Longitudinal patterns of neuroendocrine coupling from middle childhood to early adolescence.

Recent scholarship has highlighted the importance of understanding relations between hormones, rather than studying hormones in isolation. Considering neuroendocrine coupling, or the coordination of hypothalamic-pituitary-adrenal axis and hypothalamic-pituitary-gonadal axis hormones over time, is one way to investigate how systems governing stress responsiveness and pubertal development covary during critical periods. To date, however, most work has considered hormone coupling cross-sectionally. The current study investigated neuroendocrine coupling in a longitudinal sample from the Northeastern United States. Youth (N = 437, 53% male, 90% White) provided saliva samples for analysis of diurnal hormone activity at ages 9 (three samples per day across 3 days) and 12 (one sample per day on the same weekday for 4 weeks). At both timepoints, samples collected 30-min after waking were assayed for cortisol, dehydroepiandrosterone (DHEA), and testosterone. Multilevel growth modeling was used to determine how levels of morning cortisol changed in tandem with DHEA and testosterone. Morning cortisol-DHEA coupling varied by child sex, as males' cortisol-DHEA diminished over time, especially among pubertally advanced males. Females, in contrast, demonstrated strengthening cortisol-DHEA coupling over time, especially more pubertally advanced females. Morning cortisol-testosterone coupling did not vary by sex or pubertal status, demonstrating strengthening associations between ages 9 and 12. The current findings contribute to the literature on hormone coupling across development and expand this work into an earlier developmental phase than previously investigated.

Developmental pathways from preschool irritability to multifinality in early adolescence: the role of diurnal cortisol.

BACKGROUND: Early irritability predicts a broad spectrum of psychopathology spanning both internalizing and externalizing disorders, rather than any particular disorder or group of disorders (i.e. multifinality). Very few studies, however, have examined the developmental mechanisms by which it leads to such phenotypically diverse outcomes. We examined whether variation in the diurnal pattern of cortisol moderates developmental pathways between preschool irritability and the subsequent emergence of internalizing and externalizing symptoms 9 years later. METHOD: When children were 3 years old, mothers were interviewed about children's irritability and completed questionnaires about their children's psychopathology. Six years later, children collected saliva samples at wake-up and bedtime on three consecutive days. Diurnal cortisol patterns were modeled as latent difference scores between evening and morning samples. When children were approximately 12 years old, mothers again completed questionnaires about their children's psychopathology. RESULTS: Among children with higher levels of irritability at age 3, a steeper diurnal cortisol slope at age 9 predicted greater internalizing symptoms and irritability at age 12, whereas a blunted slope at age 9 predicted greater externalizing symptoms at age 12, adjusting for baseline and concurrent symptoms. CONCLUSION: Our results suggest that variation in stress system functioning can predict and differentiate developmental trajectories of early irritability that are relatively more internalizing v. those in which externalizing symptoms dominate in pre-adolescence.

Covariance Between Parent and Child Symptoms Before and During the COVID-19 Pandemic.

OBJECTIVE: COVID-19 has had unprecedented effects on American families, including increases in depression, anxiety, and irritability for both parents and children. While parents and children influence each other's psychological functioning during non-disaster times, this effect may be amplified during times of disaster. The current study investigated how COVID-19 influenced covariance of depressive symptoms and irritability in children and their parents. METHODS: Three hundred and ninety-one parents and their 8- to 17-year-old children (Mage = 10.68 years old, 70% male, 86% White) from a large sample of children and parents, primarily from Southeastern Louisiana, completed self-report measures of depression and irritability approximately 6 weeks into the COVID-19 pandemic, as well as providing retrospective reports of their symptoms prior to the pandemic. Actor-partner interdependence models were used to measure the reciprocal effects of parent symptoms on children and vice versa, both before and during the pandemic. RESULTS: Actor effects in both the depressive symptoms and irritability models suggested that pre-COVID-19 depressive symptoms and irritability were robust predictors of early-COVID-19 depressive symptoms and irritability for both parents and children. Partner effects were also detected in the irritability model, in that parental irritability prior to COVID-19 was associated with decreased child irritability during the pandemic. Both before and during the pandemic, associations between parent and child depressive symptoms and irritability scores were weaker in families evidencing greater dysfunction. CONCLUSIONS: Results suggest that COVID-19-related stress is associated with increases in both parent and child symptomatology, and that family relationships likely influence associations between these symptoms.

