While considerable efforts have been made to understand the neurobiological basis of substance addiction, the potentially “addictive” qualities of repetitive behaviors, and whether such behaviors constitute “behavioral addictions,” is relatively neglected. It has been suggested that some conditions, such as gambling disorder, compulsive stealing, compulsive buying, compulsive sexual behavior, and problem Internet use, have phenomenological and neurobiological parallels with substance use disorders. This review considers how the issue of “behavioral addictions” has been handled by latest revisions of the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Classification of Diseases (ICD), leading to somewhat divergent approaches. We also consider key areas for future research in order to address optimal diagnostic classification and treatments for such repetitive, debilitating behaviors.

The operational criteria for seasonal affective disorder (SAD) have undergone several changes since first proposed in 1984. SAD is currently included as a specifier of either bipolar or recurrent major depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The International Classification of Diseases, Tenth Edition has provisional diagnostic criteria for SAD. The most characteristic quality of SAD is that the symptoms usually present during winter and remit in the spring. Furthermore, the symptoms tend to remit when the patients are exposed to daylight or bright light therapy. The cognitive and emotional symptoms are as in other types of depression but the vegetative symptoms are the reverse of classic depressive vegetative symptoms, namely increased sleep and increased appetite. SAD is a common condition, but the exact prevalence rates vary between different studies and countries and is consistently found to be more common in women and in youth. SAD probably possibly occurs in children although not as commonly as in young adults. Some studies have found that certain ethnic groups who live at high northern latitudes may have adapted to the long arctic winter.

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a serious neurobehavioral disorder of childhood onset that often persists into adolescence and adulthood. Functional impairments, underachievement, and difficult interpersonal relationships illustrate the need for effective treatment of ADHD through adulthood.

Method: This prospective, multisite, randomized, double-blind, placebo-controlled, parallel-group, dose-escalation study was conducted to assess the efficacy, safety, and duration of action of mixed amphetamine salts extended-release (MAS XR) in adults with ADHD, combined type. Adults ≥ 18 years of age were given placebo or MAS XR 20, 40, or 60 mg/day for 4 weeks. The main outcome measures were the ADHD Rating Scale and Conners' Adult ADHD Rating Scale Short Version Self-Report (CAARS-S-S).

Results: Two hundred fifty-five subjects were randomly assigned to treatment with MAS XR or placebo. MAS XR treatment was associated with statistically and clinically significant ADHD symptom reduction at endpoint; mean ADHD Rating Scale scores were 18.5 for the 20-mg group (P=.001), 18.4 for the 40-mg group (P<.001), and 18.5 for the 60-mg group (P<.001). Adults with severe symptoms (ADHD Rating Scale score ≥32 at baseline) had significantly greater symptom reduction with the highest MAS XR dose (60 mg/day), however, this dose-response relationship was determined by post-hoc analysis. The mean MAS XR effect size was 0.8. Statistically significant (P<.05) improvements in CAARS-S-S ADHD index scores occurred at 4- and 12-hours postdose for all MAS XR groups, indicating a 12-hour duration of effect. Symptoms improved within the first treatment week. Most adverse events reported were mild or moderate in intensity, arid the most commonly reported adverse events were consistent with the known profile of stimulant medications. Vital signs and electrocardiograms showed no clinically significant cardiovascular changes.

Conclusion: These results suggest that MAS XR is safe and effective in adults with ADHD and controlled ADHD symptoms for up to 12 hours.

Introduction: Insomnia symptoms, which are common in depression, have a significant impact on function and quality of life. However, little is known about the prevalence and associated features of insomnia symptoms in representative treatment-seeking patients with depression.

Methods: Data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial were analyzed. STAR*D recruited 3,743 adult outpatients diagnosed with nonpsychotic major depressive disorder (MDD) from primary (n=18) and psychiatric care (n=23) clinics across the United States. Baseline sociodemographic and clinical features were compared between those with insomnia symptoms (84.7%) and those without (15.3%).

