Showing papers in "Harvard Review of Psychiatry in 2018"

Depression and Anxiety in Heart Failure: A Review.

Abstract: Learning objectives After participating in this activity, learners should be better able to:• Identify the relationships between depression, anxiety, and heart failure (HF).• Assess methods for accurately diagnosing depression and anxiety disorders in patients with HF.• Evaluate current evidence for treatment of anxiety and depression in patients with HF. Background In patients with heart failure (HF), depression and anxiety disorders are common and associated with adverse outcomes such as reduced adherence to treatment, poor function, increased hospitalizations, and elevated mortality. Despite the adverse impact of these disorders, anxiety and depression remain underdiagnosed and undertreated in HF patients. Methods We performed a targeted literature review to (1) identify associations between depression, anxiety, and HF, (2) examine mechanisms mediating relationships between these conditions and medical outcomes, (3) identify methods for accurately diagnosing depression and anxiety disorders in HF, and (4) review current evidence for treatments of these conditions in this population. Results Both depression and anxiety disorders are associated with the development and progression of HF, including increased rates of mortality, likely mediated through both physiologic and behavioral mechanisms. Given the overlap between cardiac and psychiatric symptoms, accurately diagnosing depression or anxiety disorders in HF patients can be challenging. Adherence to formal diagnostic criteria and utilization of a clinical interview are the best courses of action in the evaluation process. There is limited evidence for the efficacy of pharmacologic and psychotherapy in patients with HF. However, cognitive-behavioral therapy has been shown to improve mental health outcomes in patients with HF, and selective serotonin reuptake inhibitors appear safe in this cohort. Conclusions Depression and anxiety disorders in HF patients are common, underrecognized, and linked to adverse outcomes. Further research to improve detection and develop effective treatments for these disorders in HF patients is badly needed.

Pain and Depression: A Systematic Review.

Abstract: Background Pain comorbid with depression is frequently encountered in clinical settings and often leads to significant impaired functioning. Given the complexity of comorbidities, it is important to address both pain and depressive symptoms when evaluating treatment options. Aim To review studies addressing pain comorbid with depression, and to report the impact of current treatments. Method A systematic search of the literature databases was conducted according to predefined criteria. Two authors independently conducted a focused analysis of the full-text articles and reached a consensus on 28 articles to be included in this review. Results Overall, studies suggested that pain and depression are highly intertwined and may co-exacerbate physical and psychological symptoms. These symptoms could lead to poor physical functional outcomes and longer duration of symptoms. An important biochemical basis for pain and depression focuses on serotonergic and norepinephrine systems, which is evident in the pain-ameliorating properties of serotonergic and norepinephrine antidepressants. Alternative pharmacotherapies such as ketamine and cannabinoids appear to be safe and effective options for improving depressive symptoms and ameliorating pain. In addition, cognitive-behavioral therapy may be a promising tool in the management of chronic pain and depression. Conclusion The majority of the literature indicates that patients with pain and depression experience reduced physical, mental, and social functioning as opposed to patients with only depression or only pain. In addition, ketamine, psychotropic, and cognitive-behavioral therapies present promising options for treating both pain and depression.

Functional Neuroanatomy of Emotion and Its Regulation in PTSD.

Abstract: Posttraumatic stress disorder (PTSD) is a devastating disorder, linked to profound mental, physical, occupational, and functional impairment. In addition, it is a highly complex disorder, characterized by symptom heterogeneity across multiple domains. Nevertheless, emotion dysregulation arising from the exaggerated response to threat or from the inability to regulate negative emotional states plays a defining role in the pathophysiology of PTSD. In order to improve our understanding of how emotion dysregulation manifests in this illness, functional neuroimaging research over the past 20 years provides great insight into underlying neuroanatomy of each component of emotion dysregulation in the context of PTSD. While prior reviews exist on the topic of neuroimaging findings in PTSD, the present review synthesizes that work through the lens of emotion and its regulation. Studies that employed tasks of emotional responding and symptom provocation, implicit regulation (e.g., emotional Stroop and interference), explicit regulation (e.g., cognitive reappraisal), and fear conditioning/extinction were reviewed. Findings demonstrate that emotion dysregulation in PTSD arises from complications within a large neurocircuitry involving the amygdala, insula, hippocampus, anterior cingulate cortex, and prefrontal cortex. Although an exaggerated response in the amygdala and insula to negative emotional triggers is pervasive, PTSD is also marked by deficient appraisal, resolution, and management of negative emotional states subserved by the anterior cingulate cortex and prefrontal cortex during regulation. These findings further support the importance of studying emotion-regulation deficits in tandem with exaggerated symptom provocation in order to better understand the constellation of symptoms present in those with PTSD.

