Assessment of Psychosocial and Neonatal Risk Factors for Trajectories of Behavioral Dysregulation Among Young Children From 18 to 72 Months of Age.

Importance: Emotional and behavioral dysregulation during early childhood are associated with severe psychiatric, behavioral, and cognitive disorders through adulthood. Identifying the earliest antecedents of persisting emotional and behavioral dysregulation can inform risk detection practices and targeted interventions to promote adaptive developmental trajectories among at-risk children. Objective: To characterize children's emotional and behavioral regulation trajectories and examine risk factors associated with persisting dysregulation across early childhood. Design, Setting, and Participants: This cohort study examined data from 20 United States cohorts participating in Environmental influences on Child Health Outcomes, which included 3934 mother-child pairs (singleton births) from 1990 to 2019. Statistical analysis was performed from January to August 2022. Exposures: Standardized self-reports and medical data ascertained maternal, child, and environmental characteristics, including prenatal substance exposures, preterm birth, and multiple psychosocial adversities. Main Outcomes and Measures: Child Behavior Checklist caregiver reports at 18 to 72 months of age, with Dysregulation Profile (CBCL-DP = sum of anxiety/depression, attention, and aggression). Results: The sample included 3934 mother-child pairs studied at 18 to 72 months. Among the mothers, 718 (18.7%) were Hispanic, 275 (7.2%) were non-Hispanic Asian, 1220 (31.8%) were non-Hispanic Black, 1412 (36.9%) were non-Hispanic White; 3501 (89.7%) were at least 21 years of age at delivery. Among the children, 2093 (53.2%) were male, 1178 of 2143 with Psychosocial Adversity Index [PAI] data (55.0%) experienced multiple psychosocial adversities, 1148 (29.2%) were exposed prenatally to at least 1 psychoactive substance, and 3066 (80.2%) were term-born (≥37 weeks' gestation). Growth mixture modeling characterized a 3-class CBCL-DP trajectory model: high and increasing (2.3% [n = 89]), borderline and stable (12.3% [n = 479]), and low and decreasing (85.6% [n = 3366]). Children in high and borderline dysregulation trajectories had more prevalent maternal psychological challenges (29.4%-50.0%). Multinomial logistic regression analyses indicated that children born preterm were more likely to be in the high dysregulation trajectory (adjusted odds ratio [aOR], 2.76; 95% CI, 2.08-3.65; P < .001) or borderline dysregulation trajectory (aOR, 1.36; 95% CI, 1.06-1.76; P = .02) vs low dysregulation trajectory. High vs low dysregulation trajectories were less prevalent for girls compared with boys (aOR, 0.60; 95% CI, 0.36-1.01; P = .05) and children with lower PAI (aOR, 1.94; 95% CI, 1.51-2.49; P < .001). Combined increases in PAI and prenatal substance exposures were associated with increased odds of high vs borderline dysregulation (aOR, 1.28; 95% CI, 1.08-1.53; P = .006) and decreased odds of low vs high dysregulation (aOR, 0.77; 95% CI, 0.64-0.92; P = .005). Conclusions and Relevance: In this cohort study of behavioral dysregulation trajectories, associations were found with early risk factors. These findings may inform screening and diagnostic practices for addressing observed precursors of persisting dysregulation as they emerge among at-risk children.

Development, Psychopathology, and Ethnicity II: Psychiatric Disorders Among Young Adults.

OBJECTIVE: To estimate the prevalence of psychiatric disorders and their continuity since childhood among young adults from the same ethnic group living in 2 low-income contexts. METHOD: Young adults (N = 2,004; ages 15-29) were followed (82.8% retention) as part of the Boricua Youth Study, a study of Puerto Rican youths recruited at ages 5-13 in the South Bronx (SBx), New York, and Puerto Rico (PR). We estimated prevalence (lifetime; past year) of major depressive (MDD), mania, hypomania, generalized anxiety (GAD), tobacco dependence, and any other substance use disorders (SUD). RESULTS: The prevalence of every disorder was higher among young women from the SBx compared with those from PR (eg, 9.2% versus 4.1% past-year SUD; 14% versus 6.8% for MDD/GAD). Among SBx young men, tobacco dependence and illicit SUD were elevated. Across both contexts, men had higher adjusted odds of illicit SUD than women, while women had higher GAD than men. MDD did not differ by gender. Young adulthood disorders (except for alcohol use disorder and GAD) followed childhood disorders. For example, childhood externalizing disorders preceded both MDD (young men and women) and illicit SUD (young women only). CONCLUSION: Young women raised in a context where adversities like ethnic discrimination concentrate are at high risk for psychiatric disorders. In certain high-poverty contexts, young men may present with MDD as often as women. Interventions to prevent psychiatric disorders may need to address gender-specific processes and childhood disorders. However, SUD prevention among young men may need to address other factors.