Results: The most common presentation was the simultaneous presence of sleep onset, mid-nocturnal, and early morning insomnia symptoms (27.1%). Of these three types of insomnia symptoms, mid-nocturnal insomnia symptoms were the most commonly found alone (13.5%) and in combination with one or more other types (82.3%). Insomnia symptoms were associated with several indicators of a more severe depressive illness. Only a small proportion of participants with insomnia symptoms were receiving treatment for sleep disturbances at study initiation, and the vast majority of those receiving treatment still reported having insomnia symptoms.

Conclusion: In outpatients who seek treatment for nonpsychotic MDD in typical clinical settings, insomnia symptoms are very common, undertreated, and indicative of a more severe depression.

Monoamine-based treatments for depression have evolved greatly over the past several years, but shortcomings such as suboptimal efficacy, treatment lag, and residual cognitive dysfunction are still significant. Preclinical and clinical studies using compounds directly targeting glutamatergic neurotransmission present new opportunities for antidepressant treatment, with ketamine having a surprisingly rapid and sustained antidepressant effect that is presumably mediated through glutamate-dependent mechanisms. While direct modulation of glutamate transmission for antidepressant and cognition-enhancing actions may be hampered by nonspecific effects, indirect modulation through the serotonin (5-HT) system may be a viable alternative approach. Based on localization and function, 5-HT can modulate glutamate neurotransmission at least through the 5-HT1A, 5-HT1B, 5-HT3, and 5-HT7 receptors, which presents a rational pharmacological opportunity for modulating glutamatergic transmission without the direct use of glutamatergic compounds. Combining one or more of these glutamate-modulating 5-HT targets with 5-HT transporter inhibition may offer new therapeutic opportunities. The multimodal compounds vortioxetine and vilazodone are examples of this approach with diverse mechanisms, and their different clinical effects will provide valuable insights into serotonergic modulation of glutamate transmission for the potential treatment of depression and associated cognitive dysfunction.

Behavioral phenotypes are generally complex, reflecting the action of multiple different genes. Nevertheless, there is growing evidence that key gene variants can alter activity within specific neuronal circuits and, therefore, influence particular cognitive-affective phenomena. One example is the catechol-O-methyltransferase (COMT) gene, which has a common variant at codon 158. Those with valine (Val158) alleles have increased greater COMT activity and lower prefrontal extracellular dopamine compared with those with the methionine (Met158) substitution. Val158 alleles may be associated with an advantage in the processing of aversive stimuli (warrior strategy), while Met158 alleles may be associated with an advantage in memory and attention tasks (worrier strategy). Under conditions of increased dopamine release (eg, stress), individuals with Val158 alleles may have improved dopaminergic transmission and better performance. while individuals with Met158 alleles may have less efficient neurotransmission and worse performance. Some evidence suggests that Val158 alleles are associated with schizophrenia, while Met158 alleles are associated with anxiety.

Various schemes have been developed in attempts to define meaningful subtypes of obsessive-compulsive disorder (OCD). A factor analytic approach presumes that the symptom of the disorder can be described by several independent symptom dimensions. The purpose of this study was to explore the neural correlates of three symptom dimensions that were derived from previous factor analyses. Positron emission tomography was used to measure relative regional cerebral blood flow (rCBF) in 14 subjects with OCD while they engaged in a continuous performance task. Clinical indices, including factor scores, we ascertained via structured interviews plus administration of the Yale-Brown Obsessive-Compulsive Scale and checklist. The severity of Factor 1 (religious/aggressive/sexual obsessions and checking) was positively correlated with rCBF in striatum bilaterally. In addition, distinct trends were observed for the other two Factors. These findings provide initial support for a modular neurobiologic model of OCD, where dysfunction within separate component systems may principally mediate independent symptom factors. More important, this nove strategy may represent a powerful new approach to interpreting brain imaging studies of neuropsychiatric diseases.

