Depression is a widespread and serious disorder that afflicts an estimated 13.1 to 14.2 million adults in the United States each year. Even more compellingly, the lifetime prevalence rate of depression in the US has recently been estimated to include 16.2% of adults (21% women, 13% men), or >32.6 million people. There are multiple putative “causes” of depression, with approximately one-third of an individual's propensity for unipolar depression due to genetic vulnerability, while the remaining two-thirds is due to environmental factors. Although the selective serotonin reuptake inhibitor (SSRI) antidepressants are believed to mainly act by selectively binding to the serotonin (5-HT) transporter to block reuptake of 5-HT from the synapse into the presynaptic nerve terminal, thereby increasing synaptic serotonin concentrations, some of the SSRIs also exhibit other neuropharmacologic effects. One such example is the high affinity for paroxetine in blocking norepinephrine reuptake. Another is the inhibition of dopamine reuptake by sertraline. In depression, hyperactivity of corticotropin-releasing factor (CRF)-producing neurons contribute to the well-characterized hypothalamic-pituitary-adrenal axis hyperactivity of depression. Increased activity of extrahypothalamic CRF circuits are believed to contribute to several depressive symptoms. Treatment and certain SSRIs have been shown to reduce the activity of CRF neurons and may contribute to their therapeutic action. Each SSRI apparently has its own unique pharmacologic properties that likely underlie their observed differences in clinical use.

Clinical and epidemiological data suggest that generalized anxiety disorder (GAD) is a chronic illness causing patients to suffer for many years leading to significant distress in daily life functioning. The literature suggests the several conclusions. GAD is a disorder in need of appropriate treatment and often has a chronic course with comorbid conditions, such as major depression and other anxiety disorders. Benzodiazepines, while effective anxiolytic agents acutely, when prescribed for >4 weeks cause rebound anxiety and following prolonged therapy may lead to withdrawal symptoms. Antidepressants cause significant anxiety relief compared with placebo and for psychosocial treatment cognitive-behavioral therapy is an efficacious psychosocial treatment. Many GAD patients are in need of long-term medication management. Furthermore, there is limited data for patients diagnosed with GAD the treatment outcome with the combination of medication and psychotherapy both acutely and long-term; how to best sequence these treatments; for those patients who do not meet remission criteria what is the ideal approach for augmentation; and for patients with treatment-refractory GAD the empirical evidence is lacking on medication switching and augmentation strategies. Research is needed in the area of developing treatment strategies for patients suffering from treatment-refractory GAD. There is still an urgent need to explore treatment combinations and duration strategies in the management of patients suffering with GAD.

Accurate identification of individuals in the earliest symptomatic stages of psychosis offers new hope for developing more effective treatment strategies. Recently, research clinics have been set up to identify and possibly treat individuals who are seen as being at ultra-high risk of developing a psychotic disorder. This article reviews and describes measures that are currently being used and further developed in order to determine both the diagnostic criteria for the prodromal state and the severity of these putatively prodromal symptoms.

Background: Attention-deficit/hyperactivity disorder (ADHD) occurs in as many as 4% of adults yet it is often not recognized in clinical settings because the presenting symptoms may resemble those seen in other disorders or because symptoms may be masked by commonly comorbid conditions such as anxiety and depression.

Objective: The purpose of this study was to examine the diagnostic utility of instruments commonly used in the assessment of adults presenting with symptoms of ADHD.

Methods: We reviewed several widely used self-report and laboratory measures and empirically examined the utility of the Brown Attention-Deficit Disorder Scale for Adults (Brown ADD Scale) and the Conners Continuous Performance Test (CPT) in differentially identifying adults with ADHD and those with other Axis I disorders.

Results:Ninety-three adults who self-referred to the ADHD program for adults at a university medical center participated in the study. Of these, 44 had ADHD combined subtype (ADHD-CB), and 26 had ADHD, predominantly inattentive subtype (ADHD-IA). Thirty-three non-ADHD adults diagnosed with Axis I mood or anxiety disorders comprised an “Other Psychiatric” group. Rates of comorbid disorders, including substance abuse, in the ADHD groups were typical of those reported in the adult ADHD literature. Data on the Brown ADD Scale and on the CPT were available for subsets of 61 and 46 participants, respectively. Analyses showed that the ADHD-CB, ADHD-IA, and Other Psychiatric groups all received mean scores in the clinical range on the Brown ADD Scale, with a trend toward even higher elevations in the two ADHD groups. Among 12 CPT variables assessed for the three groups, the mean scores on only two variables for the ADHD-IA group were clinically elevated. Neither the Brown ADD Scale nor CPT scores evinced sufficient sensitivity and specificity to qualify them to assist in differential diagnosis of ADHD vis-a-vis other, predominantly internalizing, psychiatric disorders.