Sociodemographic factors associated with smoking risk perception in adolescents in São Paulo, Brazil

Objective: We examined the sociodemographic factors associated with smoking risk perceptions (SRP) in youth living in two very different neighborhoods in the city of São Paulo, Brazil: a middle-class central area (Vila Mariana) and a poor outer-city area (Capão Redondo). Methods: A cross-sectional survey was conducted with 180 public school-attending youth (all aged 12 years) and their parents. SRP was evaluated through self-reports. Weighted multinomial logistic regression was used to examine factors associated with SRP. Results: Smoking was considered a high-risk behavior by 70.9% of adolescents. There were significant differences in SRP associated with socioeconomic status (SES) and maternal smoking status. Having a non-smoking mother was positively associated with perceiving smoking as having low to moderate risk versus no risk (OR=3.91 [95%CI 1.27-12.02]). Attending school in Capão Redondo was associated with perceiving smoking as having high risk compared to no risk (OR=3.00 [95%CI 1.11-8.12]), and low SES was negatively associated with perceiving at least some risk in smoking versus perceiving no risk in this behavior. Conclusions: Youth whose mothers smoke appear to have lower SRP than those whose mothers do not smoke. Living in a poor outer-city area was associated with higher SRP.

Sociodemographic factors associated with smoking risk perception in adolescents in São Paulo, Brazil.

OBJECTIVE: We examined the sociodemographic factors associated with smoking risk perceptions (SRP) in youth living in two very different neighborhoods in the city of São Paulo, Brazil: a middle-class central area (Vila Mariana) and a poor outer-city area (Capão Redondo). METHODS: A cross-sectional survey was conducted with 180 public school-attending youth (all aged 12 years) and their parents. SRP was evaluated through self-reports. Weighted multinomial logistic regression was used to examine factors associated with SRP. RESULTS: Smoking was considered a high-risk behavior by 70.9% of adolescents. There were significant differences in SRP associated with socioeconomic status (SES) and maternal smoking status. Having a non-smoking mother was positively associated with perceiving smoking as having low to moderate risk versus no risk (OR=3.91 [95%CI 1.27-12.02]). Attending school in Capão Redondo was associated with perceiving smoking as having high risk compared to no risk (OR=3.00 [95%CI 1.11-8.12]), and low SES was negatively associated with perceiving at least some risk in smoking versus perceiving no risk in this behavior. CONCLUSIONS: Youth whose mothers smoke appear to have lower SRP than those whose mothers do not smoke. Living in a poor outer-city area was associated with higher SRP.

Impact of Medical Marijuana Laws on State-Level Marijuana Use by Age and Gender, 2004-2013.

In states that have passed medical marijuana laws (MMLs), marijuana use (MU) increased after MML enactment among people ages 26 and older, but not among ages 12-25. We examined whether the age-specific impact of MMLs on MU varied by gender. Data were obtained from the 2004-2013 restricted-use National Survey on Drug Use and Health, aggregated at the state level. The exposure was a time-varying indicator of state-level MML (0 = No Law, 1 = Before Law, 2 = After Law). Outcomes included past-month MU prevalence, daily MU prevalence among past-year users (i.e., 300+ days/year), and past-year marijuana use disorder (MUD) prevalence. Linear models tested the state-level MML effect on outcomes by age (12-17, 18-25, 26+) and gender. Models included a state-level random intercept and controlled for time- and state-level covariates. Past-month MU did not increase after enactment of MML in men or women ages 12-25. Among people 26+, past-month MU increased for men from 7.0% before to 8.7% after enactment (+ 1.7%, p < 0.001) and for women from 3.1% before to 4.3% after enactment (+ 1.1%, p = 0.013). Among users 26+, daily MU also increased after enactment in both genders (men 16.3 to 19.1%, + 2.8%, p = 0.014; women 9.2 to 12.7%, + 3.4%, p = 0.003). There were no statistically significant increases in past-year MUD prevalence for any age or gender group after MML enactment. Given the statistically significant increase in daily use among past-year users aged 26+ following enactment, education campaigns should focus on informing the public of the risks associated with regular marijuana use.

