New knowledge about the specific brain regions involved in depression is rapidly evolving due to advances in functional neuroimaging techniques. Several new regionally specific somatic interventions build on this modern neuroanatomic information. These latest methods promise to revolutionize the understanding and treatment of depression. This article reviews the past and current use of these techniques, with an eye toward where they are heading in the next century.

Apathy is a common neurobehavioral feature in a variety of neuropsychiatric disorders. Apathy is often interpreted as a sign of depression or as a nonspecific symptom of other medical conditions. However, recent research indicates that the essential meaning of apathy is lack of motivation. This article presents a framework for the classification and differential diagnosis of apathy and addresses issues related to the assessment and treatment of apathy in neuropsychiatric patients.

Over the past century researchers have attributed the symptoms that today are labeled as Tourette syndrome to various etiologies. Although most investigators have accepted Gilles de la Tourette's initial description of a symptom complex of tics and involuntary vocalizations, most have rejected his claim that “tic disease” resulted from hereditary degeneration. Subsequent investigators have offered an array of contradictory etiological explanations including viewing these symptoms as a subset of choreas, a result of insufficient inhibition, a failure to control infantile habits, a sequel to encephalitis and other infections, or the result of unconscious psychosexual childhood conflict. With the advent of effective pharmacologic treatments in the 1960s, psychiatrists, often urged on by the parents of afflicted children, began to insist that the disorder resulted from organic factors, most likely connected to transmission of the neurotransmitter dopamine and signaling in the basal ganglia. Since the 1970s, research has focused on a variety of possible organic substrates, but disputes over which symptoms to include in the syndrome's phenotype continue to constrain efforts to locate its etiology.

Based on previous evidence that trazodone may have antiobsessional properties, the authors assessed trazodone augmentation of selective serotonin reuptake inhibitor (SSRI) therapy in five cases of obsessive-compulsive disorder. All patients showed symptomatic improvement after trazodone was added to treatment with various SSRIs, and in many cases, trazodone also improved the tolerability of SSRI therapy.

The lifetime incidence of mood disorders is twice as great in women compared with men, with the highest risk occurring during the childbearing years. The management of mental illness during pregnancy and lactation is a particularly complex clinical situation. The cornerstone of such a clinical decision is a completion of an assessment of the risks of the illness vs the risks of treatment. The following article reviews the factors influencing infant outcome and outlines the essential elements of the process of determining risk for the use of psychotropics in women during pregnancy and lactation. As the available data rapidly change, the facets of the risk benefit assessment are consistent and often the issue of specific medication is decided by prior history and exposure.

In this article, we will first present an overview of the epidemiology and classification of headaches, distinguishing between primary headaches (in which the headache itself is the primary disorder) and secondary headaches (ie, headaches due to an underlying condition, such as a neoplastic and/or space-occupying lesion, a cerebrovascular accident, or other type of structural brain lesion). We will use the current classification system of the International Headache Society, focusing on primary headache disorders (migraine, tension-type headache, cluster headache), which we will discuss from the practical clinical perspectives of diagnosis and clinical management. Throughout this article, we will emphasize the chronicity and periodicity of headaches as a type of chronic pain syndrome.

Social phobia is an anxiety disorder that is characterized by excessive fear and/or avoidance of situations in which an individual believes that he or she may be the subject of evaluation or scrutiny while interacting with other people or performing a specific task. This article reviews the available literature on the neurobiology underlying social phobia, including autonomic nervous system effects, neuroimaging findings, pharmacologic challenge studies, and neuroendocrine responsivity and function. Overall, such studies have found few consistently demonstrable differences in neurobiology between patients with social phobia and healthy controls, but further investigations are needed.

Repeated episodes of alcohol withdrawal may exacerbate the severity of future withdrawal occurrences. The progressive intensification of withdrawal symptoms may be manifested as a kindling-like mechanism. This sensitization process may reflect persistent perturbation in excitatory and inhibitory influences on brain function. Relapse is also thought to be affected by the kindling mechanism. Successive alcohol withdrawal experiences may also lead to neurologic damage and cognitive impairments. We review the research findings regarding the alcohol withdrawal kindling hypothesis and the implications of the kindling process on mechanisms of dependence, alcohol withdrawal treatment strategies, and the long-term repercussions of alcoholism.

Genetic anticipation refers to an inheritance pattern within a pedigree showing a decrease in age of onset or an increase in disease severity or both in successive generations. This phenomenon has become the focus of important research in schizophrenia and bipolar mood disorder. The results to date have been controversial and far from conclusive. To attempt to resolve some of the earlier findings, we compared age at onset and disease severity between two generations in 24 Portuguese families ascertained for genetic linkage studies of bipolar mood disorder. There was a significant decrease in age of onset (P<. 00001) and increase in frequency of episodes (P<.0001)from the first to the second generation. This difference was significant under each of the four data-sampling schemes, one of which excluded probands. The second generation experienced onset 12.4 to 15.9 years earlier and illness 2.3 to 2.6 times more severe than did the first generation. We found no evidence for a specific effect in anticipation related to the transmitting parent's sex. Results of the present study, analyzed carefully for a variety of possible biases, suggest evidence for genetic anticipation in these Portuguese bipolar families.

