Anticipation refers to the increase in disease severity or decrease in age of onset in successive generations. The concept evolved from the theories and dogma of degeneration that were pervasive in psychiatry and medicine in the late 19th century and into the early 20th century. The term was set aside with the criticism of geneticist Lionel Penrose, who argued that anticipation was the result of ascertainment biases. The renewed interest in anticipation followed the identification of its molecular genetic basis in the form of unstable trinucleotide repeats. Subsequently, several diseases have been studied clinically for the presence of anticipation. Although anticipation has been identified in many diseases, including bipolar disorder, only diseases showing a pattern of progressive neurodegeneration have been associated with unstable trinucleotide repeats. This review summarizes the research on anticipation in bipolar disorder and other secular trends in the patterns of the illness such as the cohort effect. The changing nature of bipolar disorder is likely to be a result of combined influences from several genes, some of which are likely to be in a state of flux, as well as environmental or cultural forces that converge to give the clinical picture of anticipation.

Empirical data from research studies are vital to guiding mental health interventions following disasters. However, few data are available for this purpose. Important advances in policy and procedures for the conduct of organized research emerged from the Oklahoma City bombing, yielding cooperative working relationships among researchers and culminating in the ethical attainment of informative research data. However, the academic community was again caught off guard after the September 11, 2001, terrorist attacks.

Suggestions to surmount these obstacles include incorporating research infrastructures into disaster preparedness plans in advance; organizing the community of researchers; and working closely with major funding organizations. Methodological issues pertaining to measurement of psychopathology include the importance of obtaining diagnostic data; interpreting the meaning of symptoms in the absence of a psychiatric disorder; differentiating preexisting symptoms from those that emerged after the disaster, and optimal timing of postdisaster assessment.

There is limited systematic data assessing alternate pharmacotherapy of social anxiety disorder in patients failing to tolerate or fully respond to initial treatment; no data specifically address the efficacy of citalopram in this scenario. We present a prospective open-label trial of citalopram in 10 patients with generalized social anxiety disorder, 6 of 10 of whom had not responded to or not tolerated a prior treatment intervention for the disorder. Citalopram, at a mean dose of 55 mg (SD+12.7 mg) was well tolerated, and patients improved significantly on all outcome measures. Results of this study suggest that citalopram may be a safe and effective treatment for generalized social anxiety disorder, including patients who have failed to tolerate or respond to a prior treatment trial.

Diffusion tensor magnetic resonance imaging is an imaging modality that measures the diffusion properties of water molecules in tissues noninvasively. Water diffusion is affected by tissue constituents, such as macromolecules, membranes, organelles, as well as by tissue microstructure, architecture, and organization. From the quantities measured with diffusion tensor-magnetic resonance imaging, one can infer information about brain tissue that cannot be obtained using conventional, compositional-based (eg, proton density and chemical spectroscopy), or relaxometry-based (eg, magnetization transfer, T1, T2, and T2*) magnetic resonance imaging methods. Understanding the relationship between a measured water diffusion pattern and the underlying histological features of the tissue, however, is not simple. In the absence of a robust and comprehensive model of water diffusivity in biological tissues, the biological interpretation of diffusion measurements relies on empirical evidence. Herein, the properties of several diffusion tensor-derived quantities are reviewed, together with the experimental evidence that helps clarify their relationship with the underlying properties of brain tissue.

Chirality has become an increasingly important consideration in the development of psychoactive drugs because enantiomers often show major differences in their pharmacokinetic and pharmacologic properties. This review illustrates the implications of stereochemistry in clinical psychopharmacology using the antidepressant class of drugs as a focus. In many cases, a better understanding of stereochemistry can improve therapeutic outcomes. For example, with citalopram, the racemic formulation is effective for depression as well as panic and obsessive-compulsive disorders. However, the S-enantiomer, escitalopram, is at least twice as potent as racemic citalopram as an inhibitor of serotonin reuptake, implying that it can be used at lower doses, while offering an improved therapeutic index as well as an improved safety profile and reduced drug interaction liability. Clinical trial data support these advantages. Continuing research on the stereochemical properties of psychoactive drugs should simplify the characterization of dose-response relationships, and clarify the effects of disease states, genetic polymorphisms, pregnancy, age, and gender on stereoselective pharmacokinetics and pharmacodynamics. Better understanding of the fate of chiral psychotropic agents and the factors that influence their stereoselective disposition and actions will provide a rational basis for their expanded use in various patient populations.

