There is a significant need for advanced understanding of treatment of co-occurring posttraumatic stress disorder (PTSD) and substance use disorders (SUD). Approximately half of individuals seeking SUD treatment meet criteria for current PTSD, and individuals with co-occurring PTSD-SUD tend to have poorer treatment outcomes compared with those without such comorbidity. However, there is not sufficient empirical evidence to determine a best course of treatment for these individuals. This paper provides a review of the literature relevant to the treatment of co-occurring PTSD-SUD. To date, treatment studies have focused primarily on non-exposure-based psychosocial treatments, exposure-based psychosocial treatments, and medication trials. The most promising outcome data thus far are for psychosocial treatments that incorporate an exposure therapy component; however, further research is needed, particularly as related to how best to implement these approaches in real-world treatment settings.
Posttraumatic stress disorder; PTSD; Substance use; Substance abuse; Substance dependence; Addiction; Alcohol; Alcoholism; Cocaine; Prolonged exposure; Comorbidity; Anxiety; Treatment; Selective serotonin reuptake inhibitors; SSRI; Cognitive behavioral therapy; CBT
Substance use (SU) problems are common among adolescents, a serious health risk for them and a major public health problem, but are inadequately addressed in most pediatric health care settings. Primary care offers an excellent context for SU assessment and treatment for adolescents and their families, offering better access and a less stigmatized environment for receiving treatment than specialty programs. This paper examines the literature on the integration of substance use treatment with adolescent health care, focusing on 2 areas: Screening, Brief Intervention, and Referral to Treatment (SBIRT) in Emergency Departments and Primary Care, and School- and College-Based Health Centers.
Substance use; Adolescent; Pediatric; Psychiatric disorders; Behavioral health; Comorbidity; Screening, brief intervention, and referral to treatment; SBIRT; Alcohol; Drug; Emergency departments; Primary care; School-based health centers; SBHC; Health care; Integration; Assessment; Treatment
Attentional deficits are frequently seen in isolation as the presenting sign and symptom of neurodegenerative disease, manifest as mild cognitive impairment (MCI). Persistent ADHD in the geriatric population could well be misconstrued as MCI, leading to the incorrect assumption that such persons are succumbing to a neurodegenerative disease process. Alternatively, the molecular, neuroanatomic, or neurochemical abnormalities seen in ADHD may contribute to the development of de novo late life neurodegenerative disease. The present review examines the issue of causality vs confound regarding the association of ADHD with MCI, suggesting that both are tenable hypotheses.
Attention-deficit/hyperactivity disorder; ADHD; Adult ADHD; Older adults; Mild cognitive impairment; MCI; Alzheimer’s disease; Parkinson’s disease; Dementia with Lewy bodies; DLB; Frontotemporal dementia; FTD; Genetics; Neurotransmitter systems; Neuroimaging; Pathogenesis; Treatment
People with mental health and addictive disorders (MHADs) have higher rates of cigarette smoking, and less success in quitting smoking compared to the general population. Moreover, tobacco-related medical illness may be the leading cause of death in the MHAD population. We discuss the scope of this comorbidity, and approaches to the treatment of tobacco dependence in people with MHAD, including schizophrenia, mood disorders, anxiety disorders, and alcohol and substance use disorders. Finally, at the level of health systems, we emphasize the importance of integrated treatment of tobacco dependence in MHADs.
Mental health and addictive disorders; Nicotine dependence; Tobacco; Treatment; Smoking cessation; Psychiatric disorders; Schizophrenia; Anxiety disorders; Mood disorders; Substance use disorders; Alcoholism; Comorbidities; Pharmacotherapy; Integrated care
Recent years have seen an expansion of interest in non-pharmacological interventions for attention-deficit/hyperactivity disorder (ADHD). Although considerable treatment development has focused on cognitive training programs, compelling evidence indicates that intense aerobic exercise enhances brain structure and function, and as such, might be beneficial to children with ADHD. This paper reviews evidence for a direct impact of exercise on neural functioning and preliminary evidence that exercise may have positive effects on children with ADHD. At present, data are promising and support the need for further study, but are insufficient to recommend widespread use of such interventions for children with ADHD.
