Although the vagus nerve has traditionally been considered to perform efferent functions, in reality it performs significant afferent functions as well, carrying information from the body, head, and neck to the brain. Preliminary studies examining this afferent activity led to the theory that vagus nerve stimulation (VNS) could successfully control seizure activity in persons who are refractory to antiepileptic medications. Unlike other forms of brain stimulation, VNS is unable to directly stimulate multiple discrete areas of the brain; however, through several pathways, it is able to relay sensory information to higher brain regions. An implantable VNS device known as the VNS™ NeuroCybernetic Prosthesis (NCP) System has been used in approximately 9,000 epilepsy patients in Europe and the United States since 1994. The implant has reduced seizure frequency by an average of 25% to 30%, with minimal side effects. Studies underway are also showing some degree of success in the management of treatment-refractory depression. The future efficacy of the implantable system in other disorders may depend on whether the implant can be more precisely focused to affect different brain regions. Research in this area is underway.

Although addictive syndromes have been traditionally related to substance-use disorders, during the last few decades a novel addictive group, including the so-called “behavioral or no-drug addictions,” has been recognized and has attracted increasing attention for its relevant social impact. This group includes pathological gambling, compulsive shopping, TV/Internet/social network/videogame addictions, workaholism, sex and relationship addictions, orthorexia, and overtraining syndrome. Substance and behavioral addictions show similar phenomenological features, such as craving, dependence, tolerance, and abstinence, and perhaps they share a common possible pathophysiology. It is, however, controversial whether all or at least some of them should be considered real disorders or just normal, albeit extreme, behaviors. The aim of this article is to review current data on pharmacological treatment of behavioral addictions. As no specific and validated treatment algorithms are currently available, only an improved knowledge on their psychopathological, clinical, and neurobiological features may have relevant implications for more focused preventive and therapeutic strategies.

Vortioxetine is an antidepressant with multiple pharmacologic modes of action at targets where serotonin neurons connect with other neurons. 5HT3 receptor antagonism is one of these actions, and this leads to increased release of norepinephrine (NE), acetylcholine (ACh), and serotonin (5HT) within various brain circuits.

There is increasing evidence that supports the view that irritable bowel disorder (IBS) is a disorder of brain-gut function. Cognitive-behavioral therapy (CBT) has received increased attention in light of this recent shift in the conceptualization of IBS. This review has two main aims. The first is to provide a critical review of controlled trials on CBT for IBS. The second is to discuss ways of further developing CBT interventions that are more clinically relevant and meaningful to health care providers and individuals with a diagnosis of IBS. A theme from a CBT intervention will be presented to illustrate how CBT interventions can be incorporated within a larger social context. A review of CBT for IBS lends some limited support for improvement in some IBS symptoms and associated psychosocial distress. This conclusion needs to be expressed with some caution, however, in light of many methodological shortcomings including small sample sizes, inadequate control conditions and failure to identify primary versus secondary outcome measures. In addition, future studies will need to further develop more relevant CBT protocols that more fully integrate the patient's perspective and challenge social cognitions about this stigmatized disorder.

The past decade has witnessed a dramatic acceleration in research on the role of the neuropeptides in the regulation of eating behavior and body weight homeostasis. This expanding research focus has been driven in part by increasing public health concerns related to obesity and the eating disorders anorexia nervosa (AN) and bulimia nervosa (BN). Preclinical advances have been facilitated by the development of new molecular and behavioral research methodologies. With a focus on clinical investigations in AN and BN, this article reviews research on selected hypothalamic and gut-related peptide systems with prominent effects on eating behavior. Studies of the orexigenic peptides neuropeptide Y and the opioid peptides have shown state-related abnormalities in patients with eating disorders. With respect to gut-related peptides, there appears to be substantial evidence for blunting in the meal-related release of the satiety promoting peptide cholecystokinin in BN. Fasting plasma levels of the orexigenic peptide ghrelin have been found to be elevated in patients with AN. As discussed in this review, additional studies will be needed to assess the role of nutritional and body weight changes in neuropeptide alterations observed in symptomatic eating disorder patients, and to identify stable trait-related abnormalities in neuropeptide regulation that persist in individuals who have recovered from an eating disorder.