Development of bipolar disorder and other comorbidity among youth with attention-deficit/hyperactivity disorder.

OBJECTIVE: To examine development of bipolar spectrum disorders (BPSD) and other disorders in prospectively followed children with attention-deficit/hyperactivity disorder (ADHD). METHOD: In the Longitudinal Assessment of Manic Symptoms (LAMS) study, 531 of 685 children age 6-12 (most selected for scores > 12 on General Behavior Inventory 10-item Mania scale) had ADHD, 112 with BPSD, and 419 without. With annual assessments for 8 years, retention averaged 6.2 years. Chi-square analyses compared rate of new BPSD and other comorbidity between those with versus without baseline ADHD and between retained versus resolved ADHD diagnosis. Cox regression tested factors influencing speed of BPSD onset. RESULTS: Of 419 with baseline ADHD but not BPSD, 52 (12.4%) developed BPSD, compared with 16 of 110 (14.5%) without either baseline diagnosis. Those who developed BPSD had more nonmood comorbidity over the follow-up than those who did not develop BPSD (p = .0001). Of 170 who still had ADHD at eight-year follow-up (and not baseline BPSD), 26 (15.3%) had developed BPSD, compared with 16 of 186 (8.6%) who had ADHD without BPSD at baseline but lost the ADHD diagnosis (χ2  = 3.82, p = .051). There was no statistical difference in whether ADHD persisted or not across new BPSD subtypes (χ2  = 1.62, p = .446). Of those who developed BPSD, speed of onset was not significantly related to baseline ADHD (p = .566), baseline anxiety (p = .121), baseline depression (p = .185), baseline disruptive behavior disorder (p = .184), age (B = -.11 p = .092), maternal mania (p = .389), or paternal mania (B = .73, p = .056). Those who started with both diagnoses had more severe symptoms/impairment than those with later developed BPSD and reported having ADHD first. CONCLUSIONS: In a cohort selected for symptoms of mania at age 6-12, baseline ADHD was not a significant prospective risk factor for developing BPSD. However, persistence of ADHD may marginally mediate risk of BPSD, and early comorbidity of both diagnoses increases severity/impairment.

Associations between Parental Psychopathology and Sexual Behavior in an Outpatient Psychiatric Sample.

Early age of sexual debut is associated with an increase in negative outcomes, including higher incidence of nonconsensual sexual experiences, higher rates of sexually transmitted infections, and risky sexual practices. Little research has examined the role of parental psychopathology as a predictor of adolescent sexual activity, however. The current study aims to close this gap by examining the relationship between parental psychopathology and sexual activity in a longitudinal sample of youth. Participants were 685 adolescents from the Longitudinal Assessment of Manic Symptoms study, the majority of whom were male (67%) and White (65%). Analyses considering likelihood of sexual initiation included the full sample, whereas analyses considering predictors of the age of sexual debut included the 162 participants who reported ever having sexual intercourse (62% male, 51% White) via the Youth Risk Behavior Surveillance-High School version. Cox regression analyses suggested that maternal generalized anxiety disorder predicted decreased likelihood of initiating sex during the 8-year follow-up period, whereas paternal conduct disorder predicted increased likelihood of initiating sex. Multivariate linear regressions also showed that maternal conduct disorder predicted earlier age of sexual debut among those who had initiated, whereas paternal antisocial personality disorder predicted later age of sexual debut. These associations were observed in both male and female adolescents. Furthermore, these effects were largely not explained by the established relationship between youth psychopathology and sexual behavior. Results have implications for interventions aimed at decreasing sexual risk taking in vulnerable youth.

Not All Masks Are Created Equal: Masking Success in Clinical Trials of Children and Adolescents.

