One cannot get through a day (certainly not in the United States) without hearing about the devastation that substance abuse, addiction, and, in many cases, co-occurring disorders (ie, substance abuse or addiction in conjunction with a major psychiatric clinical syndrome and/or personality disorder) cast upon countless numbers of lives. For years, there has been a controversy as to whether addiction was simply a moral failing or a brain disease. Obviously, the latter is true.

As with any disease, addiction and co-occurring disorders are frequently considered to be primary, progressive, chronic, and, if untreated, fatal. With the advent of more sophisticated neurobiological and multivariate research, we can get beyond trivializing this serious disease entity by labeling it as a weakness or character defect, and get on with the significant work of focusing on those neurological pathways and their etiology that are responsible for addictive patterns of behavior.

Transcranial magnetic stimulation (TMS), a relatively noninvasive probe of cortical function, permits new kinds of explorations of relationships between regional brain activity and symptomatology in obsessive-compulsive disorder (OCD). In TMS, a pulsed magnetic field affects activity in cerebral cortex underlying an electromagnetic coil placed on the scalp. Results of exploratory studies suggest that the single- or paired-pulse TMS techniques, and the newer repetitive method (rTMS), in which trains of stimuli are delivered at a given frequency, are potentially useful probes of cortical mechanisms involved in psychopathologic conditions, as in studies of motor, sensory, and cognitive physiology. For example, single-pulse TMS of motor cortex can produce muscle potentials or movement. Higher-frequency repetitive stimulation (rTMS) of occipital cortex can produce phosphenes or visual extinction, stimulation of Broca's area results in word-finding difficulties or speech arrest, and rTMS of prefrontal cortex affects verbal recall and other cognitive functions. Prefrontal rTMS can alter mood in healthy individuals. Both open and controlled clinical studies suggest that single-pulse TMS, and rTMS, may have antidepressant effects. Although the cerebral cortex is the only human brain structure subject to direct magnetic stimulation with current technology, TMS may influence activity in subcortical sites via their functional relationships with cortical areas. The effects of TMS on cortical excitability may depend on a combination of factors including coil design, stimulus frequency and intensity, and possibly the functional state of the cortex before stimulation.

Myriad difficulties exist in analyzing the pharmacology of the serotonin 1A (5-HT1A) receptor. The receptor may demonstrate a different activity depending on the tissue or species used for analysis, the agent used, laboratory conditions, and differences between in vitro and in vivo effects of compounds. Affinity for 5-HT receptors also varies widely, presenting difficulties in drawing definitive conclusions on affinity values for various compounds. At least two possibilities exist to explain the diversity of pharmacology of 5-HT receptors. First, it is possible that different 5-HT1A receptor subtypes exist. Second, the 5-HT1A receptors may play a far more complex role than previously believed.

It seems obvious to most people that the brain and the rest of the body interact. Stress seems to worsen most general medical conditions, mortality is higher among widowers than married men, and almost everyone becomes moody when he or she has a viral infection. However, these are mostly anecdotal observations. The precise ways in which mind and body relate in health and disease is more elusive and, at times, controversial.

Perhaps the hardest evidence we have for a mind-body connection comes from studies showing that depression is an independent—and, surprisingly, quite a robust—risk factor for cardiovascular disease. Following acute coronary syndrome depression significantly worsens outcome, including increasing all-cause mortality rates.

Another well-documented finding, going in the opposite direction, is the high rate of depression experienced by those receiving α-interferon for the treatment of hepatitis C or malignant melanoma. Less secure is whether depression increases risk or worsens prognosis for cancer; why patients with schizophrenia are at greater risk for heart disease and cancer than the general population; if it is true that stress plays a role in exacerbations of multiple sclerosis; and what is the relationship between depression and the risk for Alzheimer's disease. In each there are conflicting epidemiological data and difficulties understanding the neural mechanisms that would broker the relationship between brain and targeted peripheral organ.

There are several investigational drugs in development for the treatment of depression. Some of the novel antidepressants in development target monoaminergic neurotransmission in accordance with the “monoamine hypothesis of depression.” However, the current conceptualization of antidepressant actions is that it is the downstream effects on protein synthesis and neuroplasticity that account for therapeutic efficacy, rather than the immediate effects on synaptic monoamine levels. Thus, a number of novel agents in development directly target components of this “neuroplasticity hypothesis of depression,” including hypothetically overactive glutamatergic neurotransmission and dysfunctional hypothalamic–pituitary–adrenal (HPA) axis functioning.

