Natural course of adolescent major depressive disorder in a community sample: predictors of recurrence in young adults

OBJECTIVE: The primary purpose was to identify factors related to the recurrence of major depressive disorder during young adulthood (19-23 years of age) in a community sample of formerly depressed adolescents. METHOD: A total of 274 participants with adolescent-onset major depressive disorder were assessed twice during adolescence and again after their 24th birthday. Lifetime psychiatric information was obtained from their first-degree relatives. Adolescent predictor variables included demographic characteristics, psychosocial variables, characteristics of adolescent major depressive disorder, comorbidity, family history of major depressive disorder and nonmood disorder, and antisocial and borderline personality disorder symptoms. RESULTS: Low levels of excessive emotional reliance, a single episode of major depressive disorder in adolescence, low proportion of family members with recurrent major depressive disorder, low levels of antisocial and borderline personality disorder symptoms, and a positive attributional style (males only) independently predicted which formerly depressed adolescents would remain free of future psychopathology. Female gender, multiple major depressive disorder episodes in adolescence, higher proportion of family members with recurrent major depressive disorder, elevated borderline personality disorder symptoms, and conflict with parents (females only) independently predicted recurrent major depressive disorder. Comorbid anxiety and substance use disorders in adolescence and elevated antisocial personality disorder symptoms independently distinguished adolescents who developed recurrent major depressive disorder comorbid with nonmood disorder from those who developed pure major depressive disorder. CONCLUSIONS: Formerly depressed adolescents with the risk factors identified in this study are at elevated risk for recurrence of major depressive disorder during young adulthood and therefore warrant continued monitoring and preventive or prophylactic treatment.     

Safety and pharmacokinetics of multiple doses of recombinant human CuZn superoxide dismutase administered intratracheally to premature neonates with respiratory distress syndrome

OBJECTIVES: To examine the safety and pharmacokinetics of multiple intratracheal (IT) doses of recombinant human CuZn superoxide dismutase (rhSOD) in premature infants with respiratory distress syndrome who are at risk for developing bronchopulmonary dysplasia (BPD). Methods. Thirty-three infants (700 to 1300 g) were randomized and blindly received saline, 2.5 mg/kg or 5 mg/kg rhSOD IT within 2 hours of surfactant administration. Infants were treated every 48 hours (as long as endotracheal intubation was required) up to 7 doses. Serial blood and urine studies, chest radiographs, neurosonograms, SOD concentration and activity measurements, and tracheal aspirate (TA) inflammatory markers were assessed throughout the 28-day study. RESULTS: SOD concentrations in serum (0.1 [0.05/0.15] microg/mL-geometric mean with lower/upper confidence intervals), tracheal aspirates (TA) (0.2 [0.1/0.3] microg/mL) and urine (0.3 [0.2/0.4] microg/mL) were similar at baseline in all 3 groups and did not change significantly in the placebo group. In the rhSOD treatment groups, SOD concentrations were increased on day 3 and did not change significantly thereafter over the 14-day dosing period (also measured on days 5, 7, and 13). SOD concentrations averaged 0.4 [0.3/0.5] microg/mL in serum, 0.8 [0.6/1.2] microg/mL in TA and 1.1 [1.0/1.3] microg/mL in urine for the low-dose group and 0.6 [0.5/0.7] microg/mL in serum, 1.1 [0.9/1.5] microg/mL in TA, and 2.2 [1.6/2.9] microg/mL in urine for the high-dose group over the 14-day dosing period. Enzyme activity directly correlated with SOD concentration and rhSOD was active even when excreted in urine. TA markers of acute lung injury (neutrophil chemotactic activity, albumin concentration) were lower in the rhSOD agroups compared with placebo. No significant differences in any clinical outcome variable were noted between groups. CONCLUSIONS: These data indicate that multiple IT doses of rhSOD increase the concentration and activity of the enzyme in serum, TA and urine, reduce TA lung injury markers and are well-tolerated. Further clinical trials examining the efficacy of rhSOD in the prevention of BPD are warranted.     

