Implementation of the "Healthy Moms, Healthy Kids" Program in Head Start: An Application of the RE-AIM QuEST Framework Centering Equity.

BACKGROUND: Marginalized mothers are disproportionately impacted by depression and face barriers in accessing mental health treatment. Recent efforts have focused on building capacity to address maternal depression in Head Start; however, it is unclear if mental health inequities can be addressed by two-generation programs in Head Start settings. Therefore, this study examined the implementation outcomes and processes of a two-generation program called "Healthy Moms, Healthy Kids" (HMHK) that provided an evidence-based depression treatment to ethnic minority Head Start mothers. METHOD: Quantitative and qualitative data were collected and merged in a convergent mixed method design in accordance with the RE-AIM Qualitative Evaluation for Systematic Translation (RE-AIM QuEST) framework. Qualitative data included interviews with 52 key stakeholders, including intervention participants and staff members, and 176 sets of meeting minutes from the implementation period. Quantitative data included intervention study data and administrative data. RESULTS: It was difficult for HMHK to reach the target population, with only 16.8% of eligible mothers choosing to participate. However, mothers who participated experienced reductions in depressive symptoms and parenting stress and shared a variety of positive impacts in interviews. The program was also more successful in enrolling Latinx mothers who were Spanish-speaking or bilingual rather than English-speaking and Black/African American mothers, limiting its reach. CONCLUSION: Providing IPT therapy groups was effective in reducing maternal depressive symptoms and stress for those who enrolled, but additional work should focus on reducing barriers to participation, considering other delivery models to meet participants' needs, and identifying culturally relevant ways to meet the needs of Black mothers.

Collaborative decision making improves interpersonal psychotherapy efficiency: A randomized clinical trial with postpartum women.

Background: Randomized controlled trials of Interpersonal Psychotherapy (IPT) and other psychotherapies for depression have required strict adherence to protocol and do not allow for clinical judgment in deciding frequency of sessions. To determine if such protocols were more effective than allowing therapists to use their clinical judgment, we compared "Clinician-Managed" IPT (CM-IPT), in which clinicians and patients with postpartum depression were allotted 12 sessions and determined collaboratively when to use them, to a once weekly 12 session protocol ("Standard IPT"). We hypothesized that CM-IPT would be more efficient, requiring fewer sessions to reach an equivalent acute outcome, and that CM-IPT would be superior over 12 months because "saved" sessions could be used for maintenance treatment. Method: We conducted a clinical trial including 140 postpartum outpatients with DSM-IV major depression who were randomly assigned to "Standard" IPT (N= 69) or CM-IPT (N= 71). Results: Both CM-IPT and S-IPT were highly efficacious with similar outcomes by 12 weeks but CM-IPT group utilized significantly fewer sessions. Both were superior to a waitlist control. Superiority comparisons at 12 months did not favor the CM-IPT condition. Limitations: Results should be replicated in a more diverse sample to increase generalizability. Conclusions: CM-IPT is more efficient in treating acute depression than mandated weekly IPT. Further, permitting clinicians and patients to use their collaborative judgment is likely to be a more efficient and effective way to conduct future research and to implement evidence-based psychotherapy in the community.

Feasibility and Acceptability of Internet-Based Interpersonal Psychotherapy for Stress, Anxiety, and Depression in Prenatal Women: Thematic Analysis.

BACKGROUND: Prenatal mental health is a global health concern. Despite the far-reaching impact of prenatal mental health issues, many women do not receive the psychological care they require. Women in their childbearing years are frequent users of the internet and smartphone apps. Prenatal women are prime candidates for internet-based support for mental health care. OBJECTIVE: This study aimed to examine the feasibility and acceptability of internet-based interpersonal psychotherapy (IPT) for prenatal women. METHODS: Semistructured interviews were conducted with women who had received internet-based IPT modules with guided support as a component of a randomized controlled trial evaluating the scale-up implementation of a digital mental health platform (The Healthy Outcomes of Pregnancy and Postpartum Experiences digital platform) for pregnant women. Qualitative thematic analysis was used to explore and describe women's experiences. Data were analyzed for emerging themes, which were identified and coded. RESULTS: A total of 15 prenatal women were interviewed to examine their experiences and views on the feasibility and acceptability of internet-based IPT modules. Participants found the content informative and appreciated the ways in which the digital mental health platform made the IPT modules accessible to users. Participants voiced some differing requirements regarding the depth and the way information was presented and accessed on the digital mental health platform. The important areas for improvement that were identified were acknowledging greater depth and clarity of content, the need for sociability and relationships, and refinement of the digital mental health platform to a smartphone app. CONCLUSIONS: This study provides useful evidence regarding treatment format and content preferences, which may inform future development. It also provides research data on the feasibility and acceptability of web-based applications for prenatal mental health care. TRIAL REGISTRATION: ClinicalTrials.gov NCT01901796; https://clinicaltrials.gov/ct2/show/NCT01901796.

