Cardiovascular disease (CVD) remains the number one cause of death in the United States and most developed countries and is expected to remain so for much of this century. Rates of obesity have increased 2–4-fold over the last 2 decades in the US and this condition is linked with early development of hypertension, hyperlipidemia, diabetes, and atherosclerosis. The prevalence of diabetes is also increasing, and the rise of diabetes in young people 18–29 years of age was 40% in the period between 1990 and 2001. The World Heart Federation (WHF) has estimated that CVD will become the number one cause of death in the world by 2020, surpassing infectious disease in developing countries. Metabolic disorders are on the rise in general. However, as highlighted in the discussions presented in this supplement, patients with serious mental illness appear to represent a special population who are particularly vulnerable, with rates that surpass the general population.

Parkinson's disease is a neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, and resting tremor. Increasingly, Parkinson's disease has been associated with a broad spectrum of non-motor symptoms, such as olfactory loss, sleep disorders, autonomic dysfunction, cognitive impairment, psychosis, depression, anxiety, and apathy. In addition, a minority of Parkinson's disease patients develop compulsive behaviors while receiving dopamine-replacement therapy, including medication hoarding, pathological gambling, binge eating, hyperlibidinous behavior, compulsive shopping, and punding. These behaviors may result in psychosocial impairment for patients and therapeutic challenges for clinicians. This article reviews the anatomic substrates, behavioral spectrum, associated factors, and potential treatments for dopamine-replacement therapy-related compulsions in Parkinson's disease.

This review begins with a description of some problems that recently have beset an influential circuit model of fear conditioning and goes on to look at neuroanatomy that may subserve conditioning viewed in a broader perspective, including not only fear but also appetitive conditioning. The column will then focus on basal forebrain functional-anatomical systems, or macrosystems, as they have come to be called. Yet, more specific attention is then given to the relationships of the dorsal and ventral striatopallidal systems and extended amygdala with the dopaminergic mesotelencephalic projection systems, culminating with the hypothesis that all macrosystems contribute to behavioral conditioning.

Both obsessive-compulsive disorder (OCD) and social phobia are common in community and clinical settings, and it should be expected that a proportion of patients with one of these conditions will also fulfill either current or lifetime criteria for the other condition. However, comorbid social phobia is more common among patients with a primary diagnosis of OCD than is comorbid OCD in patients with a primary diagnosis of social phobia. This article explores the extent of the association of OCD and social phobia in epidemiological studies, and examines the possible role of underlying depression and other disorders in mediating the appearance of the comorbid condition. Although there have been no published randomized controlled trials in patients with this particular pattern of co-morbidity, it seems sensible to adopt pharmacologic and psychologic treatment approaches which have been found efficacious in both OCD and social phobia. Pharmacologic management therefore centers on first-line treatment with a selective serotonin reuptake inhibitor. Psychologic intervention should draw on the range of cognitive and behavioral approaches required for optimal outcomes in OCD and social phobia, as discrete conditions.

Antiglutamatergic agents, such as lamotrigine, have been used successfully for the treatment of posttraumatic stress disorder (PTSD). They could be potentially acting through the stabilization of the corticotropin-releasing factor (CRF) systems. Glutamate mediates CRF release in various brain regions involved in the pathophysiology of PTSD, antiglutamatergic agents could stabilize the CRF system and, thereby, improve the symptom complex of PTSD (reexperiencing, hyperarousal, and avoidance). The role of glutamate and CRF in PTSD and other anxiety disorders are still being elucidated. However, it is clear that the glutamatergic systems play a role in the pathophysiology of PTSD.

Clinicians should have an understanding of a lumbar puncture is indicated in the differential diagnosis of dementia and delirium. In most cases, this procedure is not commonly performed in outpatient practice for the differential diagnosis of dementia. However, in patients who have acute or subacute onset or a very rapid decline—such as in suspected Creutzfeldt-Jakob disease (CJD)—cerebrospinal fluid (CSF) 14-3-3, and tau proteins can be diagnostic for at least sporadic CJD. Practice parameters from the American Academy of Neurology (AAN) suggest performing a spinal tap on patients ≤55 years of age. However, that recommendation may not always be beneficial, particularly in a patient who has a prominent family history of either Alzheimer’s disease (AD) or frontotemporal dementia. Per the AAN practice parameter, lumbar puncture for CSF analysis is indicated in the diagnosis of central nervous system (CNS) infection, carcinomatous meningitis, or CNS vasculitis.

