Safety Data Timelines for Pregnant Individuals with HIV on Antiretroviral Therapy.

Antiretrovirals are often approved by the Food and Drug Administration without sufficient safety data regarding their use in pregnancy. To quantify this delay, we calculated the interval from the approval date to their inclusion in the Antiretroviral Pregnancy Registry prospective analysis (≥ 200 first trimester exposures); median delay was six years.

Infectious disease models in zebrafish.

In recent years, the zebrafish (Danio rerio) has developed as an important alternative to mammalian models for the study of hostpathogen interactions. Because they lack a functional adaptive immune response during the first 4-6weeks of development, zebrafish rely upon innate immune responses to protect against injuries and infections. During this early period of development, it is possible to isolate and study mechanisms of infection and inflammation arising from the innate immune response without the complications presented by the adaptive immune response. Zebrafish possess several inherent characteristics that make them an attractive option to study hostpathogen interactions, including extensive sequence and functional conservation with the human genome, optical clarity in larvae that facilitates the high-resolution visualization of host cell-microbe interactions, a fully sequenced and annotated genome, robust forward and reverse genetic tools and techniques (e.g., CRISPR-Cas9 and TALENs), and amenability to chemical studies and screens. Here, we describe methods for studying hostpathogen interactions both through systemic infections and through localized infections that allow analysis of host cell response, migration patterns, and behavior. Each of the methods described can be modified for use in downstream applications that include ecotoxicant studies and chemical screens.

Comparison of severe life stress in depressed mothers and non-mothers: do children matter?

Given the high rates of maladjustment among children of depressed mothers, parenting is likely to cause significant life stress in this population, potentially worsening the course of mothers' depression. The present study is a comparison of severe life stress in 38 mothers and 62 non-mothers receiving treatment for recurrent major depression. Life stress was assessed using the Life Events and Difficulties Schedule [Brown and Harris, 1978a]. We hypothesized that mothers would evidence a greater number of severe life events and marked difficulties both in the year prior to the onset of their depressive index episode and in the time period following the onset of their current depressive episode. Prior to depression onset, mothers reported a significantly greater number of entrapping difficulties, but not marked difficulties, severe events, entrapping events, or humiliating events. However, following the onset of depression, mothers experienced a significantly greater number of severe events, entrapping events, marked difficulties, and entrapping difficulties, but not humiliating events. Mothers' elevated levels of stress were attributable to child-related stress, predominantly related to children's psychological and behavioral problems. Our findings suggest that comprehensive treatment for mothers with major depression needs to address their parenting style and any psychological problems experienced by their children.

Assessment of life stress in adolescents: self-report versus interview methods.

OBJECTIVE: To compare the investigator-based Life Events and Difficulties Schedule (LEDS) with a self-report measure (Life Events Checklist [LEC]) for the purpose of measuring life stress in adolescents with and without a diagnosis of major depressive disorder (MDD). METHOD: Adolescents (aged 13-18 years) with a recent episode of MDD based on DSM-III-R (n = 35) and normal controls free of any Axis I lifetime psychiatric disorder (n = 35) were assessed using both the LEC and the LEDS. RESULTS: Both measures predicted membership in the depressed and nondepressed groups of adolescents. Adolescents in the depressed group were more likely to report a severe event on the LEDS (97%) than adolescents in the nondepressed group (66%) (p = .001). Similarly, subjects in the depressed group endorsed a greater number of negative events (mean = 8.1) on the LEC than subjects in the nondepressed group (mean = 3.0) (p = .0001). An examination of potential provoking agents for episodes of major depression revealed that the LEC captured only 32% of preonset severe events and 36% of preonset major difficulties identified by the LEDS. CONCLUSIONS: Interpreted in light of relative advantages and disadvantages, the results suggest that checklist and interview measures each have distinct advantages depending on the purpose for which they are being used.

Nature of life events and difficulties in depressed adolescents.

OBJECTIVE: To examine the significance of acute life events and ongoing difficulties in adolescents with a recent major depressive disorder. METHOD: Adolescents (aged 13-18 years) with a recent episode of major depressive disorder based on DSM-III-R (n = 26) and normal controls free of any Axis I lifetime psychiatric disorder (n = 15) were assessed using the investigator-based Life Events and Difficulties Schedule (LEDS). RESULTS: Traditionally defined severe events were more likely to occur in the year prior to onset among depressed adolescents (46%) than in a comparable period among normal controls (20%), but these differences did not reach statistical significance. Expanding the definition of severe events to include those events focused on others important to the adolescent resulted in a significantly higher percentage of depressed adolescents having one or more refined "severe" events in the year prior to onset (62%) compared with normal controls (27%) (p < or = .02). It is interesting that one half of the depressed adolescents had two or more refined severe events occur during the year prior to onset compared with none of the normal controls (p < or = .01). Further analyses showed that depressed adolescents were significantly more likely to have a major difficulty precede the onset of their depression (27%) compared with normal controls (0%) (p < or = .04). CONCLUSIONS: The results suggest that depressed adolescents are exposed to high levels of stress prior to becoming depressed. Future investigations might benefit from using the LEDS with adolescents to assess acute and ongoing stressors.

Sleep onset abnormalities in depressed adolescents.

Sleep measures were obtained in 16 depressed and 21 control adolescents following 1 week of adherence to a uniformly imposed and strictly enforced sleep/wake schedule. Three nights of baseline electroencephalographic (EEG) sleep on the same 10:00 PM to 7:00 AM schedule revealed prolonged sleep latency and reduced rapid eye movement (REM) latency in the depressed adolescents. Following baseline measures, sleep was restricted for 2 nights (10:00 PM-4:00 AM) and measures of recovery sleep were obtained showing further sleep latency differences. There was no evidence for delta sleep changes or sleep continuity differences in depressed adolescents. These results suggest that control over sleep/wake schedules is an important methodological issue in adolescent sleep studies. Furthermore, the findings are consistent with a larger body of evidence indicating that dysregulation near sleep onset represents a primary psychobiological change in early-onset depression.