Understanding Resilience and Preventing and Treating PTSD.

Abstract: Resilience is defined as the dynamic ability to adapt successfully in the face of adversity, trauma, or significant threat. Some of the key early studies of resilience were observational studies in children. They were followed by research in adults, studies testing interventions to promote resilience in different populations, and a recent upsurge of studies on the underlying genomic and neurobiological mechanisms. Neural and molecular studies in preclinical models of resilience are also increasingly identifying active stress adaptations in resilient animals. Knowledge gained from animal and human studies of resilience can be harnessed to develop new preventive interventions to enhance resilience in at-risk populations. Further, treatment interventions focused on enhancing potentially modifiable protective factors that are consistently linked to psychological resilience can enrich currently available treatment interventions for individuals with posttraumatic stress disorder (PTSD). Translating our expanding knowledge of the neurobiology of resilience additionally promises to yield novel therapeutic strategies for treating this disabling condition. This review summarizes the vast field of resilience research spanning genomic, psychosocial, and neurobiological levels, and discusses how findings have led and can lead to new preventive and treatment interventions for PTSD.

Glucocorticoids and Hippocampal Structure and Function in PTSD.

Abstract: This review examines the putative link between glucocorticoid and hippocampal abnormalities in posttraumatic stress disorder (PTSD). Increased glucocorticoid receptor (GR) sensitivity in PTSD may permit enhanced negative feedback inhibition of cortisol at the pituitary, hypothalamus, or other brain regions comprising the hypothalamic-pituitary-adrenal (HPA) axis and would be expected to affect other physiological systems that are regulated by glucocorticoids. Molecular and transcriptional studies of cortisol are consistent with the hypothesis that cortisol actions may be amplified in PTSD as a result of enhanced GR sensitivity in monocytes and some brain regions, although cortisol levels themselves are unchanged and oftentimes lower than normal. Concurrently, magnetic resonance imaging studies have demonstrated that individuals with PTSD have smaller hippocampal volume than individuals without PTSD. Initial hypotheses regarding the mechanism underlying hippocampal alterations in PTSD focused on elevated glucocorticoid levels in combination with extreme stress as the primary cause, but this explanation has not been well supported in human studies. Lack of data from neuroimaging studies preclude a firm link between PTSD onset and hippocampal volume changes. Rather, the available evidence is consistent with the possibility that smaller hippocampal volume (like reduced cortisol levels and enhanced GR sensitivity) may be a vulnerability factor for developing the disorder; limitations of hippocampal-based models of PTSD are described. We further review neuroimaging studies examining hippocampal structure and function following manipulation of glucocorticoid levels and also examining changes in the hippocampus in relationship to other brain regions. Evidence that the GR may be an important therapeutic target for the treatment of PTSD, especially for functions subserved by the hippocampus, is discussed. Implications of the current review for future research are described, with an emphasis on the need to integrate findings of glucocorticoid abnormalities with functional-imaging paradigms to formulate a comprehensive model of HPA-axis functioning in PTSD.

Ketamine-Associated Brain Changes: A Review of the Neuroimaging Literature.

Abstract: Major depressive disorder (MDD) is one of the most prevalent conditions in psychiatry. Patients who do not respond to traditional monoaminergic antidepressant treatments have an especially difficult-to-treat type of MDD termed treatment-resistant depression. Subanesthetic doses of ketamine-a glutamatergic modulator-have shown great promise for rapidly treating patients with the most severe forms of depression. As such, ketamine represents a promising probe for understanding the pathophysiology of depression and treatment response. Through neuroimaging, ketamine's mechanism may be elucidated in humans. Here, we review 47 articles of ketamine's effects as revealed by neuroimaging studies. Some important brain areas emerge, especially the subgenual anterior cingulate cortex. Furthermore, ketamine may decrease the ability to self-monitor, may increase emotional blunting, and may increase activity in reward processing. Further studies are needed, however, to elucidate ketamine's mechanism of antidepressant action.

Glutamatergic Modulators in Depression.

