This paper summarizes the results of systematic studies published in peer-reviewed journals from 1999 to 2002 addressing post-traumatic stress reactions in children after mass disasters. Children's post-traumatic reactions are considered in five different contexts--natural disasters, large-scale human-induced accidents, spree shootings, war, and terrorism. Association of these reactions with gender and age, as well as longitudinal course, is addressed. Other post-traumatic reactions in children after a mass disaster, as well as the comorbidity of these with stress reactions, are reported. With this as background, the most relevant epidemiologic investigations conducted after the World Trade Center attacks are then described. It is expected that new knowledge in the area of children's post-traumatic reactions to disasters will result from the research initiatives launched after September 11, 2001.
Since the early 20th century, a group of nonaffective psychoses with acute onset and brief duration have been described in different countries under various names, including cycloid psychosis, bouffée délirante, and reactive psychosis. These psychoses share several characteristics, including benign course, greater prevalence in women than men and in developing countries than in industrialized countries, and high prevalence of premorbid psychological and physiologic stressors. However, the variations in names and minute details of symptomatology have overshadowed the basic similarities across these various descriptions. Confusion in classification persists in the two contemporary diagnostic systems, the DSM-IV and the ICD-10. We believe that most cases of these psychoses could be captured under a broad, unified category of nonaffective psychosis with acute onset and brief duration, and urge the authors of the upcoming revisions of the DSM and ICD to create such a category. A unified diagnostic category for these disorders would reduce unnecessary fragmentation in the diagnostic systems and assist in the progress of research on these rare conditions.
The current paper presents a novel approach to understanding and treating addiction. Drawing from work in behavioral economics and developments in the new field of neuroeconomics, we describe addiction as pathological patterns of responding resulting from the persistently high valuation of a reinforcer and/or an excessive preference for the immediate consumption of that reinforcer. We further suggest that, as indicated by the competing neurobehavioral decision systems theory, these patterns of pathological choice and consumption result from an imbalance between two distinct neurobehavioral systems. Specifically, pathological patterns of responding result from hyperactivity in the evolutionarily older impulsive system (which values immediate and low-cost reinforcers) and/or hypoactivity in the more recently evolved executive system (which is involved in the valuation of delayed reinforcers). This approach is then used to explain five phenomena that we believe any adequate theory of addiction must address.
Investigations into the genetic basis of attention-deficit/hyperactivity disorder (ADHD) continue to yield compelling results as candidate gene studies reveal more information about this elusive disorder. Family, twin, and adoption studies further the notion that ADHD is a highly heritable disorder with direct genetic and environmental influence. The year 2005 saw many ADHD candidate gene studies, with most focused on the catecholaminergic candidates. Although many genes were studied in 2005, a large portion of findings has been supportive of the roles of dopaminergic genes' relationship to clinical phenotypes and drug response. These studies often require replication. Clinical implications continue to be speculative, as larger sample sizes are needed to validate findings to the general population. Further understanding of endophenotypes and the impact of comorbidities also is necessary for proper clinical intervention. Forthwith, we provide a summary of ADHD genetic studies published in 2005.
Since the introduction of the third edition of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition in 1980, schizophrenia has been widely diagnosed with good to excellent levels of reliability. This is no small feat, as prior to the 1970s the reliability of this diagnosis over time and place was very poor. Although there have been some changes in the diagnostic algorithm for schizophrenia with subsequent revisions of the Diagnostic and Statistical Manual of Mental Disorders, there has been little change in the overall classification scheme. However, there has also been relatively little movement toward enhancing the validity of this diagnosis. Although there is broad consensus that what we now call schizophrenia is probably very heterogeneous with respect to underlying etiology and pathophysiology, attempts to identify more valid subtypes or dimensions have not progressed to the point that they are likely to be incorporated into diagnostic systems any time soon. The limited progress in defining more valid disease categories has increasingly important clinical implications as the field moves more and more to treatment by preset algorithms that are typically driven by diagnosis.
This review covers all significant randomized controlled trials and open trials of medications for the treatment of borderline personality disorder. New developments in the effectiveness of mood stabilizers and antipsychotics are discussed. Differences were found in the effectiveness of medications based on the presence or absence of depression and significant anger symptoms. Medications continue to be recommended as adjuncts to psychotherapy. Most of the trials discussed require replication, and more trials that investigate the effectiveness of medications in combination with psychotherapy are recommended.