Psychogenic nonepileptic seizures (PNES) are a functional neurological disorder/conversion disorder subtype, which are neurobehavioral conditions at the interface of neurology and psychiatry. Significant advancements over the past decade have been made in the diagnosis, management, and neurobiological understanding of PNES. This article reviews published PNES research focusing on semiologic features that distinguish PNES from epileptic seizures, consensus diagnostic criteria, the intersection of PNES and other comorbidities, neurobiological studies, evidence-based treatment interventions, and outcome studies. Epidemiology and healthcare utilization studies highlight a continued unmet medical need in the comprehensive care of PNES. Consensus guidelines for diagnostic certainty are based on clinical history, semiology of witnessed typical event(s), and EEG findings. While certain semiologic features may aid in the diagnosis of PNES, the gold standard remains capturing a typical event on video electroencephalography (EEG) showing the absence of epileptiform activity with history and semiology consistent with PNES. Medical-neurologic and psychiatric comorbidities are prevalent in PNES; these should be assessed in diagnostic evaluations and integrated into treatment interventions and prognostic considerations. Several studies, including a pilot, multicenter, randomized clinical trial, have now demonstrated that a cognitive behavioral therapy–informed psychotherapy is an efficacious treatment for PNES, and additional efforts are necessary to evaluate the utility of pharmacologic and other psychotherapy treatments. Neuroimaging studies, while requiring replication, suggest that PNES may occur in the context of alterations within and across sensorimotor, emotion regulation/processing, cognitive control, and multimodal integration brain systems. Future research could investigate similarities and differences between PNES and other somatic symptom disorders.

Objective: The authors conducted a review and meta-analysis of the literature comparing telepsychiatry with “in-person” psychiatric assessments.

Method: Approximately 380 studies on telepsychiatry published between 1956 and 2002 were identified using MEDLINE, PsycINFO, and cross-referenced bibliographies. Of these, 14 studies with an N>10 compared telepsychiatry with in-person psychiatry (I-P) using objective assessment instruments or satisfaction instruments. Three of these studies compared high bandwidth (HB) with low bandwidth (LB) telepsychiatry.

Results: Fourteen studies of 500 patients met inclusion criteria and were included in the meta-analysis. Telepsychiatry was found to be similar to I-P for the studies using objective assessments. Effect sizes were on average quite small, suggesting no difference between telepsychiatry and I-P. Bandwidth was found to be a significant moderator. Three moderators were tested, effect sizes remained largely heterogeneous, and further analyses are needed to determine the direction of effect. There was no difference between I-P and telepsychiatry between the HB and LB groups, although there are anecdotal data suggesting that H B was slightly superior for assessments requiring detailed observation of subjects.

Conclusion: Out of a large telepsychiatry literature published over the past 40+ years, only a handful of studies have attempted to compare telepsychiatry with I-P directly using standardized assessment instruments that permit meaningful comparisons. However, in those studies, the current meta-analysis concludes there is no difference in accuracy or satisfaction between the two modalities. Over the next few years, we expect telepsychiatry to replace I-P in certain research and clinical situations.

The evidence for the involvement of the serotonergic system in the pathogenesis of obsessive-compulsive disorder (OCD) is circumstantial at best, despite being the focus for most pathophysiological research over the last 2 decades. This hypothesis was initially motivated by the observed differential efficacy of selective serotonin reuptake inhibitors in alleviating OCD symptoms. Direct evidence that serotonergic perturbations are implicated in the pathophysiology of OCD is still sparse. There is growing evidence, from both preclinical and clinical studies, that the dopamine system may also be involved in the pathogenesis of OCD, and that dopaminergic and serotonergic pathways play a role in the genesis and maintenance of obsessive-compulsive symptoms. The complex interactions between both systems, the phenotypic heterogeneity of the disorder, and the limitations of the available tests to probe both systems, make it as yet impossible to draw firm conclusions as to how these systems are implicated. Further studies with more selective pharmacologic agents and neurocognitive probes in humans, studies using deep brain stimulation in combination with neuroimaging, and the development of better animal models for OCD may further our understanding of this disabling condition.

