Anxiety Disorders: Yale University

Leckman JF, Bloch MH, King RA. · Child Study Center, Yale University School of Medicine, 230 South Frontage Road, New Haven, CT 06520-7900, USA. · Dialogues Clin Neurosci. · Pubmed #19432385 No free full text.

Abstract: In the absence of definitive etiological markers for obsessive-compulsive disorder (OCD% obsessive-compulsive (OC) symptom dimensions may offer a fruitful point of orientation. These dimensions can be understood as defining potentially overlapping clinical features that may be continuous with "normal" worries first evident in childhood. Although the understanding of the dimensional structure of OC symptoms is still imperfect, a recent large-scale meta-analysis has confirmed the presence of at least four separa ble symptom dimensions in children, as well as adults, with OCD. A dimensional approach does not exclude other methods to parse OCD. Thus far, a pediatric age of onset, the presence of other family members with OCD, and the individual's "tic-related" status appear to be potentially useful categorical distinctions. Although the OC symptom dimensions appear to be valid for all ages, it is unlikely that the underlying genetic vulnerability factors and neurobiological substrates for each of these symptom dimensions are the same across the course of development.

Pittenger C, Coric V, Banasr M, Bloch M, Krystal JH, Sanacora G. · Clinical Neuroscience Research Unit, Yale University School of Medicine, New Haven, Connecticut, USA. · CNS Drugs. · Pubmed #18698875 No free full text.

Abstract: Recent advances implicate amino acid neurotransmission in the pathophysiology and treatment of mood and anxiety disorders. Riluzole, which is approved and marketed for the treatment of amyotrophic lateral sclerosis, is thought to be neuroprotective through its modulation of glutamatergic neurotransmission. Riluzole has multiple molecular actions in vitro; the two that have been documented to occur at physiologically realistic drug concentrations and are therefore most likely to be clinically relevant are inhibition of certain voltage-gated sodium channels, which can lead to reduced neurotransmitter release, and enhanced astrocytic uptake of extracellular glutamate.Although double-blind, placebo-controlled trials are lacking, several open-label trials have suggested that riluzole, either as monotherapy or as augmentation of standard therapy, reduces symptoms of obsessive-compulsive disorder, unipolar and bipolar depression, and generalized anxiety disorder. In studies of psychiatrically ill patients conducted to date, the drug has been quite well tolerated; common adverse effects include nausea and sedation. Elevation of liver function tests is common and necessitates periodic monitoring, but has been without clinical consequence in studies conducted to date in psychiatric populations. Case reports suggest utility in other conditions, including trichotillomania and self-injurious behaviour associated with borderline personality disorder. Riluzole may hold promise for the treatment of several psychiatric conditions, possibly through its ability to modulate pathologically dysregulated glutamate levels, and merits further investigation.

Bloch MH. · Yale Child Study Center, 230 South Frontage Road, New Haven, CT 06520, USA. · Curr Psychiatry Rep. · Pubmed #18627671 No free full text.

Abstract: Tourette's disorder is a childhood-onset neuropsychiatric disorder characterized by multiple motor and vocal tics. Many children with Tourette's disorder improve throughout adolescence. However, some adults with Tourette's disorder still experience severe symptoms and significant disability. This article examines the evidence base for current treatments for Tourette's disorder. Emerging treatments such as deep brain stimulation, habit reversal therapy, and repetitive trans-cranial magnetic stimulation are also discussed.

Zdanys K, Tampi RR. · Yale University School of Medicine, Department of Psychiatry, LV-121 Yale New Haven Psychiatric Hospital, 184 Liberty Street, New Haven, CT 06519, United States. · Prog Neuropsychopharmacol Biol Psychiatry. · Pubmed #18262702 No free full text.

Abstract: Recent data points to glutamatergic dysfunction in mood disorders, anxiety disorders, obsessive-compulsive disorder, and schizophrenia. Memantine, a drug approved by the FDA for the treatment of moderate to severe Alzheimer's disease that acts at the N-methyl-d-aspartate receptor, has been used off-label for various psychiatric disorders. Although promising, the available data for the use of memantine in these disorders is limited. Given this data, the routine use of memantine for depression, schizophrenia, obsessive-compulsive disorder, substance abuse, pervasive developmental disorders, bipolar disorder, and binge eating disorder cannot be recommended at this time.