Chorionic gonadotropin inhibits rat mammary carcinogenesis through activation of programmed cell death

Human chorionic gonadotropin (hCG) inhibits the progression of 7,12- dimethylbenz[a]anthracene (DMBA) induced mammary carcinomas. In order to determine whether this phenomenon was mediated by induction of programmed cell death or apoptosis, 45-day-old virgin Sprague-Dawley rats received 8 mg DMBA/100 g body weight; 20 days later they were injected daily with 100 IU hCG for 40 days (DMBA + hCG group). Age- matched untreated, hCG- and DMBA + saline treated rats were used as controls. Tissues were collected at the time of DMBA administration and at 5, 10, 20 and 40 days of hCG injection. RNA from mammary glands, adenocarcinomas and ovaries was probed for transforming growth factors (TGF) alpha and beta, and the apoptotic genes TRPM2, ICE, bcl2, bcl-XL, bcl-XS, p53 and c-myc. The mammary glands of hCG-treated animals with or without DMBA exhibited elevated expression of TRPM2, ICE, bcl-XS, c- myc and p53; and elevation in the apoptotic index. Mammary adenocarcinomas developed in those animals treated with hCG showed an elevation in the expression of p53, c-myc and ICE genes in comparison with the levels detected in the adenocarcinomas developed by the animals treated with DMBA alone. No significant alterations in the expression of any of the genes tested was observed in ovarian RNAs. These results led us to conclude that hCG induces programmed cell death in the mammary gland initiated in the carcinogenic process, that this process is p53 dependent, and is modulated by c-myc expression. Our data also indicate the possibility that a cell death program dependent on the bcl2 family exists, because of the potential involvement of p53, bcl-XS and Bax in apoptosis. This additional mechanism of tumor inhibition makes hCG treatment a useful approach for the prevention and therapy of breast cancer.      

Cloning and characterization of DXS6673E, a candidate gene for X-linked mental retardation in Xq13.1

In several families with non-specific X-linked mental retardation (XLMR) linkage analyses have assigned the underlying gene defect to the pericentromeric region of the X chromosome, but none of these genes have been isolated so far. Here, we report on the cloning and characterization of a novel gene, DXS6673E, that maps to Xq13.1, is subject to X-inactivation and is disrupted in the 5' untranslated region by a balanced X;13 translocation in a mentally retarded female. The DXS6673E gene is highly conserved among vertebrates and its expression is most abundant in brain. It encodes a hydrophilic protein of 1358 amino acids (aa) that does not show sequence homology to other known proteins. A segment of this protein consisting of neutral and hydrophobic aa with a proline residue in every second position may represent a transmembrane domain. Almost complete sequence identity was found between the 3' end of the DXS6673E gene and two expressed sequence tags (ESTs) and between the 5' end of the DXS6673E gene and a third EST. Moreover, weaker sequence similarity was observed between coding regions and two other ESTs.      

Vagal rebound during resolution of tearful crying among depressed and nondepressed individuals

Respiratory sinus arrhythmia (RSA) is an index of the vagal control of heart rate that is associated with emotion regulatory capacity. To examine RSA in depressed and nondepressed participants in the context of an emotion-regulatory challenge, we presented a sad film to induce crying, a behavior associated with heightened parasympathetic activation. We predicted that nondepressed persons who cried would show elevations in RSA during the onset and the resolution of crying. By contrast, we predicted that depressed individuals who cried would fail to exhibit increased RSA over the course of their crying episodes. As hypothesized, nondepressed participants exhibited RSA increases that accompanied the resolution of tearful crying, consistent with a homeostatic function for crying, whereas depressed subjects who cried did not exhibit increased RSA. Results suggest that the physiological self-regulatory mechanisms invoked by crying are compromised in depression.     

Molecular basis of choroideremia (CHM): Mutations involving the rab escort protein-1 (REP-1) gene

Choroideremia (CHM) is an X-linked recessive eye disease that results from mutations involving the Rab escort protein-1 (REP-1) gene. In 18 patients deletions of different sizes have been found. Two females suffering from CHM were reported to have translocations that disrupt the REP-1 gene. In 22 patients, small mutations have been identified. Interestingly, these are all nonsense, frameshift or splice-site mutations; with one possible exception, missense mutations have not been found. This comprises all the known mutations in the disease. Hum Mutat 9:110–117, 1997. © 1997 Wiley-Liss, Inc.     