Attention-deficit/hyperactivity disorder (ADHD) is a common neuropsychiatric disorder that affects many domains of life. Studies have shown that adequate treatment of ADHD can affect the course of the disorder in a fundamental manner. While nonpharmacologic treatments such as education and various psycho-social interventions are used in the management of ADHD, pharmacotherapy is the mainstay of treatment for this disorder. Psychostimulants are the only group of agents that have been approved for the ADHD indication and are considered to be first-line treatment for the disorder. Methylphenidate, amphetamines, andpemoline are the most commonly used agents in this group. The stimulants have been successfully used for many years and their efficacy has been confirmed by a large number of clinical studies. Recent pharmacological advances have been made with longer-acting stimulants, new isomers, and more advanced drug delivery systems that enable more convenient dosing schedules with drug effects lasting throughout the day. Other nonstimulant medications have been shown to have anti-ADHD activity as well, although more research is needed on the efficacy and utility of these treatments. Antihypertensive medications and antidepressants, such as tricyclics and bupropion, have been studied and may have applications in the treatment of specific subgroups of patients with comorbid conditions or for patients who do not respond to stimulant treatment.

In spite of their prevalence and persistence, why are behavioral and psychological symptoms of dementia difficult for clinicians to assess and manage? This paper provides an overview of the methodological challenges encountered in measuring behavioral disturbances of dementia. Specifically, conceptual constructs of behavioral and psychological symptoms of dementia, the strengths and weaknesses of the currently existing rating instruments, analytic methodologies, and the utility of technological devices are outlined in the service of formulating future directions in behavioral and psychological symptoms of dementia assessment research.

Elucidation of genetic factors in schizophrenia and bipolar disorder remains a challenging task to psychiatric researchers. As a rule, data from genetic linkage and association studies are quite controversial. In this article, we further explore the possibility that in addition to DNA sequence variation, a putative epigenetic dysregulation of brain genes plays an important role in the etiopathogenesis of major psychosis. We provide an epigenetic interpretation of unclear genetic findings specifically pertaining to chromosome 22 in schizophrenia and bipolar disorder. It is suggested that epigenetic strategies, when applied in conjunction with traditional genetic ones, may significantly expedite the uncovering of the molecular causes of major psychosis.

Several factitious epileptic syndromes have been associated with famous literary characters. While these syndromes include symptoms other than pseudoseizures, and while pseudoseizures can occur in other syndromes, a review of these disorders provides insights into factitious seizures and epilepsy.

What role do medications play in the overall treatment of autistic spectrum disorders? In this review, the decision-making process involving identifying symptoms, initiating a pharmacological intervention, and monitoring that process is discussed. A review of the literature with an emphasis on controlled trials in autistic spectrum disorders is also undertaken.

Serotonin (5-hydroxytryptamine, 5-HT) has long been suspected to play a role in the etiology of depression, and modern neurochemical techniques have confirmed this suspicion. Furthermore, all drugs known to be selective (a relative term) serotonin transporter (SERT) inhibitors are effective antidepressants. Of the selective serotonin reuptake inhibitors (SSRIs) approved in a number of countries for use in depression, panic disorder, and obsessive-compulsive disorder, citalopram is the most selective. Citalopram has been used worldwide to treat an estimated 35 million patients, with an excellent safety record. Citalopram is a racemic drug, and its effects on serotonin transport are thought to reside in the S-enantiomer, known as (S)-citalopram or escitalopram. Escitalopram is the most selective SSRI yet developed. Its receptor binding properties and activity in preclinical animal models of depression predict that escitalopram would be effective in the treatment of depression, with approximately twice the potency of the racemate. The pivotal clinical trials of escitalopram not only support this conclusion, but also suggest escitalopram possesses advantages over citalopram in terms of both efficacy and safety. In conclusion, escitalopram is a promising candidate for use as a first-line antidepressant.