Bloch MH, Landeros-Weisenberger A, Sen S, Dombrowski P, Kelmendi B, Coric V, Pittenger C, Leckman JF. · Yale Child Study Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA. <> · Am J Med Genet B Neuropsychiatr Genet. · Pubmed #18186076 No free full text.

Abstract: We investigated the association between the long (l) and short (s) alleles of the serotonin transporter polymorphism (5-HTTLPR) in the promoter region of the SLC6A4 gene and obsessive-compulsive disorder (OCD) using meta-analysis to combine all published data from case-control and family based association studies (2,283 cases). In stratified meta-analysis we investigated whether age of sample (child and adult), ethnicity (Caucasian and Asian) and study design (case-control and family-based association studies) moderated any association. In the overall meta-analysis we found no evidence of association between genetic variation at the 5-HTTLPR locus and OCD. We did find significant heterogeneity between studies. In the stratified meta-analyses, we demonstrated a significant association between the l-allele and OCD in family-based association studies and in studies involving children and Caucasians. Our meta-analysis suggests the possibility that the l-allele may be associated with OCD in specific OCD subgroups such as childhood-onset OCD and in Caucasians. Further meta-analyses based on individual patient data would be helpful in determining whether age of OCD onset, gender and the presence of comorbid illness (e.g., tics) moderates the relationship between 5-HTTLPR and OCD.

Chwastiak LA, Ehde DM. · Department of Psychiatry, Yale University School of Medicine, Yale New Haven Psychiatric Hospital, 184 Liberty Street, New Haven, CT 06519, USA. · Psychiatr Clin North Am. · Pubmed #17938046 links to  free full text

Abstract: MDD and anxiety disorders are highly prevalent among persons who have MS and have been associated with decreased adherence to MS treatment and poorer functional status and quality of life. Effective treatment is available for MDD, but this disorder continues to be underdetected and undertreated by MS providers. Treatment with pharmacotherapy is particularly challenging in this patient population, given the somatic symptom overlap between MS and depression and the increased burden of side effects. Larger randomized, controlled trials are needed to elucidate further the effectiveness of pharmacotherapy and to identify subgroups of patients who would benefit from this type of treatment for depression. There have been few rigorous studies of the prevalence and impact of anxiety disorders, substance use disorders, or serious mental illness such as bipolar disorder or schizophrenia, in MS samples.

Lombroso PJ, Scahill L. · Child Study Center, Yale University School of Medicine, New Haven, CT 06520, United States. · Brain Dev. · Pubmed #17937978 links to  free full text

Abstract: Tourette syndrome and obsessive-compulsive disorder are neuropsychiatric disorders that have sparked considerable interest over the decades. They are the focus of research for a remarkable diversity of disciplines, ranging from neuroimagers and prenatal epidemiologists to experts in the neural circuits that connect the cortex with the basal ganglia, as well as neuroimmunologists focusing on brain-based autoimmune phenomena. Several hypotheses have been put forward to explain the onset and exacerbation of these illnesses. Here, we discuss the clinical phenomenology and treatment options that are currently available. New psychopharmacological agents are being used that are based on a greater understanding of the neurobiology and are being used in combination with behavioral interventions. Longitudinal clinical investigations into clinical symptoms and the natural course are providing additional clues on the underlying pathophysiology. Recent advances in research models are also reviewed in an attempt to clarify some of the molecular etiologies that lead to these disorders.

Southwick SM, Vythilingam M, Charney DS. · Yale University School of Medicine, National Center for Post-Traumatic Stress Disorder, VA Connecticut Healthcare System, West Haven, Connecticut 06516, USA. · Annu Rev Clin Psychol. · Pubmed #17716089 No free full text.

Abstract: This review discusses neurobiological and psychosocial factors associated with stress-induced depression and compares these factors with those believed to characterize stress resilience. Neurobiological factors that are discussed and contrasted include serotonin, the 5-HT1A receptor, polymorphisms of the 5-HT transporter gene, norepinephrine, alpha-2 adrenergic receptors, neuropeptide Y, polymorphisms of the alpha-2 adrenergic gene, dopamine, corticotropin-releasing hormone (CRH), dehydroepiandrosterone (DHEA), cortisol, and CRH receptors. These factors are described in the context of brain regions believed to be involved in stress, depression, and resilience to stress. Psychosocial factors associated with depression and/or stress resilience include positive emotions and optimism, humor, cognitive flexibility, cognitive explanatory style and reappraisal, acceptance, religion/spirituality, altruism, social support, role models, coping style, exercise, capacity to recover from negative events, and stress inoculation. The review concludes with potential psychological, social, spiritual, and neurobiological approaches to enhancing stress resilience, decreasing the likelihood of developing stress-induced depression/anxiety, and treating stress-induced psychopathology.