Abstract: LEARNING OBJECTIVE After participating in this activity, learners should be better able to evaluate the evidence supporting the antidepressant effects of glutamatergic modulators.Both preclinical and clinical studies have implicated glutamatergic system dysfunction in the pathophysiology of mood disorders such as bipolar depression and major depressive disorder. In particular, rapid reductions in depressive symptoms have been noted in response to subanesthetic doses of the glutamatergic modulator ketamine in subjects with major depressive disorder or bipolar depression. These results have prompted the repurposing or development of other glutamatergic modulators, both as monotherapy or adjunctive to other therapies. Here, we highlight the evidence supporting the antidepressant effects of various glutamatergic modulators, including (1) broad glutamatergic modulators (ketamine, esketamine, dextromethorphan, dextromethorphan-quinidine [Nuedexta], AVP-786, nitrous oxide [N2O], AZD6765), (2) subunit (NR2B)-specific N-methyl-D-aspartate (NMDA) receptor antagonists (CP-101,606/traxoprodil, MK-0657 [CERC-301]), (3) glycine-site partial agonists (D-cycloserine, GLYX-13, sarcosine, AV-101), and (4) metabotropic glutamate receptor modulators (AZD2066, RO4917523/basimglurant, JNJ40411813/ADX71149, R04995819 [RG1578]).

Fear Processing, Psychophysiology, and PTSD.

Abstract: The processing and regulation of fear is one of the key components of posttraumatic stress disorder (PTSD). Fear can involve both acute and potential threats that can manifest in different behaviors and result from activity within different neural nodes and networks. Fear circuits have been studied extensively in animal models for several decades and in human neuroimaging research for almost 20 years. Therefore, the centrality of fear processing to PTSD lends the disorder to be more tractable to investigation at the level of brain and behavior, and provides several observable phenotypes that can be linked to PTSD symptoms. Moreover, psychophysiological metrics of fear conditioning offer tools that can be used to shift diagnostic paradigms in psychiatry toward neurobiology-consistent with a Research Domain Criteria approach to PTSD. In general, mammalian fear processing can be divided into fear learning (or acquisition), during which an association develops between previously neutral stimuli and aversive outcomes, and fear extinction, in which the latter associations are suppressed by a new form of learning. This review describes translational research in both fear acquisition and extinction, along with their relevance to PTSD and PTSD treatment, focusing specifically on the empirical value and potential clinical utility of psychophysiological methods.

Conceptualization, Assessment, and Treatment of Traumatic Stress in First Responders: A Review of Critical Issues.

Abstract: First responders are regularly confronted with exposure to traumatic events, including potentially life-threatening situations as well as the grave injuries and deaths of colleagues and civilians. Evidence indicates that the prevalence of posttraumatic stress disorder (PTSD) is substantially higher among first responders than the general population. This article provides information about the outpatient trauma services at McLean Hospital's LEADER (Law Enforcement, Active Duty, Emergency Responder) program to assist clinicians who encounter these first responders in their practices or who are specifically interested in working with this patient population. We begin by synthesizing the literature on the prevalence of PTSD in first responders following work-related exposure to traumatic stress, and by addressing the occupation-specific risk factors and the third-variable risk factors that may contribute to potentiated risk. We then discuss assessment strategies and treatment options used in our program, which is tailored for individuals who are dealing with mental health issues stemming from occupation-specific traumatic-stress exposure. We also address the unique challenges of treating traumatized first responders with more complex issues such as traumatic stress exposure across the lifespan and safety issues, including acute suicidality. We conclude by discussing notable gaps in the literature, including the need to investigate why and how women present with different PTSD symptoms than men and how these differences need to be taken into account in determining appropriate treatment for women.

Living High and Feeling Low: Altitude, Suicide, and Depression.

Abstract: LEARNING OBJECTIVES After participating in this activity, learners should be better able to:• Assess epidemiologic evidence that increased altitude of residence is linked to increased risk of depression and suicide• Evaluate strategies to address hypoxia-related depression and suicidal ideation ABSTRACT: Suicide and major depressive disorder (MDD) are complex conditions that almost certainly arise from the influences of many interrelated factors. There are significant regional variations in the rates of MDD and suicide in the United States, suggesting that sociodemographic and environmental conditions contribute. Here, we review epidemiological evidence that increases in the altitude of residence are linked to the increased risk of depression and suicide. We consider the possibility that chronic hypobaric hypoxia (low blood oxygen related to low atmospheric pressure) contributes to suicide and depression, which is suggested by animal models, short-term studies in humans, and the effects of hypoxic medical conditions on suicide and depression. We argue that hypobaric hypoxia could promote suicide and depression by altering serotonin metabolism and brain bioenergetics; both of these pathways are implicated in depression, and both are affected by hypoxia. Finally, we briefly examine treatment strategies to address hypoxia-related depression and suicidal ideation that are suggested by these findings, including creatine monohydrate and the serotonin precursors tryptophan and 5-hydroxytryptophan.

Interoception in Psychiatric Disorders: A Review of Randomized, Controlled Trials with Interoception-Based Interventions.

