“The implementation gap prevents our nation from reaping the benefit of billions of US tax dollars spent on research and, more important, prolongs the suffering of millions of Americans who live with mental disorders.”—President's New Freedom Commission on Mental Health 2003. Despite the development of effective treatments, depression is still ranked as one of the top ten causes of disability worldwide according to the World Health Organization. It often takes years if not decades to translate evidence-based depression treatments into nonacademic, community-based practices. This research-to-practice gap can lead to millions of dollars of funded research being wasted when the treatments themselves never reach the populations in need [1]. Without a clear strategy to foster implementation and acceptance at the community provider level, a “voltage drop” is experienced when an evidence-based depression treatment developed in tightly-controlled academic settings is then introduced into real-world settings [2]. Moreover, current clinical trials populations are still highly selective (<5% of the diagnosed population) despite the movement towards “community-based research.” There is a paucity of effective strategies or implementation approaches for getting effective treatments for depression and other mental disorders off the academic shelf and into the hands of those who need them. Subsequently, there is a need for further cross-disciplinary research on effective processes to facilitate the uptake of evidence-based treatments in real-world practices. Implementation science is an emerging field poised to address the organizational, provider, and patient-level barriers to the adoption of new treatments for depression as well as for other conditions. The National institute of Mental Health defines implementation as the “use of strategies to adopt and integrate evidence-based health interventions and change practice patterns within specific settings [3].” This current issue explores novel approaches based on implementation science for enhancing the uptake of depression treatments. The articles address a range of concepts, both at a higher level on tools for and theories of effective implementation and at the practical level of lessons learned on the ground. This series of articles also focuses on implementing evidence-based programs to improve depression outcomes particularly for underserved populations including lower income patients, adolescents, and women with postpartum depression. Four articles describe the application of implementation theory and measures to inform changes in mental health practice in general and for depression treatment in particular. J. K. Benzer et al. describe barriers and facilitators to coordinated mental health care in primary care settings. Key findings were used to refine an implementation theory for coordinated depression care included the importance of organizational factors such as resources, provider training and workflow designs, and an understanding and appreciation of mental health and primary care practice boundaries. Two additional articles describe complementary approaches for engaging providers in the implementation of new mental health treatments. E. Aisenberg et al. describe a process for building a community-academic partnership to implement telephone cognitive-behavioral therapy for rural Latinos. The article points to how such partnerships can facilitate the adaptation of evidence-based practices in community settings by garnering frontline participant feedback on which elements need to be changed to implement a more scalable and culturally appropriate program. Similarly, D. E. Goodrich et al., using the Enhanced Replicating Effective Programs implementation framework, describe the implementation of an outreach program for Veterans with mental disorders, and what lessons were learned in regards to activating and empowering providers to “lead from the middle” and work within their systems to facilitate patient access. In addition, the paper by A. J. Lewis et al. describes how qualitative data can be applied to develop fidelity and implementation measures to assess update of a family-focused depression intervention. Providers are key stakeholders in the implementation process, yet few studies have focused on the development of effective implementation strategies to facilitate provider training in and sustainability of using evidence-based depression treatments. Three of the papers in this special issue address the challenges in training clinicians in new mental health treatments, and whether training leads to long-term adoption and use of these practices, in particular, problem-solving therapy (PST). J. A. Cartreine et al. describe a web-based training program to further disseminate PST training to novice clinicians and whether long-term coaching by more experienced providers to further boost training effectiveness might be needed. In the paper by R. M. Crabb et al., clinicians undergoing training in PST were followed over to assess the long-term impact of the training on adoption and spread. S. W. Stirman et al. identified key reasons for variation in cognitive behavioral therapy training outcomes across community-based practices and the importance of garnering feedback from frontline providers prior to implementing training initiatives. Additional studies in this issue involved the implementation of depression treatments, notably in real-world populations. J. A. Waxmonsky et al. found that implementing a depression chronic care management programs in a public sector health plan led to significantly reduced depression severity over a 12-month period with a modest increase in health care costs. R. R. Dopp et al. present results of a novel program for adolescents with depression, demonstrating an alternative way to address mood symptoms that in turn also address other major chronic conditions such as obesity. Finally, B. P. Yawn et al. present a systematic review of postpartum depression treatment programs in which the most effective components included formal psychiatric evaluation, colocation of mental health care, and tracking of long-term outcomes. Ultimately, implementation science can inform the adoption and adaptation of effective depression treatments, primarily through a better understanding of the importance of building partnerships with end-users such as health care organizations and frontline providers, understanding barriers to adoption of effective treatments at these levels, and developing interventions that use organizational strategies such as collaborative care or systematic training programs to facilitate adoption. Moreover, there will be additional opportunities for researchers and practitioners to apply the lessons learned from this emerging field to develop more effective and practical depression treatments from the beginning, as well as the use of provider and health care organization-level strategies to ensure their adoption and sustainability in the real world. To this end, new skills will need to be acquired, including the measurement of factors facilitating or impeding treatment uptake, especially at the provider and system level using both qualitative and quantitative methods, application of nonrandomized controlled study designs that take into account variations in provider and organizational differences, as well as the inclusion of real-world patient populations that to date are not well-represented in depression clinical trials. Moreover, by placing greater emphasis on partnerships, frontline provider input, and practical treatment strategies, mental health implementation researchers will be poised to lead the development of the next generation of effective depression treatments. Amy M. Kilbourne Mark Williams Mark S. Bauer Patricia Arean

