de vida nesta amostra de pacientes. / Hemifacial spasm (HFS) is a movement disorder characterized by involuntary, unilateral, intermittent, tonic or clonic contractions of muscles innervated by the ipsilateral facial nerve. Although considered as a benign disorder, it promotes a significant influence on the quality of life of the patients through the physical and emotional impairment it promotes, ranging from impairment in reading and other visual functions to social embarrassment, and associated psychiatric disorders, such as depression and anxiety. Objective.: To describe the clinical and demographic characteristics, as well as the frequency of psychiatric symptoms of generalized anxiety, social anxiety and depression, and the relation of these symptoms with quality of life in this sample of patients. Methods.: 111 patients with primary HFS were evaluated. A general questionnaire was used to collect demographic and clinical data associated with the evolution and treatment of the movement disorder with botulinum toxin (BTX). The psychiatric symptoms were evaluated through scales validated for the Brazilian population. The quality of life assessment was based on a specific validated scale for functional evaluation in patients with HFS. Results.: The mean age at onset was 49 ± 13.1 (range: 12-77) and time to diagnosis of 3 ± 1.5 years, with a predominance of females (2.08 :1). The left side was affected in 61 (54.9%) patients and the orbicularis oculi muscles were the first affected in the majority of cases (85.5%). A large part (n = 87) reported insidious onset and gradual evolution. Nervousness, stress, and anxiety are important contributors to worsening spasm, reported by more than 82% (n = 92) of HFS patients, and moments of relaxation, tranquility, rest, and leisure activities were responsible for relieving spasm in 57 interviewees. More than 90% (n = 96) reported significant improvement of spasm after BTX application, and 24.5% (n = 26) reported some adverse effects in the last application, with lip asymmetry and ocular dryness being the most frequent. On the psychiatric symptoms, 41,7% (n = 45) presented scores that suggest some degree of depression, up to 56.4% (n = 57) generalized anxiety and 34.2% (n = 38) anxiety or social phobia. Reading as a physical functional domain and shame, sadness and concern for other people\'s reactions were the major functional losses described in these patients

Community nurses have a critical role in caring for people and families affected by HIV/AIDS in the home setting. Despite this, there is a dearth of Australian literature describing the health needs of these clients who are referred to them. This study identified the demographic, clinical and psychoemotional aspects of adult clients with HIV/AIDS in Sydney, Australia, who were referred to community nurses and died between 1993 and 1995. Retrospective data from the records of 73 clients identified on 171 Community Nursing Referral Forms completed within the study period from an inpatient HIV/AIDS Unit was analysed using descriptive statistics and content analysis. The sample was demographically similar to the general population of people with HIV/AIDS during the study period. The most commonly identified clinical aspects of clients included oral candida, mycobacterium avium complex, anaemia, drug intolerance, cytomegalovirus, pain, fever, diarrhoea, weight loss and cough. The most commonly identified psychoemotional variables were depressed mood, anxiety, grief and nonadherence to suggested interventions, with the most common emergent theme being the physical effects of HIV/AIDS illness. Emotional support, symptom monitoring and home assessments were the most common requests made of community nurses. The study sample represented 14% of people who died following AIDS in New South Wales during this known peak period of AIDS diagnoses and deaths following AIDS. As a result of this study, documentation exists describing the characteristics of clients with advanced HIV/AIDS referred to community nurses. Current and future clients with advanced HIV/AIDS referred to community nurses may experience a similar clinical picture to that identified in this study. The findings can be used to reveal relationships amongst the key variables; lay the foundation for further comparative, theory or hypothesis driven studies; and demonstrate how this influences the community nursing role, strategies, interventions and outcomes.

The familial aggregation of Major Depressive Disorder (MDD) has been repeatedly demonstrated. Several studies have investigated associations between various clinical characteristics of MDD in probands and overall rates of MDD in relatives. Few studies, however, have considered the familial aggregation of clinical characteristics of MDD. The aim of the present report is to examine mother–offspring associations of a variety of clinical characteristics of MDD in a general population sample. Data were derived from baseline and 4-year-follow-up data of 933 adolescents and their biological mothers of the Early Developmental Stages of Psychopathology (EDSP) study, a prospective-longitudinal community study. MDD and its characteristics were assessed with the Munich-Composite International Diagnostic Interview. We found that children of mothers who had a lifetime history of severe MDD and high number of symptoms, high impairment and/or melancholia, revealed elevated odds of MDD regarding the same characteristics as their mothers (ORs between 5.2 and 13.9). The observed associations did not differ by the children’s sex. DSM-IV melancholia and severity as well as impairment were found to aggregate within families. This finding can be interpreted as a validation of the DSM-IV MDD severity subtypes as well as of the melancholic specifier. Severe and melancholic MDD reveal a considerable high degree of familiar aggregation making the search for mechanisms involved in the familiar transmission of these forms of MDD particularly promising.