Abstract: Interoception, or the process of sensing, interpreting, and integrating internal bodily signals, has increasingly been the subject of scientific research over the past decade but is still not well known in clinical practice. The aim of this article is to review clinical treatment interventions that use interoception, to synthesize the current research knowledge, and to identify the gaps where future research is needed. We conducted a comprehensive literature search on randomized, controlled trials that both include interoception in treatment interventions for individuals with psychiatric disorders and measure aspects of interoception using self-report measures. Out of 14 randomized, controlled trials identified, 7 found that interventions with interoception were effective in ameliorating symptoms. These studies included individuals with anxiety disorders, eating disorders, psychosomatic disorders, and addictive disorders. All of the intervention studies with positive clinical outcomes also demonstrated changes on interoceptive measures; however, these measures were often related to specific illness symptoms. Interoception may be a mechanism of action in improving clinical symptomatology, though studies incorporating general, symptom-independent interoceptive measures remain scarce. To further our understanding of the role interoception has in psychiatric disorders and their treatment, more studies integrating interoceptive measures are needed, along with a clearer definition of interoceptive terms used.

Suicidal Risk and Affective Temperaments, Evaluated with the TEMPS-A Scale: A Systematic Review.

Abstract: Background Among risk factors for suicidal behavior, there is growing interest in associations with stable affective temperament types, particularly based on assessment with the TEMPS-A self-rating scale. Aim As research on this topic has not been reviewed systematically, we synthesized relevant, reported research findings. Methods Systematic searching identified peer-reviewed reports pertaining to associations of suicidal behavior or ideation with affective temperament types evaluated with TEMPS-A. We summarized available findings and applied quantitative meta-analytic methods to compare scale scores in suicidal versus nonsuicidal subjects. Results In 21 of 23 TEMPS-A studies meeting inclusion criteria, anxious, cyclothymic, depressive, or irritable temperament scores were significantly higher with previous or recent suicide attempts or ideation in both psychiatric and general population samples compared to nonsuicidal controls, whereas hyperthymic temperament scores were lower in 9 of 11 reports. These findings were synthesized by random-effects meta-analyses of standardized mean differences in TEMPS-A temperament scores in suicidal versus nonsuicidal subjects. Associations ranked: depressive ≥ irritable > cyclothymic > anxious > hyperthymic (negative). Conclusions Affective temperaments, especially depressive and irritable, were strongly associated with suicidal risk, whereas hyperthymic temperament appeared to be protective.

Evidenced-Based Treatment of Posttraumatic Stress Disorder: An Updated Review of Validated Psychotherapeutic and Pharmacological Approaches.

Abstract: Learning objectives After participating in this activity, learners should be better able to:• Evaluate psychotherapeutic and pharmacologic approaches to treating patients with posttraumatic stress disorder. Abstract A strong evidence base exists for psychological and pharmacological interventions for the treatment of posttraumatic stress disorder (PTSD). The published literature investigating the effectiveness of these treatments in reducing the symptoms and impairments associated with PTSD has expanded substantially in recent years. This review provides a concise overview of the empirical literature examining these treatment approaches. Evidence-based, trauma-focused therapies are recommended as first-line interventions, with the most support for cognitive- and exposure-based approaches. Prolonged exposure and cognitive processing therapy are the two most cited and rigorously investigated. Various other evidence-supported protocols are discussed. Pharmacotherapies can be used when evidence-based psychotherapies are not available or are ineffective, or on the basis of patient preference. Pharmacotherapy with the most support for PTSD includes selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. Evidence supports the implementation of these interventions across genders, populations, and settings. Given that little research directly compares the effectiveness of different PTSD interventions and their mechanisms of action, it remains uncertain how to best select and tailor treatments to optimize individual outcomes. Future directions and novel, ongoing research are discussed.

Prescription Benzodiazepine Use Among Older Adults: A Critical Review.

Abstract: Objectives Despite evidence for many potential risks, use of benzodiazepines (BZDs) among older adults is common The authors evaluated the available evidence for BZD effectiveness and tolerability for use in older adults in three psychiatric conditions for which BZDs are commonly prescribed: insomnia, anxiety disorders, and behavioral and psychological symptoms of dementia Design Electronic databases, including PubMed/MEDLINE, were searched to identify articles that (1) included patients ≥50 years of age, (2) focused on patients diagnosed with insomnia, anxiety disorders, or behavioral and psychological symptoms of dementia, and (3) were either a randomized, placebo-controlled trial or a randomized trial comparing a BZD with either another psychotropic medication or psychotherapy Results Thirty-one studies met the inclusion criteria Of the three clinical indications evaluated, treatment of insomnia had the greatest available evidence for use of BZDs among older adults, with 21 of 25 trials demonstrating improved sleep outcomes with use of BZDs Only one trial was found to meet eligibility criteria for BZD use in anxiety disorders, demonstrating benefit over placebo Five studies for use in behavioral disturbances in dementia were included, of which only one demonstrated improvement over placebo Conclusion This systematic review suggests that BZD prescribing to older adults is significantly in excess of what the available evidence suggests is appropriate Future trials should focus on efforts to reduce both acute and chronic BZD use among older adults while improving access to effective non-pharmacologic treatment alternatives

Compassion and Loving-Kindness Meditation: An Overview and Prospects for the Application in Clinical Samples.

