Although significant progress has been made over the last decade in the treatment of obsessive-compulsive disorder (OCD), approximately 20% of OCD patients remain refractory to nonsurgical therapies, including pharmacologic and cognitive-behavioral therapy. Because a number of neural circuits involving the basal ganglia, thalamus, limbic system, and frontal lobes have been implicated in the pathophysiology of OCD, the need for an effective intervention in these patients has brought the focus on surgical approaches, including cingulotomy and capsulotomy procedures. Unlike free-hand surgical approaches used in the past, current neurosurgical interventions have been greatly enhanced by advances in technology, which allow lesioning to an accuracy of 1 mm. Today's neurosurgical approaches have shown significant benefit in as many as 60% of refractory patients, while preserving personality and cognitive functioning and limiting morbidity. A study of gamma knife capsulotomy conducted at Brown University School of Medicine showed that 40% of patients undergoing two lesioning procedures were much or very much improved 2 years postsurgery. The inherent obstacles to conducting placebo-controlled studies in these severely ill patients mean that further study is required to identify optimal candidates for surgical intervention.

In an open nonblind clinical trial, clomipramine was administered to five previously medicated prepubertal boys with autistic disorder and severe mental retardation unmanageable due to behavior and motor problems. Although all five boys initially displayed marked behavioral symptom reduction, they developed behavioral newotoxicity necessitating discontinuation of clomipramine for all five and immediate hospitalization for three. Serious adverse effects included increased seizure frequency and symptoms of a serotonin syndrome. Our findings indicate that clomipramine enhances adaptive behavior and produces serious adverse effects in severely retarded autistic children whose symptoms were complicated by dyskinesias.

In the past decade, clozapine, risperidone, and olanzapine were marketed for the first time in the United States, and other new antipsychotic drugs are expected to follow soon. Also within the past decade, the efficacy of serotonin-reuptake inhibitors (SRIs) has been demonstrated in patients with obsessive-compulsive disorder (OCD) and the serotonin hypothesis of OCD has been articulated clearly.

Can a medical illness or its treatment qualify as an emotionally traumatic event and can it cause posttraumatic stress disorder symptoms? If so, can the view of a medical illness as a traumatic experience enhance our ability to understand patients' adjustment to illness and their emotional reactions to it? Is it important to identify posttraumatic symptoms and try to address them in medically ill patients? These questions form the backbone for this review. Because many questions remain unanswered (or the answers are not definitive yet), we concisely summarize the issues and present our own view of the most pressing questions for further research.

This case report illustrates the relationship between stress and obsessive-compulsive disorder (OCD) by describing an unusual case of OCD sequelae following a suicide attempt. The patient is a 29-year-old married woman who suffered a major depressive episode without OCD and tried to commit suicide by drinking household cleaner. Following the attempt, violent obsessive thoughts of harming herself and others emerged along with avoidance behavior. After exposure therapy, there was a decrease in her obsessive thoughts, less anxiety, and no avoidance behavior. This report highlights not only the existence of “posttraumatic obsession” but also the importance of accurate interpretation of suicidal preoccupation, leading to the diagnosis of OCD rather then suicidal ideation secondary to depression.

This study investigates lifetime prevalence rates, demographic characteristics, childhood conduct disorder and adult antisocial features, suicide attempts, and cognitive impairment in individuals with obsessive-compulsive disorder (OCD) uncomplicated by or comorbid with any other psychiatric disorder. The data are from the NIMH Epidemiological Catchment Area (ECA) study, and the current analyses compared subjects with uncomplicated OCD (no history of any other lifetime psychiatric disorder) comorbid OCD (with any other lifetime disorder), other lifetime psychiatric disorders, and no lifetime psychiatric disorders across these variables. OCD in its uncomplicated and comorbid form had significantly higher rates of childhood conduct symptoms, adult antisocial personality disorder problems, and of suicide attempts than did no or other disorders. Comorbid OCD subjects had higher rates of mild cognitive impairment on the Mini-Mental Status Exam than did subjects with other disorders. These findings suggest that a subgroup of OCD patients may have impulsive features, including childhood conduct disorder symptoms and an increased rate of suicide attempts; wider clinical attention to these outcomes is needed.