Many forensic psychiatric settings serve unique populations who have, in addition to traditional psychiatric symptoms, diverse legal and criminogenic needs. A lack of clear treatment standards that address all aspects of forensic care can lead to inefficient or inappropriate interventions and contribute to institutional violence.

In community settings, negative symptoms and cognitive deficits are the primary barriers to independent living, stable relationships, and employment for individuals suffering from schizophrenia-spectrum disorders. In contrast, however, positive psychotic symptoms (e.g., command hallucinations and persecutory delusions) often drive behavior which serves as the gateway to arrest and criminalization. Historically, the keystone of treatment for positive psychotic symptoms has been antagonism of dopamine D2 receptors in the mesolimbic tract. In this article, we review and explore the principles underlying dopamine antagonism for the treatment of psychosis; optimization of dopamine antagonists in treating positive psychotic symptoms; the advantages of depot dopamine antagonist antipsychotics in forensic settings; the concepts of pharmacokinetic and pharmacodynamic treatment failures; and the role of medication plasma concentrations in optimizing and managing treatment.

The neurobiology of trichotillomania (TTM) has only recently received attention from the neuropsychiatrie community, and the number of studies in this area is limited. Nevertheless, there is tentative support for the hypothesis that serotonergic, dopaminergic, and opioid systems mediate hair-pulling symptoms, and that corticostriatal circuits also play a role. An understanding of the neurobiology of TTM may be of value not only for the treatment of this disorder, but also for other stereotypic behaviors.

The notion that subtle cognitive, emotional, behavioral, and functional deviations from norms are present in many individuals several years before a formal diagnosis of schizophrenia has been around for almost a century. This notion has been at the base of the developmental hypothesis of schizophrenia and has been the impetus for the use of cognition as an endophenotype for studying the illness. The recent enthusiasm for prodromal research derives from two unrelated and controversial claims: that short duration of untreated psychosis is associated with better prognosis and that novel antipsychotic drugs have a better safety profile, supposedly enabling early intervention at a relatively lower risk of side effects to the patient.

At the current level of knowledge, the risk-benefit assessment of prodromal interventions turns out to be an almost unsolvable conundrum. On one hand, the age of onset of psychosis and schizophrenia, early and mid-ado-lescence, coincides with the age at which life-long social and vocational characteristics are shaped. Any intervention that could produce even minimal delay in onset of active psychosis or ameliorate its early course might have a life-long impact. Therefore, the idea of prodromal intervention cannot be easily dismissed. On the other hand, in absence of accurate markers for imminent psychosis and strong data indicating that treatment during the prodromal phase is effective, exposing adolescents to the stigma associated with the illness and the adverse effects of antipsychotics has raised serious hesitations among many researchers and clinicians.

Until recently, little was known about the epidemiology of attention-deficit/hyperactivity disorder (ADHD) in adults. Bottom-up studies following children with ADHD into adolescence had shown variable rates of persistence, some of which depended on the definitions used. The traditional diagnosis was complicated by the introduction of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, which stated that ADHD could be diagnosed with inattentive symptoms alone. This resulted in diagnostic inconsistency as earlier investigations demanded the presence of hyperactivity while others did not. Diagnosis also depended on the site, the cohort, whether interviews versus rating scales were employed, and whether the subject or their parent were the source of information.

Mr. F is a 60-year-old Caucasian, married, unemployed male who presented to the outpatient department of the Veterans Administration (VA) ∼10 months ago with a chief complaint of sleep difficulties. Approximately 12 years ago he had been diagnosed with posttraumatic stress disorder (PTSD) and a major depressive episode (MDE). He received very little treatment, either medication or therapy, at that time. He presented after being followed in a Veteran's Center for weekly to biweekly supportive therapy with a counselor for ∼6 months. He had gone to the Veteran's Center due to the encouragement of his wife. She had noted that he was becoming increasingly irritable and isolative at home and she had asked him to seek help for his anger and irritability. An event occurred in which he broke a chair after watching war-related news coverage and that made her insist that he present for treatment.