Scholl J, Allen PJ. · Pediatric Emergency Room, Yale-New Haven Hospital, New Haven, CT, USA. · Pediatr Nurs. · Pubmed #17708185 No free full text.

Abstract: This article reviews the literature related to functional abdominal pain (FAP) in childhood, including the definition, etiology, contributing factors, clinical diagnosis, therapy and management, and associated long-term health effects. FAP is determined when no specific structural, infectious, inflammatory, or biochemical cause can be found in a child with chronic pain. The presence of abdominal pain as an isolated symptom is more suggestive of FAP, whereas multiple symptoms are more likely to be due to an organic or biochemical condition. While the exact cause of FAP is not completely understood, most researchers and clinicians agree that it is of multi-factorial etiology coupled with an altered brain-gut interaction. Children are highly susceptible to influences around them and can experience pain in response to normal childhood feelings and experiences. Psychological disorders such as anxiety and depression are common in both children with FAP and their parents. Children with FAP tend to have low levels of self-directedness, internalize their feelings and worries, and ruminate over issues they cannot control. The biopsychosocial model has proved to be a worthwhile framework for children with FAP, as it recognizes the interaction between social and environmental influences, psychological processes, and the state of the body. Interventions that focus on the child's cognitive processes associated with abdominal pain and the family's response to the pain have increased efficacy over standard education and reassurance. Providing children and families with techniques to use when experiencing pain decreases alterations in normal daily activities and improves long-term health outcomes.

Swain JE, Scahill L, Lombroso PJ, King RA, Leckman JF. · Child Study Center of Yale University, New Haven, CT, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #17667475 No free full text.

Abstract: OBJECTIVE: This is a review of progress made in the understanding of Tourette syndrome (TS) during the past decade including models of pathogenesis, state-of-the-art assessment techniques, and treatment. METHOD: Computerized literature searches were conducted under the key words "Tourette syndrome," "Tourette disorder," and "tics." Only references from 1996-2006 were included. RESULTS: Studies have documented the natural history of TS and the finding that tics usually improve by the end of the second decade of life. It has also become clear that TS frequently co-occurs with attention-deficit/hyperactivity disorder), obsessive-compulsive disorder, and a range of other mood and anxiety disorders. These comorbid conditions are often the major source of impairment for the affected child. Advances have also been made in understanding the underlying neurobiology of TS using in vivo neuroimaging and neurophysiology techniques. Progress on the genetic front has been less rapid. Proper diagnosis and education (involving the affected child and his or her parents, teachers, and peers) are essential prerequisites to the successful management of children with TS. When necessary, modestly effective antitic medications are available, although intervening to treat the comorbid attention-deficit/hyperactivity disorder and/or obsessive-compulsive disorder is usually the place to start. CONCLUSIONS: Prospective longitudinal studies and randomized clinical trials have led to the refinement of several models of pathogenesis and advanced our evidence base regarding treatment options. However, fully explanatory models are needed that would allow for more accurate prognosis and the development of targeted and efficacious treatments.

Leckman JF, Rauch SL, Mataix-Cols D. · Child Study Center, Yale University School of Medicine, New Haven, CT 06520-7900, USA. · CNS Spectr. · Pubmed #17514082 links to  free full text

Abstract: In the absence of definitive etiological markers of vulnerability or a unitary profile of pathophysiology for obsessive-compulsive disorder (OCD), obsessive-compulsive (OC) symptom dimensions seem to offer a fruitful point of orientation. The complex clinical presentation of OCD can be summarized using a few consistent and temporally stable symptom dimensions. These can be understood as a spectrum of potentially overlapping features that are likely to be continuous with "normal" worries and extend beyond the traditional nosological boundaries of OCD. Although the understanding of the dimensional structure of obsessive-compulsive symptoms (OCS) is still imperfect, this quantitative approach to phenotypic traits has the potential to advance our understanding of OCD and may aid in the identification of more robust endophenotypes. Preliminary data suggest that these dimensional phenotypes may be useful in studies of the natural history, genetics, neurobiology, and treatment outcome of OCD. A dimensional approach is not mutually exclusive of other methods to parse the larger spectrum of disorders related to OCD. Thus far, age-of-onset of OCS and the individual's "tic-related" status seem to be particularly useful categorical distinctions. Finally, existing assessment methods are inadequate and new dimensional scales are needed to take full advantage of a dimensional approach in clinical and population-based studies.