Implementation of Group Interpersonal Psychotherapy in primary care.

OBJECTIVE: To show the implementation process of IPT-G in primary care, including facilitating and obstructing factors, implementation strategies, and training and supervision of primary care professionals. METHODS: Quantitative (cross-sectional and longitudinal) analysis of pre and post-knowledge tests; qualitative analyses of the training courses; patient recruitment; conduction of IPT-G sessions; supervision of IPT-G therapists; application of a semi-structured questionnaire to assess, investigate, and develop strategies against the identified barriers. RESULTS: About 120 clinicians answered the pre-test; 84 completed the post-test. Pre- and post-test scores of IPT-G knowledge were significantly different. Twenty initially trained clinicians completed additional supervision in IPT-G. Qualitative analysis identified twelve barriers and six facilitators to IPT-G implementation in individual, organizational, and systemic contexts. CONCLUSIONS: Implementation of IPT-G in primary care is a complex process with several steps. In the first step, health professionals were successfully trained in IPT-G. However, subsequent steps were more complex. Therefore, careful planning of IPT-G implementation is essential to maximize the success of this innovation.

Intermittent treatment of BRAFV600E melanoma cells delays resistance by adaptive resensitization to drug rechallenge.

Patients with melanoma receiving drugs targeting BRAFV600E and mitogen-activated protein (MAP) kinase kinases 1 and 2 (MEK1/2) invariably develop resistance and face continued progression. Based on preclinical studies, intermittent treatment involving alternating periods of drug withdrawal and rechallenge has been proposed as a method to delay the onset of resistance. The beneficial effect of intermittent treatment has been attributed to drug addiction, where drug withdrawal reduces the viability of resistant cells due to MAP kinase pathway hyperactivation. However, the mechanistic basis of the intermittent effect is incompletely understood. We show that intermittent treatment with the BRAFV600E inhibitor, LGX818/encorafenib, suppresses growth compared with continuous treatment in human melanoma cells engineered to express BRAFV600E, p61-BRAFV600E, or MEK2C125 oncogenes. Analysis of the BRAFV600E-overexpressing cells shows that, while drug addiction clearly occurs, it fails to account for the advantageous effect of intermittent treatment. Instead, growth suppression is best explained by resensitization during periods of drug removal, followed by cell death after drug readdition. Continuous treatment leads to transcriptional responses prominently associated with chemoresistance in melanoma. By contrast, cells treated intermittently reveal a subset of transcripts that reverse expression between successive cycles of drug removal and rechallenge and include mediators of cell invasiveness and the epithelial-to-mesenchymal transition. These transcripts change during periods of drug removal by adaptive switching, rather than selection pressure. Resensitization occurs against a background of sustained expression of melanoma resistance genes, producing a transcriptome distinct from that of the initial drug-naive cell state. We conclude that phenotypic plasticity leading to drug resensitization can underlie the beneficial effect of intermittent treatment.