The co-occurrence and correlates of anxiety disorders among adolescents with intermittent explosive disorder.

We examined the lifetime prevalence of anxiety disorders (ADs) among adolescents with lifetime intermittent explosive disorder (IED), as well as the impact of co-occurring ADs on anger attack frequency and persistence, additional comorbidity, impairment, and treatment utilization among adolescents with IED. IED was defined by the occurrence of at least three anger attacks that were disproportionate to the provocation within a single year. Data were drawn from the National Comorbidity Survey-Adolescent Supplement (N = 6,140), and diagnoses were based on structured lay-administered interviews. Over half (51.89%) of adolescents with IED had an AD, compared to only 22.88% of adolescents without IED. Compared to adolescents with IED alone, adolescents with IED and comorbid ADs: (a) were more likely to be female; (b) reported greater impairment in work/school, social, and overall functioning; (c) were more likely to receive an additional psychiatric diagnosis, a depressive or drug abuse diagnosis, or diagnoses of three or more additional disorders; and (d) had higher odds of receiving any mental/behavioral health treatment as well as treatment specifically focused on aggression. Adolescents with IED alone and those with comorbid ADs did not differ in the number of years experiencing anger attacks or the highest number of anger attacks in a given year. ADs frequently co-occur with IED and are associated with elevated comorbidity and greater impairment compared to IED alone. Gaining a better understanding of this comorbidity is essential for developing specialized and effective methods to screen and treat comorbid anxiety in adolescents with aggressive behavior problems.

Age Differences in Daily and Nondaily Cannabis Use in the United States, 2002-2014.

OBJECTIVE: Adult cannabis use has increased in the United States since 2002, particularly after 2007, contrasting with stable/declining trends among youth. We investigated whether specific age groups disproportionately contributed to changes in daily and nondaily cannabis use trends. METHOD: Participants ages 12 and older (N = 722,653) from the 2002-2014 National Survey on Drug Use and Health reported past-year cannabis use frequency (i.e., daily = ≥300 days/year; nondaily = 1-299 days/year; none). Multinomial logistic regression was used to model change in past-year daily and nondaily cannabis use prevalence by age group (i.e., 12-17, 18-25, 26-34, 35-49, 50-64, ≥65), before and after 2007. Multinomial logistic regressions estimated change in relative odds of cannabis use frequency over time by age, adjusting for other sociodemographics. RESULTS: Daily cannabis use prevalence decreased in ages 12-17 before 2007 and increased significantly across adult age categories only after 2007. Increases did not differ significantly across adult ages 18-64 and ranged between 1 and 2 percentage points. Nondaily cannabis use decreased among respondents ages 12-25 and 35-49 before 2007 and increased across adult age categories after 2007, particularly among adults 26-34 (i.e., 4.5 percentage points). Adjusted odds of daily versus nondaily cannabis use increased after 2007 for ages 12-64. CONCLUSIONS: Increases in daily and nondaily cannabis use prevalence after 2007 were specific to adult age groups in the context of increasingly permissive cannabis legislation, attitudes, and lower risk perception. Although any cannabis use may be decreasing among teens, relative odds of more frequent use among users increased in ages 12-64 since 2007. Studies should assess not only any cannabis use, but also frequency of use, to target prevention efforts of adverse effects of cannabis that are especially likely among frequent users.

Trauma Exposure and Externalizing Disorders in Adolescents: Results From the National Comorbidity Survey Adolescent Supplement.