Tronson NC, Taylor JR. · Department of Psychiatry, Division of Molecular Psychiatry, Center for Genes and Behavior, Yale University School of Medicine, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park Street, New Haven, Connecticut 06508, USA. · Nat Rev Neurosci. · Pubmed #17342174 No free full text.

Abstract: Memory reconsolidation has been argued to be a distinct process that serves to maintain, strengthen or modify memories. Specifically, the retrieval of a previously consolidated memory has been hypothesized to induce an additional activity-dependent labile period during which the memory can be modified. Understanding the molecular mechanisms of reconsolidation could provide crucial insights into the dynamic aspects of normal mnemonic function and psychiatric disorders that are characterized by exceptionally strong and salient emotional memories.

Knobf MT. · Yale School of Nursing, New Haven, CT, USA. · Semin Oncol Nurs. · Pubmed #17303518 No free full text.

Abstract: OBJECTIVES: To review the evidence on psychosocial responses in breast cancer survivors (BCS); identify factors that influence those responses; and propose patterns of psychosocial functioning that may provide a framework for assessment and intervention. DATA SOURCES: Research articles/abstracts; literature reviews. CONCLUSION: The majority of breast cancer survivors demonstrate a pattern of recovery. Age, information, communication, social and emotional support, family, and degree of symptom distress are known factors influencing QOL outcomes. IMPLICATIONS FOR NURSING PRACTICE: Assessment of psychosocial functioning is essential to identify needs and risk factors. Interventions should be targeted to meet informational needs, promote effective communication, manage uncertainty, control symptoms, enhance social and emotional support, and address cultural differences.

Muralidharan A, Bhagwagar Z. · Department of Psychiatry, Yale University, New Haven, CT 06510, USA. · CNS Drugs. · Pubmed #17140277 No free full text.

Abstract: Levetiracetam is a newer antiepileptic agent that was first approved by the US FDA in 1999 as an adjunctive therapy for the treatment of refractory partial epilepsy in adults. Since then, it has been approved for a wider patient population, i.e. as adjunctive therapy for partial seizures in patients >4 years of age (worldwide) and as first-line monotherapy for partial seizures in patients >16 years of age (in Europe); and as adjunctive therapy for juvenile myoclonic seizures (in Europe and the US). It has a favourable pharmacokinetic profile and appears to act at a specific site in the CNS. Pharmacodynamic evidence indicates that levetiracetam indirectly facilitates GABAergic function, and an increasing body of evidence suggests an important role for GABA in the pathophysiology of mood disorders. Preclinical studies using animal models of depression, anxiety and mania provide evidence for levetiracetam as a mood stabiliser. Preliminary clinical evidence from case reports and open-label pilot studies indicates that the drug, both as add-on therapy and as monotherapy, has efficacy in a wide range of bipolar spectrum disorders. Most recently, a 31% remission rate was reported in patients with bipolar disorder who were in the depressed phase at baseline and who received levetiracetam as add-on therapy for 8 weeks in an open-label trial. While these results are encouraging, placebo-controlled data are needed to further clarify the role of levetiracetam in the treatment of mood disorders.

Leckman JF, Bloch MH, Scahill L, King RA. · Yale Child Study Center, New Haven, CT 06510, USA. · J Child Neurol. · Pubmed #16970864 No free full text.