The current study assessed the success of masking omega-3 (Ω3) and psychotherapy in clinical trials of youth with depression or bipolar spectrum disorder. Participants were youth ages 7-14 with DSM-IV-TR diagnosed depressive (n = 72) or bipolar spectrum (n = 23) disorders. Inclusion diagnoses were depressive disorder, cyclothymic disorder, or bipolar disorder not otherwise specified. Exclusion diagnoses included bipolar I or II disorder, chronic medical condition or autism. Youth participated in 2 × 2 randomized controlled trials, in which they received Ω3 or placebo (PBO) and psychoeducational psychotherapy (PEP) or active monitoring (AM). Participants and study staff (including independent interviewers) were masked to Ω3/PBO allocation. Besides the masked independent interviewers, one coprincipal investigator (Co-PI) was fully masked to both conditions and completed all consensus conference ratings postrandomization. At the endpoint assessment or last completed interview, interviewers and the masked Co-PI guessed whether each child was assigned to Ω3 or PBO and to PEP or AM. Masking failure was calculated using the degree of correct guesses above chance level using binomial tests across all participants for Ω3 versus PBO and PEP versus AM. For all guessers, Ω3 allocation was guessed correctly approximately half the time (50%-52.5%). Rates of correct guessing were higher for PEP, but only the interviewer guesses were correct significantly more often (58.5%-68.7%) than chance. Reporting of masking success should be an essential element of RCTs. Psychotherapy is generally more difficult to mask, but with attentive masking procedures reasonable masking can be achieved.

Parents' clinical depression and children's problem behaviors: A multi-level meta-analytic examination.

BACKGROUND: Previous meta-analyses considering associations between parental depression (PD) and child symptoms have considered PD based primarily on self-report of depression symptoms. The present meta-analysis, in contrast, evaluated the effect of parents' clinically-diagnosed depressive disorders (PDD) on child internalizing and externalizing symptoms and considered both family- and study-level variables that influenced the strength of these effects. METHODS: We examined 111 effect sizes nested in 40 studies including a clinical assessment of parents' major or persistent depressive disorder and measures of children's internalizing or externalizing behaviors published between 2000 and 2020. We used a multi-level meta-analytic framework to account for nesting of multiple effect sizes within studies. RESULTS: PDD was associated with children's internalizing (weighted mean r = 0.211) and externalizing (weighted mean r = 0.204) behaviors. Family- and study-level variables moderated these relations, including the inclusion of fathers in the sample, the specific measure of internalizing behavior, reporting of diagnostic reliability, and informant for problem behaviors. LIMITATIONS: Limitations include exclusive consideration of internalizing and externalizing symptoms (versus other symptom types or problems) and the limited number of father-only studies from which to base conclusions about the relative effect of maternal vs. paternal depression. CONCLUSIONS: The similarity between the current findings and previous meta-analyses suggests that researchers studying the effects of PD may be able to bypass more exhaustive clinical interviews for less burdensome depression symptom inventories. Furthermore, our findings suggest that researchers and clinicians should consider how PD impacts not just child depressive symptoms, but myriad problem behaviors.

Early menarcheal age and risk for later depressive symptomatology: the role of childhood depressive symptoms.

Previous research has investigated the relationship between pubertal timing and depression in girls, with most results suggesting that earlier menarche predicts more depression in adolescence. However, few studies have controlled for the potentially confounding effects of childhood depressive symptoms. The current study uses a prospective, longitudinal sample of 1,185 girls (47.8 % Caucasian) to examine the relationships between pubertal timing, childhood depressive symptoms, and adolescent depressive symptomatology. Using multiple linear regression analyses, our results suggest that higher levels of childhood depressive symptoms and earlier menarche have independent effects on adolescent depressive symptoms. Surprisingly, childhood depressive symptomatology predicted later age of menarche, although the magnitude of this effect was small. Taken together, the results suggest that early childhood depressive symptoms and early menarche represent independent pathways to later depressive symptoms.

Moody kids years later: Long-term outcomes of youth from the Omega-3 and therapy (OATS) studies.