Conclusion: The results indicate a need for closer examination of executive and adaptive functioning in adults with ADHD compared with those with internalizing disorders in order to identify features that could assist in differential diagnosis.

Although modern community-based studies have shown that a majority of people with newly diagnosed epilepsy will enter long-term remission, seizures remain refractory to treatment in a substantial proportion of this population—perhaps as much as 40%. A consensus is being reached that, for operational purposes, pharmacoresistance can be suspected when two appropriately chosen, well-tolerated, first-line antiepileptic drugs (AEDs) or one monotherapy and one combination regimen have failed due to lack of efficacy. Poor prognostic factors include lack of response to the first AED, specific syndromes, symptomatic etiology, family history of epilepsy, psychiatric comorbidity, and high frequency of seizures. These observations suggest that prognosis can often be determined early in the course of the disorder. We propose a management paradigm that aims to maximize the chance of successful AED therapy, including the early use of “rational polytherapy” for patients not responding to monotherapy, and to identify efficiently patients suitable for “curative” resective surgery, in particular those with mesial temporal lobe epilepsy. An orderly approach to each epilepsy syndrome will optimize the chance of perfect seizure control and help more patients achieve a fulfilling life.

Interest in early and preventive interventions in patients with psychotic disorders has increased over the past few years as a result of die intuitive appeal of such interventions. Results of studies point to an association between longer duration of untreated psychosis and poor outcome, atypical antipsychotic agents less likely to cause extrapyramidal side effects, and a shift from hospital to community-based care for many patients with severe mental illness. Treatment strategies specifically directed to firsUepisode psychosis may help to improve outcomes. Such strategies include the use of lower doses of antipsychotic medications, the predominant use of atypical antipsychotic agents, and the deployment of psychological interventions that address the unique needs of young, first-episode patients and their families.

Eating disorders have been viewed as psychiatric illnesses that are strongly influenced by societal pressures towards thinness and attractiveness. Although the environmental context of these disorders must not be neglected, recent research in the area of genetic epidemiology suggests a substantial influence of genetic factors on liability to eating disorders. This review presents a synthesis of current knowledge about genetic factors implicated in the etiology of eating disorders.

Treatment-resistant depression (TRD) represents a significant challenge for physicians. About one third of patients with major depressive disorder fail to experience sufficient symptom improvement despite adequate treatment. Despite this high occurrence of TRD there was no general consensus on diagnosis criteria for TRD until 1997 when researchers proposed a model of defining and staging TRD. In 1999, others defined operational criteria for the definition of TRD. Treatment of TRD is commonly separated into pharmacologic and nonpharmacologic methods. This review gives a short overview of these two methods. The nonpharmacologic methods include psychotherapy, electroconvulsive therapy, and vagus nerve stimulation. Pharmacologic methods include switching to another antidepressant monotherapy, and augmentation or combination with two or more antidepressants or other agents. This review especially focuses on the augmentation of the antidepressant therapy with atypical antipsychotics.

Background: Cognitive, social, and affective impairments are major features of schizophrenia, despite not being represented in the formal diagnostic criteria. These impairments are associated with major reductions in quality of life for patients with schizophrenia. Treatment with newer antipsychotic medications has been reported to improve all of these areas of functioning, but most studies have not examined the direct association between changes in cognitive functioning and other aspects of the illness.

Objectives: The goal of this analysis was to examine relationships between cognitive and affective symptoms and their impact on social impairments in patients switched to ziprasidone treatment.

Methods: In this study, which is a re-analysis of previously published data, 270 patients were switched from previous treatment with conventional antipsychotics, risperidone, or olanzapine to treatment with ziprasidone. Patients were tested with a cognitive assessment battery, rated with the Positive and Negative Syndrome Scale (PANSS), and received other assessments of safety and tolerability. PANSS scores were divided into factors based on previously published factor analyses, with a focus on the cognitive, prosocial, and anxiety-depression factors.

Results: Statistically significant improvements for global cognitive functioning and the three PANSS subscales were found across the studies. When the data were pooled for a path analysis, changes in cognitive functioning indexed by the PANSS cognitive subscales was the primary predictor of improvements in PANSS prosocial functions, with changes in anxiety-depression accounting for much less variance.