White matter fiber pathways are key structural components of the brain and its functional organization. The limbic system carries a great deal of its anatomic connectivity via the cingulum bundle. By allowing the in vivo delineation of the stem of the major fiber pathway systems, diffusion tensor magnetic resonance imaging has opened a new window into the detailed structure of the white matter in health and disease. Topographic, biophysical, and volumetric information about fiber tracts will provide a more complete understanding of the brain. By appreciating its interconnections, the precise anatomical knowledge of the cingulum bundle will improve our understanding of the limbic system and may enable improvements in the assessment and treatment of neuropsychiatric disorders. In this study, the stem of the cingulum bundle was investigated and defined in terms of its trajectory, anisotropy, and volume, in four normal human subjects, using diffusion tensor imaging.

Smell identification deficits are consistently found in schizophrenia (SZ), but little is known about the nature and characterization of this deficit or its relationship to the phenomenology of the illness. This study aims to further delineate smell identification errors in SZ by examining the relationship of patient demographic differences with smell-identification performance. Our results showed that a patient's gender and education were related to odor-identification scores, with better performance seen in female patients and in those with greater educational attainment. However, there was no effect related to age, ethnicity, or socioeconomic status on odor identification. A smell identification deficit was also unrelated to clinical characteristics of the patients, including age at first hospitalization, number of psychiatric hospitalizations, and duration of illness. Odor identification also did not differ by SZ subtype, nor between SZ and schizoaffective disorder patients. These findings emphasize that odor identification deficits in SZ are unrelated to clinical illness features, cannot be explained by other confounds related to olfaction in the general population, and may be core features related to the SZ disease process.

Depression is an important public health problem affecting about 15% of the general population; however, little is known about possible changes in the brain that might underlie the disorder. Neuroimaging has been a powerful tool to map actual changes in the brain structure of depressed patients that might be directly related to their symptoms of depression. Some imaging studies of brain structure have shown smaller hippocampal volume with the chronicity of depression correlating to a reduction in volume. Although the meaning of these findings is unclear, other studies have shown increased amygdala volume. Studies have found reductions in volume of the frontal cortex, with some studies showing specific reductions in subregions of the frontal cortex, including the orbitofrontal cortex. Findings of an increase in white matter lesions in elderly patients with depression have been replicated and correlated with late-onset depression, as well as impairments in social and cognitive function. These findings point to alterations in a circuit of brain regions hypothesized to include the frontal cortex, hippocampus, amygdala, striatum, and thalamus, that underlie symptoms of depression.

It has become standard practice to base the diagnosis of dementia on the combination of neuropsychological and non-behavioral findings. The present article provides a short, clinically oriented synopsis of the targets, investigational procedures, and difficulties of the modern neuropsychological approach to the diagnosis of dementia. Over the years, neuropsychology has developed assessment tools to evaluate the cognitive and behavioral abnormalities of many dementias. Validated tests of memory, language, executive, and other cognitive functions are used to screen for dementia and identifying certain dementia profiles. Behavioral assessment procedures are available for non-cognitive neurodegenerative alterations. At present, problems arise mainly with the behavioral heterogeneity of certain dementia syndromes. Especially problamatic are discrimination of age-associated or mild cognitive impairments from incipient dementia and the impact of psychiatric symptoms on cognitive functions. It is concluded that neuropsychology offers a valuable contribution to the diagnosis and differential diagnosis of dementia.

Anxiety-disordered patients and individuals with high trait anxiety tend to interpret ambiguous information as threatening. The purpose of this study was to investigate whether interpretive biases would also occur in body dysmorphic disorder (BDD), which is characterized by a preoccupation with imagined defects in one's appearance. We tested whether BDD participants, compared with obsessive-compulsive disorder participants and healthy controls, would choose threatening interpretations for ambiguous body-related, ambiguous social, and general scenarios. As we hypothesized, BDD participants exhibited a negative interpretive bias for body-related scenarios and for social scenarios, whereas the other groups did not. Moreover, both clinical groups exhibited a negative interpretive bias for general scenarios.