The clinical value of the current Diagnostic and Statistical Manual of Mental Disorders diagnosis of adjustment disorder is controversial. The aim of this article is to review the literature on adjustment disorder and to present suggestions for the improvement of this diagnostic category in future classification systems. The literature utilized for this review was retrieved by MEDLINE (1967 until May 2009) and was supplemented by a manual search of the literature. The analysis of the literature indicates that the diagnosis of adjustment disorder is not characterized by consistent clinical description and prognosis, adequate differentiation from other disorders, or specific psychometric and neurobiologic features. The spectrum of affective disturbances entailed by the diagnosis of adjustment disorder appears to be too broad. A major problem seems to lie in the fact that it is an exclusion diagnosis that overlaps with subthreshold manifestations of mood and anxiety disorders. More precise characterizations of stress-related disturbances are available.

Research on deep brain stimulation (DBS) for treatment-resistant psychiatric disorders has established preliminary efficacy signals for treatment-resistant depression. There are only few studies on DBS that included patients suffering from bipolar disorder. This article gives an overview of these studies concerning DBS targets, antidepressant efficacy, and the occurrence of manic/hypomanic symptoms under stimulation. First, promising results show that all patients experienced significant improvement in depressive symptomatology. In a single case, hypomanic symptoms occurred, but they could be resolved by adjusting stimulation parameters. Furthermore, this article highlights important clinical differences between unipolar and bipolar depression that have to be considered throughout the course of treatment.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by chronic abdominal discomfort or pain in the absence of detectable organic disease. IBS is common and is associated with a significant impairment in health-related quality of life. Enhanced perception of visceral stimuli (“visceral hypersensitivity”) appears to be an important patho-physiological mechanism. Early IBS studies using functional brain imaging techniques suggest an alteration in central pain modulation circuits, rather than an increased sensitivity of peripheral visceral pain pathways. The frequent comorbidity with psychiatric disorders suggests the possibility of shared pathophysiological mechanisms and etiologic factors.

Evidence from a recent randomized controlled trial of surgical versus medical therapy of temporal lobe epilepsy proves that antero'mesial resection is safe and more effective than medical therapy. The number of patients needed to treat for one patient to become free of disabling seizures is two, which is superior to most interventions in neurology. A meta-analysis of non-randomized trials gives almost identical results; about two-thirds of patients become seizure-free, compared with only 8% with medical therapy. The results are remarkably similar among studies from different parts of the world. Quality of life improves early after epilepsy surgery, the improvements are both statistically and clinically significant, and they are sustained. Surgical morbidity with clinically important permanent sequelae is 2%. Epilepsy surgery remains underutilized in developed countries and it does not exist in all but a few developing countries. Current randomized trials are underway to explore the effect of early surgery versus optimum medical therapy on the prevention of disability in patients with mesial temporal lobe epilepsy, and to examine the effectiveness of novel interventions, such as minimally invasive surgery and brain stimulation.

Chronic pain syndromes are often treatment refractory and pose an enormous burden of suffering for the individual. Chronic pelvic pain (CPP) is generally defined as noncyclic pain of at least 6 months duration and severe enough to require medical care or cause disability. CPP has been estimated to have a prevalence of 15% among women of reproductive age. Women are at increased risk for both major depression and chronic pain syndromes such as CPP, and are more likely to report antecedent stressful events, have higher rates of physical and sexual abuse, and subsequently develop posttraumatic stress disorder. High rates of sexual and physical abuse and other trauma have been shown among women with CPP, including symptoms of dyspareunia (pain during intercourse), dysmenorrhea (pain during menstruation), and vulvar pain. A detailed and comprehensive evaluation of the patient with CPP should include a thorough gynecologic exam and a full mental health assessment. Treatment of CPP must include an integrated approach targeted at both the psychiatric comorbidity and pain symptoms. A multidisciplinary treatment team offers the best chance for success with CPP, and it is critical to suggest psychiatric treatment (psychopharmacology and/or psychotherapy) in addition to traditional medical and surgical approaches.

Bipolar disorder (BD) is among the most impairing psychiatric disorders affecting children and adolescents, despite our best psychopharmacological and psychotherapeutic treatments. Cognitive remediation, defined as a behavioral intervention designed to improve cognitive functions so as to reduce psychiatric illness, is an emerging brain-based treatment approach that has thus far not been studied in pediatric BD. The present article reviews the basic principles of cognitive remediation, describes what is known about cognitive remediation in psychiatric disorders, and delineates potential brain/behavior alterations implicated in pediatric BD that might be targets for cognitive remediation. Emerging data show that cognitive remediation may be useful in children and adults with schizophrenia, ADHD, and anxiety disorders, and in adults with BD. Potential targets for cognitive remediation in pediatric BD include face processing, response inhibition, frustration, and cognitive flexibility. Further study is warranted to determine if cognitive remediation for these targets, or others, may serve as a novel, brain-based treatment for pediatric BD.