Attention-deficit/hyperactivity disorder (ADHD) is present in 4% to 6% of adults in the United States. In the National Co-morbidity Survey Replication, a diagnosis of ADHD was associated with greater marital problems, unemployment, difficulties in the workplace, and frequent workplace absence. Despite these findings, the body of knowledge regarding impairment in adult ADHD is far from complete. Building upon our knowledge of impairment in adults with ADHD will result in a broader range of treatment outcomes which may be measured and targeted.

Body dysmorphic disorder (BDD) is characterized by preoccupation with a defect in appearance. Concepts of beauty play a particularly crucial role in humans' mental and social life, and may have specific psychobiologic and evolutionary underpinnings. In particular, there is a growing literature on the neurocircuitry underpinning the body schema, body image and facial expression processing, and aesthetic and symmetry judgments. Speculatively, disruptions in cognitive-affective processes relevant to judgments about physical beauty lead to BDD.

Obsessive-compulsive disorder (OCD) is a relatively common, often chronic and disabling disorder with high rates of partial and/or absent response to standard, recommended treatments, such as selective serotonin reuptake inhibitors (SSRIs) and psychotherapy. This article presents the cases of four patients suffering from OCD and comorbid mood or anxiety disorders, who were treated with SSRIs at adequate doses for at least 12 weeks, showing a partial response. Quetiapine treatment was added to SSRIs at a dose of 25 mg/day and titrated up to 200 mg/day. Patients were followed up for 6 months. After 12 weeks, all the patients were classified as “much improved” on the Clinical Global Impression–Improvement scale and showed a Yale-Brown Obsessive-Compulsive Scale score reduction ≥35%. After 6 months of follow-up, all the patients maintained the same level of improvement. Although quetiapine augmentation to SSRIs has shown mixed results in published controlled trials in the acute treatment (12 weeks) of patients with treatment-resistant OCD, this case series indicates that patients who benefit from this pharmacologic regimen in the acute phase tend to maintain such an improvement. Larger follow-up studies are warranted to confirm our findings.

There is an ongoing debate about how best to conceptualize the unconscious. Early psychodynamic views employed theories influenced by physics to explain clinical material, while subsequent cognitivist views relied on computational models of the mind to explain laboratory data. More recently, advances in cognitive-affective neuroscience have provided new insights into the workings of unconscious cognition and affect. We briefly review some of this recent work and its clinical implications.

Obsessive-compulsive disorder (OCD) is now recognized as a frequent and disabling disorder among children and adolescents. The phenomenology is similar to adult OCD, but several reports have indicated that compulsions are more prominent in children and that children are more inclined than adults to include their family surroundings in ritualistic behavior. It is also clear that young children engage in a significant amount of repetitive, ritualistic compulsive activity that appears to be a normal part of their behavioral repertoire.

Although the cause of childhood-onset OCD is unknown, many factors are likely to contribute to the heterogenous clinical phenotypes, including both genetic and environmental factors. The neurobiological circuitry involved in childhood-onset OCD is likely to involve alterations to the same cortico-striatothalamic circuitry implicated in adult OCD, but the develop-mental differences have yet to be fully delineated. The treatment response patterns of adults and children are generally inconsis-tent with each other, and specific OCD subtypes may also respond differentially.

Phenotypic characterization can be undertaken either categorically, as seen with traditional diagnostic categories, or dimensionally. Extended phenotypes can be defined in terms of symptoms and course of the illness, or neuroimaging and neurobiologic study findings, or treatment responses. Phenotypic characterization must also reflect an understanding of the rituals and repetitive behaviors that are associated with normal development. (A proposed categorization of OCD subtypes appears in the “Table library.”)

Although anxiety and mood disorders are listed as separate disorders in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, they frequently coexist. They may be expressed phenotypically as comorbidities or as the provisional entity mixed anxiety-depressive disorder. Patients with both anxiety and depression are more symptomatic, use more health care resources, and have a worse prognosis than those with a single disorder. Recognizing and treating these patients are challenges for physicians because the symptoms of the two disorders often overlap. Administration of effective treatment, comprising both anxiolytic and antidepressant effects, can reduce patient distress and disability, as well as inappropriate utilization of medical services. Medications such as tricyclic antidepressants, selective serotonin reuptake inhibitors, nefazodone, venlafaxine XR (extended release) and mirtazapine, are highly effective in treating comorbid depression and anxiety. These newer agents now represent the pharmacotherapeutic treatments of choice for the comorbid conditions.