This article re-examines the popular concept of Internet addiction, discusses the key problems associated with it, and proposes possible alternatives. The concept of Internet addiction is inadequate for several reasons. Addiction may be a correct designation only for the minority of individuals who meet the general criteria for addiction, and it needs to be better demarcated from various patterns of excessive or abnormal use. Addiction to the Internet as a medium does not exist, although the Internet as a medium may play an important role in making some behaviors addictive. The Internet can no longer be separated from other potentially overused media, such as text messaging and gaming platforms. Internet addiction is conceptually too heterogeneous because it pertains to a variety of very different behaviors. Internet addiction should be replaced by terms that refer to the specific behaviors (eg, gaming, gambling, or sexual activity), regardless of whether these are performed online or offline.

Rapid urbanization worldwide is associated to an increase of population in the urban settings and this is leading to new emerging mental health issues. This narrative mini-review is based on a literature search conducted through PubMed and EMBASE. A total of 113 articles published on the issue of urban mental health have been selected, cited, reviewed, and summarized. There are emerging evidences about the association between urbanization and mental health issues. Urbanization affects mental health through social, economic, and environmental factors. It has been shown that common mental syndromes report higher prevalence in the cities. Social disparities, social insecurity, pollution, and the lack of contact with nature are some of recognized factors affecting urban mental health. Further reserach studies and specific guidelines should be encouraged to help policy makers and urban designers to improve mental health and mental health care facilities in the cities; additional strategies to prevent and reduce mental illness in the urban settings should be also adopted globally.

Aggression is a behavior with evolutionary origins, but is often both destructive and maladaptive in today’s society. Research over the past several decades has confirmed the involvement of neurotransmitter function in aggressive behavior. This research has centered around the “serotonin hypothesis.” As this literature continues to grow, guided by pre-clinical research and aided by the application of increasingly sophisticated neuroimaging methodology, a more complex picture has emerged. As current pharmacological and therapeutic interventions are effective but imperfect, it is hoped that new insights into the neurobiology of aggression will reveal novel avenues for treatment of this destructive and costly behavior.

Are brief cognitive-behavioral treatments for posttraumatic stress disorder (PTSD) also effective for the wider range of symptoms conceptualized as complex PTSD? Female rape victims, most of whom had extensive histories of trauma, were randomly assigned to cognitive-processing therapy, prolonged exposure, or a delayed-treatment waiting-list condition. After determining that both types of treatment were equally effective for treating complex PTSD symptoms, we divided the sample of 121 participants into two groups depending upon whether they had a history of child sexual abuse. Both groups improved significantly over the course of treatment with regard to PTSD, depression, and the symptoms of complex PTSD as measured by the Trauma Symptom Inventory. Improvements were maintained for at least 9 months. Although there were group main effects on the Self and Trauma factors, there were no differences between the two groups at posttreatment once pretreatment scores were covaried. These findings indicate that cognitive-behavioral therapies are effective for patients with complex trauma histories and symptoms patterns.

Animal models are invaluable in preclinical research on human psychopathology. Valid animal models to study the pathophysiology of depression and specific biological and behavioral responses to antidepressant drug treatments are of prime interest. In order to improve our knowledge of the causal mechanisms of stress-related disorders such as depression, we need animal models that mirror the situation seen in patients. One promising model is the chronic psychosocial stress paradigm in male tree shrews. Coexistence of two males in visual and olfactory contact leads to a stable dominant/subordinate relationship, with the subordinates showing obvious changes in behavioral, neuroendocrine, and central nervous activity that are similar to the signs and symptoms observed during episodes of depression in patients.