Attention-deficit/hyperactivity disorder (ADHD) is highly heritable. Confirmed association has been reported for several candidate genes, including DAT1, DRD4, SNAP-25, DRD5, 5HTT, HTR1B, and DBH; however, these confer relatively small risk. Family-based linkage studies have identified a number of chromosomal regions containing potential ADHD predisposing loci, some overlapping in two or more studies, including 5p, 6q, 7p, 11q, 12q, and 17p. New large-scale studies that apply recent technological advances to perform high-density genotyping of the entire genome, in combination with information on the haplotype structure of the human genome, now allow testing of single-nucleotide polymorphism association with disease phenotype without any a priori hypothesis. They may contribute further to our understanding of the genetic factors involved in ADHD. The heterogeneous complex ADHD phenotype, as well as epigenetic factors may be contributing to the challenge of genetic studies. Samples that include limited age ranges may have better success at uncovering genes whose expression is limited to specific developmental stages.
The author has reviewed bipolar disorder-relevant abstracts from the July 2008 Munich CINP (Collegium Internationale Neuro-Psychopharmacologicum) meeting. Seven abstracts are summarized, focusing on the psychopharmacologic treatment of bipolar depression, the neuropsychological effects of psychotropic drugs used to treat bipolar disorder, and the relationship of mood stabilizers and antidepressants to emotional instability over time.
The author has reviewed selected bipolar disorder- and major depression-relevant abstracts from the 2009 9th World Congress of Biological Psychiatry Meeting in Paris. The seven selected abstracts, which represent a small percentage of the presentations made at the meeting, explore the relationship between bipolar and unipolar diagnoses and suicidal behavior, the differentiation of bipolar I and bipolar II disorder, and some novel non-industry-supported treatments of bipolar and unipolar depression.
A growing evidence base on the management of social anxiety disorder has yielded many meta-analyses and guidelines on the pharmacotherapy of this clinically important condition. We aimed to update a pharmacotherapy algorithm for the treatment of social anxiety disorder that was developed to be concise and user friendly and that was addressed to the primary care practitioner in particular. The updated algorithm attempts to summarize succinctly the recent literature in this area, as well as to include the views of an international panel of experts with diverse experience. The algorithm comprises eight sequential steps, beginning with those focused on diagnosis and initiating treatment and ending with the management of the treatment-refractory patient.
Nightmares are a universal and timeless phenomenon. They occur in most healthy adults as well as a significant portion of clinical populations, especially those exposed to trauma. Considerable advances in the pharmacological and psychological treatment of post-traumatic nightmares have occurred over the last decade with continuing advances in psychological interventions over the last few years. Pharmacologically, the medication prazosin is showing robust clinical effects with minimal side effects. Psychologically, imagery rehearsal therapy commands the greater portion of the nightmare literature due to its established efficacy. These issues are reviewed in the following paper along with recommendations for future studies.
There is a need to synthesize the growing body of literature on the pharmacotherapeutic management of patients with obsessive-compulsive disorder for clinicians working at a primary care level. We have aimed to generate a simple, easy-to-follow algorithm for the primary care practitioner. This seven-step algorithm addresses diagnosis of obsessive-compulsive disorder, initiation of pharmacotherapy, monitoring and maintenance treatment, and guidelines for the management of patients who are resistant to initial therapy. In creating this algorithm, we have drawn on the body of published evidence, as well as on expert opinion.
Down syndrome (DS), or trisomy 21, is the most common identifiable genetic cause of mental retardation. The syndrome is unique with respect to its cognitive, behavioral, and psychiatric profiles. The well-known cheerful and friendly demeanor often creates a personality stereotype, with parents and observers commenting on the positive attributes. Despite these strengths, approximately 20% to 40% of children with DS have recognized behavioral problems. Such problems persist through adulthood, with a decrease in externalizing symptoms of aggressiveness and attention problems and the emergence of internalizing symptoms of depression and loneliness. In adulthood, the presence of early-onset dementia of the Alzheimer type and cognitive decline may pose a challenge in recognizing these internalizing symptoms. Understanding the age-related changes in cognitive functioning and behavioral profiles in individuals with DS provides insight into clinical and treatment implications.