Comorbid chronic pain is common in depressed patients. It is predictive of a poor prognosis for depression and is a major risk factor for suicidal behavior. Depression and chronic pain may result from a common neurobiological dysfunction of monoamine cell bodies in the basal ganglia. Amitriptyline, which inhibits both serotonin and norepinephrine reuptake, is a preferred treatment of chronic pain although it is not officially indicated for this condition. Chronic pain can be modeled in animals where amitriptyline has been shown to be highly effective. Similar effects are obtained with the serotonin norepinephrine reuptake inhibitors milnacipran, duloxetine, and venlafaxine, whereas selective serotonin reuptake inhibitors (SSRIs) are only weakly active. Both animal and clinical studies of chronic pain show that dual-acting reuptake inhibitors are more active than selective norepinephrine reuptake inhibitors, which are, in turn, more active than SSRIs. A meta-analysis of placebo-controlled studies confirmed that dual-action antidepressants, but not SSRIs, were effective in reducing chronic lower-back pain. Milnacipran, duloxetine, and venlafaxine, have all been reported to be effective in a number of chronic pain conditions, including the treatment of fibromyalgia where their analgesic effects are independent of comorbid depression.

Outpatient diversion programs present an opportunity for severely mentally ill defendants to receive psychiatric treatment and have alleged offenses dismissed by the court. Moreover, the successful completion of pretrial diversion is associated with fewer post-program arrest and jail days. The target patient population for such programs is typically people with schizophrenia spectrum disorders, but the care of such patients in outpatient settings presents challenges for monitoring treatment fidelity, specifically antipsychotic adherence, as low adherence rates are associated with increased rates of recidivism. Presented here is a review of evidence-based strategies that must be employed to track antipsychotic adherence in outpatient diversion programs, including pill counts, use of long-acting injectable antipsychotics, and determination of plasma antipsychotic levels to assess adherence and the adequacy of antipsychotic treatment. Antipsychotic therapy remains the foundation of schizophrenia treatment, but only through the use of all available modalities can clinicians maximize the odds that schizophrenia patients in pretrial diversion maintain psychiatric stability and successfully complete mental health court mandates.

Following the introduction of lamotrigine in 1994 as a treatment for epilepsy in the United States, the drug has seen progressively greater application in psychiatry, particularly as a treatment for bipolar disorder. This review critically evaluates the support for lamotrigine use across a broad range of psychiatric disorders as well as discuss its pharmacology, side-effect profile, and interactions with other medications.

Seasonal affective disorder is a common variant of recurrent major depressive disorder or bipolar disorder. Treatment with bright artificial light has been found to be effective in this condition. However, for patients who do not respond to light therapy or those who lack compliance, conventional drug treatment with antidepressants also has been proposed. Substances with selective serotonergic or noradrenergic mechanisms should be preferred over older antidepressants. Although there are a number of open and controlled studies evaluating different compounds, these studies were often limited by relatively small sample sizes. Furthermore, there are no studies specifically addressing bipolar seasonal depression. This article will review the published literature on pharmacotherapy of seasonal affective disorder.

Although not all individuals who work outside of standard daytime hours develop physical and psychiatric issues, there is a substantial portion of shift workers who develop shift work disorder. Shift work disorder is due to a misalignment between an individual's endogenous circadian rhythms and environmental stimuli, and can have potentially serious consequences to an individual's health and quality of life. This article reviews the neurobiological and genetic underpinnings of shift work disorder, and describes how desynchronization of the molecular clock may lead to both physical and psychiatric illnesses. Diagnostic tools and treatment guidelines to address the circadian misalignment, excessive sleepiness, and insomnia experienced by patients with shift work disorder are also discussed.

Combination pharmacotherapy has proven effective in a number of psychiatric disorders, including depression and schizophrenia. However, compared with other affective disorders, few studies have explored the use of combination therapy in alcoholism, and the majority have been limited to animal models. There is evidence to support a role for combination therapy in alcoholism. For example, several neurochemical systems, including the dopaminergic, serotonergic, and opioidergic, appear to affect alcohol intake. Studies in several different types of alcohol-preferring rats have suggested that coadministration of agents to target more than one of these systems simultaneously may produce beneficial effects on alcohol intake, while avoiding problematic effects, such as alterations in food or water intake. Data from preliminary clinical studies have shown trends toward combination therapy reducing alcohol intake in humans. While such findings are encouraging, they must be explored further in larger, randomized, double-blind trials.