Implementation of Group Interpersonal Psychotherapy in primary care

ABSTRACT OBJECTIVE To show the implementation process of IPT-G in primary care, including facilitating and obstructing factors, implementation strategies, and training and supervision of primary care professionals. METHODS Quantitative (cross-sectional and longitudinal) analysis of pre and post-knowledge tests; qualitative analyses of the training courses; patient recruitment; conduction of IPT-G sessions; supervision of IPT-G therapists; application of a semi-structured questionnaire to assess, investigate, and develop strategies against the identified barriers. RESULTS About 120 clinicians answered the pre-test; 84 completed the post-test. Pre- and post-test scores of IPT-G knowledge were significantly different. Twenty initially trained clinicians completed additional supervision in IPT-G. Qualitative analysis identified twelve barriers and six facilitators to IPT-G implementation in individual, organizational, and systemic contexts. CONCLUSIONS Implementation of IPT-G in primary care is a complex process with several steps. In the first step, health professionals were successfully trained in IPT-G. However, subsequent steps were more complex. Therefore, careful planning of IPT-G implementation is essential to maximize the success of this innovation.

Effectiveness of an Interpersonal Psychotherapy (IPT) Group Depression Treatment for Head Start Mothers: A Cluster-Randomized Controlled Trial.

BACKGROUND: Maternal depression is known to be a serious problem with higher rates among poor and racial/ethnic minority mothers that can have numerous negative impacts on their children. These mothers have less access to effective care and may be wary of traditional mental health care because of the stigma. The purpose of this study was to test whether an adaptation of an Interpersonal Psychotherapy group for perinatal depression could be effective in reducing depressive symptoms of mothers whose children were enrolled in Head Start. METHODS: Forty-nine mothers, randomized by site, were recruited into the intervention group, 70 into the control group. They were measured on depressive symptoms, parenting stress, parenting behavior, and parent child interaction at intake, at end of the group, and 6 months following. RESULTS: The intervention group was lower in depressive symptoms at the end of treatment with a further decrease 6 months post intervention. There was no change in the control group. The intervention group also improved in parenting stress. LIMITATIONS: The sample size for the intervention group was smaller than desired. CONCLUSIONS: This study supports the effectiveness of this 12 session IPT group which was highly effective for a population of Head Start mothers. It is a strategy that can be adapted to other settings that serve low income mothers.

Transcultural adaptation of interpersonal psychotherapy in Asia.

Interpersonal Psychotherapy (IPT) has been utilized with great efficacy and effectiveness across many cultural settings. The attachment theory upon which IPT rests provides a strong foundation for IPT cross-culturally: regardless of their geographic location, people are people and their relationships are important. Though the structure of families and individual social roles varies greatly across cultures, people relate to one another. They become distressed when they have problems with interpersonal conflict, change, and loss of relationships. In this article, we review the basics of IPT and then describe the ways in which cultural adaptations can be made for people in Asia. Both are large tasks-to summarize IPT concisely while providing sufficient information is difficult; describing cultural adaptions for people in geographical areas from Russia to China to India to Southeast and Central Asia and all of the ethnic and language groups that area includes is nigh well impossible within a review article. Thus we have restricted our cultural overview to areas in which we have experience clinically and in which we have been active with IPT training, supervision, and implementation. All of the work we describe, however, elaborate on the principles of cultural adaptations which can be used to implement IPT in other local contexts.

Interpersonal Psychotherapy to Reduce Psychological Distress in Perinatal Women: A Systematic Review.