BACKGROUND: This naturalistic follow-up study examines outcomes for youth with depression (n = 25) or subsyndromal bipolar disorder (n = 13) 2-5 years after participation in randomized clinical trials (RCTs) of omega-3 fatty acids (Ω3), individual family psychoeducational psychotherapy (IF-PEP), and their combination METHODS: Forty percent (38/95) of RCT families completed a follow-up assessment RESULTS: Relapse rates and conversion to bipolar disorder were consistent with published literature. Original treatment assignment did not impact current functioning. Overall, participants' mood severity, executive functioning, and global functioning continued to be better than at RCT baseline. Depressive symptoms increased significantly from end of RCT. Manic symptom severity, executive functioning, and global functioning remained comparable to end of RCT. The majority of parents and youth reported improved youth emotion regulation skills and family communication. They considered study participation beneficial, with increased understanding of mood disorders being the top reason. Half of youth commenced or continued Ω3 and 58% commenced or continued psychotherapy post-RCT, suggesting some degree of consumer satisfaction; these youth had lower depression severity than other participants. LIMITATIONS: Only 40% returned to this naturalistic follow-up; they were less likely to have an African-American parent, were of higher income, and youth were more symptomatic at end of RCT than those who did not return CONCLUSIONS: Improvement from RCT baseline continued although depressive symptom severity increased from end of RCT to follow-up. Meaningful improvements in youth and family functioning persisted 2-5 years later. Interventions that prevent relapse or conversion to BPSD are still needed for these vulnerable populations.

Reciprocal effects of maternal and child internalizing symptoms before and after a natural disaster.

After natural disasters, mothers and children are vulnerable to internalizing symptoms, such as depression and anxiety, and levels of mothers' and children's symptoms are significantly associated. However, the disaster literature has rarely examined reciprocal effects within families. The present study capitalizes on the occurrence of Hurricane Sandy during the course of an ongoing longitudinal study to address this gap. Three-hundred and 47 children (54.2% male, 84.7% Caucasian) and their mothers completed measures of internalizing symptoms when the children were 9-years-old. Hurricane Sandy occurred an average of 1 year later. Eight weeks after the hurricane, mothers and children completed the same measures again. Mothers also reported on their family's stress exposure from Hurricane Sandy. After controlling for predisaster symptoms, longitudinal actor-partner interdependence models indicated that mother's and children's internalizing symptoms were linked. Mothers' prehurricane depression symptoms also predicted increases in children's depression symptoms over time independent of hurricane-related stress. Children's prehurricane anxiety symptoms predicted increases in mothers' depression symptoms only at low levels of hurricane-related stress. Rather than the emergence of reciprocal effects, mother's depression symptoms and children's internalizing symptoms changed in tandem after Hurricane Sandy. High levels of Hurricane Sandy stress did not produce symptom spillover effects, but rather may have interrupted the unfolding of normative developmental parent-child reciprocal symptom processes. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Parental depression moderates the relationships of cortisol and testosterone with children's symptoms.

BACKGROUND: Previous research on the hormone-symptom relationship in children suggests that certain hormone patterns may be associated with symptoms, but only under certain circumstances. Having a parent with a history of depression may be one circumstance under which dysregulated hormone patterns are especially associated with emotional and behavioral symptoms in children. The current study sought to explore these relationships in a community sample of 389 9-year-old children. METHODS: Children's salivary cortisol and testosterone levels were collected at home over three consecutive days; parental psychiatric histories were assessed using semi-structured diagnostic interviews; and children's internalizing and externalizing symptoms were rated by the child's mother. RESULTS: Having two parents with a history of depression moderated the associations of reduced total daily cortisol output with higher externalizing scores, as well as the association of reduced testosterone with higher internalizing scores. A maternal history of depression, on the other hand, moderated the relationship between higher cortisol awakening response and higher internalizing scores. Furthermore, lower daily cortisol output was associated with higher internalizing scores among girls, but not boys, with two parents with a history depression. LIMITATIONS: Limitations include the cross-sectional nature of the current analyses, as well as the limited racial, ethnic, and geographical diversity of the sample. CONCLUSIONS: Taken together, the current results suggest that the relationship between hormones and internalizing and externalizing symptoms in children may vary as a function of parental depression and child sex, knowledge that may inform intervention efforts aimed at preventing psychopathology in children whose parents have a history of depression.

Is evidence-based treatment helping my patient? Utilizing modified Brinley plots to measure clinical change.

Using both group (nomothetic) and individual (idiographic) approaches to measuring clinical change may provide more information about the effectiveness of an intervention than either approach alone. The current study re-examined previously published data from two randomized clinical trials of omega-3 fatty acids and Individual-Family Psychoeducational Psychotherapy as treatment for mood disorders in youth, using modified Brinley plots, a method of illustrating individuals' treatment response in the context of group information. Although the original nomothetic approach provided information about the average effect of treatment, modified Brinley plots gave more information about individual children's outcomes. Practicing clinicians in particular could use modified Brinley plots to track treatment trajectories and outcomes for specific clients and subsequently use these data to inform treatment planning.