Attention-deficit/hyperactivity disorder; ADHD; Cortical development; Neurocognitive functioning; Aerobic exercise; Cognitive remediation strategies; Nonpharmacological intervention; Neural growth; Cognitive development; Executive functioning; Treatment; Outcomes
Late life depression (LLD) is an important area of research given the growing elderly population. The purpose of this review is to examine the available evidence for the biological basis of LLD. Structural neuroimaging shows specific gray matter structural changes in LLD as well as ischemic lesion burden via white matter hyperintensities. Similarly, specific neuropsychological deficits have been found in LLD. An inflammatory response is another possible underlying contributor to the pathophysiology of LLD. We review the available literature examining these multiple facets of LLD and how each may affect clinical outcome in the depressed elderly.
Late life depression; LLD; Elderly; Ischemic lesion burden; White matter hyperintensities; Neuropsychological factors; Cognitive deficits; Inflammatory markers; Treatment outcome; Structural neuroimaging
Major depressive disorder (MDD) is common and costly. Primary care remains a major access point for depression treatment, yet the successful clinical resolution of depression in primary care is uncommon. The clinical response to depression suffers from a “treatment cascade”: the affected individual must access health care, be recognized clinically, initiate treatment, receive adequate treatment, and respond to treatment. Major gaps currently exist in primary care at each step along this treatment continuum. We estimate that 12.5% of primary care patients have had MDD in the past year; of those with MDD, 47% are recognized clinically, 24% receive any treatment, 9% receive adequate treatment, and 6% achieve remission. Simulations suggest that only by targeting multiple steps along the depression treatment continuum (e.g. routine screening combined with collaborative care models to support initiation and maintenance of evidence-based depression treatment) can overall remission rates for primary care patients be substantially improved.
Major depressive disorder; Depression treatment cascade; Recognition; Treatment; Remission; Primary care; Public health
Anorexia nervosa (AN) is a complex illness and highly challenging to treat. One promising approach to significantly advance our understanding of the underlying pathophysiology of AN involves developing a cognitive neuroscience model of illness. Cognitive neuroscience uses probes such as neuropsychological tasks and neuroimaging techniques to identify the neural underpinnings of behavior. With this approach, advances have been made in identifying higher order cognitive processes that likely mediate symptom expression in AN. Identification of related neuropathology is beginning. Such findings have led to the development of complex neurobehavioral models that aim to explain the etiology and persistence of AN. Future research will use these advanced tools to test and refine hypotheses about the underlying mechanisms of AN.
Anorexia nervosa; AN; Neuropsychology; Neuroimaging; Cognitive neuroscience; Cognitive flexibility; Set-shifting; Central coherence; Reward; Corticostriatal systems; Insula
Depression is a common condition among children and adolescents, with lasting detrimental effects on health, and social and occupational functioning. Despite being well-positioned to treat depression, primary care providers (PCPs) cite significant barriers. This review aims to summarize recent evidence to provide practical guidance to PCPs on the management of pediatric depression in their practices. Following identification and assessment, PCPs should provide general initial management. Children and adolescents with mild depression can be managed with active support and symptom monitoring, while those with moderate-to-severe depression can be treated with psychotherapy and/or antidepressants, which may involve referral to mental health specialty care. Less is known about the treatment of depression in children under the age of 12 years, who may be candidates for earlier referral to mental health specialty care. PCPs have the potential to improve the recognition and management of depression in young people, having lasting individual and societal benefits.
Child and adolescent; Depression; Primary care; Guidelines; Assessment; Management; Psychotherapy; Cognitive-behavioral therapy; CBT; Interpersonal therapy; IPT; Selective serotonin reuptake inhibitors; SSRI; Psychiatry
The authors review the science linking depression with diabetes. Some recent heuristic research is identified that highlights progress in the field and is directing future research. Issues in the management of depression in diabetes are outlined, including interactions of depression and insulin resistance.
Pharmacological management of attention-deficit hyperactivity disorder (ADHD) has expanded beyond stimulant medications to include alpha 2 adrenergic agonists. These agents exert their actions through presynaptic stimulation and likely involve facilitation of both dopamine and noradrenaline neurotransmission, which are both thought to play critical roles in the pathophysiology of ADHD. Further, frontostratial dysfunction giving rise to neuropsychological weaknesses has been well-established in patients with ADHD and may explain how alpha 2 agents exert their beneficial effects. In the following review, we consider relevant neurobiological underpinnings of ADHD with respect to why alpha 2 agents may be effective in treating this condition. We also review new formulations of alpha 2 agonists, emerging data on their use in ADHD, and implications for clinical practice. Integrating knowledge of pathphysiological mechanisms and mechanisms of drug action may inform our medication choices and facilitate treatment of ADHD and related disorders.
