Childhood-onset schizophrenia is a rare pediatric onset psychiatric disorder continuous with and typically more severe than its adult counterpart. Neuroimaging research conducted on this population has revealed similarly severe neural abnormalities. When taken as a whole, neuroimaging research in this population shows generally decreased cortical gray matter coupled with white matter connectivity abnormalities, suggesting an anatomical basis for deficits in executive function. Subcortical abnormalities are pronounced in limbic structures, where volumetric deficits are likely related to social skill deficits, and cerebellar deficits that have been correlated to cognitive abnormalities. Structures relevant to motor processing also show a significant alteration, with volumetric increase in basal ganglia structures likely due to antipsychotic administration. Neuroimaging of this disorder shows an important clinical image of exaggerated cortical loss, altered white matter connectivity, and differences in structural development of subcortical areas during the course of development and provides important background to the disease state.

In initial studies using animal models of depression, we primarily focused on the similarities of transcranial magnetic stimulation (TMS) to electroconvulsive therapy (ECT). However, our investigations show that TMS has its own, unique, potentially diagnostic and therapeutic effects, distinct from those of ECT. These effects need further exploration in animal and clinical studies.

Background: We investigated clinical factors to determine their relationship to treatment resistance among bipolar patients who had a consultation at a tertiary care facility.

Methods: Patients were separated into two categories: rapid-cycling disorders and nonrapid-cycling disorders. We hypothesized that there would be less usage of lithium carbonate among nonrapid-cycling treatment-resistant patients than among rapid cyclers and also that there would be higher rates of comorbidity seen among nonrapid-cycling than rapid-cycling patients in order to account for these particular patients being treatment resistant.

Findings: Continued recyling and persistent depression characterized rapid cyclers, whereas persistent depression characterized nonrapid cyclers. Less than 30% of patients had adequate lithium treatment and there was no significant difference comparing rapid cyclers with non-rapid cyclers. Rates of comorbidity were also not significantly different between these groups. We also assessed a number of other factors.

Conclusion: Some of these factors were significant, but when a Bonferonni correction was applied, these significant differences were not maintained. The study of treatment resistance among nonrapid-cycling bipolar patients merits further research.

In a variety of mammalian species, prenatal androgens organize brain structures and functions that are later activated by steroid hormones in postnatal life. In humans, studies of individuals with typical and atypical development suggest that sex differences in reproductive and nonreproductive behavior derive in part from similar prenatal and postnatal steroid effects on brain development. This paper provides a summary of research investigating hormonal influences on human behavior and describes how sex differences in the prevalences and natural histories of developmental psychopathologies may be consistent with these steroid effects. An association between patterns of sexual differentiation and specific forms of psychopathology suggests novel avenues for assessing the effects of sex steroids on brain structure and function, which may in turn improve our understanding of typical and atypical development in women and men.

During the past 10 years, there has been a welcome influx of novel agents for the treatment of epilepsy. Many show advantages compared to older agents, including better adverse effect profiles and lack of drug-drug interactions. The sheer number of agents now available makes distinction among them confusing at times. Agents differ in spectrum of action, pharmacokinetic profile (affecting dosing schedule and drug interactions), and titration time. This review highlights the differences between the various new agents and the more traditional antiseizure drugs. Evidence for the widespread use of these compounds outside their indication, particularly for diseases other than epilepsy, is reviewed as well.

Prior to adolescence, the rates of depression are similar in girls and boys, or are slightly higher in boys. However, with the onset of puberty, the gender proportion of depression dramatically shifts to a 2:1 female to male ratio. What is the relationship between menarche and the onset of major depression in early adolescence? A recent theoretical model proposes that vulnerability to depression may be rooted in normal female hormonal maturational processes and gender socialization. Information regarding the management of depression in adolescent and young adult women is provided, including gender differences in the presentation of depressive symptoms, instruments to facilitate assessment, and treatment options. Pubertal and other hormonal changes should be monitored prospectively along with individual, genetic, constitutional, and psychological characteristics. The burden of illness associated with onset of depression following menarche reinforces the importance of expeditious recognition and intervention.

Depression affects 6.5 million of the 35 million Americans ≥65 years of age. While depression usually begins earlier in life and recurs periodically, it can present for the first time in people 80–90 years of age as well. Depression throughout the lifespan has a genetic/biological component but is also very much affected by social environmental factors. As people age, demographic factors, social support, and negative life events remain important to overall mental health, while physical illness and disability begin to take on a much more prominent role. Depression in the elderly is associated with impairment, dependency, disability, and significant distress for the individual and their family. This population is likely to present with concomitant cognitive dysfunction and medical illness, which can complicate the identification and treatment of psychiatric conditions. Bereavement is almost universal in late life and is sometimes a deterrent to appropriate diagnosis and treatment of depression. Physical frailty and diminishing social resources further complicate the treatment of depression in the elderly. Elderly individuals respond well to standard pharmacotherapy and psychotherapy treatments for depression. However, due to the high rate of relapse of depression in this population, continuous treatment is often warranted. This monograph will review depression in the elderly in the context of social disruptions, such as bereavement, caregiver strain, interpersonal conflict, role transitions, and social isolation; late-onset vascular depression and cognitive impairment; and physical illness including disability.

The World Health Organization has determined that obsessive-compulsive disorder (OCD) is the 10th leading medical cause of disability across the globe. Unfortunately, a substantial proportion of patients with OCD fail to respond to medication trials. In the pivotal double-blind, placebo-controlled trials that established the efficacy of clomipramine and the selective serotonin reuptake inhibitors (SSRIs), 40% to 60% of patients were nonresponders to a given drug. Moreover, patients who do not respond to their first medication trial may be less likely than treatment-naive patients to respond to subsequent trials. For example, only 33% of patients participating in double-blind trials who had failed trials of one or more serotonin reuptake inhibitors (SRIs) benefited from a subsequent trial of sertra-line, compared with 53% of those who were treatment naive (Rasmussen, Baer, Eisen, and Shera, unpublished data, 15th Annual Meeting, American Psychiatric Association, May 17-22, 1997).