Conclusion: These results suggest a direct relationship between improvements in cognitive and prosocial functioning in patients with schizophrenia and indicate that treatments that enhance cognitive functioning, such novel antipsychotics, have the potential to improve aspects of outcome in schizophrenia even in short-term treatment studies. This issue should be addressed in future double-blind studies of the effects of atypical medications in schizophrenia.

Family psychoeducation programs have emerged as a strongly supported evidence-based practice in the treatment of schizophrenia and bipolar disorder. Over 30 randomized clinical trials demonstrated that psychoeducation programs reduce relapse, improve symptomatic recovery, and enhance psychosocial and family outcomes. Recent work supports family psychoeducation strategies for other disorders, including major depression, obsessive-compulsive disorder, and borderline personality disorder. This review summarizes the research evidence supporting prominent models of family psychoeducation. Professional and peer-led family education programs are also reviewed and differentiated from family psychoeducation. Directions for future research studies to enhance the evidence base and inform treatment recommendations are proposed. Finally, strategies for implementation of family psychoeducation in routine clinical practice are discussed.

Dosing patterns with second-generation antipsychotic medications (SGAs) are dynamic, with some SGAs surpassing current recommendations while others are declining in dose since their initial regulatory guidelines. Pertinent recent studies and available pharmacoepidemiologic reports, information, and expert consenses are reviewed herein to illuminate current thinking on the topic of dosing with SGAs. There is a need for fixed-dose studies of each SGA. Additionally, dosing should be a primary consideration when designing and subsequently interpreting comparative studies between SGAs.

The prevalence of Alzheimer's disease (AD) and dementia continues to rise. However, a significant number of patients are undiagnosed or untreated. Given the complexities of detecting cognitive impairment and the early signs of AD, this review discusses how advances in brain imaging can help assist in improving overall management. Imaging techniques and surrogate markers may provide unique opportunities to diagnose accurately AD in presymptomatic stages with practical consequences for patients, caregivers, and physicians. The possible outcomes for using imaging and surrogate markers as adjuncts to clinical examination and as screening tools for AD, as well as tangible and intangible advantages to early diagnosis and treatment, will be discussed. The specific value of using advanced serial imaging in patients with a genetic disposition to AD will be evaluated. If neurons can be protected from neurodegenerative damage in early stages, this may preserve patient cognition, function, and quality of life, and may confer considerable societal healthcare benefits.

This paper identifies instruments and measures that may be appropriate for randomized clinical trials in participants with autism spectrum disorders (ASDs). The Clinical Global Impressions scale was recommended for all randomized clinical trials. At this point, however, there is no “perfect” choice of outcome measure for core features of autism, although we will discuss five measures of potential utility. Several communication instruments are recommended, based in part on suitability across the age range. In trials where the intention is to alter core features of ASDs, adaptive behavior scales are also worthy of consideration. Several “behavior complexes” common to ASDs are identified, and instruments are recommended for assessment of these. Given the prevalence of cognitive impairment in ASDs, it is important to assess any cognitive effects, although cognitive data from ASD randomized clinical trials, thus far, are minimal. Guidance from trials in related pharmacologic areas and behavioral pharmacology may be helpful. We recommend routine elicitation of side effects, height and weight, vital signs, and (in the case of antipsychotics) extrapyramidal side-effects assessment. It is often appropriate to include laboratory tests and assessments for continence and sleep pattern.

Pregnancy and childbirth typically are associated with positive emotions and with motherhood, but the reality is that this is not the case for all women or for all pregnancies. This review addresses a different aspect of these reproductive events, focusing on stressful circumstances surrounding pregnancy, as well as times when the pregnancy itself becomes a stressful life event. Pregnancy-related topics that tend to receive less attention will be emphasized. These include issues related to infertility; unplanned pregnancy; stress associated with testing and diagnosis of common medical complications; peripartum cardiomyopathy; fear of childbirth; and pregnancy foss as a risk factor for psychopathology. Epidemiologie information wiu be presented, as will relevant psychosocial factors related to each phenomenon. Healtitcare providers should be sensitive to the distress and anxiety experienced by many women and their families as a consequence of these adverse events and the stressful challenge of any consequential decisionmaking, as well as stressors in their broader life context that can further exacerbate their distress, and make mental health referrals as appropriate.