Since currently available antipsychotic medications predominantly treat hallucinations, delusions, disorganized thoughts and behavior, and related agitation/aggression, attention has traditionally been focused on managing positive symptoms. However, prominent negative symptoms and clinically relevant cognitive impairment affect approximately 40% and 80% of people with schizophrenia, respectively. Moreover, negative and cognitive symptoms are closely related to functional outcomes, and contribute substantially to the overall illness burden. Therefore, approaches to describe, measure, and manage these symptom domains are relevant. This article summarizes the phenomenology, prevalence, assessment, and treatment of negative and cognitive symptoms in patients with schizophrenia, including pharmacologic and nonpharmacologic management strategies that can be used in clinical care now, as well as pharmacologic approaches that are being tested. Currently, no approved treatments targeting negative or cognitive symptomatology in schizophrenia are available. It is hoped that progress in the understanding of the neurobiology of these important symptom domains of schizophrenia will help develop effective treatment strategies in the future. However, until this goal is achieved, clinicians should avoid therapeutic nihilism. Rather, the severity and impact of negative and cognitive symptoms should be determined, quantified, and monitored. Further, psychosocial treatments have shown therapeutic benefits. Thus, cognitive behavioral therapy, cognitive remediation, social skills training, and computer-assisted training programs should be offered in conjunction with antipsychotic treatment. Several non-antipsychotic augmentation strategies can be tried off-label. Treatment plans that incorporate currently available management options for negative and cognitive symptomatology in patients with schizophrenia should be adapted over time and based on the individual’s needs, with the aim to enhance overall outcomes.

Although cognitive-behavioral therapy (CBT) is an effective treatment for posttraumatic stress disorder (PTSD), many patients fail to attain remission with CBT. The authors propose augmentation of CBT with oxytocin in the treatment of PTSD. Oxytocin has a combination of pharmacologic effects that result in a “sense of safety” for the patient, which is a prerequisite to successful treatment of PTSD. We suggest a dual explanatory mechanism as to why oxytocin may be effective: through a reduction of fear response (decreasing amygdala activation, inhibiting fear response, and enhancing extinction learning) and through an increase of social interaction (activating social reward-related brain regions increasing engagement in the therapeutic alliance). Given that PTSD is marked by deficits in anxiety/stress regulation and in social functioning, and that oxytocin is implicated in both of these areas, oxytocin seems a likely candidate for treatment of patients with PTSD. Further clinical studies of the therapeutic value of oxytocin are indicated.

Studies of the hypothalamic-pituitary-adrenal (HPA ) axis in persons with posttraumatic stress disorder (PTSD) have produced variable findings. This review focuses on the factors likely to have affected the outcome of these studies, including population characteristics and experimental design. Also discussed is a possible role for the adrenal neurosteroid dehydroepiandrosterone (DHEA) as a mediator of HPA axis adaptation to extreme stress and the psychiatric symptoms associated with PTSD. The antiglucocorticoid properties of DHEA may contribute to an upregulation of HPA axis responses as well as mitigate possible deleterious effects of high cortisol levels on the brain in some PTSD subpopulations. The neuromodulatory effects of DHEA and its metabolite DHEAS at γ-arninobutyric acid and N-methyl-D-aspartate receptors in the brain may contribute to psychiatric symptoms associated with PTSD. The possible importance of other neurohormone systems in modulating HPA axis and symptom responses to traumatic stress is also discussed. Understanding the complex interactions of these stress-responsive neurosteroid and peptide systems may help explain the variability in patterns of HPA axis adaptation, brain changes, and psychiatric symptoms observed in PTSD and lead to better targeting of preventive and therapeutic interventions.

The hippocampus plays an important role in emotional and cognitive processing, and both of these domains are affected in patients with major depressive disorder (MDD). Extensive preclinical research and the notion that modulation of serotonin (5-HT) neurotransmission plays a key role in the therapeutic efficacy of selective serotonin reuptake inhibitors (SSRIs) support the view that 5-HT is important for hippocampal function in normal and disease-like conditions. The hippocampus is densely innervated by serotonergic fibers, and the majority of 5-HT receptor subtypes are expressed there. Furthermore, hippocampal cells often co-express multiple 5-HT receptor subtypes that can have either complementary or opposing effects on cell function, adding to the complexity of 5-HT neurotransmission. Here we review the current knowledge of how 5-HT, through its various receptor subtypes, modulates hippocampal output and the activity of hippocampal pyramidal cells in rodents. In addition, we discuss the relevance of 5-HT modulation for cognitive processing in rodents and possible clinical implications of these results in patients with MDD. Finally, we review the data on how SSRIs and vortioxetine, an antidepressant with multimodal activity, affect hippocampal function, including cognitive processing, from both a preclinical and clinical perspective.