Much attention has been given to the role of catecholamine dysfunction in posttraumatic stress disorder (PTSD), and only recently have researchers begun to focus on serotonin (5-HT) in PTSD. Serotonin appears to be a factor in responses followin extreme stress, such as those that precede PTSD. In this review, the authors provide a brief overview of the concept of PTSD and specific issues of clinical concern. The role 5-HT in the neurobiology of PTSD is explored in a review of animal model studies and of clinical investigations of paroxetine binding, pharmacologic challenges, and neuroimaging. Data on the use of 5-HT in PTSD treatment are provided in a review of both open-label and controlled studies of serotonergically active drugs.

As defined by the Diagnostic and Statistical Manual, Fourth Edition (DSM-IV), trichotillomania (TTM) is a complex syndrome of distressing, often uncontrolled, urge-driven hair pulling. Generally under-diagnosed, it is known to afflict approximately 1–2% of the population. Historically, the morbidity and psychosocial sequelae associated with this disorder have been seriously minimized. Clinical intervention remains a challenge with conflicting documentation of treatment efficacy and often-reported treatment relapse.

The dedication of an entire issue of CNS Spectrums to this disorder highlights the recent recognition of the clinical importance and scientific complexity of this condition. As guest editors of this issue, we welcome the opportunity to educate clinicians, clinical researchers, and basic scientists regarding current perspectives and challenges inherent in this disorder. It is our hope that these papers will encourage our professional audience to think critically about this condition, empirically study it, and work to improve the suffering of those afflicted with it. Furthermore, it should serve as a resource for hair pullers and their families, in conjunction with the soon-to-be-released American Psychiatric Association text, Trichotillomania: Current Developments.

Over the last two decades, there has been a resurgence of interest in cerebral mechanisms underlying many psychiatric disorders. The changes in our understanding of the syndrome called obsessive-compulsive disorder (OCD) reflect this shift of perspective. Although OCD remains a syndrome that is quintessentially psychiatric, it has been increasingly recognized that it also has a neurological dimension that merits study in its own right, using the concepts and tools of clinical neurology.

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.

The recurrent and frequently chronic course of affective disorders requires careful delineation of the number, frequency, and pattern of prior and current episodes and their response to pharmacotherapies to help develop optimal assessment and treatment approaches for these Potentially lethal medical illnesses. To better track and monitor the longitudinal course of unipolar and bipolar illness and to promote more effective management, we developed the retrospective and prospective National Institute of Mental Health Life Chart Methodology (NIMH-LCM). The principles of retrospective and prospective life charting are the focus of this article. Following introductory background information on affective disorders, the influence of Kraepelin's work and his use of life charts are reviewed as the basis and framework for the NIMH-LCM. The use of life charting both retrospectively and prospectively is discussed, with examples of its utility and benefits.

The lack of selective agonists and antagonists for serotonin 5-HT1B/1D receptors has made it difficult to determine the neurochemical, behavioral, and clinical effects controlled by 5-HT1B/1D receptors. However, by combining data from various compounds with different receptor affinity profiles, it is possible to tentatively determine those effects that result from interactions at the 5-HT1B/1D receptors.

This discussion contains a review of the in vitro and in vivo neuropharmacology of the 5-HT1B/1D group of receptor subtypes, and attempts to identify their possible functions and potential implications in central nervous system disorders.

Parkinson's disease is the most common basal ganglia disorder that is caused by the degeneration of dopaminergic neurons in the substantia nigra. This article reviews the normal physiology of the basal ganglia in the normal state, as well as the pathophysiology of Parkinson's disease (PD) and other movement disorders associated with the basal ganglia. Also discussed is the pathophysiological basis for the surgical treatment of PD.

The current tools used to define and diagnose mental disorders, including the Diagnostic and Statistical Manual of Mental Disorders and the International Classification of Diseases, have added specificity to the psychiatric nomenclature. However, their stereotypic rigidity in classification has resulted in the failure to identify the full range of potentially debilitating psychiatric symptoms with which patients may present. A spectrum model of psychopathology is more adept at recognizing the subclinical or threshold symptomatology that may occur concomitantly with core psychiatric disorders. The authors discuss the development of a spectrum approach to the diagnosis of mental disorders, which offers the potential to improve treatment selection and therapeutic outcomes.

Autism and related disorders occur in as many as one in 500 children. Recognizing the need for uniform recommendations to help guide the initial diagnostic evaluation and referrals in this area, an initial working group of the Cure Autism Now Foundation promulgated the following consensus guidelines for autism screening and diagnostic referral. Although these recommendations were formulated using the best information currently available, they are likely to be modified as the results of additional studies become available; however, they provide a useful tool for clinicians involved in the management of children with autism and related developmental abnormalities.

An overview is provided regarding neuroimaging in obsessive-compulsive disorder (OCD). The author emphasizes convergent research results across various experimental paradigms and their implications for neurobiological models of OCD. The article concludes with an outline of future considerations that highlights emerging concepts and techniques. This work was intended to serve as a concise summary of the field, and thus to provide a springboard for discussion about this topic at the upcoming International Obsessive Compulsive Disorder Conference.