BACKGROUND: Interpersonal psychotherapy (IPT) is a psychological intervention with established efficacy in the prevention and treatment of depressive disorders. Previous systematic reviews have not evaluated the effectiveness of IPT on symptoms of stress, anxiety, depression, quality of life, relationship satisfaction/quality, social supports, and an improved psychological sense of wellbeing. There is limited information regarding moderating and mediating factors that impact the effectiveness of IPT such as the timing of the intervention or the mode of delivery of IPT intervention. The overall objective of this systematic review was to evaluate the effectiveness of IPT interventions to treat perinatal (from pregnancy up to 12 months postpartum) psychological distress. METHODS: MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily (Ovid), EMBASE (Ovid), PsycINFO (Ovid), Cochrane Central Register of Controlled Trials (OVID), CINAHL with Full Text (Ebsco), Social Work Abstracts (Ebsco), SocINDEX with Full Text (Ebsco), Academic Search Complete (Ebsco), Family & Society Studies Worldwide (Ebsco), Family Studies Abstracts (Ebsco), and Scopus databases were searched from inception until 31 January 2019. Two researchers independently screened articles for eligibility. Of the 685 screened articles, 43 met the inclusion criteria. The search was re-run on 11 May 2020. An additional 204 articles were screened and two met the inclusion criteria, resulting in a total of 45 studies included in this review. There were 25 Randomized Controlled Trials, 10 Quasi-experimental studies, eight Open Trials, and two Single Case Studies. All included studies were critically appraised for quality. RESULTS: In most studies (n = 24, 53%), the IPT intervention was delivered individually; in 17 (38%) studies IPT was delivered in a group setting and two (4%) studies delivered the intervention as a combination of group and individual IPT. Most interventions were initiated during pregnancy (n = 27, 60%), with the remaining 18 (40%) studies initiating interventions during the postpartum period. LIMITATIONS: This review included only English-language articles and peer-reviewed literature. It excluded government reports, dissertations, conference papers, and reviews. This limited the access to grassroots or community-based recruitment and retention strategies that may have been used to target smaller or marginalized groups of perinatal women. CONCLUSIONS: IPT is an effective intervention for the prevention and treatment of psychological distress in women during their pregnancy and postpartum period. As a treatment intervention, IPT is effective in significantly reducing symptoms of depression and anxiety as well as improving social support, relationship quality/satisfaction, and adjustment. Systematic Review Registration: PROSPERO CRD42019114292.

Interpersonal psychotherapy for perinatal women: a systematic review and meta-analysis protocol.

BACKGROUND: Interpersonal psychotherapy (IPT) is an intervention that has established efficacy in the prevention and treatment of depressive disorders. Previous systematic reviews have not evaluated the effectiveness of IPT on symptoms of stress, anxiety, depression, quality of life, relationship satisfaction/quality, social supports, and an improved psychological sense of well-being. There is limited data regarding factors that moderate and mediate the effectiveness of IPT including the timing of the intervention or the mode of delivery of IPT intervention. The objective of this systematic review and meta-analysis is to evaluate the effectiveness, feasibility, and acceptability of IPT interventions to treat perinatal psychological distress and to summarize the evidence on predictors, mediators, and moderators of IPT. METHODS: We will include peer-reviewed studies that recruited perinatal women. The search strategy will involve the following databases: MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid), Cochrane Central Register of Controlled Trials (Ovid), CINAHL with Full Text (EBSCO), Social Work Abstracts (EBSCO), SocINDEX with Full Text (EBSCO), Academic Search Complete (EBSCO), Family & Society Studies Worldwide (EBSCO), Family Studies Abstracts (EBSCO), and Scopus. Study inclusion criteria include (1) randomized controlled trials, quasi-experimental studies, and pre-post studies that evaluated the effectiveness of IPT; (2) qualitative studies that evaluated feasibility and acceptability of IPT; (3) study sample included and analyzed perinatal women; and (4) publication language was English. Using pilot-tested screening and data extraction forms, two reviewers will independently review studies in three steps: (1) abstract/title screening, (2) full-text screening of potentially accepted studies, and (3) data extraction of accepted studies. Disagreements will be resolved by a third reviewer. Studies will be aggregated for meta-synthesis and meta-analysis should the data allow for this. Two independent reviewers will grade methodological quality. DISCUSSION: Findings from this review will inform future development and implementation of IPT intervention research for perinatal women. Identifying key factors of successful IPT interventions will inform intervention design and adaptation of IPT interventions to increase the likelihood that perinatal women will engage in and benefit from IPT interventions. This review will also identify key considerations for increasing the effectiveness of IPT interventions during the perinatal period. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019114292.

Internet-based interpersonal psychotherapy for stress, anxiety, and depression in prenatal women: study protocol for a pilot randomized controlled trial.

