Showing papers in "Cns Spectrums in 1999"

Randomized controlled trial of yogic meditation techniques for patients with obsessive-compulsive disorder.

Abstract: The objective of this study was to compare efficacy of two meditation protocols for treating patients with obsessive-compulsive disorder (OCD). Patients were randomized to two groups-matched for sex, age, and medication status-and blinded to the comparison protocol. They were told the trial would last for 12 months, unless one protocol proved to be more efficacious. If so, groups would merge, and the group that received the less efficacious treatment would also be afforded 12 months of the more effective one. The study was conducted at Children's Hospital, San Diego, Calif. Patients were selected according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised (DSM-III-R) criteria and recruited by advertisements and referral. At baseline, Group 1 included 11 adults and 1 adolescent, and Group 2 included 10 adults. Group 1 employed a kundalini yoga meditation protocol and Group 2 employed the Relaxation Response plus Mindfulness Meditation technique. Baseline and 3-month interval testing was conducted using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Symptoms Checklist-90-Revised Obsessive Compulsive (SCL-90-R OC) and Global Severity Index (SCL-90-R GSI) scales, Profile of Moods scale (POMS), Perceived Stress Scale (PSS), and Purpose in Life (PIL) test. Seven adults in each group completed 3 months of therapy. At 3 months, Group 1 demonstrated greater improvements (Student's independent groups t-test) on the Y-BOCS, SCL-90-R OC and GSI scales, and POMS, and greater but nonsignificant improvements on the PSS and PIL test. An intent-to-treat analysis (Y-BOCS) for the baseline and 3-month tests showed that only Group 1 improved. Within-group statistics (Student's paired t-tests) showed that Group 1 significantly improved on all six scales, but Group 2 had no improvements. Groups were merged for an additional year using Group 1 techniques. At 15 months, the final group (N=11) improved 71%, 62%, 66%, 74%, 39%, and 23%, respectively, on the Y-BOCS, SCL-90-R OC, SCL-90-R GSI, POMS, PSS, and PIL; P<0.003 (analysis of variance). This study demonstrates that kundalini yoga techniques are effective in the treatment of OCD.

Altered CSF 5-HIAA Disposition in Pathologic Male Gamblers.

Abstract: Previous reports concerning the cerebrospinal fluid (CSF) of pathologic gamblers have described disturbed norepinephrine and dopamine (but not serotonin) functioning in the central nervous system. We analyzed neurotransmitter metabolites in two consecutive 6-mL samples of CSF obtained from 10 pathologic male gamblers punctured at the L4-5 level following 8 hours of fasting along with strict bed rest. Data were compared with those for healthy male controls. In conformity with findings in healthy male controls, we found gradients in CSF 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), but not 4-hydroxy-3-methoxyphenyl glycol (HMPG). Expressing the CSF concentrations as nmol x L-1 x min-1 of tapping time (an estimate of the mass flow through the needle), the levels of 5-HIAA and HMPG (but not HVA) were found to be significantly lower in gamblers. Levels of 5-HIAA and HVA showed a significant correlation in gamblers but not in healthy controls. Taking tapping time into account, the CSF levels of HMPG and 5-HIAA were significantly lower in gamblers. We concluded that, in light of previous CSF findings of disturbed norepinephrine and dopamine function, altered indolamine function cannot be fully ruled out.

Social Phobia: Clinical and Research Perspectives

Abstract: Foreword. Acknowledgments. Introduction. Phenomenology and Prevalence. Clinical phenomenology and comorbidity. Epidemiology. Personality function. Social anxiety in children and adolescents. Theory and Research. Heritability of social anxiety. Psychodynamic perspectives. Cognitive and behavioral aspects. Biological aspects. Assessment and Treatment. Assessment and measurement. Cognitive-behavioral group treatment: description, case presentation, and empirical support. ?-Blockers and benzodiazepines in pharmacotherapy. Monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, and other antidepressants in pharmacotherapy. Epilogue. Index.

Alcohol Withdrawal: Neuroadaptation and Sensitization

Abstract: Repeated episodes of alcohol withdrawal may exacerbate the severity of future withdrawal occurrences. The progressive intensification of withdrawal symptoms may be manifested as a kindling-like mechanism. This sensitization process may reflect persistent perturbation in excitatory and inhibitory influences on brain function. Relapse is also thought to be affected by the kindling mechanism. Successive alcohol withdrawal experiences may also lead to neurologic damage and cognitive impairments. We review the research findings regarding the alcohol withdrawal kindling hypothesis and the implications of the kindling process on mechanisms of dependence, alcohol withdrawal treatment strategies, and the long-term repercussions of alcoholism.