Alzheimer's disease (AD) is a debilitating condition affecting millions of elderly citizens. The quality of life for AD patients significantly deteriorates in the face of worsening cognitive deficits and disabling functional declines, both contributing to manifestations of difficult behaviors. Of the estimated 4 million individuals with AD, only 60% of probable AD cases are diagnosed, with little more than half of those receiving treatment. One of the possible reasons for this problem is the large role primary care physicians (PCPs) have in diagnosing and treating AD. The barriers that PCPs confront to adequately manage these patients will be discussed. Finally, the specific challenges that geriatric psychiatrists will face in addressing these issues in an environment where there is only a limited number of trained geriatric psychiatrists will be discussed, as well as the possible role that new technology could have in finding the solution to this difficult problem.

Central nervous system (CNS) vasculitis is a rare entity, especially when it occurs in isolation; it is seen more commonly as part of a multisystem vasculitis. Common presenting symptoms include persistent headache, encephalopathy, and multifocal signs. We discuss the case of a 68-year-old female who presented twice in 1 month with confusion and choreaform movements. Extensive workup was negative for a connective tissue disease or other conditions in the differential, including neurosarcoidosis, Creutzfeldt-Jakob disease, and neurosyphilis. The only significant findings were elevated erythrocyte sedimentation rate, inflammatory signs in the CNS, and diffuse slowing of the electroencephalogram. A presumptive diagnosis of isolated angiitis of the central nervous system (IACNS) was made and the patient was successfully treated with steroids. She recovered fully with no residual symptoms. The diagnosis of IACNS is often difficult given there are no definitive laboratory investigations or pathognomonic presentation. However, a series of signs, symptoms, and laboratory findings have been proposed that are helpful in making the diagnosis. To our knowledge, IACNS presenting primarily with delirium has not been previously reported in the literature. The diagnosis of IACNS is purely speculative for this case, as the gold standard for diagnosis, a leptomeningeal cortical biopsy, was not performed.

Depression and anxiety are among the top 10 health problems for which complementary and alternative therapies (CATs) are most frequently used, and medicinal herbs are among the most popular of these treatments. St. Johns wort(Hypericum perforaturn) is a perennial herb that has become a widely used depression therapy. Extracts of hypericum have shown affinity for receptors within multiple neurochemical systems. The primary active substance responsible for the antidepressant effect is not well defined, but most work has concentrated specifically on the hypericin and hyperforin components. Although hypericum has demonstrated significant antidepressant and antianxiety effects in multiple studies, there are several recent studies that do not support the previous evidence. In all reported studies, hypericum extracts have been well tolerated. In addition, new psychiatric uses for hypericum in obsessive-compulsive disorder, generalized anxiety disorder, menopausal symptoms, and alcohol dependence have been reported. Because patients are choosing to pursue CAT as a first-line therapy, psychiatrists will need to have a better understanding of phytomedicines used for treating depression and anxiety, and thus be better prepared to serve as effective allies of their patients.

Behavioral patterns of addiction include compulsive drug-seeking, persistent abuse of substances despite the often dire consequences on social functioning and physical health, and the high probability of relapse even after prolonged drug-free periods.The recent focus on the biological basis of addiction has provided evidence to support the hypothesis that behavioral manifestations for addiction are influenced by biological factors, and biological factors often produce behavioral changes that can further increase risk. The current understanding of the role of the dopaminergic, glutamatergic, γ-aminobutyric acidergic, and opioid receptor systems in the pathophysiology of addiction as well as the clinical implications of these systems for new and emerging treatments will be discussed. This article will also review the pharmacologic agents used in the treatment of substance abuse disorders and presents evidence-based data for their safety, efficacy, and feasibility of use in different patient populations.

A 48-year-old woman suffering from treatment-resistant psychogenic stiff neck and severe depression had been treated with a varied regimen of medications, including antidepressants, neuroleptics, and antiepileptics. These treatments did not result in improvement. Therefore, she was treated with a combination of sertraline and risperidone. Depressive symptoms decreased within a few weeks of treatment initiation. The psychogenic stiff neck, which had begun to improve within the first 2 weeks, had disappeared completely after 6 months of treatment with risperidone alone. This case report suggests that risperidone may be effective in some neurological motor disorders comorbid with mood disorders.

Galantamine is US-Food and Drug Administration FDA-approved for mild-to-moderate Alzheimer’s disease. However, its unique pharmacological portfolio speaks to the idea of a pluripotent agent with a broad therapeutic potential. Here, authors briefly discuss these off-label clinical indications synthesizing the extant evidence.