guanfacine; clonidine; prefrontal; noradrenaline; ADHD
Relapse is a highly prevalent phenomenon in addiction. This paper examines the new research on identifying biological factors that contribute to addiction relapse risk. Prospective studies examining relapse risk are reviewed, and clinical, biological, and neural factors that predict relapse risk are identified. Clinical factors, patient-related factors, and subjective and behavioral measures such as depressive symptoms, stress, and drug craving all predict future relapse risk. Among biological measures, endocrine measures such as cortisol and cortisol/corticotropin (ACTH) ratio as a measure of adrenal sensitivity and serum brain-derived neurotrophic factor were also predictive of future relapse risk. Among neural measures, brain atrophy in the medial frontal regions and hyperreactivity of the anterior cingulate during withdrawal were identified as important in drug withdrawal and relapse risk. Caveats pertaining to specific drug abuse type and phase of addiction are discussed. Finally, significant implications of these findings for clinical practice are presented, with a specific focus on determining biological markers of relapse risk that may be used to identify those individuals who are most at risk of relapse in the clinic. Such markers may then be used to assess treatment response and develop specific treatments that will normalize these neural and biological sequelae so as to significantly improve relapse outcomes.
Addiction relapse; Stress dysregulation; Drug craving; Cortisol; Cortisol/ACTH ratio; Serum BDNF; Anterior cingulate; Biomarkers; Human studies; Biological factors; Vulnerability
As presently defined, post-traumatic stress disorder (PTSD) is an amalgam of symptoms falling into: re-experiencing of the trauma, avoidance of reminders of it, emotional numbing and hyperarousal. PTSD has a well-known proximate cause, commonly occurring after a life-threatening event that induces a response of intense fear, horror, and helplessness. Much of the advancement in understanding of the neurobiology of PTSD has emerged from conceptualizing the disorder as one that involves substantial dysfunction in fear processing. This article reviews recent knowledge of fear processing markers in PTSD. A systematic search was performed of reports within the specific three-year publication time period of January 2010 to December 2012. We identified a total of 31 studies reporting fear processing markers in PTSD. We further categorized them according to the following classification: (1) neural-activation markers (n=10), (2) psychophysiological markers (n=14), and (3) behavioral markers (n=7). Across most studies reviewed here, significant differences between individuals with PTSD and healthy controls were shown. Methodological, theoretical and clinical implications were discussed.
Posttraumatic stress disorder (PTSD); Trauma; Fear processing; Emotional regulation; ACTH; Cortisol; Electromyogram; Emotional reactivity; Fear conditioning; Fear-potentiated startle; Heart rate response; Heart rate variability; HPA; Hydrocortisone; Psychophysiological; Skin conductance response; Functional MRI (fMRI); Activation; Attentional bias; Dot-probe; Emotional stroop; Eye tracking
Trichotillomania (TTM) is an impulse control disorder characterized by chronic hair-pulling, distress, and impairment. Although the negative effects of TTM are documented and often readily evident, there remains a paucity of psychopathology and treatment research on this disorder, particularly in pediatric populations. In an effort to improve assessment of pediatric TTM, several TTM-specific instruments for youth have now been developed to reliably identify symptoms and examine related phenomenology. Instrument development has now yielded instruments to evaluate TTM and related symptoms in the context of clinical trials of youth, and the first randomized controlled trial of any treatment for pediatric TTM was recently published. Using the initial pediatric TTM studies as building blocks, future research is now needed to create a stronger body of knowledge about the relative and combined efficacy of potential interventions for TTM in youth, as well as to examine the effects of TTM phenomenology and comorbidity on treatment outcome. Dissemination efforts must also be heightened for this knowledge to best reach these vulnerable populations.
Trichotillomania; Pediatric; Hair-pulling; Impulse control disorders; Cognitive-behavioral therapy; Habit reversal training; Pharmacotherapy; Combined treatments
Several studies have examined levels of proinflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. This meta-analysis was conducted to examine the association between obsessive-compulsive disorder (OCD) and plasma serum levels of proinflammatory cytokines. Twelve studies met inclusion criteria. The meta-analysis demonstrated a significant reduction in IL-1β levels in OCD. No significant difference in plasma levels of IL-6 or TNF-α was demonstrated. Stratified subgroup analysis revealed possible moderating effects of age and medication use on IL-6 levels. Studies including children on psychotropic medication had lower plasma IL-6 levels. Stratified subgroup analysis revealed a moderating effect of comorbid depression on TNF-α levels. Elevated TNF-α levels were reported in studies that included individuals with comorbid depression. Future studies examining immune function in OCD should adjust for potential confounding due to medication use and comorbid depression. Further studies assessing cerebrospinal fluid cytokine levels in OCD are also needed.