A microdeletion at chromosome 22q11 is the most frequently known interstitial deletion found in humans, occurring in approximately one of every 4000 live births. Its occurrence is associated with a characteristic facial dysmorphology, a range of congenital abnormalities, and psychiatric problems, especially schizophrenia. The prevalence of psychosis in those with 22q11 deletion syndrome is high (30%), suggesting that haploinsufficiency of a gene or genes in this region may confer a substantially increased risk. In addition, several studies provide evidence for linkage to schizophrenia on 22q, suggesting that a gene in this region could confer susceptibility to schizophrenia in nondeleted cases. Recent studies have provided compelling evidence that haploinsufficiency of TBX1 is likely to be responsible for many of the physical features associated with the deletion. However, although a number of genes have been implicated as possible schizophrenia susceptibility loci, further confirmatory studies are required.
22q11 deletion syndrome (22q11DS) is a chromosomal disorder that results in variable multisystem abnormalities, including conotruncal cardiac malformations, aplasia or hypoplasia of the thymus and/or parathyroid glands, immunodeficiency, dysmorphic facial features, and cleft palate and other nasopharyngeal and dental anomalies. Individuals with 22q11DS also exhibit cognitive and behavioral difficulties, including delayed motor and speech-language development, mental retardation, low academic achievement, impaired spatial reasoning, poor attentional and executive functioning, attention-deficit hyperactivity disorder, autism spectrum disorders, mood disorders, and/or schizophrenia spectrum disorders. Interventions should be designed based on the results of periodic developmental and neuropsychological assessments and psychiatric screening. Future research should focus on understanding deletion-related gene-environment interactions and their effects on developmental and behavioral outcomes, identifying neurodegenerative processes in 22q11DS, and developing preventive models of behavioral and psychopharmacologic treatment.
Velocardiofacial syndrome, now known as 22q11.2 deletion syndrome (22qDS), is estimated to affect more than 700 children born in the United States each year. Some clinical studies have found increased rates of schizophrenia in adults with 22qDS. However, these studies have been limited by small sample size and possible ascertainment bias. The psychiatric disorders most commonly reported in children and adolescents with 22qDS have been attention-deficit/hyperactivity disorder, oppositional defiant disorder, anxiety disorders, and major depression. Psychotic symptoms have been observed in 14% to 28% of children with 22qDS, but their clinical significance remains uncertain. A 5-year follow-up study of 22qDS children who reported psychotic symptoms at baseline found they had an increased risk for a subsequent psychotic disorder. Thus, a broad differential diagnosis should be considered when 22qDS children present with psychotic symptoms. Longitudinal studies are needed to better understand the full extent of the psychopathology associated with 22qDS.
Prepulse Inhibition (PPI) of the startle response and the P50 auditory-evoked potential suppression are used to assess impairments in the regulation of the neural substrates and to determine the clinical significance of inhibitory deficits in schizophrenia. The study of gating deficits in schizophrenia and in related animal model studies have already advanced our understanding of the neural substrates of information processing abnormalities in patients with schizophrenia. Individuals with schizotypal personality disorder as well as clinically unaffected family members of patients with schizophrenia show PPI and P50 suppression deficits. These "schizophrenic spectrum" populations are not grossly psychotic, nor are they receiving antipsychotic medications. Therefore, the gating deficits are presumed to reflect core (eg, intermediate phenotypic) schizophrenia-linked information processing abnormalities. Several studies have reported that gating deficits are associated with clinical ratings of psychiatric symptoms, thought disorder, and neuropsychologic deficits in patients with schizophrenia. In addition, recent human pharmacologic studies have indicated that gating deficits can be reversed by rationally-selected compounds. Animal model studies have generally shown convergence with the human studies and may lead to improved identification of efficacious new antipsychotic medications for patients with schizophrenia.