BACKGROUND: Psychological distress, defined as depression, anxiety and perceived stress, during pregnancy is common, with 15-25% of women experiencing clinically significant levels of such distress. Despite the far-reaching impact of prenatal psychological distress on mothers and their children, and that women are receptive to screening, few providers routinely screen for prenatal psychological distress and less than one in five women will receive the mental health care that they require. There is a lack of certainty regarding the most effective treatments for prenatal psychological distress. No online interpersonal psychotherapy (IPT) trials have been conducted that focus on improving psychological distress in prenatal women. The purpose of this pilot randomized controlled trial is to evaluate the perspectives of pregnant women on the feasibility and acceptability of online IPT (e-IPT) delivered during pregnancy. METHODS: A pilot randomized controlled trial design with repeated measures will evaluate the feasibility and acceptability of e-IPT for pregnant women compared to routine prenatal care. Qualitative interviews with 15-30 individuals in the intervention group will provide further data on the feasibility and acceptability of the intervention. Assessment of feasibility will include the ease of accessing and completing the intervention. Women will also be asked about what barriers there were to starting and completing the e-IPT. Assessment of acceptability will inquire about the perception of women regarding the intervention and its various features. A sample size of 160 consenting pregnant women aged 18 years and older will be enrolled and randomized into the experimental (e-IPT) or control (routine care) condition. The secondary outcome measures include: depression, anxiety and stress symptoms; self-efficacy; self-mastery; self-esteem; relationship quality (spouse, immediate family members); coping; and resilience. All participants will complete the aforementioned measures at baseline during pregnancy (T1), 3 months postrandomization (T2), at 8 months of pregnancy (T3), and 3 months postpartum (T4). DISCUSSION: The results of this pilot randomized controlled trial will provide data on the feasibility and acceptability of the intervention and identify necessary adaptations. This study will allow for optimization of full trial processes and inform the evaluation strategy, including sample size calculations for the full randomized controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01901796. Registered on 18 December 2014.

A placebo controlled treatment trial of sertraline and interpersonal psychotherapy for postpartum depression.

BACKGROUND: The purpose of the present study was to test the efficacy of sertraline and Interpersonal Psychotherapy (IPT) relative to pill placebo in a two site randomized controlled trial over a period of 12 weeks. It was hypothesized that sertraline and IPT would be more efficacious than pill placebo with respect to depression and social adjustment. METHODS: 162 breastfeeding and non-breastfeeding women experiencing a major depressive episode in the first year postpartum from two sites in Iowa and Rhode Island were randomly assigned to IPT, sertraline-clinical management (CM), or pill placebo-CM. CM included infant-focused psychoeducation. Interview-based and self-report measures of depression and social adjustment were obtained at baseline, 4-weeks, 8-weeks, and 12-weeks of treatment. Linear mixed effects regression (LMER) was used for the longitudinal data analysis. RESULTS: There was no significant effect for treatment condition associated with the primary outcome measure, the HamD-17, but there was a significant effect for sertraline-CM relative to the IPT and placebo conditions over the duration of the trial based on the General Depression scale of the Inventory of Depression and Anxiety Symptoms. There was a main effect for time in that study subjects across all three conditions showed significant improvement for the duration of the trial. LIMITATIONS: Limitations of the present study included significant non-engagement with assigned condition and differential effects of IPT across the two study sites. CONCLUSIONS: There was improvement for all postpartum women in all conditions. The results do suggest that active interventions with or without medication delivered over a period of twelve weeks can lead to significant improvement in depression and social adjustment among postpartum women. ClinicalTrials.gov identifier: NCT00602355.

Prehospital Predictors of Emergent Intervention After Helicopter Transfer for Spontaneous Intraparenchymal Hemorrhage.