OBJECTIVE: Exposure to violence and other forms of potentially traumatic events (PTEs) are common among youths with externalizing psychopathology. These associations likely reflect both heightened risk for the onset of externalizing problems in youth exposed to PTEs and elevated risk for experiencing PTEs among youth with externalizing disorders. In this study, we disaggregate the associations between exposure to PTEs and externalizing disorder onset in a population-representative sample of adolescents. METHOD: We analyzed data from 13- to 18-year-old participants in the National Comorbidity Survey Replication-Adolescent Supplement (NCS-A) (N = 6,379). Weighted survival models estimated hazard ratios (HRs) for onset of oppositional defiant disorder (ODD), conduct disorder (CD), and substance use disorders (SUDs) associated with PTEs, and for exposure to PTEs associated with prior-onset externalizing disorders. Multiplicative interaction terms tested for effect modification by sex, race/ethnicity, and household income. RESULTS: All types of PTEs were associated with higher risk for SUD (HRs = 1.29-2.21), whereas only interpersonal violence (HR = 2.49) was associated with onset of CD and only among females. No associations were observed for ODD. Conversely, ODD and CD were associated with elevated risk for later exposure to interpersonal violence and other/nondisclosed events (HRs = 1.45-1.75). CONCLUSION: Externalizing disorders that typically begin in adolescence, including SUDs and CD, are more likely to emerge in adolescents with prior trauma. ODD onset, in contrast, is unrelated to trauma exposure but is associated with elevated risk of experiencing trauma later in development. CD and interpersonal violence exposure exhibit reciprocal associations. These findings have implications for interventions targeting externalizing and trauma-related psychopathology.

Cannabis use, attitudes, and legal status in the U.S.: A review.

Cannabis is widely used among adolescents and adults. In the U.S., marijuana laws have been changing, and Americans increasingly favor legalizing cannabis for medical and recreational uses. While some can use cannabis without harm, others experience adverse consequences. The objective of this review is to summarize information on the legal status of cannabis, perceptions regarding cannabis, prevalence and time trends in use and related adverse consequences, and evidence on the relationship of state medical (MML) and recreational (RML) marijuana laws to use and attitudes. Twenty-nine states now have MMLs, and eight of these have RMLs. Since the early 2000s, adult and adolescent perception of cannabis use as risky has decreased. Over the same time, the prevalence of adolescent cannabis use has changed little. However, adult cannabis use, disorders, and related consequences have increased. Multiple nationally representative studies indicate that MMLs have had little effect on cannabis use among adolescents. However, while MML effects have been less studied in adults, available evidence suggests that MMLs increase use and cannabis use disorders in adults. While data are not yet available to evaluate the effect of RMLs, they are likely to lower price, increase availability, and thereby increase cannabis use. More permissive marijuana laws may accomplish social justice aims (e.g., reduce racial disparities in law enforcement) and generate tax revenues. However, such laws may increase cannabis-related adverse health and psychosocial consequences by increasing the population of users. Dissemination of balanced information about the potential health harms of cannabis use is needed.

The widening gender gap in marijuana use prevalence in the U.S. during a period of economic change, 2002-2014.

AIM: Concurrently with increasingly permissive attitudes towards marijuana use and its legalization, the prevalence of marijuana use has increased in recent years in the U.S. Substance use is generally more prevalent in men than women, although for alcohol, the gender gap is narrowing. However, information is lacking on whether time trends in marijuana use differ by gender, or whether socioeconomic status in the context of the Great Recession may affect these changes. METHODS: Using repeated cross-sectional data from the National Survey on Drug Use and Health (2002-2014), we examined changes over time in prevalence of past-year marijuana use by gender, and whether gender differences varied across income levels. After empirically determining a change point in use in 2007, we used logistic regression to test interaction terms including time, gender, and income level. RESULTS: Prevalence of marijuana use increased for both men (+4.0%) and women (+2.7%) from 2002 to 2014, with all of the increase occurring from 2007 to 2014. Increases were greater for men, leading to a widening of the gender gap over time (p<0.001). This divergence occurred primarily due to increased prevalence among men in the lowest income level (+6.2%) from 2007 to 2014. CONCLUSION: Our findings are consistent with other studies documenting increased substance use during times of economic insecurity, especially among men. Corresponding with the Great Recession and lower employment rate beginning in 2007, low-income men showed the greatest increases in marijuana use during this period, leading to a widening of the gender gap in prevalence of marijuana use over time.