At the Fourth International Obsessive-Compulsive Disorder Conference, held in February 2000 in St. Thomas, US Virgin Islands, an afternoon panel was devoted to considering issues and strategies related to treatment-refractory OCD. The panel presentations were divided into three groups: time to response and outcome after long-term followup; pharmacologic strategies for nonresponders; and new data concerning nonpharmacologic interventions.

Repetitive transcranial magnetic stimulation (rTMS) is a relatively new technique for activating the cerebral cortex through the scalp and skull. By inducing electrical currents in the brain, rTMS is able to produce a variety of effects, including muscle twitching, changes in motor performance, disruption of cognitive and perceptual processes, and changes in mood. Although the technique is noninvasive and easily tolerated by patients and normal subjects, rTMS can produce epileptic seizures and, potentially, other undesirable effects on brain function. Further studies will be required to fully define the safe ranges of the stimulation parameters.

Objective: To better understand the efficacy and tolerability of atypical antipsychotics among racial groups, we reviewed data from four short-term (4–6 weeks), fixed-dose, placebo-controlled trials of ziprasidone for black, white, and overall populations of patients with schizophrenia.

Methods: Efficacy of ziprasidone in the black, white, and overall schizophrenic populations was compared to placebo using standard efficacy measures (Positive and Negative Syndrome Scale [PANSS] total, PANSS negative, Brief Psychiatric Rating Scale [BPRS], Clinical Global Impression-Severity [CGI-S], CGI-Improvement [CGI-I]).

Results: Black patients receiving ziprasidone demonstrated statistically significant improvements from baseline in PANSS total, PANSS negative, and BPRS, and improvements in CGI-S and CGI-I (n=99–149) compared with placebo (n=41–66); improvements were comparable to those observed in the overall population (n=451–639) and the white population (n=310–430). Interaction effect (treatment by race) was not significant for any efficacy variables. Ziprasidone was well-tolerated among black patients (n=175). Adjusted mean (least squares mean) overall weight gain in black patients receiving ziprasidone (n=124) was 1.8 kg. There were no increases in total cholesterol, triglycerides, or random glucose in the black population.

Conclusion: Ziprasidone has similar efficacy and safety in black patients with schizophrenia compared with patients in the white and overall populations.

It is just 3 or 4 weeks after my diagnosis of Tourette syndrome (TS). I have been slowly and conscientiously titrating upward the dose of medication prescribed by my neurologist, waiting skeptically, but not without hope, for some amelioration of my tics. A typical scientist/patient, I have downloaded all available information about this drug from the Internet and have been recalculating the increasing dose in mg/kg body weight every few days. Today I have ducked out of my lab and am doing a very hard training run along the Muddy River in Boston, gearing up for my 21st year of spring and summer races, when I am caught unprepared by a flash of insight. I am speeding along the path with a smoothness and crispness of rhythm that I have seldom felt—maybe just one of those rare great days?—when it occurs to me that I am taking a good deep breath every four strides, in-and-out without fail, every four strides. And only at that moment do I realize that I have always suffered from “skipping” breaths, even on the hardest runs, and have always taken it for granted. Indeed, I have always assumed that all other runners' breathing is as ragged as my own. But now—how remarkable!—I am not missing a single precious breath. This, I realize, is because my phonic tic is gone. So my teammates and competitors must have never missed those breaths, not a single one, because they don't have TS!

Many psychiatric disorders are influenced by genetic factors, but the genetic components of complex diseases may not follow clear inheritance patterns. Although the patients may share a common clinical phenotype, the cause of the syndrome may consist of a heterogeneous collection of both genetic and/or environmental components. One method to minimize genetic heterogeneity in studies of complex disorders is to select a very homogenous study population. The average number of families with the same last name, when corrected for population size, is an excellent marker for the degree of homogeneity. We used surname analysis to evaluate the homogeneity of the Portuguese population of Madeira, comparing it with previous data on the homogeneity of populations of mainland Portugal, the Azores, and both rural and urban US populations. The average number of families with the same last name corrected for population size was 33.84 in Madeira, 30.88 in the Azores, and 21.42 in Coimbra (mainland Portugal) compared with 1.13 in rural and 0.38 in urban United States. This surname analysis supports the premise that the Portuguese population is a highly homogenous population, with the highest homogeneity in Madeira and the Azores, making it a good study population for molecular genetic analyses.

A number of myths exist concerning the psychological impact of breast cancer. Primary among these is the belief that women with breast cancer have greater emotional disability than individuals with other diseases or the population at large. While research has shown that women cope remarkably well with a diagnosis of breast cancer, an understanding of the key periods of anxiety and primary stressors is crucial to the overall psychological and medical management plan. While psychopharmacologic therapy may be indicated for women with breast cancer, it is rarely sufficient and should be combined with effective psychosocial interventions such as group therapy.

In treating schizophrenia there has been a shift in focus, with more attention being paid to early intervention based on the notion that effective treatment at this point can improve outcome. Most of this work has centred on pharmacotherapeutic interventions during the first psychotic break. More recently, attention has turned to the potential value of intervening even earlier, that is during the so-called “prodrome” that has been identified as predating the first psychotic break by as much as 4–5 years. We now have a limited number of published reports addressing this topic and these are reviewed here.