Gender differences in the prevalence of depression are well documented. To further explore the relation between gender and depression, this study used daily diaries to examine gender differences within thirteen behavioral domains and whether differential frequency of overt behaviors and environmental reward mediated the relationship between gender and depression severity. The sample included 82 undergraduate students [66% females; 84% Caucasian; Mean age = 20.2 years]. Overall, females engaged in a significantly greater breadth of behavioral domains and reported a higher level of environmental reward. Females spent more time in the domains of health/hygiene, spiritual activities, and eating with others. Males spent more time in the domains of physical activity, sexual activity, and hobbies and recreational experiences. Females found social activities, passive/sedentary behaviors, eating with others, and engagement in “other” activities more rewarding. Gender had a significant direct effect on depression severity, with females reporting increased depression. This effect was attenuated by the mediator (total environmental reward) such that to the extent females exhibited increased environmental reward, the gender effect on depression was attenuated. These data support behavioral models of depression, indicate increased reinforcement sensitivity among females, and have clinical relevance in the context of assessment and behavioral activation interventions for depression.

The construct validity of two depression measures, Zung's Self-rating Depression Scale (SDS) and the Asian Adolescents Depression Scale (AADS), was investigated. Three studies were conducted using two samples collected in two stages, and the results were used to construct the Asian Depression Scale (ADS). Participants responded to the SDS and AADS in random order of presentation during stage 1; two months later, validation variables were collected. Study 1 found that the SDS is a reliable and valid measure of depression for Singaporean Chinese, but it does not cover the interpersonal dimension found in the AADS. Study 2 combined the two measures and found six factors. One of these factors, negative social self, which was a unique Asian depressive symptom cluster, consisted only of AADS items, while the affective manifestation and psychosomatic symptoms factor primarily consisted of items from the SDS. Study 3 selected high-loading items from the identified factors to construct the ADS, which showed excellent internal reliability, and good convergent and discriminant validity. Incremental predictive validity found on criterion data collected in stage 2, supported the nonspuriousness of the Asian Depression Scale.

Aim of the current study is to examine whether previous depressive symptoms modify possible effects of religiousness on mood in the last week of life. After-death interviews with proxy respondents of deceased sample members of the Longitudinal Aging Study Amsterdam provided information on depressed mood in the last week of life, as well as on the presence of a sense of peace with the approaching end of life. Other characteristics were derived from interviews with the sample members when still alive. Significant interactions were identified between measures of religiousness and previous depressive symptoms (CES-D scores) in their associations with mood in the last week of life. Among those with previous depressive symptoms, church-membership, church-attendance and salience of religion were associated with a greater likelihood of depressed mood in the last week of life. Among those without previous depressive symptoms, church-attendance and salience of religion were associated with a higher likelihood of a sense of peace. For older adults in the last phase of life, supportive effects of religiousness were more or less expected. Fore those with recent depressive symptoms, however, religiousness might involve a component of existential doubt.

Objective. To compare the direct mental health care costs between individuals with Seasonal Affective Disorder randomized to either fluoxetine or light therapy. Methods. Data from the CANSAD study was used. CANSAD was an 8-week multicentre double-blind study that randomized participants to receive either light therapy plus placebo capsules or placebo light therapy plus fluoxetine. Participants were aged 18–65 who met criteria for major depressive episodes with a seasonal (winter) pattern. Mental health care service use was collected for each subject for 4 weeks prior to the start of treatment and for 4 weeks prior to the end of treatment. All direct mental health care services costs were analysed, including inpatient and outpatient services, investigations, and medications. Results. The difference in mental health costs was significantly higher after treatment for the light therapy group compared to the medication group—a difference of $111.25 (z = −3.77, P = 0.000). However, when the amortized cost of the light box was taken into the account, the groups were switched with the fluoxetine group incurring greater direct care costs—a difference of $75.41 (z = −2.635, P = 0.008). Conclusion. The results suggest that individuals treated with medication had significantly less mental health care cost after-treatment compared to those treated with light therapy.

