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.

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.

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.

Many patients who present physical symptoms that their doctors cannot explain by physical disease have persisting symptoms and impairment. An influential view has been that such symptoms are the somatization of emotional distress, but there has also been concern that medical practice contributes to shaping these presentations. Analysis of patients' accounts indicate that they approach these consultations with a sense of being the expert on the nature and reality of their symptoms and, in primary care at least, they seek convincing explanations, engagement, and support.They often describe doctors as doubting that their symptoms are real and as not taking their symptoms seriously. Observational research has demonstrated that patients presenting idiopathic symptoms in primary care generally provide cues to their need for explanation or to psychosocial difficulties. Their doctors tend to provide simple reassurance rather than detailed explanations, and often disregard psychosocial cues. Patients seem to intensify their presentation in consequence, elaborating and extending their accounts of their symptoms, perhaps in the effort to engage their doctors and demonstrate the reality of their symptoms. When doctors propose physical investigation and treatment in response to such escalating presentation, they thereby inadvertently somatize patients' psychological presentation. Consultations, therefore, have elements of contest, whereby patients seek engagement from doctors who seek to disengage. Although provision of a medical label, such as a functional diagnosis, can legitimize patients' complaints and avoid contest, this is at the risk of indicating that medicine can take responsibility for managing the symptoms. More collaborative relationships rely on doctors recognizing patients' authority in knowing about their symptoms, and providing tangible explanations that make sense to the patient and allow them to tolerate or manage the symptoms. Researchers need to study how doctors can best achieve these aims within routine consultations.

Beginning this month and appearing periodically in future columns, “Trends in Psychopharmacology” will cover a new concept and hot topic in the field, namely, that of “multifunctional drugs.” The concept is presented in overview here. Future installments will cover specific drugs in greater depth. Multifunctional drugs include those agents with more than one putative therapeutic mechanism of action.

Vagus nerve stimulation (VNS) in humans generally refers to stimulation of the left vagus nerve at the cervical level. VNS is an established treatment largely devoid of severe side effects for medically refractory partial-onset seizures and has been used in more than 16,000 patients. Over the past 5 years, applications in other neuropsychiatric disorders have been investigated, with a special emphasis on depression. Recent data from an open-label, multi-center pilot study involving 60 patients suggest a potential clinical usefulness in the acute and maintenance treatment of drug-resistant depressive disorder. The perspective of VNS as a long-term treatment with the advantage of assured compliance makes it an interesting technique to potentially treat drug-resistant depression. However, definite therapeutic effects of clinical significance remain to be confirmed in large placebo-controlled trials. Results of clinical pilot studies involving patients suffering from obesity and Alzheimer's disease indicate that VNS might induce weight loss and improve cognition. Besides its clinical usefulness, VNS can be used as a research tool, allowing neuro-physiologic investigations of the parasympathetic system and its interactions with other parts of the central nervous system.

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.

Objective: To assess the frequency of suicidal ideation and suicide attempts in patients with Parkinson's disease.

Methods: The Mini International Neuropsychiatric Interview (MINI), Beck Depression Inventory (BDI), and Hamilton Rating Scale for Depression (HAM-D) were administered to 90 consecutive, non-demented Parkinson's disease patients. They were also submitted to a complete neurologic examination which included brief cognitive batteries, the Mini Mental Status Exam, and Frontal Assessment Battery. We analyzed the scores of the section of the MINI related to the risk of suicide as well as the specific questions of BDI and HAM-D concerning suicidal ideation.

Results: No patient had ever attempted suicide. According to MINI, suicidal ideation was present in 13 patients (14.4%) with Parkinson's disease. All instruments assessed the risk of suicide in a similar way. Suicidal ideation was associated only with lower age (P=.022), lower age of Parkinson's disease onset (P=.021), panic disorder (P=.004), social anxiety disorder (P=.007), and major depression (P<.001). Logistic regression analysis indicated that major depression was the main predictor of suicidal ideation.

Conclusion: Suicide attempts seem to be uncommon in Parkinson's disease, despite the fact that the rates of suicidal ideation are possibly elevated. Depression seems to be the most important predictor of suicidal ideation in Parkinson's disease.