Genetic contributions to phenotypic variation in general intelligence have been studied extensively. Less research has been conducted on genetic contributions to specific cognitive abilities, such as attention, memory, working memory, language, and motor functions. However, the existing data indicate a significant role of genetic factors in these abilities. Stages of information processing, such as sensory gating, early sensory registration, and cognitive analysis, also show evidence of genetic contributions. Recent molecular studies have begun to identify candidate genes for specific cognitive functions. Future research, identifying endophenotypes based on cognitive profiles of neuropsychiatric disorders, may also assist in the detection of genes that increase susceptibility to major psychiatric disorders.

The September 11, 2001, attack on New York City was the largest human-made disaster in United States history. In the first few days after the attack, it became clear that the scope of the attacks (including loss of life, property damage, and financial strain) was unprecedented and that the attacks could result in substantial psychological sequelae in the city population. Researchers at the Center for Urban Epidemiologic Studies at the New York Academy of Medicine designed and implemented an assessment of the mental health of New Yorkers 5—8 weeks after the attacks. To implement this research in the immediate postdisaster period, researchers at the center had to develop, in a compressed time interval, new academic collaborations, links with potential funders, and unique safeguards for study respondents who may have been suffering from acute psychological distress. Results of the assessment contributed to a New York state mental health needs assessment that secured Federal Emergency Management Agency funding for mental health programs in New York City. This experience suggests that mechanisms should be in place for rapid implementation of mental health assessments after disasters.

Both elevated cardiovascular mortality and low cardiovagal (parasympathetic) heart rate variability (HRV)—a risk factor for postmyocardial infarction—are reported in schizophrenia (SZ). Since a number of medications have strong effects of cardiac conductivity, we thought it important to examine if typical neuroleptic medications might also affect HRV. We examined cardiac vagal activity during both neuroleptic treatment and a drug-free condition in seven SZ patients who were participating in a pilot double-blind, crossover study of placebo and haloperidol treatment. Twenty-four–hour Holter electrocardiograms were analyzed for high frequency HRV, quantitated as the percent of successive normal interbeat intervals greater than 50 milliseconds (PNN50), which is a good index of parasympathetic cardiac modulation. The patients showed unchanged PNN50 (8.4±9.5 versus 8.3±10.5; t=.22, df=6, P=.5) between the haloperidol treatment and drug-free conditions. Despite the elapsed time, change in medication, and altered clinical state, the PNN50s were highly correlated (Spearman r=.98, P=.000). SAPS positive symptom scores declined with treatment from 12.8±6.5 to 8.5±3.5; paired t=3.26: df=6; P=.01. PNN50s were significantly associated with positive (r=-.86, df=6, P=.012) and negative symptom scores (r=-.87, df=6, P=.01). We found low cardiovagal modulation in medication-free SZ patients that was associated with core SZ symptoms and was unchanged by haloperidol and benztropine treatment. The reduced HRV in SZ patients at baseline may render them at greater cardiovascular risk than healthy subjects when treated with medications having strong cardiovascular effects.

Treatment resistance is reported in up to 40% of older patients with major depression. Before labeling an episode of depression as treatment resistant, it is important to ensure that the diagnosis is correct and that the patient has received and adhered to an adequate dose of treatment for an appropriate length of time. It is also important to assess the patient for comorbid physical and psychiatric conditions that can contribute to treatment resistance. In patients who do not experience remission of symptoms with an adequate trial of medication, the following options can be considered: augmenting the antidepressant with a drug that is not primarily an antidepressant, adding a second antidepressant to the first, switching to a different antidepressant medication, or switching to electroconvulsive therapy. This paper reviews the concept of treatment-resistant depression and discusses its assessment and management in the elderly. The author concludes that when a systematic stepped-care approach to treatment is followed, most older patients with major depression will experience remission of symptoms.