The present study assessed the rate of depressive personality (DP), as measured by the self-report instrument depressive personality disorder inventory (DPDI), among 159 clients entering psychotherapy at an outpatient university clinic. The presenting clinical profile was evaluated for those with and without DP, including levels of depressed mood, other psychological symptoms, and global severity of psychopathology. Clients were followed naturalistically over the course of therapy, up to 40 weeks, and reassessed on these variables again after treatment. Results indicated that 44 percent of the sample qualified for DP prior to treatment, and these individuals had a comparatively more severe and complex presenting disposition than those without DP. Mixed-model repeated-measures analysis of variance was used to examine between-groups changes on mood and global severity over time, with those with DP demonstrating larger reductions on both outcome variables, although still showing more symptoms after treatment, than those without DP. Only eleven percent of the sample continued to endorse DP following treatment. These findings suggest that in routine clinical situations, psychotherapy may benefit individuals with DP.

Several pharmacological agents acting on monoamine neurotransmission are used for the management of mental illnesses. Regulation of PI3K/AKT and GSK3 pathways may constitute an important signaling center in the subcellular integration of the synaptic neurotransmission. The pathways also modulate neuronal cell proliferation, migration, and plasticity. There are evidences to suggest that inflammation of neuron contributes to the pathology of depression. Inflammatory activation of neuron contributes to the loss of glial elements, which are consistent with pathological findings characterizing the depression. A mechanism of anti-inflammatory reactions from antidepressant medications has been found to be associated with an enhancement of heme oxygenase-1 expression. This induction in brain is also important in neuroprotection and neuroplasticity. As enzymes involved in cell survival and neuroplasticity are relevant to neurotrophic factor dysregulation, the PI3K/AKT/GSK3 may provide an important signaling for the neuroprotection in depression. In this paper, we summarize advances on the involvement of the PI3K/AKT/GSK3 pathways in cell signaling of neuronal cells in mental illnesses.

Bipolar depression is often refractory to treatment and is frequently associated with anxiety symptoms and elevated suicide risk. There is a great need for adjunctive psychotherapeutic interventions. Treatments with effectiveness for depressive and anxiety symptoms as well as suicide-related thoughts and behaviors would be particularly beneficial. Mindfulness-based interventions hold promise, and studies of these approaches for bipolar disorder are warranted. The aim of this paper is to provide a conceptual background for such studies by reviewing key findings from diverse lines of investigation. Results of that review indicate that cortical midline structures (CMS) appear to link abnormal self-referential thinking to emotional dysregulation in mood disorders. Furthermore, CMS and striatal dysfunction may play a role in the neuropathology underlying suicide-related thoughts and behaviors. Thus, combining studies of mindfulness interventions targeting abnormal self-referential thinking with functional imaging of CMS and striatal function may help delineate the neurobiological mechanisms of action of these treatments.

Background. Studies with the Temperament and Character Inventory (TCI) in depressive disorders have shown changes (Δ) of the character of Self-Directedness (SD) and the temperament of Harm Avoidance (HA). The central question of this study is which of these two changes is most proximally related to the production of depressive symptoms. Methods. The start and endpoint data from a two-year followup of 58 depressed patients were reanalyzed. We used the ΔHA and ΔSD scores as well as the Δ scores on three dimensions of psychopathology, called Emotional Dysregulation (ED), Retardation (RET), and Anxiety (ANX). The presence of the main relation between personality and psychopathology was tested in all patients and in four subcategories. The data were analyzed by MANCOVA and Structural Equation Modelling (SEM). Results. ΔHA and ΔSD correlated negatively, and only ΔSD was related (negatively) to ΔED. This pattern was found in all subcategories. SEM showed ΔHA and ΔSD had an ambiguous causal interrelationship, while ΔSD, ΔRET, and ΔANX had unidirectional effects on ΔED. Conclusion. The results correspond with a central pathogenetic role for a state-related deficit at the character level in depression. This may have important consequences for investigations of endophenotypes and clinical treatment.