Obsessive-compulsive disorder; OCD; Cytokine; Proinflammatory; Meta-analysis; Interleukin; IL-1β; IL-6; Tumor necrosis factor; TNF-α; Anxiety disorders; Depression; PANDAS; Review
Safe and effective medication for attention deficit hyperactivity disorder (ADHD) is available and recommended as first-line treatment for the core symptoms of inattention, overactivity and impulsiveness. Despite impaired functioning during adolescence, many discontinue medication treatment. For children, healthcare decisions are usually made by the parent; older youth make their own decisions. Beliefs and attitudes may differ widely. Some families understand that ADHD is a neurobiological condition and accept that medication is indicated, for others, such treatment is unacceptable. Converging evidence describes negative perceptions of the burden associated with medication use as well as concerns about potential short and long term adverse effects. Indeed experiences of adverse effects are a frequent explanation for discontinuation among youth. Ways to improve shared decision making among practitioners, parents and youth, and to monitor effectiveness, safety and new onset of concurrent difficulties are likely to optimize outcomes.
Attention deficit hyperactivity disorder; ADHD; Psychostimulants; Atomoxetine; Medication adherence; Patient compliance; Adverse effects; Treatment refusal; Treatment outcome; Childhood; Adolescence; Psychiatry
Since the early 20th century, a group of non-affective psychoses with acute onset and brief duration have been described in different countries and under various names, including cycloid psychosis, bouffée délirante, and reactive psychosis. These psychoses share a number of characteristics, including benign course, greater prevalence in women than men and in developing countries than industrialized countries, and high prevalence of premorbid psychological and physiological stressors. However, the variations in names and minute details of symptomatology have overshadowed the basic similarities across these various descriptions. Confusion in classification persists in the two contemporary diagnostic systems, the DSM-IV and the ICD-10. We believe that most cases of these psychoses could be captured under a broad, unified category of non-affective psychosis with acute onset and brief duration, and urge the authors of the upcoming revisions of the DSM and ICD to create such a category. A unified diagnostic category for these disorders would reduce unnecessary fragmentation in the diagnostic systems and assist in the progress of research on these rare conditions.
In general, recommendations for the DSM-V and future diagnoses of psychiatric disorders include a dimensional approach to complement the standard categorical approach. For the assessment of attention-deficit/hyperactivity disorder (ADHD), dimensional approaches to supplement the rigid categorical approach of the DSM-IV abound. Historically, dimensions based on severity of symptoms of ADHD and severity of general psychopathology have been used. General dimensional approaches described by a workgroup organized by the American Psychiatric Association are reviewed to provide background and context for a discussion of old and new dimensional approaches to complement future categorical diagnosis of ADHD in the DSM-V.
Alcoholism and drug dependence are common psychiatric disorders with a heritability of about 50%; therefore genetic and environmental influences are equally important. Early-life stress is a predictor of adolescent problem drinking/drug use and alcohol/drug dependence in adulthood, but moderating factors governing the availability of alcohol/drug are important. The risk–resilience balance for addiction may be due in part to the interaction between genetic variation and environment stressors (G×E); this has been confirmed by twin studies of inferred genetic risk. Measured genotype studies to detect G×E effects have used a range of alcohol consumption and diagnostic phenotypes and stressors ranging from early-life to adulthood past year life events. In this article, the current state of the field is critically reviewed and suggestions are put forth for future research.
Childhood maltreatment; Sexual abuse; Physical abuse; Gene–environment interactions; Alcoholism; Drug dependence; Stressful life events; Crossover of risk; Differential susceptibility hypothesis; Alcohol dependence; Cocaine dependence; Adolescent problem drinking; HPA axis; Stress circuitry; Cortisol; Reward pathway; Dopamine; Corpus callosum; SLC6A4; 5-HTTLPR; MAOA-LPR; CRHBP; CRHR1; FKBP5; GABRA2; COMT; PER1; KCNJ6
In recent years, there have been increasing efforts to develop early detection and prevention strategies for patients at risk of the development of psychotic disorders. These efforts have led to improved recognition and characterization of psychotic symptoms in youth. This review focuses on the evaluation of children and adolescents with psychotic symptoms who are experiencing functional impairment but who do not meet current criteria for schizophrenia. For this article, emphasis is placed on the evaluation of symptoms, differential diagnosis, and consideration of potential interventions.