Obsessive-compulsive disorder (OCD) has long been considered a treatment-refractory mental condition. Neither pharmacologic nor psychodynamic therapy has been proven to treat OCD effectively. Yet the prognosis for OCD has changed dramatically in recent years with the introduction of behavior therapy and the use of selective serotonin reuptake inhibitors (SSRIs). Many studies have shown that behavior therapy, especially exposure with response prevention, and SSRIs reduce obsessive-compulsive symptoms significantly. Still, many unanswered questions—including the role of cognitive therapy in the treatment of OCD, exposure therapy vs multimodal behavioral therapy, individual versus group therapy, outcome predictors in adults, adolescents, and children, and the role of combination treatment using an SSRI and cognitive-behavioral therapy—remain. This article will explore these issues as well as suggest directions for further research into OCD.

The familial nature of Tourette syndrome (TS) was first described by Georges Gilles de la Tourette in 1885. Formal investigations of TS since the 1970s have consistently demonstrated an increased risk for TS among relatives of patients with TS. Family studies, twin studies, and segregation analyses all indicate that TS has significant genetic determinants. The mode of transmission, while mildly controversial, is generally believed to be due to at least one major locus inherited either as an autosomal dominant trait with reduced penetrance, or as a trait with intermediate inheritance in which some heterozygotic persons manifest the disorder. There is evidence for a TS spectrum of symptoms that includes chronic tics and obsessive-compulsive disorder. Systematic genome linkage studies of TS are progressing. To date, however, no significant linkage findings exist, although the search has included many neurologically relevant candidate genes.

Magnetoencephalography (MEG) is an electrophysiologic brain imaging technology that has been applied to the study of mental illness, particularly schizophrenia. Like electroencephalography, it provides excellent temporal resolution, and in combination with magnetic resonance imaging, can also provide good spatial resolution. Studies of the auditory system in schizophrenia using MEG have demonstrated an abnormality in functional cerebral asymmetry, in which persons with schizophrenia typically show reduced, or reversed, cerebral asymmetry compared with normal subjects. This abnormality is sex-specific; it is more pronounced in males with schizophrenia. These findings have not been demonstrated using other neuroimaging strategies. Thus, MEG appears to offer a unique and valuable contribution to psychiatric neuroimaging. Current research and clinical applications of MEG are limited, however, by the high cost of instrumentation. The cost of MEG systems should improve as more applications are developed, in schizophrenia as well as other neuropsychiatric conditions, and hospitals begin to invest in the technology.

CNS Spectrums is a peer-reviewed journal that publishes original scientific literature and reviews on a wide variety of neuroscientific topics of interest to the clinician. CNS Spectrums publishes 12 issues yearly. As the immense prevalence of comorbid diseases among patients seen by psychiatrists and neurologists increases, these physicians will jointly diagnose and treat the neuropsychiatrically ill. Our mission is to provide these physicians with an editorial package that will enhance and increase their understanding of neuropsychiatry. To this end, manuscripts that address crossover issues germane to neurology and psychiatry will be given immediate priority.

The use of different imaging modalities provides the clinician and researcher with different views of anatomy and physiology at unprecedented levels of detail. Multimodal imaging allows for noninvasive measurement of structure and function in humans during complex behavior, and thus provides information about the inner workings of the brain previously unavailable. The present paper examines the various imaging techniques available, and describes their application to the clinic—in the case of epilepsy—and to research—in the case of schizophrenia. Because the electroen-cephalogram has a dynamic response in milliseconds, it provides the best temporal sensitivity of functional measures of brain activity. When coupled with high-resolution magnetic resonance imaging measures of brain structure, this multimodal approach provides a powerful tool for understanding brain activity. Clinically, the use of multimodal imaging has provided greater precision in localization of the epileptogenic focus. For researchers attempting to determine the underlying causes of schizophrenia, the use of multimodal imaging has helped lead the field away from a specific lesion view to a more distributed system abnormality view of this disorder.

Increasing recognition of the prevalence and impairment associated with social phobia has spurred the development of effective psychosocial treatments for this disorder. Exposure-based interventions have the most empirical support. This article applies the tripartite model of anxiety to social phobia, describes state-of-the-art psychosocial treatments, and highlights studies on the comparative and combined efficacy of psychological and pharmacologic treatments. Clinical issues related to treatment implementation, limitations of extant psychosocial interventions, and suggestions for future research are also discussed.

Tic disorders may manifest in a wide variety of clinical presentations, ranging from single tics of relatively short duration to a series of complex tics that may last for years. An understanding of the etiology of various tic disorders is essential to establish a differential diagnosis of Tourette syndrome (TS). Because TS is incurable, improvement in quality of life is the primary goal of pharmacologic therapy. Although neuroleptics have been the most effective medications to date in managing the symptoms of TS, they may have significant adverse effects that limit their use. Several alternative pharmacologic options are either available or under investigation.

Twin and family studies of obsessive-compulsive disorder (OCD) have gleaned important data regarding the influence of genetic factors in the development of this disorder. These studies have shown that understanding the importance of genetic factors in OCD is largely dependent upon how the phenotype is classified. The last decade of research has found that substantial variability of symptomatology exists across individuals diagnosed with OCD. Considering this, a number of analyses have been conducted to determine if possible subtypes of OCD exist, including analysis of age of onset, cluster analysis, factor analysis, and segregation analysis. These methodologies, and possibly others, could aid in identifying the genes involved in the development of OCD.

Although the incidence of cancer and cancer-related deaths has declined in recent years, undertreatment of cancer-related pain continues to be a significant problem. By thoroughly assessing chronic malignant pain (CMP) as it relates to cancer and achieving a more complete understanding of the CMP syndromes experienced by cancer patients, psychiatrists and neurologists can formulate accurate diagnoses of patients' clinical pain syndromes and construct well-defined, individual management plans for each patient.