OBJECTIVE: Helicopter transport may shorten transportation times for emergent neurosurgical intervention. The usefulness of helicopter transport after spontaneous intraparenchymal hemorrhage is not well studied. This study seeks to clarify factors that are associated with urgent surgical intervention in patients with spontaneous intracerebral hemorrhage following helicopter transport. METHODS: Records were reviewed for patients with spontaneous intraparenchymal hemorrhage transported by helicopter to Dartmouth-Hitchcock Medical Center between January 2008 and December 2011. Records were evaluated for factors associated with emergent tertiary-level care intervention during the first 24 hours of admission. RESULTS: A total of 107 patients met inclusion criteria, with a mean age of 67.2 years. At presentation, 79 (75.24%) were hypertensive, 22 (21.57%) had an increased international normalized ratio, and 47 (45.19%) were intubated. Thirty-three patients (30.8%) underwent 1 or more neurosurgical interventions within 24 hours of arrival, with an additional 6 (5.6%) patients undergoing neurosurgical intervention after 24 hours after admission. On univariate analysis, age, Glasgow Coma Scale (GCS) score, and clot volume were significant predictors of neurosurgical intervention within 24 hours of interfacility helicopter transport. A lobar clot, presence of intraventricular hemorrhage, and presence of >1 cm of midline shift were also associated with neurosurgical intervention within 24 hours. On multivariate analysis, younger age, GCS score of 3-8, and lobar hemorrhage were independent predictors of neurosurgical intervention within 24 hours. CONCLUSIONS: Two thirds of patients did not undergo any surgical intervention during the first 24 hours of admission after interfacility helicopter transfer. Factors associated with urgent neurosurgical intervention included younger age, low GCS score, and presence of lobar hemorrhage.

Trajectories of maternal depressive symptoms during pregnancy and the first 12 months postpartum and child externalizing and internalizing behavior at three years.

BACKGROUND: Most evidence of the association between maternal depression and children's development is limited by being cross-sectional. To date, few studies have modelled trajectories of maternal depressive symptoms from pregnancy through the early postpartum years and examined their association with social emotional and behavior functioning in preschool children. The objectives of this study were to: 1) identify distinct groups of women defined by their trajectories of depressive symptoms across four time points from mid-pregnancy to one year postpartum; and 2) examine the associations between these trajectories and child internalizing and externalizing behaviors. METHODS: We analyzed data from the All Our Families (AOF) study, a large, population based pregnancy cohort of mother-child dyads in Alberta, Canada. The AOF study is an ongoing pregnancy cohort study designed to investigate relationships between the prenatal and early life period and outcomes for children and mothers. Maternal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale. Children's behavioral functioning at age 3 was assessed using the Behavior Scales developed for the Canadian National Longitudinal Survey of Children and Youth. Longitudinal latent class analysis was conducted to identify trajectories of women's depressive symptoms across four time points from pregnancy to 1 year postpartum. We used multivariable logistic regression to assess the relationship between trajectories of maternal depressive symptoms and children's behavior, while adjusting for other significant maternal, child and psychosocial factors. RESULTS: 1983 participants met eligibility criteria. We identified four distinct trajectories of maternal depressive symptoms: low level (64.7%); early postpartum (10.9%); subclinical (18.8%); and persistent high (5.6%). In multivariable models, the proportion of children with elevated behavior symptoms was highest for children whose mothers had persistent high depressive symptoms, followed by mothers with moderate symptoms (early postpartum and subclinical trajectories) and lowest for minimal symptoms. After accounting for demographic, child and psychosocial factors, the relationships between depression trajectories and child hyperactivity/inattention, physical aggression (subclinical trajectory only) and separation anxiety symptoms remained significant. CONCLUSION: These findings suggest both externalizing and internalizing children's behaviors are associated with prolonged maternal depressive symptoms. There is a good case for the need to move beyond overly simplistic clinical cutoff approaches of depressed/not depressed in screening for perinatal depression. Women with elevated depressive symptoms at clinical and subclinical levels need to be identified, provided with evidence-based treatment, and monitored with repeat screening to improve maternal mental health outcomes and reduce the risk of associated negative outcomes on children's early social-emotional and behavior development.

A New Community-Based Model for Training in Evidence-Based Psychotherapy Practice.

It is critical that evidence-based practices (EBP's) be provided to patients. Efforts to train clinicians in the community in EBP's, however, has been hindered by a lack of resources and rigid and resource intensive models of training. We describe efforts to overcome these barriers in a large scale community-based training program for Interpersonal Psychotherapy implemented with over 1400 clinicians in Los Angeles working within the Los Angeles County Department of Mental Health public system of care. The program, described in detail, is a potential template for training for community-based clinicians in evidence-based psychotherapy practices.

Misleading signs in acute vertigo.