Abstract: Tourette syndrome is a neurodevelopmental disorder characterized by motor and vocal tics--rapid, repetitive, stereotyped movements or vocalizations. Tourette syndrome typically has a prepubertal onset, and boys are more commonly affected than girls. Symptoms usually begin with transient bouts of simple motor tics. By age 10 years, most children are aware of nearly irresistible somatosensory urges that precede the tics. These urges likely reflect a defect in sensorimotor gating because they intrude into the child's conscious awareness and become a source of distraction and distress. A momentary sense of relief typically follows the completion of a tic. Over the course of hours, tics occur in bouts, with a regular intertic interval. Tics increase during periods of emotional excitement and fatigue. Tics can become "complex" in nature and appear to be purposeful. Tics can be willfully suppressed for brief intervals and can be evoked by the mere mention of them. Tics typically diminish during periods of goal-directed behavior, especially those that involve both heightened attention and fine motor or vocal control, as occur in musical and athletic performances. Over the course of months, tics wax and wane. New tics appear, often in response to new sources of somatosensory irritation, such as the appearance of a persistent vocal tic (a cough) following a cold. Over the course of years, tic severity typically peaks between 8 and 12 years of age. By the end of the second decade of life, many individuals are virtually tic free. Less than 20% of cases continue to experience clinically impairing tics as adults. Tics rarely occur in isolation, and other coexisting conditions--such as behavioral disinhibition, hypersensitivity to a broad range of sensory stimuli, problems with visual motor integration, procedural learning difficulties, attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder, depression, anxiety, and emotional instability--are often a greater source of impairment than the tics themselves. Emerging behavioral treatments of Tourette syndrome are based in part on an understanding of the moment-to-moment experience of somatosensory urges and motor response. With identification of specific genes of major effect and advances in our understanding of the neural circuitry of sensorimotor gating, habit formation, and procedural memory--together with insights from postmortem brain studies, in vivo brain imaging, and electrophysiologic recordings--we might be on the threshold of a deeper understanding of the phenomenology and natural history of Tourette syndrome.

De Los Reyes A, Kazdin AE. · Department of Psychology, Yale University, New Haven, CT 06520, USA. · Psychol Rev. · Pubmed #16802881 No free full text.

Abstract: An international movement has focused on identifying evidence-based interventions that were developed to change psychological constructs and that are supported by controlled studies. However, inconsistent findings within individual intervention studies and among multiple studies raise critical problems in interpreting the evidence, and deciding when and whether an intervention is evidence-based. A theoretical and methodological framework (Range of Possible Changes [RPC] Model) is proposed to guide the study of change in intervention research. The authors recommend that future quantitative reviews of the research literature use the RPC Model to conceptualize, examine, and classify the available evidence for interventions. Future research should adopt the RPC Model to both develop theory-driven hypotheses and conduct examinations of the instances in which interventions may or may not change psychological constructs.

Bloch MH, Landeros-Weisenberger A, Kelmendi B, Coric V, Bracken MB, Leckman JF. · Child Study Center, Yale University School of Medicine, New Haven, CT 06520, USA. · Mol Psychiatry. · Pubmed #16585942 No free full text.

Abstract: As many as half of obsessive-compulsive disorder (OCD) patients treated with an adequate trial of serotonin reuptake inhibitors (SRIs) fail to fully respond to treatment and continue to exhibit significant symptoms. Many studies have assessed the effectiveness of antipsychotic augmentation in SRI-refractory OCD. In this systematic review, we evaluate the efficacy of antipsychotic augmentation in treatment-refractory OCD. The electronic databases of PubMed, PsychINFO (1967-2005), Embase (1974-2000) and the Cochrane Central Register of Controlled Trials (CENTRAL, as of 2005, Issue 3) were searched for relevant double-blind trials using keywords 'antipsychotic agents' or 'neuroleptics' and 'obsessive-compulsive disorder'. Search results and analysis were limited to double-blind, randomized control trials involving the adult population. The proportion of subjects designated as treatment responders was defined by a greater than 35% reduction in Yale Brown Obsessive-Compulsive Scale (Y-BOCS) rating during the course of augmentation therapy. Nine studies involving 278 participants were included in the analysis. The meta-analysis of these studies demonstrated a significant absolute risk difference (ARD) in favor of antipsychotic augmentation of 0.22 (95% confidence interval (CI): 0.13, 0.31). The subgroup of OCD patients with comorbid tics have a particularly beneficial response to this intervention, ARD=0.43 (95% CI: 0.19, 0.68). There was also evidence suggesting OCD patients should be treated with at least 3 months of maximal-tolerated therapy of an SRI before initiating antipsychotic augmentation owing to the high rate of treatment response to continued SRI monotherapy (25.6%). Antipsychotic augmentation in SRI-refractory OCD is indicated in patients who have been treated for at least 3 months of maximal-tolerated therapy of an SRI. Unfortunately, only one-third of treatment-refractory OCD patients show a meaningful treatment response to antipsychotic augmentation. There is sufficient evidence in the published literature, demonstrating the efficacy of haloperidol and risperidone, and evidence regarding the efficacy of quetiapine and olanzapine is inconclusive. Patients with comorbid tics are likely to have a differential benefit to antipsychotic augmentation.