Gender discrimination, educational attainment, and illicit drug use among U.S. women.

PURPOSE: While gender inequality has been a topic of concern for decades, little is known about the relationship between gender discrimination and illicit drug use. Further, whether this association varies by education level is unknown. METHODS: Among 19,209 women participants in Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (2004-2005), we used logistic regression to test the association between gender discrimination (measured with four items from the Experiences of Discrimination instrument) and three outcomes: past-year illicit drug use, frequent drug use, and drug use disorders. We then tested whether associations differed by education level. RESULTS: Gender discrimination was reported by 9% of women and was associated with past-year drug use [adjusted odds ratio (aOR) = 2.67; 95% confidence interval (CI) 2.17-3.29], frequent drug use (aOR = 2.82; CI 1.99-4.00), and past-year drug use disorders (aOR = 3.15; CI 2.16-4.61). All specific domains of gender discrimination (on the job, in public, with institutions, being called a sexist name) were associated with all drug use outcomes. The association between gender discrimination and past-year drug use was stronger among women with less than a high school education (aOR = 6.33; CI 3.38-11.85) compared to those with more education (aOR = 2.45; CI 1.97-3.04; p interaction < 0.01). CONCLUSIONS: Gender discrimination is consistently and strongly associated with illicit drug use and drug use disorders among U.S. women, with significantly higher odds for drug use among women with less than a high school education. Future research should examine whether explicitly addressing distress from discrimination could benefit women in drug treatment, especially among clients with lower educational attainment.

Childhood Trauma and Illicit Drug Use in Adolescence: A Population-Based National Comorbidity Survey Replication-Adolescent Supplement Study.

OBJECTIVE: Although potentially traumatic events (PTEs) are established risk factors for substance use disorders among adults, little is known about associations with drug use during adolescence, an important developmental stage for drug use prevention. We examined whether childhood PTEs were associated with illicit drug use among a representative sample of US adolescents. METHOD: Data were drawn from the National Comorbidity Survey Replication-Adolescent Supplement (NCS-A), which included adolescents aged 13 to 18 years (N = 9,956). Weighted logistic regression models estimated risk ratios for lifetime use of marijuana, cocaine, nonmedical prescription drugs, other drugs, and multiple drugs. RESULTS: Exposure to any PTE before age 11 years was reported by 36% of the sample and was associated with higher risk for use of marijuana (risk ratio [RR] = 1.50), cocaine (RR = 2.78), prescription drugs (RR = 1.80), other drugs (RR = 1.90), and multiple drugs (RR = 1.74). A positive monotonic relationship was observed between number of PTEs and marijuana, other drug, and multiple drug use. Interpersonal violence was associated with all drug use outcomes. Accidents and unspecified events were associated with higher risk for marijuana, cocaine, and prescription drug use. CONCLUSION: Potentially traumatic events in childhood are associated with risk for illicit drug use among US adolescents. These findings add to the literature by illustrating a potentially modifiable health behavior that may be a target for intervention. The results also highlight that adolescents with a trauma history are a high-risk group for illicit drug use and may benefit from trauma-focused prevention efforts that specifically address traumatic memories and coping strategies for dealing with stressful life events.

Racial discrimination, socioeconomic position, and illicit drug use among US Blacks.

PURPOSE: We assessed the relationship of self-reported racial discrimination with illicit drug use among US Blacks, and whether this differed by socioeconomic position (SEP). METHODS: Among 6587 Black participants in Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (2004-2005), we used multiple logistic regression models to test the association between racial discrimination (measured on the 6-item Experiences of Discrimination scale) and past-year illicit drug use, and whether this differed by SEP. RESULTS: Racial discrimination was associated with past-year drug use [adjusted odds ratio (aOR) 2.32; 95 % confidence interval (CI) 1.70, 3.16] and with frequent drug use (aOR 1.91; 95 % CI 1.22, 2.99). For frequent illicit drug use, this relationship was stronger among higher SEP participants (aOR 3.55; 95 % CI 2.09, 6.02; p interaction < 0.01). CONCLUSIONS: The stronger association between racial discrimination and frequent illicit drug use among higher SEP Blacks suggests a complex interplay between disadvantaged and privileged statuses that merits further investigation. The finding of a significant difference by SEP highlights the importance of considering differences within heterogeneous race/ethnic groups when investigating health disparities.