The modern therapeutic approach to most psychiatric diseases involves a combination of well-supervised psychotherapy, pharmacotherapy, and electroconvulsive therapy. Patients who fail to adequately respond to these modern treatment methods and remain severely disabled may be considered for surgical intervention. Cingulotomy, capsulotomy, subcaudate tractotomy, and limbic leucotomy are the most common psychosurgical procedures performed today, with response rates in the 35% to 65% range. Modern stereotactic techniques have reduced complication rates, but controversy remains regarding the optimal surgical procedure. The major psychiatric diagnostic categories that might respond to surgery include treatment-refractory major affective disorders, obsessive-compulsive disorder, and chronic anxiety states. Surgery should be considered as one part of an entire treatment plan and must be followed by an appropriate psychiatric rehabilitation program. It should only be carried out by an expert multidisciplinary team consisting of a neurologist a neurosurgeon, and a psychiatrist with experience in these disorders. Surgical intervention remains a reasonable therapeutic option for select patients with a disabling psychiatric disease and may be underutilized.

Our knowledge of the prevalence and demographic and clinical characteristics of obsessive-compulsive disorder (OCD) has, until recently, been based almost exclusively on patient samples. The epidemiology of OCD was first described in a large United States household sample from the Epidemiologic Catchment Area (ECA) study. Since these original observations, the rates of OCD in household populations determined from diagnostic procedures similar to those used in the United States have been published from different parts of the world. Detailed comparisons of rates, sex ratios, age at onset, and demographic and clinical characteristics of OCD in these samples are now available.

This article reports on the cross-national epidemiology of OCD from seven international epidemiologic surveys, including the United States ECA study. Each survey used the Diagnostic Interview Schedule (DIS), a highly structured interview, developed for use in epidemiologic surveys, that yields Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III) psychiatric diagnoses. All investigators provided the data from their study to be pooled at Columbia University, and the prevalence rates were standardized to the age and sex distribution of the five-site ECA household population so that more precise estimates and comparisons could be made.

Leptin is an adipocyte-derived hormone, which is involved predominantly in the long-term regulation of body weight and energy balance by acting as a hunger suppressant signal to the brain. Leptin is also involved in the modulation of reproduction, immune function, physical activity, and some endogenous endocrine axes. Since anorexia nervosa (AN) and bulimia nervosa (BN) are characterized by abnormal eating behaviors, dysregulation of endogenous endocrine axes, alterations of reproductive and immune functions, and increased physical activity, extensive research has been carried out in the last decade in order to ascertain a role of this hormone in the pathophysiology of these syndromes. In this article, we review the available data on leptin physiology in patients with eating disorders. These data support the idea that leptin is not directly involved in the etiology of AN or BN. However, malnutrition-induced alterations in its physiology may contribute to the genesis and/or the maintenance of some clinical manifestations of AN and BN and may have an impact on the prognosis of AN.

Basic and clinical studies over the past 10 years have lead to a fundamental shift in our understanding of mood disorders. These studies demonstrate that mood disorders and stress are accompanied by structural alterations in the brain; moreover, these structural alterations are reversible with antidepressant treatment. These alterations include changes in the length and number of neuronal processes, the number of neurons and glia, and even the rate of neurogenesis in the adult brain. Work is also being conducted to identify the molecular mechanisms underlying these changes and the adaptations that are critical to the therapeutic actions of antidepressant treatment. Some of the intracellular targets include second messengers, gene transcription factors, and neurotrophic factors that could oppose the actions of stress and depression. Taken together, this exciting new work describes and details structural alterations of limbic brain regions that are extremely dynamic and adaptive. Further understanding of the abnormalities in these systems that lead to mood disorders will provide more efficacious and possibly faster-acting therapeutic interventions.

While monoaminergic hypotheses of psychopathology remain popular, there has been growing interest in the role of neurotrophins in neuropsychiatric disorders. Basic laboratory work has documented the importance of neurotrophins in neuronal survival and synaptic plasticity, and a range of clinical studies has provided analogous evidence of their role in neuropathology. Work on gene variants in brain-derived neurotrophic factor, and associated changes in structural and function brain imaging, have further contributed to our understanding of this area. Much remains to be done to delineate fully the relevant mechanisms by which brain-derived neurotrophic factor and other neurotrophins contribute to psychopathology, and to develop targeted therapeutic interventions. Nevertheless, the neurotrophin hypothesis has already given impetus to a range of valuable research.