Factors Influencing Emerging Adults' Use of Outpatient Mental Health Services.

Rates of treatment utilization decline as adolescents make the transition to adulthood even though young adults are particularly vulnerable to the negative outcomes of untreated mental illness. Although a variety of factors have been explored to explain decreased treatment utilization in this age group, previous research has almost exclusively employed cross-sectional methods rather than following a group of youth as they enter adulthood. The current study aims to address this methodological limitation by assessing treatment utilization in emerging adults who began participating in a longitudinal study during childhood. One hundred and thirty seven youth who turned 18 during the 96-month follow-up period were included in the current analyses. Demographic and socioeconomic variables such as sex, race, and insurance status and clinical variables such as psychiatric diagnoses and perceptions of treatment effectiveness were investigated as factors potentially associated with outpatient treatment use before and after age 18. Prior to age 18, youth reported using outpatient services at 75% of their visits, but after age 18, outpatient treatment utilization dropped to around 50%. White race, increased parental stress, and increased parental perception of treatment usefulness were associated with greater treatment use prior to age 18, whereas only increased youth perception of symptom-related dysfunction were associated with increased treatment use after age 18. Findings point to the importance of including youth preferences and perceptions of dysfunction in treatment decisions across adolescence in order to optimize treatment use following the transition to adulthood.

Patterns of neuroendocrine coupling in 9-year-old children: Effects of sex, body-mass index, and life stress.

Previous investigations have explored stress and pubertal hormones in parallel; it has been a recent development, however, to explore the relationships between different hormones during puberty, and how this hormonal cross-talk may be influenced by the environment. The current study investigated neuroendocrine coupling, or the extent to which hormones are correlated within the individual, and also investigated early life stressors that may influence coupling. Participants were 405 adrenarcheal children (mean Tanner stage=1.73 for girls and 1.38 for boys) from a longitudinal study who provided saliva samples for analysis of cortisol, dehydroepiandrosterone (DHEA), and testosterone. Saliva was collected when children were 9-years-old, while early life stressors were assessed at each longitudinal assessment (ages 3, 6, and 9). Results from multi-level modeling (MLM) analyses provided evidence of positive cortisol-dehydroepiandrosterone (DHEA) and cortisol-testosterone coupling in middle childhood, and identified body mass index as a predictor of the strength of hormone coordination. While exposure to stressful life events did not impact cortisol-DHEA coupling patterns, stress interacted with sex to predict looser cortisol-testosterone coupling in girls, but not boys. The current study adds to the existing literature on the development of neuroendocrine coupling, and provided further evidence of sex differences in the impact of stress. Furthermore, hormone coupling may be investigated in the future as a mechanism by which puberty is associated with negative behavioral outcomes.

Neural Biomarker and Early Temperament Predict Increased Internalizing Symptoms After a Natural Disaster.

OBJECTIVE: Although most people will experience a traumatic event at some point in their life, only some will develop significant psychological symptoms in the aftermath. In the current study, we use a preexisting longitudinal study located in Long Island to examine the impact of Hurricane Sandy on internalizing symptoms in a large sample of children. We focused on temperamental fear and a biomarker of risk for anxiety, the error-related negativity (ERN). The ERN is a negative deflection in the event-related potential (ERP) occurring when individuals make mistakes and is increased in anxious individuals. METHOD: The final sample consisted of 223 children who had undergone an observational assessment of fear at age 3 years and an electroencephalogram assessment of the ERN at age 6 years. At the age 9 year assessment, internalizing symptoms were assessed, and then again after the hurricane (∼65 weeks later). RESULTS: A significant three-way interaction among fearfulness, hurricane stressors, and the ERN in predicting posthurricane increases in internalizing symptoms suggested that children who were high in fear at age 3 years and experienced elevated hurricane stressors were characterized by subsequent increases in internalizing symptoms, but only when they were also characterized by an increased ERN at age 6 years. CONCLUSION: These findings support a diathesis-stress model, suggesting that early temperament and prestressor biological markers confer risk for increased psychological symptoms following environmental stressors.

Examining the concurrent and longitudinal relationship between diurnal cortisol rhythms and conduct problems during childhood.