Ultra high risk (UHR); Prodrome; At-risk; Psychosis; Psychotic symptoms; Children; Adolescents; Schizophrenia; Youth
A growing body of research suggests that the construct of emotion regulation is important for understanding the onset, maintenance, and treatment of anxiety disorders. In this review, we provide a selective overview of this emerging field and highlight the major sources of evidence. First, evidence suggests that the construct of emotion regulation can be differentiated from the construct of emotion. Second, there is a large and consistent body of research demonstrating that emotion regulation strategies can modulate emotional responding, and this finding is observed in both behavioral and neuroimaging studies. Third, measures of emotion regulation explain incremental variance in measures of anxiety disorder symptoms not accounted for by measures of negative affect. Although the research implicating emotion regulation in the anxiety disorders is promising, future research will be necessary to further clarify causal mechanisms explaining how emotion regulation confers vulnerability for anxiety disorders and to improve the clarity and consistency of definitions of emotion regulation.
Emotion Regulation; Anxiety
Weight gain remains a well recognized yet difficult to treat adverse effect of many anti-psychotic drugs including agents of the first and second generation. The weight gain liabilities of antipsychotic drugs are partly associated with their ability to increase appetite. Most behavioral interventions for weight control remain of limited efficacy, possibly because they do not specifically target the neuroendocrine factors regulating appetite. Identifying new weight management interventions directly acting on the biochemical and neuroendocrine mechanisms of anti-psychotic induced weight gain may help to improve the efficacy of behavioral weight management programs. Such potentially specific strategies include (1) using diets which do not increase appetite despite calorie restriction; (2) countering thirst as an anticholinergic side-effect; (3) discouraging cannabis use and (4) adding metformin to a behavioral intervention. In view of our currently rather limited treatment repertoire it seems timely systematically to explore such novel options.
Antipsychotics; Anticholinergic; Appetite; Cannabis; Diabetes; Diet; Insulin; Leptin; Ketogenic; Metabolic syndrome; Metformin; Prevention; Thirst; Weight gain; Behavioral interventions; Psychotic disorders; Psychiatry
Depression is a risk factor for cardiac morbidity and mortality in patients with coronary heart disease, especially in those with a recent history of acute coronary syndrome. To improve risk stratification and treatment planning, it would be useful to identify the characteristics or subtypes of depression that are associated with the highest risk of cardiac events. This paper reviews the evidence concerning several putative depression subtypes and symptom patterns that may be associated with a high risk of morbidity and mortality in cardiac patients, including single-episode major depressive disorder, depression that emerges after a cardiac event, somatic symptoms of depression, and treatment-resistant depression.
Coronary disease; Coronary heart disease; Subtype; High risk; Depression; Depressive disorder; Major depressive disorder; Treatment-resistant depression; Myocardial infarction; Mortality; Myocardial ischemia
Alcohol dependence; Behavioral treatment; Moderation; Mediation; Negative mood; Craving; Relapse; Coping with craving; Cognitive-behavioral therapy; Mechanisms of action
Studies consistently report that groups of individuals with major depressive disorder (MDD) demonstrate increased levels of a variety of peripheral inflammatory biomarkers when compared with groups of nondepressed individuals. These findings are often interpreted as meaning that MDD, even in medically healthy individuals, may be an inflammatory condition. In this article, we examine evidence for and against this idea by looking more closely into what the actual patterns of inflammatory findings indicate in terms of the relationship between MDD and the immune system. Data are presented in support of the idea that inflammation only contributes to depression in a subset of patients versus the possibility that the depressogenic effect of inflammatory activation is more widespread and varies depending on the degree of vulnerability any given individual evinces in interconnected physiologic systems known to be implicated in the etiology of MDD. Finally, the treatment implications of these various possibilities are discussed.
Major depression; Fatigue; Immune; Inflammation; Cytokines; Interleukin-6; Tumor necrosis factor-α; p38 mitogen-activated kinase; Psychosocial stress; Glucocorticoids; Autonomic nervous system; Tryptophan; Kynurenine; Quinolinic acid