Beyond the clinically indicated lumbar puncture, there is utility of CSF biomarkers, including CSF Aβ42, total tau, and phospho-tau, which are the best studied. These biomarkers may be useful for cases involving atypical presentations of dementia, eg, when it is difficult to determine if the patient has AD versus frontotemporal dementia. They may be most useful for cases in which there is an atypical presentation of the fluorodeoxyglucose PET image or PET image features of both AD and frontotemporal dementia.

Manic depression, or bipolar disorder, is a multifaceted illness with an inevitably complex treatment. The current article summarizes the current status of our knowledge and practice concerning its diagnosis and treatment. While the prototypic clinical picture concerns the “classic” bipolar disorder, today mixed episodes with incomplete recovery and significant psychosocial impairment are more frequent. The clinical picture of these mixed episodes is variable, eludes contemporary classification systems, and possibly includes a constellation of mental syndromes currently classified elsewhere. Treatment includes the careful combination of lithium, antiepileptics, atypical antipsychotics, and antidepressants, but not all of the agents in these broad categories are effective for the treatment of bipolar disorder.

Pain, spasticity, tremor, spasms, poor sleep quality, and bladder and bowel dysfunction, among other symptoms, contribute significantly to the disability and impaired quality of life of many patients with multiple sclerosis (MS). Motor symptoms referable to the basal ganglia, especially paroxysmal dystonia, occur rarely and contribute to the experience of distress. A substantial percentage of patients with MS report subjective benefit from what is often illicit abuse of extracts of the Cannabis sativa plant; the main cannabinoids include delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol. Clinical trials of cannabis plant extracts and synthetic Δ9-THC provide support for therapeutic benefit on at least some patient self-report measures. An illustrative case is presented of a 52-year-old woman with MS, paroxysmal dystonia, complex vocal tics, and marijuana dependence. The patient was started on an empirical trial of dronabinol, an encapsulated form of synthetic Δ9-THC that is usually prescribed as an adjunctive medication for patients undergoing cancer chemotherapy. The patient reported a dramatic reduction of craving and illicit use; she did not experience the “high” on the prescribed medication. She also reported an improvement in the quality of her sleep with diminished awakenings during the night, decreased vocalizations, and the tension associated with their emission, decreased anxiety and a decreased frequency of paroxysmal dystonia.

Tics and Tourette syndrome are common comorbidities of patients diagnosed with attention-deficit/hyperactivity disorder (ADHD). One of the mainstay pharmacologic therapies for ADHD has been stimulants. However, this class of drugs has been associated with tic exacerbations, thus limiting their utility in this patients subgroup. Atomoxetine has been explored as an alternative treatment as one of the few non-stimulants available to treat ADHD. Early data identifies atomoxetine's influence on Tourette symptomatology to be not merely equivocal but potentially suppressive in the manifestation of tics. There are, however, case studies describing patients experiencing recurrences of tics following treatment with atomoxetine. We present a unique case of a patient, without any prior history of a movement disorder, who developed tics following a single dose of atomoxetine that did not improve until interventional therapy was initiated.

Objective: To identify characteristics of patients diagnosed with unipolar depression who may have undiagnosed bipolar disorder.

Methods: Patients diagnosed with unipolar depression by a healthcare provider were identified through the Consumer Health Sciences National Health and Wellness Survey. Manic symptoms, comorbid conditions, psychiatric symptomatology, use of healthcare resources, and patient demographics were identified through Internet-based questionnaires. A self-report adapted version of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision criteria identified symptoms consistent with a manic episode. Psychological well-being was measured by the Psychological General Well-Being Index.

Results: Of the 1,602 respondents who met inclusion criteria, 219 (14% or ~1 out of 7) reported symptoms consistent with a manic episode and were considered at risk for undiagnosed bipolar disorder. These respondents were younger and had a lower socioeconomic status. At-risk patients rated their depression as more severe and experienced greater impairment of psychological well-being. More than 70% of those at risk reported speaking with a healthcare provider about their mania symptoms. Comorbid mental disorders, especially anxiety-related conditions, were common in these patients.

Conclusion: These findings underscore the importance of evaluating unipolar patients for bipolar disorder and may help clinicians identify symptoms and comorbidities associated with patients with unipolar depression at risk for undiagnosed bipolar disorder.