Over the last 25 years, there has been a rapid expansion of our knowledge base of social phobia (SP). Although there are a number of well-validated treatment modalities, including pharmacotherapy and cognitive-behavioral therapy, significant gaps remain in our ability to achieve full remission in most patients. Despite advances in the neurobiology of SP, the etiology has yet to be determined. Investigations examining potential predictors of response have provided little guidance in selecting an appropriate treatment modality. These gaps in our knowledge have pushed us to examine issues related to treatment resistance. This paper presents a review of the current literature and issues related to treatment-resistant SP, including a discussion of the functional impairment associated with SP, definitions of treatment response and remission, as well as outcome measures that have been used in clinical investigations of SP. In addition, criteria for a standard treatment trial, predictors of treatment response, a review of treatment resistance studies, and potential directions for future research are examined. The most promising strategies to attain remission, will likely involve augmenting selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors with agents such as anticonvulsants, benzodiazepines, and antipsychotics as well as combining pharmacotherapy with cognitive-behavioral therapy. Our current treatment target of simply attaining a response needs to be refocused, so that an asymptomatic state and high end state functioning become the final goal of treatment.

Major depressive disorder (MDD) is a debilitating illness affecting 7% to 12% of men and 20% to 25% of women. It is usually a recurrent illness, with up to 30% of patients experiencing a depressive episode lasting over 2 years. Depression may also increase the morbidity and mortality of numerous medical conditions, such as cardiac disease, myocardial infarction, chronic pain, diabetes, cerebrovascular events, and respiratory illnesses. The goal of antidepressant therapy is to achieve full remission and functional recovery, and continuing treatment beyond the acute phase is usually necessary to maintain remission. In contrast with full remission, individuals who experience residual symptoms, however mild, have a higher chance of experiencing one or more additional episodes.

The risk of suicide is greatly increased in individuals with schizophrenia. Previous research has identified several potential risk factors for suicidal behavior in schizophrenia, although their ability to independently predict suicide is limited. The objective of this review was to systematically analyze and identify the interaction between the proposed risk factors in the literature that may predict suicidal behavior in schizophrenia. Articles that explored suicidal behavior and suicide risk in schizophrenia that were published between 1980 and August of 2015, indexed in PubMed, MEDLINE, and Scopus were systematically reviewed. Many studies proposed a range of biopsychosocial risk factors that may independently lead to suicide in schizophrenia. These risk factors appear to be mainly related to stress, a history of suicidal behavior, and psychotic symptoms. It is clear, however, that many of these factors do not act independently and in fact require the reciprocal interaction of several of them to pose a risk for suicide in schizophrenia. Independently, the power of many risk factors to predict suicide is limited. Future studies should continue to adopt a multidimensional approach by considering the interaction of several factors in assessing the risk for suicide in schizophrenia.

What are the conceptual and empirical bases for current interventions for acute stress reactions following trauma exposure? This review compares the two major alternatives to managing acute stress reactions, outlines their conceptual bases and critiques the evidence for their efficacy in preventing subsequent stress disorders. The review integrates current evidence for cognitive behavior therapy with recent neuroscience findings that fear reduction learning can be enhanced by modulating glutamaterigc systems. D-cycloserine provides exciting opportunities to enhance the effects of cognitive-behavioral therapy, and points to closer understanding of the biological mechanisms that underpin clinical gains achieved by psychological therapies.

What is the long-term outcome of patients with obsessive-compulsive disorder (OCD) who are treatred with exposure and response (ritual) prevention (EX/RP) alone, serotonergic medications alone, or their combination? How is the long-term outcome of these patients affected by the discontinuation? Follow-up assessments were conducted with 62 patients treated for OCD an average of 17 months posttreatment (range: 6–43 months). Patients received one of three treatments: serotonergic medications (fluvoxamine or clomipramine), intensive behavior therapy involving EX/RP, or intensive EX/RP with concurrent antidepressant medication. At follow-up, no differences in OCD symptom severity were found among the three treatment groups. However, when current medication use was taken into consideration, differences among the three treatment groups emerged. Among patients who were medication-free at the time of follow-up assessment (n=37), those in the EX/RP-alone and EX/RP-with-medication groups had lower symptom severity ratings than those in the medication-only group on 4 out of 6 measures. There were no differences in OCD severity ratings among patients taking medications at follow-up (n=25). Although these findings are interpreted with caution due to the uncontrolled nature of the study, results suggested that long-term outcome may be superior following EX/RP than following serotonergic medications, after discontinuation. For patients who remain on medications, the treatment produced benefits equivalent to EX/RP.