Abstract: Objectives This article presents a brief overview of the empirical evidence of well-established mindfulness interventions and an in-depth review of less-established compassion-based interventions (CBIs) and loving-kindness meditation (LKM). Definitions, cognitive and physiological mechanisms, and methods of assessment are discussed. Method A literature review using the databases Google Scholar, PsycINFO, and PubMed was conducted. Results Whereas the efficacy of mindfulness-based stress reduction and mindfulness-based cognitive therapy has been documented in many trials, only seven randomized, controlled trials have been completed on CBIs and LKM. In these trials, CBIs were effective in treating psychotic disorders, affective disorders with psychotic features, major depressive disorder, eating disorders, and patients with suicide attempts in the past year; LKM was effective in treating chronic pain; and a combination of both was effective for borderline personality disorder. A larger number of nonrandomized studies indicate that CBIs and LKM may be effective in treating a wide range of clinical conditions, including depression, anxiety disorders, chronic pain, and posttraumatic stress disorder. Conclusions Further studies are needed to confirm the promising effects of CBIs and LKM. Preliminary evidence suggests that both approaches might be beneficial across various clinical populations. Future studies need to clarify whether these approaches might be options as stand-alone treatments or as adjuncts or augmentation of evidence-based methods in psychotherapy.

Clinical and Environmental Risk Factors for Bipolar Disorder: Review of Prospective Studies.

Abstract: LEARNING OBJECTIVES After participating in this activity, learners should be better able to:• Evaluate factors that have been identified in prospective studies as predicting the onset of bipolar disorder ABSTRACT: The prodromal phase of bipolar disorder (BD) remains incompletely characterized, limiting early detection of BD and delaying interventions that might limit future morbidity and disability. Retrospective and family-risk studies have consistently found evidence of prodromal psychopathology in subjects later diagnosed with BD. Here, we review prospective studies of clinical risk factors and exposures identified before diagnosis of BD: our findings are consistent with those from retrospective and family-risk studies. Affective psychopathology often precedes diagnosis to suggest a homotypic trajectory in developing BD. Early non-affective (heterotypic) psychopathological disturbances, including anxiety and disruptive behavior disorders, as well as environmental factors and exposures, have been found in prospective studies to increase the risk of BD, but tend to lack specificity in predicting BD. Findings from prospective studies are encouragingly similar to those of retrospective and family-risk studies.

Differential Susceptibility to the Environment and Borderline Personality Disorder.

Abstract: Evolutionary models of psychopathology can shed light on gene-environment interactions. Differential susceptibility to the environment means that heritable traits can have positive or negative effects, depending on environmental context. Thus, traits that increase risk for mental disorders when the environment is negative can be adaptive when the environment is positive. This model can be applied to borderline personality disorder, with predictors such as emotional dysregulation and impulsivity seen as temperamental variations leading to negative effects in an unfavorable environment but to positive effects in a favorable environment. This model may also be useful in conceptualizing the mechanisms of effective therapy for borderline personality disorder.

A Fourth Wave of Psychotherapies: Moving Beyond Recovery Toward Well-Being.

Abstract: As psychotherapies have proliferated, a number of authors have recently distinguished three waves of approaches, based on historical, theoretical and practical considerations. First-wave therapies, which include psychodynamic therapy, aim at enhancing autonomy and mastery through insight, and rely on the therapist as expert. A second wave of therapies, including cognitivebehavioral therapy (CBT), gestalt therapy, and family systems theory, are more present and problem focused. They are also more theory driven than third-wave therapies, which focus more on solutions and conscious action, and are heterogeneous in technique. Third-wave approaches include acceptance and commitment therapy, dialectical behavior therapy, behavioral activation, schema therapy, and mindfulness-based CBT. These three waves, while often enhancing resilience through learning social and emotional skills, are primarily directed at correcting deficits responsible for dysfunction. By comparison, many of the newest and most novel mental health interventions can productively be characterized as a fourth wave. This group of approaches, built on the legacy of existential psychotherapy and related humanistic approaches, aims beyond insight, mastery, and problem solving toward the achievement of positive well-being. These valueand virtueoriented approaches include positive psychology interventions, loving-kindness and compassion meditation, and dignity-andgratitude-promoting, meaning-centered, forgiveness-oriented, and spiritually informed therapies. They overlap with traditional religious/spiritual practices that utilize prayer, scripture study, sacraments, and supportive communities to help individuals achieve valued ideals and to flourish. Although the diverse group of approaches categorized here as fourth wave raise challenging conceptual, as well as practical and ethical, questions for clinicians regarding

Community, Public Policy, and Recovery from Mental Illness: Emerging Research and Initiatives.