A follow-up study of immunotherapy-treated birch-allergic patients: effect on the expression of chemokines in the nasal mucosa

Background Specific immunotherapy (SIT) is the only treatment producing lasting clinical improvement in patients with allergy. We investigated the long‐term effect of SIT treatment on the expression of chemokines: eotaxin, RANTES (regulated upon activation, normal T cell expressed and secreted) and thymus and activation‐regulated chemokine (TARC), and their receptors CCR3 and CCR4 in biopsies of nasal mucosa from birch‐allergic individuals. Methods Sixteen patients who completed a 3‐year treatment programme 3–5 years ago, and 12 untreated, matched controls were included in the study. Patients recorded symptoms and use of rescue medication before and during the pollen season. Nasal mucosa samples obtained before and during the season were stained for eosinophil and mast cell markers and for eotaxin, RANTES, TARC, CCR3 and CCR4. Results During the pollen season, rhinoconjunctivitis symptoms increased in both SIT and control groups (P=0.001 and 0.002, respectively). However, SIT patients had 37% fewer symptoms than controls. Medication use increased in both groups (P=0.002) during the season but the SIT group used 28% less than the controls (P=0.02). The number of eosinophils in the nasal mucosa increased in the control group (P=0.01) and the difference between the groups was significant during the season (P=0.01). No seasonal increase in the numbers of mast cells was seen, but during the pollen season, more (P=0.02) AA⁺ cells were found in the controls than in the SIT group. The number of eotaxin⁺ and RANTES⁺ cells increased in the control group (P=0.01 and 0.03, respectively) and the difference between groups during the season was significant (P=0.01 and 0.01, respectively). The TARC⁺ cell numbers were lower in the SIT group during the season (P=0.003). The CCR3⁺ cells increased only in the control group during the pollen season and remained unchanged in SIT patients, while CCR4⁺ cell numbers increased in both the control (P=0.03) and SIT (P=0.02) groups. Conclusion This study confirmed that decreased numbers of eosinophils in the nasal mucosa is a long‐lasting effect of birch SIT. SIT also prevented seasonal rises in the number of cells expressing the chemokines eotaxin and RANTES.     

Neuroticism and Ruminative Response Style as Predictors of Change in Depressive Symptomatology

Several investigations have demonstrated thatneuroticism and ruminative response style are associatedwith increased risk for depression. The current studyexamined the effects of neuroticism and ruminative response style on changes in depressivesymptoms over an 8- to 10-week interval. Analysesindicated that the effects of neuroticism and ruminativeresponse style were moderated by initial level ofdepressive symptomatology. Specifically, neuroticism andruminative response style predicted changes indepressive symptoms more strongly in individuals whowere initially higher in levels of depression than they did in those with lower initial levels ofdepressive symptoms. These data were consistent with apath model in which ruminative response style mediatedthe effect of neuroticism on depression.     

Panic attacks and psychopathology among youth

OBJECTIVE: To determine the association between panic attacks and mental disorders among youth in the community. METHOD: Data were drawn from the Methods for the Epidemiology of Child and Adolescent Mental Disorders study (n = 1285), a community-based sample of youth aged 9-17. Multiple logistic regression analyses were used to determine the association between panic attacks and the range of mental disorders, diagnosed with the Diagnostic Interview Schedule for Children 2.3. RESULTS: Panic attacks were prevalent among 3.3% of the sample. Panic attacks were associated with an increased likelihood of any anxiety disorders [OR = 4.6 (2.5, 8.5)] and any affective disorder [OR = 5.8 (2.8, 11.7)], as well as social phobia [OR = 2.3 (1.0, 5.4)], specific phobia [OR = 3.4 (1.1, 10.1)], agoraphobia [OR = 2.9 (1.1, 7.6)], generalized anxiety disorder [OR = 4.8 (1.9, 12.1)], separation anxiety disorder [OR = 3.1 (1.3, 7.7)], major depression [OR = 3.6 (1.6, 8.3)], dysthymia [OR = 6.7 (2.9, 15.5)], and hypomania [OR = 26.1 (5.5, 124.1)]. CONCLUSION: These data are consistent with, and extend, previous clinical findings by showing that panic attacks are associated with increased likelihood of a range of affective and anxiety disorders, but not substance use disorders, among youth in the community. The use of longitudinal study designs in future investigations may be useful in increasing our understanding of the mechanisms underlying these associations.