Previous literature indicates that both hypoactivity and hyperactivity of the HPA axis may be related to conduct disorder and externalizing behaviors in young children. Using a longitudinal sample of 283 typically-developing children, the current study examined both the concurrent and the longitudinal association between HPA functioning and externalizing behavior problems, such as conduct problems. Diurnal cortisol rhythms and externalizing problems were assessed at ages 6 and 9. Results suggest that concurrent HPA functioning is not significantly related to externalizing behavior at ages 6 or 9. However, more blunted cortisol rhythms at age 6 (less change across the day from morning to evening) predicted a greater increase in externalizing behavior between age 6 and age 9 than did steeper cortisol rhythms. Further analyses revealed that this association was driven by conduct problems and aggressive behavior, rather than attention problems. The relationship between HPA functioning and subsequent externalizing behavior in children adds to the limited longitudinal work on this topic, suggesting that the association changes over time. These results may serve to clarify the inconsistencies in the cross-sectional literature, particularly with respect to young school-age children.

Neural Reactivity to Emotional Stimuli Prospectively Predicts the Impact of a Natural Disaster on Psychiatric Symptoms in Children.

BACKGROUND: Natural disasters expose entire communities to stress and trauma, leading to increased risk for psychiatric symptoms. Yet, the majority of exposed individuals are resilient, highlighting the importance of identifying underlying factors that contribute to outcomes. METHODS: The current study was part of a larger prospective study of children in Long Island, New York (n = 260). At age 9, children viewed unpleasant and pleasant images while the late positive potential (LPP), an event-related potential component that reflects sustained attention toward salient information, was measured. Following the event-related potential assessment, Hurricane Sandy, the second costliest hurricane in United States history, hit the region. Eight weeks after the hurricane, mothers reported on exposure to hurricane-related stress and children's internalizing and externalizing symptoms. Symptoms were reassessed 8 months after the hurricane. RESULTS: The LPP predicted both internalizing and externalizing symptoms after accounting for prehurricane symptomatology and interacted with stress to predict externalizing symptoms. Among children exposed to higher levels of hurricane-related stress, enhanced neural reactivity to unpleasant images predicted greater externalizing symptoms 8 weeks after the disaster, while greater neural reactivity to pleasant images predicted lower externalizing symptoms. Moreover, interactions between the LPP and stress continued to predict externalizing symptoms 8 months after the hurricane. CONCLUSIONS: Results indicate that heightened neural reactivity and attention toward unpleasant information, as measured by the LPP, predispose children to psychiatric symptoms when exposed to higher levels of stress related to natural disasters, while greater reactivity to and processing of pleasant information may be a protective factor.

Negative emotionality and its facets moderate the effects of exposure to Hurricane Sandy on children's postdisaster depression and anxiety symptoms.

According to diathesis-stress models, temperament traits such as negative emotionality (NE) may moderate the effects of stressors on the development of symptoms of psychopathology, although little research has tested such models in children. Moreover, there are few data on whether specific facets of NE (sadness, fear, or anger) may specifically moderate the effects of stress on depression versus anxiety. Finally, there is a paucity of research examining whether childhood temperament moderates the effect of disaster exposure on depressive or anxiety symptoms. Hurricane Sandy, which affected many thousands of people in New York State and the surrounding regions in October 2012, offers a unique opportunity to address these gaps. Seven to eight years prior to Hurricane Sandy, 332 children 3 years old completed lab-based measures of NE and its facets. Six years later, when they were 9 years old, each mother rated her child's depressive and anxiety symptoms. Approximately 8 weeks post-Sandy (an average of 1 year after the age 9 assessment), mothers again rated their child's depressive and anxiety symptoms, as well as a measure of exposure to stress from Hurricane Sandy. Adjusting for symptom levels at age 9, higher levels of stress from Hurricane Sandy predicted elevated levels of depressive symptoms only in participants with high levels of temperamental sadness and predicted elevated levels of anxiety symptoms only in participants high in temperamental fearfulness. These findings support the role of early childhood temperament as a diathesis for psychopathology and highlight the importance of considering facets of temperament when examining their relationship to psychopathology. (PsycINFO Database Record

A randomized controlled trial of duloxetine versus placebo in the treatment of nonmajor chronic depression.