Cognitive ability in childhood and the chronicity and suicidality of depression.

BACKGROUND: There is inconsistent evidence regarding the influence of general cognitive abilities on the long-term course of depression. AIMS: To investigate the association between general childhood cognitive abilities and adult depression outcomes. METHOD: We conducted a cohort study using data from 633 participants in the New England Family Study with lifetime depression. Cognitive abilities at age 7 were measured using the Wechsler Intelligence Scale for Children. Depression outcomes were assessed using structured diagnostic interviews administered up to four times in adulthood between ages 17 and 49. RESULTS: In analyses adjusting for demographic factors and parental psychiatric illness, low general cognitive ability (i.e. IQ<85 v. IQ>115) was associated with recurrent depressive episodes (odds ratio (OR) = 2.19, 95% CI 1.20-4.00), longer episode duration (rate ratio 4.21, 95% CI 2.24-7.94), admission to hospital for depression (OR = 3.65, 95% CI 1.34-9.93) and suicide ideation (OR = 3.79, 95% CI 1.79-8.02) and attempt (OR = 4.94, 95% CI 1.67-14.55). CONCLUSIONS: Variation in cognitive abilities, predominantly within the normal range and established early in childhood, may confer long-term vulnerability for prolonged and severe depression. The mechanisms underlying this vulnerability need to be established to improve the prognosis of depression among individuals with lower cognitive abilities.

Associations between exposure to intimate partner violence, armed conflict, and probable PTSD among women in rural Côte d'Ivoire.

BACKGROUND: Objectives were to assess associations between intimate partner violence (IPV), violence during armed conflict (i.e. crisis violence), and probable post-traumatic stress disorder (PTSD). METHODS: Using a sample of 950 women in rural Côte d'Ivoire, logistic generalized estimating equations assessed associations between IPV and crisis violence exposures with past-week probable PTSD. RESULTS: Over one in 5 (23.4%) women reported past-year IPV, and over one in 4 women (26.5%) reported experiencing IPV prior to the past year (i.e. remote IPV). Crisis violence was experienced by 72.6% of women. In adjusted models including demographics, crisis violence (overall and specific forms), and IPV (remote and past-year), women who reported past-year IPV had 3.1 times the odds of reporting probable past-week PTSD (95%CI: 1.8-5.3) and those who reported remote IPV had 1.6 times the odds (95%CI: 0.9-2.7). Violent exposures during the crisis were not significantly associated with probable PTSD (any crisis violence: aOR: 1.04 (0.7-1.5); displacement: aOR: 0.9 (95%CI: 0.5-1.7); family victimization during crisis: aOR: 1.1 (95%CI: 0.8-1.7); personal victimization during crisis: aOR: 1.7 (95%CI: 0.7-3.7)). CONCLUSION: Past-year IPV was more strongly associated with past-week probable PTSD than remote IPV and violence directly related to the crisis. IPV must be considered within humanitarian mental health and psychosocial programming.

Prevalence of cardiovascular risk factors among racial and ethnic minorities with schizophrenia spectrum and bipolar disorders: a critical literature review.