Abstract: This commentary examines the roles that communities and public policies play in the definition and processes of recovery for adults with mental illness. Policy, clinical, and consumer definitions of recovery are reviewed, which highlight the importance of communities and policies for recovery. This commentary then presents a framework for the relationships between community-level factors, policies, and downstream mental health outcomes, focusing on macroeconomic, housing, and health care policies; adverse exposures such as crime victimization; and neighborhood characteristics such as social capital. Initiatives that address community contexts to improve mental health outcomes are currently under way. Common characteristics of such initiatives and select examples are discussed. This commentary concludes with a discussion of providers', consumers', and other stakeholders' roles in shaping policy reform and community change to facilitate recovery.

Symptoms and Experience of Depression Among Chinese Communities in the West: A Scoping Review.

Abstract: Despite the increasing presence of Chinese communities in the West, their experiences of depression and the variations in symptoms or presentation are not well understood. Using Arksey and O'Malley's methodical framework, we conducted a scoping review of the published literature, using electronic databases MEDLINE and PsycINFO, and searched for articles published since 1999. Out of 1177 articles identified, 21 met the inclusion criteria. Thematic synthesis revealed valuable scholarly work on (1) depression rates, migration, and contextual determinants, (2) causation beliefs and help seeking, (3) acculturation and symptoms, (4) presenting symptoms and somatization, and (5) culturally sensitive assessment and care. Overall, this review has identified the importance of contextual determinants in the development of depression, low rates of seeking of professional help, subtle variations in somatization, and knowledge gaps in culturally sensitive care. The findings suggest that, rather than treating migration as a cause of mental distress, the accompanying conditions and events need to be further examined and addressed as potential risk or protective factors. Subtle variations in somatization are also evident, and future scholarly work should examine the notion of cultural scripts-namely, that people attend and react to particular experiences in culturally based ways. For this reason (among others), practice models need to develop strategies for culturally sensitive care, such as co-construction of illness narratives and finding common ground. Given the stigma of mental illness and the low level of seeking professional help, the role of primary care should be expanded. Further studies investigating mental health issues beyond depression are also warranted in the studied community.

Characterizing, Assessing, and Treating Cognitive Dysfunction in Major Depressive Disorder.

Abstract: Learning objectives After participating in this activity, learners should be better able to:• Characterize cognitive dysfunction in patients with major depressive disorder.• Evaluate approaches to treating cognitive dysfunction in patients with major depressive disorder. Abstract Cognitive dysfunction is a core psychopathological domain in major depressive disorder (MDD) and is no longer considered to be a pseudo-specific phenomenon. Cognitive dysfunction in MDD is a principal determinant of patient-reported outcomes, which, hitherto, have been insufficiently targeted with existing multimodal treatments for MDD. The neural structures and substructures subserving cognitive function in MDD overlap with, yet are discrete from, those subserving emotion processing and affect regulation. Several modifiable factors influence the presence and extent of cognitive dysfunction in MDD, including clinical features (e.g., episode frequency and illness duration), comorbidity (e.g., obesity and diabetes), and iatrogenic artefact. Screening and measurement tools that comport with the clinical ecosystem are available to detect and measure cognitive function in MDD. Notwithstanding the availability of select antidepressants capable of exerting procognitive effects, most have not been sufficiently studied or rigorously evaluated. Promising pharmacological avenues, as well as psychosocial, behavioral, chronotherapeutic, and complementary alternative approaches, are currently being investigated.

Uncharted Waters: Developing Mental Health Services for Survivors of Domestic Human Sex Trafficking.