Autism is heterogeneous with respect to clinical symptoms and etiology. A significant limitation in research of the neurobiology and treatment of autism has been the lack of attention to this heterogeneity. A dimensional approach to the study of autism is valuable in linking key symptoms to the neurobiology and treatment of the disorder in a clinically meaningful way. In this article, we outline a dimensional approach to the autism spectrum, discuss the three core dimensions of autism and their neurobiology, and review the possible links of serotonin, anterior cingulate gyrus activity, and the immune marker D8/17 to the repetitive behavior/compulsivity dimensions.

Bipolar disorders are a group of psychiatric disorders with profound negative impact on affected patients. Even if their symptomatology has long been recognized, diagnostic criteria have changed over time and diagnosis often remains difficult. The Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), issued in May 2013, comprises several changes regarding the diagnosis of bipolar disorders compared to the previous edition. Diagnostic categories and criteria for bipolar disorders show some concordance with the internationally also widely used Tenth Edition of the International Statistical Classification of Diseases and Related Health Problems (ICD-10). However, there are also major differences that are worth highlighting. The aim of the following text is to depict and discuss those.

Benzodiazepines (BZs) are clinically used as anxiolytic, hypnotic, anticonvulsant, and antispasmodic drugs. Research using transgenic mouse models has suggested that the effects of BZs involve multiple subtypes of the γ-aminobutyric acid type A (GABAA) receptor, identified by specific α subunits (α1, α2, α3, α5). This review discusses the experimental uses of β-carboline-3-carboxylate-t-butyl ester (βCCT), a drug that binds preferentially to the GABAA α1 subtype but exerts no action (ie, is a pharmacologic antagonist at the GABAA α1 subtype receptor). βCCT blocks the anxiolytic-like effects of BZs, although studies in primates suggests this antagonism may reflect multiple receptor populations. βCCT antagonized the ataxic but not muscle relaxant effects of BZs, a finding that implicates the GABAA α1 subtype receptor in ataxia but not muscle relaxation. The potential clinical utility of βCCT is discussed, both in terms of treatment (ie, hepatic encephalopathy) and as a diagnostic imaging agent. Altogether, these results indicate that subtype-selective antagonists represent a useful approach to studying receptor mechanisms underlying the behavioral effects of BZ-type drugs.

The introduction of deep brain stimulation (DBS) as a treatment for medication-refractory essential tremor in the late 1980s revealed, for the first time, that “chronically” implanted brain hardware had the potential to modulate neurologic function with surprisingly low morbidity. Over time, the therapeutic promise of DBS has become evident in Parkinson's disease and dystonia. In some experienced centers, complex tremor disorders, such as posttraumatic Holmes tremor and the tremor of multiple sclerosis, are being increasingly targeted. More recently, other indications, including obsessive-compulsive disorder, Tourette's syndrome, major depression, and chronic pain, have been proposed. As the field has expanded, our knowledge about potential cognitive side effects of DBS has also expanded. This article reviews the current knowledge regarding the impact of stimulation of the subthalamic nucleus, globus pallidus internus, and ventralis intermedius nucleus of the thalamus on symptoms in essential tremor, Parkinson's disease, and dystonia. Also discussed are the emerging targets, what is known about the cognitive sequelae of DBS, and what has been learned about the complications and therapeutic failures.

We report two cases of serotonin syndrome in elderly patients during treatment of psychotic depression with atypical antipsychotics and antidepressants. The first case is a 69-year-old man who was admitted for depression with psychosis and treated with trazodone, risperidone, and sertraline. Subsequently, he developed myoclonus, tremor, cogwheel rigidity, and diaphoresis. The second case is a 72-year-old female initially admitted to a medical inpatient unit for a change in mental status that presented as increased confusion, lethargy, slurred speech, and a fever of 101.5°. She had been on phenelzine and quetiapine. In both cases, all symptoms resolved within 24 hours of the psychotropics being stopped. In both cases, we believe that serotonin syndrome was produced by a combination of an antidepressant and an atypical antipsychotic. There have been several case reports of serotonin syndrome from similar combinations of antidepressant and atypical antipsychotic treatment. Clinicians treating elderly patients with a combination of serotonergic antidepressants and atypical antipsychotics for psychotic depression should be aware of the potential for serotonin syndrome.