OBJECTIVE: Numerous double-blind studies have assessed the efficacy of antidepressants in treating chronic depressive disorder, including dysthymic disorder, low-grade chronic depression. However, there are no double-blind, placebo-controlled studies of serotonin-norepinephrine reuptake inhibitors in chronic depressive disorder. METHOD: Outpatients with chronic depressive disorder, but without concurrent major depressive disorder (MDD), were randomly assigned to prospective double-blind duloxetine (beginning at 30 mg/d, increased to a maximum dose of 120 mg/d) versus placebo for 10 weeks. Inclusion criteria were current DSM-IV-TR diagnosis of dysthymic disorder or depression not otherwise specified, age 18-75 years, and a Hamilton Depression Rating Scale (HDRS) score ≥ 12. Exclusion criteria included current major depression. The study was conducted between August 2006 and December 2011. HDRS, Cornell Dysthymia Rating Scale (CDRS), Clinical Global Impressions (CGI), Beck Depression Inventory (BDI), Global Assessment of Functioning (GAF), Social Adjustment Scale (SAS), and other assessments were administered at each visit. We hypothesized that duloxetine would be superior to placebo in (1) 24-item HDRS total score, (2) the percentage of subjects classified as responders and remitters, and (3) secondary measures (CDRS, BDI, CGI). Response was defined as > 50% decrease in 24-item HDRS and CGI-Improvement scale score of 1 or 2 ("very much improved" or "much improved"). Remission was defined as HDRS-17 item score ≤ 4 and 0 on item 1 of the HDRS (depressed mood). RESULTS: 65 subjects were enrolled, of whom 57 began medication. They ranged in age from 19 to 70 years (mean ± SD = 41.63 ± 11.22) and included 24 women and 33 men. Baseline 24-item HDRS score (mean ± SD) for both groups was 20.75 ± 4.92. After 10 weeks, duloxetine-treated subjects had significantly lower 24-item HDRS scores than placebo-treated subjects (time-by-drug group effect on analysis of variance: F1,55 = 9.43, P = .003). Responder and remitter analyses significantly favored duloxetine treatment. The response rate was 65.5% for duloxetine versus 25.0% for placebo (χ(2)(1) = 9.43, P = .003); and the remitter rate was 55.2% for duloxetine versus 14.3% for placebo (χ(2)(1) = 10.46, P = .002). After 10 weeks, duloxetine-treated subjects did not differ significantly better from placebo-treated subjects on the SAS (time-by-drug group effect on analysis of variance: F(1,46) = 0.35, P = .555) or on the GAF (time-by-drug group effect on analysis of variance: F(1,51) = .01, P = .922). CONCLUSIONS: Results on the 24-item HDRS, CGI, and CDRS suggest that duloxetine is efficacious in acute treatment of chronic nonmajor depressive disorder. Response and remission rates also differed significantly, favoring duloxetine treatment, but BDI, GAF, and social functioning (Social Adjustment Scale) did not. Duloxetine appears to be effective in acute treatment of nonmajor chronic depression. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00360724.

Social problem solving and depressive symptoms over time: a randomized clinical trial of cognitive-behavioral analysis system of psychotherapy, brief supportive psychotherapy, and pharmacotherapy.

OBJECTIVE: Depression is associated with poor social problem solving, and psychotherapies that focus on problem-solving skills are efficacious in treating depression. We examined the associations between treatment, social problem solving, and depression in a randomized clinical trial testing the efficacy of psychotherapy augmentation for chronically depressed patients who failed to fully respond to an initial trial of pharmacotherapy (Kocsis et al., 2009). METHOD: Participants with chronic depression (n = 491) received cognitive-behavioral analysis system of psychotherapy (CBASP; McCullough, 2000), which emphasizes interpersonal problem solving, plus medication; brief supportive psychotherapy (BSP) plus medication; or medication alone for 12 weeks. RESULTS: CBASP plus pharmacotherapy was associated with significantly greater improvement in social problem solving than BSP plus pharmacotherapy, and a trend for greater improvement in problem solving than pharmacotherapy alone. In addition, change in social problem solving predicted subsequent change in depressive symptoms over time. However, the magnitude of the associations between changes in social problem solving and subsequent depressive symptoms did not differ across treatment conditions. CONCLUSIONS: It does not appear that improved social problem solving is a mechanism that uniquely distinguishes CBASP from other treatment approaches.