Abstract: In recent years, heightened attention has been paid to commercial sexual exploitation, including domestic human sex trafficking (HST), with mental health concerns named the most dominant health concern among survivors. Human sex trafficking is associated with significant and long-term mental health consequences. Research to date has emphasized ways to identify survivors in health care settings. Once identified, however, few specialized services are available to help survivors exit and recover. The current services infrastructure for HST has been compared to the disjointed social response to intimate partner violence before the women's movement helped develop a system of battered women's shelters. Although research has highlighted the need for a multidisciplinary and interagency response to HST, including mental health care, best practices have not yet been formulated. Furthermore, available services are fragmented across sectors. With psychology and psychiatry taking tentative steps to develop services for HST survivors, this article identifies six principles to help avoid a fragmented and potentially retraumatizing clinical and systemic response. The overarching goal is to design services that are flexible, accessible, trauma informed, survivor driven, responsive to stages of change, multidisciplinary, and enduring, especially given the centrality of healthy attachments and community in trauma recovery. Principles are derived from the limited available research on HST services and from examples of efficacious interventions for patient groups with similar characteristics. The discussion is also informed by composite clinical vignettes from a specialized clinic for adult survivors of HST, housed in a major teaching hospital. Finally, practice recommendations and strategies for building interdisciplinary collaborations are discussed.

Development of a Boston Treatment Program for Youth at Clinical High Risk for Psychosis: Center for Early Detection, Assessment, and Response to Risk (CEDAR).

Abstract: Over the past two decades, increasing attention has been given to the importance of early intervention for psychosis This article describes the development of the Center for Early Detection, Assessment and Response to Risk (CEDAR), which focuses on early identification and treatment of youth at clinical high risk for psychosis There are relatively few models in the United States for such programs, and we present our developmental story, focusing mainly on the CEDAR Clinic, as a case study of how such a program can develop We describe the rationale, infrastructure, and services provided at the CEDAR Clinic, and present some descriptive data from the CEDAR Clinic through 2016 A case example is provided to illustrate treatment at CEDAR We hope that the cultural history of our program's development is informative for clinicians and policy makers as one model of how to build an early intervention service We believe that this article is timely in view of the growing momentum in the United States for developing programs for intervening as early as possible for youth at clinical high risk for psychosis

Ambushed by Memories of Trauma: Memory-Processing Interventions in an Adolescent Boy with Nocturnal Dissociative Episodes.

Abstract: CASE HISTORYAt presentation to the Accident and Emergency Department, BJ was a 16-year-old boy in eleventh grade, with a one-month history of unusual sleep-related behaviors. As the latest example, BJ had awakened one morning to find a painful cut on his arm and a bloodied knife in the kitchen; he h

Efficacy and Safety of Intensive Transcranial Magnetic Stimulation.

Abstract: Repetitive transcranial magnetic stimulation (rTMS) is customarily applied on a daily basis for prolonged periods of time for the treatment of psychiatric diseases. The process is demanding in terms of staff and patient time, and the onset of the effect is slow. Recently, intensive rTMS protocols have been introduced in which stimulation is applied to the same area more than once a day with a higher than standard number of pulses. This article reviews 16 articles to determine the safety and efficacy of such protocols. Intensive rTMS seems to be effective in various mental disorders. It appears to have, in general, the same adverse events as classic, long-term, daily rTMS, and it is largely well tolerated by the patients. One episode of depersonalization, one of increased suicidal thoughts, and two of induced mania were observed in the 16 studies reviewed. The advantages of intensive rTMS are in the possible acute effect of the stimulation and in the possible reduction in the time required to achieve remission in depression (and potentially other disorders). It remains uncertain whether intensive rTMS is more effective than sham stimulation or once-daily, long-term rTMS.

Partners of Individuals with Borderline Personality Disorder: A Systematic Review of the Literature Examining Their Experiences and the Supports Available to Them.

Abstract: Over a third of individuals with borderline personality disorder (BPD) are in long-term romantic partnerships, yet little is known about the experiences of their partners. Because difficulties in interpersonal relationships are a hallmark of BPD, it is especially important to understand the support needs of their romantic partners. This systematic review investigates the experiences of romantic partners of adult individuals with BPD and the interventions designed to support them. Twenty-two articles were found, 13 of which pertained to partner experiences and 9 to interventions. Thematic analysis was used to identify three main themes in the descriptions of partners' experiences: emotional challenges, dual roles as both a romantic partner and parental/therapeutic figure, and lack of control. The available interventions, which consisted of educational and skills-based programs with limited efficacy data, addressed only a small portion of the subthemes identified in the literature describing partners' experiences. The discrepancy between the needs identified in the partner-experience literature and the interventions available suggests a need to develop and evaluate more partner-oriented programming. Such programming should use psychoeducation, peer support, and individual- and relationship-based skills development to address and therefore improve the experiences of partners of individuals with BPD.

Mirtazapine Therapy for Posttraumatic Stress Disorder: Implications of Alpha-Adrenergic Pharmacology on the Startle Response.