Recent data suggest that the presence of psychotic symptoms in patients suffering from posttraumatic stress disorder (PTSD) may represent an underrecognized and unique subtype of PTSD. Among combat veterans with PTSD, 30% to 40% report auditory or visual hallucinations and/or delusions. The presence of psychotic symptoms in PTSD is associated with a more severe level of psychopathology, similar to that of chronic schizophrenia. In this review, the differential diagnosis of psychotic symptoms in PTSD is discussed, including possible comorbid schizophrenia, psychotic depression, substance-induced psychosis, and personality disorder. A recent biologic study supporting the existence of a unique subtype of PTSD with psychotic features is also addressed, as are the similarities between PTSD with psychotic features and psychotic depression disorder. Finally, data on the treatment implications of psychotic symptoms in PTSD are presented. The intriguing recent findings on psychotic symptoms in PTSD need further investigation in noncombat-related PTSD populations before findings can be generalized to all individuals with PTSD.

This study was conducted to show that catatonia is a predisposing factor for neuroleptic malignant syndrome (NMS) and to review the nosological relationship between catatonia and NMS. Seventeen consecutive cases of NMS were analyzed prospectively with reference to clinical and investigative findings before and after exposure to a neuroleptic. The series comprised eight males and nine females, ranging in age from 18 years to 65 years. Prior to neuroleptic exposure, all patients exhibited features compatible with criteria for catatonia (mutism/excitement) according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised, (DSM-III-R). Following neuroleptic administration (single dose in nine cases), patients deteriorated into a febrile, rigid, and obtunded state accompanied by autonomic dysfunction and raised creatine phosphokinase levels. These features were consistent with a diagnosis of NMS. Neuroleptics were discontinued and supportive medical treatment instituted. Benzodiazepines were beneficial in eight cases in relieving stupor, but bromocriptine and dantrolene were generally ineffective. In all patients diagnosed with NMS in the authors' series, catatonia was an invariable prodromal state. It appears that the administration of a neuroleptic intensified the preexisting catatonic state and precipitated a malignant variant of the disorder, which is currently recognized as NMS. The authors, therefore, challenge the separate nosological status of NMS and catatonia and suggest that these syndromes are part of a unitary pathophysiological disorder.

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.

Introduction: Although the association between mood disorders, and particularly bipolar disorders, comorbidity and suicidality in posttraumatic (PTSD) patients is well established, less information is available on the impact of subsyndromal mood symptoms. The aim of the present study was, thus, to explore the frequency and relationship between subthreshold mood symptoms, assessed by a specific and validated questionnaire, and suicidality in PTSD patients.

Method: Sixty-five PTSD outpatients without bipolar disorders and 65 healthy control subjects were asked to complete the Mood Spectrum-SR-Lifetime Version (MOODS-SR), a questionnaire exploring the presence of subthreshold affective symptoms. Logistic regression models were used to analyze the relationships between suicidality, explored by six items of the MOODS-SR combined and dichotomized to denote the presence or absence of suicidal ideations/plans and/or attempts, and the number of manic/hypomanic or depressive symptoms.

Results: Statistically significant and positive associations were found between the presence of manic/hypomanic and depressive symptoms and the likelihood of suicidal ideation or attempts.

Conclusion: Besides depressive, even subthreshold manic/hypomanic features seem to be associated with higher suicidality in PTSD patients.

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 Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) categorization of mental disorders places “separation anxiety disorder” within the broad group of anxiety disorders, and its diagnosis no longer rests on establishing an onset during childhood or adolescence. In previous editions of DSM, it was included within the disorders usually first diagnosed in infancy, childhood, or adolescence, with the requirement for an onset of symptoms before the age of 18 years: symptomatic adults could only receive a retrospective diagnosis, based on establishing this early onset. The new position of separation anxiety disorder is based upon the findings of epidemiological studies that revealed the unexpectedly high prevalence of the condition in adults, often in individuals with an onset of symptoms after the teenage years; its prominent place within the DSM-5 group of anxiety disorders should encourage further research into its epidemiology, etiology, and treatment. This review examines the clinical features and boundaries of the condition, and offers guidance on how it can be distinguished from other anxiety disorders and other mental disorders in which “separation anxiety” may be apparent.

Functional neurological disorders (FND)—also called psychogenic, nonorganic, conversion, and dissociative disorders—constitute one of the commonest problems in neurological practice. An occupational therapist (OT) is commonly involved in management, but there is no specific literature or guidance for these professionals. Classification now emphasizes the importance of positive diagnosis of FND based on physical signs, more than psychological features. Studies of mechanism have produced new clinical and neurobiological ways of thinking about these disorders. Evidence has emerged to support the use of physiotherapy and occupational therapy as part of a multidisciplinary team for functional movement disorders (FMD) and psychotherapy for dissociative (nonepileptic) attacks. The diagnosis and management of FND has entered a new evidence-based era and deserves a standard place in the OT neurological curriculum. We discuss specific management areas relevant to occupational therapy and propose a research agenda.