Scahill L, Erenberg G, Berlin CM, Budman C, Coffey BJ, Jankovic J, Kiessling L, King RA, Kurlan R, Lang A, Mink J, Murphy T, Zinner S, Walkup J, Anonymous00057. · Yale Child Study Center, 230 South Frontage Road, P.O. Box 207900, New Haven, CT 06520, USA. · NeuroRx. · Pubmed #16554257 No free full text.

Abstract: To develop a guide to clinical assessment and pharmacotherapy for children and adults with Tourette syndrome (TS), we reviewed published literature over the past 25 years to identify original articles and reviews on the assessment and pharmacological treatment of Tourette syndrome, attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). The literature search also included a survey of reviews published in book chapters. The assessment section was compiled from several reviews. Pharmacological treatments were classified into those with strong empirical support (as evidenced by two positive placebo-controlled studies for tics, OCD, or ADHD in TS samples); modest empirical support (one positive placebo-controlled study), or minimal support (open-label data only). We conclude that accurate diagnosis, including identification of comorbid conditions, is an essential step toward appropriate treatment for patients with TS. In many patients with TS, symptom management requires pharmacotherapy for tics or coexisting conditions. The evidence supporting efficacy and safety for medications used in patients with TS varies. But this evidence offers the best guide to clinical practice.

King RA. · Tourette's/OCD Clinic, Yale Child Study Center, New Haven, Connecticut, USA. · Adv Neurol. · Pubmed #16536364 No free full text.

This publication has no abstract.

Feygin DL, Swain JE, Leckman JF. · Child Study Center, Yale University, P.O. Box 207900, New Haven, CT 06520-7900, United States. · Prog Neuropsychopharmacol Biol Psychiatry. · Pubmed #16530315 No free full text.

Abstract: One of the most curious questions plaguing subscribers of evolutionary theory is how natural selection's fine-tuned editing function could allow disease to persist. For evolutionary psychiatrists, the existence of psychopathology is thus perplexing. To illustrate a potential answer to one instance of this broad question, we examine the correlates of obsessive-compulsive disorder (OCD) within our normal repertoire of thought and action. The evidence presents a picture of OCD as a dysregulation of normal behaviors and mental states throughout the course of human development. We speculate that such correspondence may be more than a coincidence and that OCD is a consequence of a dysregulation of the neural circuits that are crucially involved in threat detection and harm avoidance. These neural systems are also likely to underlie aspects of religious experience and ritual as well as the wonders of romantic and early parental love.

Pittenger C, Krystal JH, Coric V. · Yale University Department of Psychiatry, New Haven, Connecticut 06508, USA. · NeuroRx. · Pubmed #16490414 No free full text.

Abstract: SUMMARY: Obsessive-compulsive disorder (OCD) is a common psychiatric disorder that produces significant morbidity. The introduction of serotonin reuptake inhibitors in the 1980s represented an important advance in the treatment of OCD. However, few patients show complete remission of their symptoms, and some patients show minimal improvement with existing treatments. We review current treatment strategies and initial data supporting the efficacy of glutamate modulating agents as a novel class of pharmaceuticals for the treatment of OCD. Functional neuroimaging studies repeatedly reported metabolic hyperactivity in the cortico-striato-thalamo-cortical circuitry in patients with OCD. Recent magnetic resonance spectroscopy studies provide evidence of elevated glutamate levels in several brain regions in patients suffering from OCD. These findings raised the possibility that agents that reduce glutamate hyperactivity or its consequences in the CNS might be efficacious as novel therapeutic interventions. Indeed, initial evidence from our group suggests that the antiglutamatergic agent riluzole (Rilutek), which was developed for the treatment of amyotrophic lateral sclerosis, is effective in treatment-resistant OCD. Case reports suggest that other agents that modulate glutamatergic activity may likewise be effective. This new application of glutamate modulating agents holds promise for the treatment of this disabling and often inadequately treated disease.