The acute vestibular syndrome is common and usually has a benign cause. Sometimes, however, even experienced neurologists can find it difficult to determine the cause clinically. Furthermore, neuroimaging is known to be insensitive.We describe two cases of acute vestibular syndrome where conflicting clinical findings contributed to a delay in making the correct diagnosis. The first patient with symptomatic vertigo had signs consistent with horizontal benign paroxysmal positional vertigo but also had an abnormal horizontal head impulse test, superficially suggesting acute vestibular neuritis but later accounted for by the finding of a vestibular schwannoma (acoustic neuroma). The second patient also had an abnormal horizontal head impulse test, with skew deviation suggesting stroke as the cause. However, later assessment identified that a long-standing fourth nerve palsy was the true cause for her apparent skew. We discuss potential errors that can arise when assessing such patients and highlight ways to avoid them.

Specificity of Phosphorylation Responses to Mitogen Activated Protein (MAP) Kinase Pathway Inhibitors in Melanoma Cells.

The BRAF-MKK1/2-ERK1/2 pathway is constitutively activated in response to oncogenic mutations of BRAF in many cancer types, including melanoma. Although small molecules that inhibit oncogenic BRAF and MAP kinase kinase (MKK)1/2 have been successful in clinical settings, resistance invariably develops. High affinity inhibitors of ERK1/2 have been shown in preclinical studies to bypass the resistance of melanoma and colon cancer cells to BRAF and MKK1/2 inhibitors, and are thus promising additions to current treatment protocols. But still unknown is how molecular responses to ERK1/2 inhibitors compare with inhibitors currently in clinical use. Here, we employ quantitative phosphoproteomics to evaluate changes in phosphorylation in response to the ERK inhibitors, SCH772984 and GDC0994, and compare these to the clinically used MKK1/2 inhibitor, trametinib. Combined with previous studies measuring phosphoproteomic responses to the MKK1/2 inhibitor, selumetinib, and the BRAF inhibitor, vemurafenib, the outcomes reveal key insights into pathway organization, phosphorylation specificity and off-target effects of these inhibitors. The results demonstrate linearity in signaling from BRAF to MKK1/2 and from MKK1/2 to ERK1/2. They identify likely targets of direct phosphorylation by ERK1/2, as well as inhibitor off-targets, including an off-target regulation of the p38α mitogen activated protein kinase (MAPK) pathway by the MKK1/2 inhibitor, trametinib, at concentrations used in the literature but higher than in vivo drug concentrations. In addition, several known phosphorylation targets of ERK1/2 are insensitive to MKK or ERK inhibitors, revealing variability in canonical pathway responses between different cell systems. By comparing multiple inhibitors targeted to multiple tiers of protein kinases in the MAPK pathway, we gain insight into regulation and new targets of the oncogenic BRAF driver pathway in cancer cells, and a useful approach for evaluating the specificity of drugs and drug candidates.

The comorbidity of Axis I disorders in depressed pregnant women.

Depression during pregnancy is highly prevalent and is associated with increased risk of a variety of negative psychological and medical outcomes in both mothers and offspring. Antenatal depression often co-occurs with significant anxiety, potentially exacerbating morbidities for women and their children. However, screening during the antenatal period is frequently limited to assessment of depression so that other significant comorbid disorders may be missed. Follow-up assessment by clinicians has similarly focused primarily on detection of depressive symptoms. Anxiety, obsessive compulsive disorder, and post-traumatic stress disorder, among others, often go undetected in perinatal care settings, even when depression is identified. Failing to recognize these comorbid diagnoses may lead to inadequate treatment or only partial alleviation of distress. Consequently, screening for and assessment of comorbid disorders is warranted. In this study, 382 pregnant women (M age = 25.8 [SD = 5.3] years, 85.0% Caucasian) receiving care at a university hospital clinic and Maternal Mental Health Care centers in eastern Iowa and who screened positive for depression on the Beck Depression Inventory completed the Structured Clinical Interview for DSM-IV to assess comorbid mental health symptoms and diagnoses. Overall, findings demonstrate high rates of anxiety disorders among women both with and without current major depression, although depressed women reported higher rates of generalized anxiety disorder and post-traumatic stress disorder. Notably, however, incidence-specific symptoms were comparable across groups. Routine screening of both anxiety and depression during pregnancy should be conducted.