Tardive dyskinesia can now be successfully treated by inhibiting the vesicular monoamine transporter type 2 (VMAT2).

Insufficient treatment of psychosis often manifests as violent and aggressive behaviors that are dangerous to the patient and others, and that warrant treatment strategies which are not considered first-line, evidence-based practices. Such treatment strategies include both antipsychotic polypharmacy (simultaneous use of 2 antipsychotics) and high-dose antipsychotic monotherapy. Here we discuss the hypothesized neurobiological substrates of various types of violence and aggression, as well as providing arguments for the use of antipsychotic polypharmacy and high-dose monotherapy to target dysfunctional neurocircuitry in the subpopulation of patients that is treatment-resistant, violent, and aggressive. In this review, we focus primarily on the data supporting the use of second-generation, atypical antipsychotics both at high doses and in combination with other antipsychotics.

A small but growing neuroimaging literature has begun to examine the neural mechanisms underlying the difficulty that substance-use dependent (SUD) groups have with ignoring salient, drug-related stimuli. Drug-related attentional bias appears to implicate the countermanding forces of cognitive control and reward salience. Basic cognitive neuroscience research suggests that ignoring emotionally evocative stimuli in our environment requires both up-regulation of control networks and down-regulation of processing in emotion and reward regions. Research to date suggests that attentional biases for drug-related stimuli emerge from a failure to sufficiently increase control of attention over salient, but task-irrelevant stimuli. While SUD samples have typically shown increased activity in the cognitive control regions (ie, lateral prefrontal and dorsal anterior cingulate), during attentional bias such increases appear to have been insufficient for the concomitant increases in processing by the emotion/reward regions (ie, amygdala, insula, and striatum). Given the potential contribution of attentional biases to perpetuating drug use and the development of interventions (both pharmaceutical and cognitive-behavioral) to treat biases, understanding the neural basis of successfully reducing bias remains an important, but as yet unanswered, question for our field.

This article discusses the neurocircuitry and the neurochemical systems, as well as the molecular elements within these systems, that are believed to be important in the etiology of alcoholism. Alcoholism is a complex behavioral disorder characterized by excessive consumption of alcohol; a narrowing of the behavioral repertoire toward excessive consumption; the development of tolerance and dependence; and impairment in social and occupational functioning. Animal models of the complete syndrome of alcoholism are difficult if not impossible to achieve, but validated animal models exist for many of the different components of the syndrome.

Recent work has begun to define the neurocircuits responsible for the major sources of positive and negative reinforcement that are key to animal models of excessive alcohol intake. Alcohol appears to interact with alcohol-sensitive elements within neuronal membranes that convey the specificity of neurochemical actions. Positive reinforcement appears to be mediated by an activation γ-aminobutyric acid A receptors, release of opioid peptides and dopamine, inhibition of glutamate receptors, and interaction with serotonin systems. These neurocircuits may be altered by chronic alcohol administration. This is reflected by their exhibiting opposite effects during acute alcohol withdrawal, and by the recruitment of other neurotransmitter systems, such as the stress neuropeptide corticotropin-releasing factor. These neuropharmacologic actions are believed to produce allostatic changes in set-point, which set up the vulnerability to relapse that is so characteristic of alcoholism. Future challenges include a focus on understanding exactly how these neuroadaptive changes convey vulnerability to relapse in animals with a history of alcohol dependence.

Behavioral addictions are considered as the repetitive occurrence of impulsive behaviors without consideration of their potential negative consequences. These addictions represent an increasing cost to society and are an important new field of research in psychiatric genetics. There has been a growing body of evidence on the familial aggregation and genetic influences on the development of behavioral addictions and mainly on pathological gambling. The aim of this article is to critically review findings of family and molecular genetic studies on behavioral addictions, focusing on pathological gambling and commenting on other disorders where appropriate. This review provides a comprehensive approach to genetic studies on behavioral addiction and points out the necessity of expanding the genetic research in this field. Future directions for genetic studies in this field are also discussed.