The pharmacotherapy of cocaine dependence is a rapidly developing field of research that may soon produce efficacious medications. Expanding research on reward-related brain circuitry, which is acutely activated and chronically dysregulated by cocaine, has helped reveal the neurobiological features of cocaine dependence and is guiding pharmacologic strategies that have significant potential to improve clinical outcome. Cocaine dependence is a multifaceted disorder with distinct clinical components that may respond to different pharmacologic approaches. Pharmacologic strategies for this disorder include blocking euphoria, reducing withdrawal and negative mood symptoms, ameliorating craving, and enhancing the prefrontal cortical function that seems to be impaired in cocaine-dependent patients. One medication may not be sufficient to treat these diverse elements of cocaine dependence because preliminary studies report efficacy with medications that have opposite actions on reward-related circuits. This review highlights pertinent advances in cocaine neurobiology, recent clinical trials, and controversies in the pharmacologic treatment of cocaine dependence.
The concept of using stimulants to treat cocaine and methamphetamine dependence is largely based on the "replacement" therapy model that has shown efficacy for treating nicotine and opiate dependence. Although results have been mixed, some evidence supports using stimulant medication to reduce cocaine use. There are not enough data to date to determine the efficacy of stimulants for methamphetamine dependence. Drawbacks of stimulants as treatments include the potential for abuse of the treatment, which necessitates careful screening and monitoring of patients. Possible reasons for efficacy of stimulants include enhancement of monoamine function dysregulated by chronic cocaine or methamphetamine use. Newer medications that enhance dopamine function but lack the abuse potential of older stimulants are being studied. It is hoped that these medications will provide safe, effective treatment for cocaine and methamphetamine dependence, but more research on this topic is needed.
Scientific interest in how the brain processes reward has burgeoned during the past 50 years since the discovery that rats will do tasks such as pressing a lever to obtain electrical stimulation of the brain. This interest was additionally encouraged by the observation of an association between reward and dopamine activity in the mesocorticolimbic system. In this article, we will discuss the complex nature of reward processing and recent animal studies and human functional neuroimaging studies to elucidate the current understanding of the neural substrates of reward processing and its components. Lastly, we will review recent theoretical and empirical work investigating the role of brain reward circuitry in several psychiatric disorders, including substance use disorders, schizophrenia, pathologic gambling, major depressive disorder, and attention-deficit/hyperactivity disorder.
Elderly patients with depression commonly suffer from concurrent symptoms of anxiety or comorbid anxiety disorders. Such comorbidity is associated with a more severe presentation of depressive illness, including greater suicidality. Additionally, most antidepressant treatment studies of elderly individuals with depression have found poorer treatment outcomes in those with comorbid anxiety, for example, delayed or diminished response and increased likelihood of dropout from treatment. In terms of treatment of anxious depression, there is evidence that tricyclic antidepressants and serotonin reuptake inhibitors are not different from each other in terms of efficacy or tolerability. Rather than the specific choice of antidepressant medication, it appears that quality of clinical management has the greatest impact on likelihood of remission in anxious depressed elderly individuals. Co-prescription of benzodiazepines is sometimes warranted for severe anxiety, but increases the risk of cognitive or motor impairment. Psychotherapy, including cognitive-behavioral therapy and interpersonal therapy, which are efficacious for late-life depression in general, should also be considered for treatment alone or in combination with appropriate medication. Future research areas are also addressed in this paper.
Mild cognitive impairment (MCI) covers a spectrum of cognitive impairment, bordered by normal cognitive performance on one end and frank dementia on the other. How wide the net for MCI is cast will affect the prevalence and severity of its functional consequences. Many studies suggest that MCI is an early stage of Alzheimer's disease. Therefore, investigation of the functional impact of MCI offers an important opportunity to examine the quality-of-life impact of a prodromal stage of Alzheimer's disease. In this review, the authors examine the nosology of the condition, the subjective experience of having an MCI diagnosis, and cross- sectional and prospective studies that have examined the topic.
Cortical electrophysiologic event-related potentials are multidimensional measures of information processing that are well-suited for efficiently parsing automatic and controlled components of cognition that span the range of deficits evidenced in schizophrenia patients. These information processes are key cognitive measures that are recognized as informative and valid targets for understanding the neurobiology of schizophrenia. These measures may be used in concert with the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) neurocognitive measures in the development of novel treatments for schizophrenia and related neuropsychiatric disorders. The employment of novel event-related potential paradigms designed to carefully characterize the early spectrum of perceptual and cognitive information processing allows investigators to identify the neurophysiologic basis of cognitive dysfunction in schizophrenia and to examine the associated clinical and functional impairments.