OBJECTIVE: People with serious mental illness (SMI) die at least 11 years earlier than the general U.S. population, on average, due largely to cardiovascular disease (CVD). Disparities in CVD morbidity and mortality also occur among some U.S. racial and ethnic minorities. The combined effect of race/ethnicity and SMI on CVD-related risk factors, however, remains unclear. To address this gap, we conducted a critical literature review of studies assessing the prevalence of CVD risk factors (overweight/obesity, diabetes mellitus, metabolic syndrome, hypercholesterolemia, hypertension, cigarette smoking, and physical inactivity) among U.S. racial/ethnic groups with schizophrenia-spectrum and bipolar disorders. METHODS AND RESULTS: We searched MEDLINE and PsycINFO for articles published between 1986 and 2013. The search ultimately yielded 40 articles. There was great variation in sampling, methodology, and study populations. Results were mixed, though there was some evidence for increased risk for obesity and diabetes mellitus among African Americans, and to a lesser degree for Hispanics, compared to non-Hispanic Whites. Sex emerged as an important possible effect modifier of risk, as women had higher CVD risk among all racial/ethnic subgroups where stratified analyses were reported. CONCLUSIONS: Compared to general population estimates, there was some evidence for an additive risk for CVD risk factors among racial/ethnic minorities with SMI. Future studies should include longitudinal assessment, stratification by sex, subgroup analyses to clarify the mechanisms leading to potentially elevated risk, and the evaluation of culturally appropriate interventions to eliminate the extra burden of disease in this population.

Economic inequalities in the effectiveness of a primary care intervention for depression and suicidal ideation.

BACKGROUND: Economic disadvantage is associated with depression and suicide. We sought to determine whether economic disadvantage reduces the effectiveness of depression treatments received in primary care. METHODS: We conducted differential-effects analyses of the Prevention of Suicide in Primary Care Elderly: Collaborative Trial, a primary-care-based randomized, controlled trial for late-life depression and suicidal ideation conducted between 1999 and 2001, which included 514 patients with major depression or clinically significant minor depression. RESULTS: The intervention effect, defined as change in depressive symptoms from baseline, was stronger among persons reporting financial strain at baseline (differential effect size = -4.5 Hamilton Depression Rating Scale points across the study period [95% confidence interval = -8.6 to -0.3]). We found similar evidence for effect modification by neighborhood poverty, although the intervention effect weakened after the initial 4 months of the trial for participants residing in poor neighborhoods. There was no evidence of substantial differences in the effectiveness of the intervention on suicidal ideation and depression remission by economic disadvantage. CONCLUSIONS: Economic conditions moderated the effectiveness of primary-care-based treatment for late-life depression. Financially strained individuals benefited more from the intervention; we speculate this was because of the enhanced treatment management protocol, which led to a greater improvement in the care received by these persons. People living in poor neighborhoods experienced only temporary benefit from the intervention. Thus, multiple aspects of economic disadvantage affect depression treatment outcomes; additional work is needed to understand the underlying mechanisms.

Phase II study of erlotinib plus temozolomide during and after radiation therapy in patients with newly diagnosed glioblastoma multiforme or gliosarcoma.

PURPOSE: This open-label, prospective, single-arm, phase II study combined erlotinib with radiation therapy (XRT) and temozolomide to treat glioblastoma multiforme (GBM) and gliosarcoma. The objectives were to determine efficacy of this treatment as measured by survival and to explore the relationship between molecular markers and treatment response. PATIENTS AND METHODS: Sixty-five eligible adults with newly diagnosed GBM or gliosarcoma were enrolled. We intended to treat patients not currently treated with enzyme-inducing antiepileptic drugs (EIAEDs) with 100 mg/d of erlotinib during XRT and 150 mg/d after XRT. Patients receiving EIAEDs were to receive 200 mg/d of erlotinib during XRT and 300 mg/d after XRT. After XRT, the erlotinib dose was escalated until patients developed tolerable grade 2 rash or until the maximum allowed dose was reached. All patients received temozolomide during and after XRT. Molecular markers of epidermal growth factor receptor (EGFR), EGFRvIII, phosphatase and tensin homolog (PTEN), and methylation status of the promotor region of the MGMT gene were analyzed from tumor tissue. Survival was compared with outcomes from two historical phase II trials. RESULTS: Median survival was 19.3 months in the current study and 14.1 months in the combined historical control studies, with a hazard ratio for survival (treated/control) of 0.64 (95% CI, 0.45 to 0.91). Treatment was well tolerated. There was a strong positive correlation between MGMT promotor methylation and survival, as well as an association between MGMT promotor-methylated tumors and PTEN positivity shown by immunohistochemistry with improved survival. CONCLUSION: Patients treated with the combination of erlotinib and temozolomide during and following radiotherapy had better survival than historical controls. Additional studies are warranted.