The behavioral syndrome of trichotillomania (TTM) is well characterized, but challenges pertaining to TTM remain in several areas, including diagnostic classification, assessment of severity, and determination of relevance of comorbid psychiatric disorders. Acute pharmacological studies have focused on serotonin transport inhibitors, and preliminary evidence suggests that inhibition of both serotonin and norepinephrine transporters (ie, by clomipramine and venlafaxine) provides a clinical improvement. Dopamine antagonists are promising agents in need of systematic evaluation in TTM. Cognitive-behavioral therapy appears to achieve a decrease in acute symptoms in many patients. However, longitudinal maintenance of benefits has not been rigorously tested with either pharmacological or behavioral therapy. Clinical impressions and treatment data indicate that achieving durability of treatment benefits remains a major challenge in many patients with TTM, although there is evidence of improved outcome with comprehensive multimodal treatment.

This paper describes a model of psychopathology termed the panic-agoraphobic spectrum. The model has been constructed by identifying different psychopathologic and clinical domains that incorporate and extend the diagnosis of panic disorder as described in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV).

Categorical classifications do not take into account the subthreshold, atypical, and often enduring symptoms that accompany the core manifestations of full-blown mental disorders. These often-neglected spectrums of symptoms, however, may be as distressing and debilitating as the full-blown disorders and can have unrecognized importance in selection of and response to treatment. At the Department of Psychiatry, Neurobiology, Pharmacology, and Biotechnology, Institute of Psychiatry of the University of Pisa, Italy, a spectrum approach to mental disorders (eg, bipolar, obsessive-compulsive, eating, and panic disorders) has been used extensively and has proven effective in clinical practice.

The need for systematic identification and assessment of a broad array of symptoms and behavioral features has led, as a first step, to the conceptualization of the panic-agoraphobic spectrum model. In collaboration with researchers from the University of Pittsburgh, PA, and elsewhere, the University of Pisa scientists have further refined the panic-agoraphobic spectrum model and have developed a structured interview for this spectrum called the Structured Clinical Interview for Panic-Agoraphobic Spectrum. The rationale, clinical usefulness, and heuristic significance of the panic-agoraphobic spectrum model are discussed below.

This article presents an overview of sensorymotor aspects of obsessive-compulsive disorder (OCD). These phenomena have received less attention than obsessions and compulsions, but are nonetheless important in the development, maintenance, phenomenology, and treatment of the disease. In many individuals, seemingly disparate sensory-motor symptoms can be conceptualized as part and parcel of OCD. Sensory-motor aspects are discussed within the context of faulty information processing and related to neuropsychiatric systems characteristic of OCD. As the pathophysiology of OCD is highly extensive, not all sensory-motor symptoms discussed here will be observed in every individual.

The great revolution that took place in physics at the beginning of this century, which led to a total reshaping of the science and a different approach to natural phenomena, could serve as a model for future developments in other disciplines such as neuroscience. When investigated by traditional methods, the complexity of brain mechanisms remains quite elusive; the use of new strategies should, therefore, be a high priority.

Although holistic interpretations of brain functions and dysfunctions still seem futuristic, the application of chaos theories may be one way of making these interpretations more understandable. In fact, chaos mathematics can be applied to brain activity, such as that recorded, by electroencephalogram (EEG), and to the interpretation of psychopathology. Similarly, clinical phenomena could be explained in terms of nonlinear dynamics. Moreover, the application of chaos theories to psychiatry might permit the study of the relationships between genetic and environmental factors in determining syndromes and symptoms. This could encourage the development of a nonlinear dynamic psychiatry which, in turn, would allow a better understanding of research findings and, perhaps, open new horizons to psychiatric intervention.

As gambling becomes available to more and more individuals in this country, the problem of compulsive or pathological gambling (PG) will also increase. As with other forms of addiction, both environmental and genetic factors are involved in PG. Identification of the genes that play a role in increasing a person's risk for PG will lead to a better understanding of the disorder and to more rational and effective treatment. Although studies of the molecular genetics of PG are just beginning, a number of interesting observations have been made and are reviewed in this article. As with other addictive behaviors, abnormalities in dopaminergic reward pathways a likely to be involved. Consistent with this, we have observed a significant association between PG and the D1, D2, D3, and D4 dopamine receptor genes. The fact that each these genes has an effect is consistent with a polygenic inheritance of a susceptibility to PG The involvement of multiple dopamine genes consistent with the “reward deficiency syndrome,” which suggests that addictive impulsive disorders are due, at least in part, to genetic abnormalities of the dopamine reward pathways. On the basis of this hypothesis, we describe other genes also likely to play a role in a person's susceptibility to PG.

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.

Driving to the symposium, the vague anxiety and discomfort I had heen experiencing for the past few days finally culminated in the realization that 7 years ago that day, I awoke from my first night as an inpatient at a psychiatric unit.

Since then and because of that, I've learned a great deal about depressive and manic-depressive illness. I've learned about stigma and shame. I've learned about the devastation that the violence we benignly call “mood disorder” wreaks on families. I have been awed by the array of treatments we've found to ease the suffering, and humbled by the fact that we still have a long way to go. I have become painfully aware of how unenlightened the world still is about psychiatric illness, and saddened by the cruel irony that the only thing more stigmatizing than suffering from a psychiatric illness is seeking treatment for it.