Abstract: Posttraumatic stress disorder (PTSD), a serious mental illness that occurs secondary to traumatic event exposure, has four distinct symptom clusters: reexperiencing, avoidance, negative alterations in cognition and mood, and arousal. The lifetime prevalence of PTSD in the general U.S. population is estimated to be 6.4%–6.8%, as compared to 8% for military veterans. Largely accepted first-line therapies for PTSD include cognitive and behavioral therapies as well as selective serotonin reuptake inhibitor (SSRI) and selective serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressants. Paroxetine and sertraline are currently the only SSRIs approved by the Food and Drug Administration (FDA) for treating PTSD, though a recent meta-analysis suggests sertraline and venlafaxine as the most efficacious pharmacotherapeutic options available. Sensorimotor gating is a process by which an organism identifies the surrounding stimuli within the environment, filtering out any extraneous information in order to shift attention solely to that which is determined to be the most relevant. Deficits in sensorimotor gating then lead to an influx of information, both relevant and irrelevant, thus affecting attention and cognition. These deficits have been found in patients with schizophrenia and with PTSD—two disease states in which hyperarousal and hallucinations or other visual disturbances may occur. Aweak pre-stimulus, however, can be used to decrease the magnitude of response to a subsequently more intense stimulus. This practice, known as pre-pulse inhibition (PPI), is also used to measure changes in sensorimotor gating. Multiple neurotransmitters have been shown to alter

A Brief Overview of Advances in LGBT Mental Health Advocacy in Lebanon.

Abstract: In the past decade, Lebanon, a small country in theMiddle East, has witnessed significant developments with respect to mental health advocacy for lesbian, gay, bisexual, and transgender (LGBT) persons. These advances have taken place due to the interplay between civil society entities, including nongovernmental organizations (NGOs) and professional organizations, and to a lesser extent due to the contributions of academic centers and targeted government programs. In this column we detail the milestones that Lebanon has achieved with respect to LGBT mental health care. We examine how these achievements were realized, with a special focus on the role of the key players who were involved. Finally, we discuss the lessons learned from the experience of collaborative advocacy in Lebanon and draw parallels between these efforts and similar endeavors in the United States over the past four decades. We conclude with recommendations for ongoing LGBTmental health promotion in Lebanon and potentially the rest of the Arab world.

A Potential Role for the Noncoding Transcriptome in Psychiatric Disorders.

Abstract: Understanding the complexity and regular function of the human brain is an unresolved challenge that hampers the identification of disease-contributing components and mechanisms of psychiatric disorders. It is accepted that the majority of psychiatric disorders result from a complex interaction of environmental and heritable factors, and efforts to determine, for example, genetic variants contributing to the pathophysiology of these diseases are becoming increasingly successful. We also continue to discover new molecules with unknown functions that might play a role in brain physiology. One such class of polymeric molecules is noncoding RNAs; though discovered years ago, they have only recently started to receive careful attention. Furthermore, recent technological advances in the field of molecular genetics and high-throughput sequencing have facilitated the discovery of a broad spectrum of RNAs that show no obvious coding potential but may provide additional layers of complexity and regulation to the molecular mechanisms underlying psychiatric disorders. Their exquisite enrichment and expression profiles in the brain may point to important functions of these RNAs in health and disease. This review will therefore aim to provide insight into the expression of noncoding RNAs in the brain, their function, and potential role in psychiatric disorders.

Animal Models in Psychiatric Disease: A Circuit-Search Approach

Abstract: Our collective desire to understand how the “normal” vs. “diseased” brain works drives our ongoing need for nonhuman animal research. Our current understanding of circuits within the brain, and the techniques required to investigate neural activity, stem from animal work. These techniques often require invasive methods, which necessitate animal models. Unfortunately, this means that our investigative approaches are subject to the same limitations that animal models had before these new techniques were developed. In this article I briefly overview these limitations, then outline a relatively new strategy that enables us to establish a causal relationship between a specific neurocircuit abnormality and disease. This approach utilizes novel techniques designed to selectively target mutations to specific brain circuits in the mouse. Such a strategy allows the researcher to “home in” on how a gene affects a single brain circuit. This is powerful because it avoids an often-cited problem that plagues traditional animal models: non-targeted mutations disrupt a myriad of circuits. Rather than mutating all brain cells, targeting a gene known to be highly penetrant for human disease to an individual, relatively conserved, circuit element helps us determine whether that circuit is involved in generating an abnormal behavioral phenotype. This will provide invaluable clues about where and how psychiatric disease originates in humans. Finally, I briefly discuss how computational neuroscience-based techniques and noninvasive, low-risk neuromodulation techniques could be employed to test hypotheses generated by these animal models in humans, leading to both greater understanding of neurocircuits underlying psychiatric disease and possibly new treatments.