Rasmusson AM, Picciotto MR, Krishnan-Sarin S. · Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. · J Psychopharmacol. · Pubmed #16401662 No free full text.

Abstract: As smoking rates in the general population continue to fall in response to new information and changing social values, the continued high rate of smoking among persons with psychiatric disorders has caught the attention of society at many levels: public health officials, medical and mental health care providers, and concerned family members alike. As a consequence, research studies aimed at quantifying the problem and understanding its cause have increased dramatically over the past several years. The following review first examines epidemiological studies that have revealed a bidirectional causal relationship between tobacco dependence and posttraumatic stress disorder (PTSD), one of several mental health disorders in which tobacco dependence remains prevalent and resistant to intervention. Second, we use a translational neuroscience perspective to discuss possible neurobiological mediators of the relationship between PTSD and tobacco dependence, hoping to spur further human and animal research that will elucidate pathogenetic mechanisms involved and inspire novel treatment interventions. Finally, to enable more effective clinical research in this area, we provide an overview of effective scientific methods for assessing and managing 'smoking status' as an experimental variable in clinical research studies of PTSD as well as other mental health disorders.

Kugaya A, Sanacora G. · Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. · CNS Spectr. · Pubmed #16400244 links to  free full text

Abstract: The monoamine theory has implicated abnormalities in serotonin and norepinephrine in the pathophysiology of major depression and bipolar illness and contributed greatly to our understanding of mood disorders and their treatment. Nevertheless, some limitations of this model still exist that require researchers and clinicians to seek further explanation and develop novel interventions that reach beyond the confines of the monoaminergic systems. Recent studies have provided strong evidence that glutamate and other amino acid neurotransmitters are involved in the pathophysiology and treatment of mood disorders. Studies employing in vivo magnetic resonance spectroscopy have revealed altered cortical glutamate levels in depressed subjects. Consistent with a model of excessive glutamate-induced excitation in mood disorders, several antiglutamatergic agents, such as riluzole and lamotrigine, have demonstrated potential antidepressant efficacy. Glial cell abnormalities commonly associated with mood disorders may at least partly account for the impairment in glutamate action since glial cells play a primary role in synaptic glutamate removal. A hypothetical model of altered glutamatergic function in mood disorders is proposed in conjunction with potential antidepressant mechanisms of antiglutamatergic agents. Further studies elucidating the role of the glutamatergic system in the pathophysiology of mood and anxiety disorders and studies exploring the efficacy and mechanism of action of antiglutamatergic agents in these disorders, are likely to provide new targets for the development of novel antidepressant agents.

Stover CS, Berkowitz S. · National Center for Children Exposed to Violence, Yale University Child Study Center, New Haven, Connecticut 06510, USA. · J Trauma Stress. · Pubmed #16382437 No free full text.

Abstract: The acknowledgment of the existence of age-specific posttraumatic stress symptoms in infants, toddlers, and preschoolers points to the urgent need for standardized assessment tools for violence exposure and trauma symptoms in young children. The authors review the assessment measures currently available for the evaluation of potentially traumatic events (PTE) and posttraumatic stress disorder (PTSD) symptoms in children less than 6 years old. Each measure is described and its strengths and weaknesses discussed in a developmental context, while also considering the specific difficulties inherent to the assessment of young children. Recommendations for further test development are given.

Tielsch AH, Allen PJ. · Yale University School of Nursing, USA. · Pediatr Nurs. · Pubmed #16229131 No free full text.

Abstract: This literature review focuses on the Human Figure Drawing (HFD) methods put forth by Elizabeth Koppitz as a screening instrument. Children's drawings have potential as a mental health screening aide for health care practitioners in the primary care setting. This paper focuses on self-portrait drawings as a screening technique for emotional well-being, anxiety, and depression in school-aged children (6-12 years old). Using Koppitz's emotional indicators checklist for mental health, practitioners can use the child's HFD as a quick screening tool. Although the HFD is not diagnostic and can not be used as the sole indicator for anxiety or depression, two or more emotional indicators may signal to the clinician that further psychiatric assessment and referral is needed.