Brain Reward Circuits in Alcoholism

Abstract: This article discusses the neurocircuitry and the neurochemical systems, as well as the molecular elements within these systems, that are believed to be important in the etiology of alcoholism. Alcoholism is a complex behavioral disorder characterized by excessive consumption of alcohol; a narrowing of the behavioral repertoire toward excessive consumption; the development of tolerance and dependence; and impairment in social and occupational functioning. Animal models of the complete syndrome of alcoholism are difficult if not impossible to achieve, but validated animal models exist for many of the different components of the syndrome.Recent work has begun to define the neurocircuits responsible for the major sources of positive and negative reinforcement that are key to animal models of excessive alcohol intake. Alcohol appears to interact with alcohol-sensitive elements within neuronal membranes that convey the specificity of neurochemical actions. Positive reinforcement appears to be mediated by an activation γ-aminobutyric acid A receptors, release of opioid peptides and dopamine, inhibition of glutamate receptors, and interaction with serotonin systems. These neurocircuits may be altered by chronic alcohol administration. This is reflected by their exhibiting opposite effects during acute alcohol withdrawal, and by the recruitment of other neurotransmitter systems, such as the stress neuropeptide corticotropin-releasing factor. These neuropharmacologic actions are believed to produce allostatic changes in set-point, which set up the vulnerability to relapse that is so characteristic of alcoholism. Future challenges include a focus on understanding exactly how these neuroadaptive changes convey vulnerability to relapse in animals with a history of alcohol dependence.

Chronic malignant pain in cancer patients.

Abstract: Although the incidence of cancer and cancer-related deaths has declined in recent years, undertreatment of cancer-related pain continues to be a significant problem. By thoroughly assessing chronic malignant pain (CMP) as it relates to cancer and achieving a more complete understanding of the CMP syndromes experienced by cancer patients, psychiatrists and neurologists can formulate accurate diagnoses of patients' clinical pain syndromes and construct well-defined, individual management plans for each patient.

Augmentation of Antidepressant Pharmacotherapy: A Preclinical Approach Using the Mouse Forced Swimming Test

Abstract: Until recently, several weeks of treatment were required in order to obtain a clinically significant antidepressant response using pharmacotherapy. The present study, using the mouse forced swimming test, investigated possible antidepressant augmentation strategies, together with the probable mechanisms involved in such potentiations. It is clear from this and other similar studies that it is possible to enhance the activity of antidepressant drugs with the addition of other compounds (ie, clonidine, quinine, glyburide, pindolol, or buspirone). These data indicate that direct/indirect manipulation of serotonergic receptor systems potentiates the effect antidepressant drugs (ie, selective serotonergic reuptake inhibitors) in the mouse forced swimming test, and thus establish this model as a reliable preclinical tool for the investigation of possible antidepressant augmentation strategies. It also appears that this model can be used as a method for identifying the mechanisms involved in such treatment strategies.

Symptoms in Obsessive-Compulsive Disorder and Tourette Syndrome: A Spectrum?.

Abstract: There is clear overlap in the clinical symptoms of obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). As a result, OCD (with or without tics) and TS (with or without obsessive-compulsive symptoms [OCS]) have been conceptualized to form a disorder spectrum—an overlapping set of phenotypes reflecting presumed commonality at the level of the underlying genetics and neuropathology. We identified the characteristics of a research sample of patients with OCD or TS, based on information obtained in semistructured clinical interviews, to examine the similarities and differences in the clinical symptoms across this spectrum. This sample conformed to known age-of-onset and sex distribution patterns for OCD and TS. Previously reported patterns of predominant aggressive and sexual obsessions and touching compulsions were observed in subjects with tic-related OCD, compared with non—tic-related OCD (ie, OCD alone). The majority of patients with tic-related OCD experienced horrifically violent obsessions that were less common in OCD alone and much less common in TS. Nonetheless, symptomatic and functional impairment in TS subjects was clearly related to the intensity of their OCS. The specific obsessions and compulsions associated with clinical impairment in TS differed from those associated with impairment in OCD. These results suggest that, despite the many overlapping dimensions of these disorders, the symptoms and associated impairment in “pure” OCD, tic-related OCD, and TS do not form a simple continuous spectrum.

Gender differences in major depressive disorder and bipolar disorder.

Abstract: This paper reviews the literature on gender differences in major depressive disorder (MDD) and bipolar disorder (BPD). Beginning in adolescence, women are at a higher risk than men of becoming depressed. Avenues of investigation that might ultimately help to explain this phenomenon include studies of gender differences in the processing of emotional stimuli, the psychotropic effects of gonadal steroids, and environment/gene interactions in men and women. With the exception of the elevated suicide rate among men, consistent gender differences in the course and symptoms of MDD have not been found. In BPD, women are more likely than men to develop a rapid-cycling course. Gender differences in treatment response, particularly in regard to mood stabilizing medications, warrant further study.

The savant syndrome and autistic disorder.

Abstract: Savant syndrome, characterized by remarkable islands of mental ability in otherwise mentally handicapped persons, may occur in autistic as well as nonautistic individuals. Overall, approximately 10% of autistic persons exhibit savant abilities; roughly 50% of those with savant syndrome have autism, and the remaining 50% have other forms of developmental disability. Most commonly, savant syndrome takes the form of extraordinary musical abilities, but may also include calendar-calculation, artistic, mathematical, spatial, mechanical, and memory skills. While savant syndrome was first described more than a century ago, only recently have researchers begun to employ a more uniform nomenclature and more standardized testing in an effort to compare the abilities of savants with those of normal persons. Males show signs of savant syndrome approximately four times more often than females. Along with imaging study findings, this fact suggests the presence of a developmental disorder involving left-brain damage with right-brain compensation.

Low platelet monoamine oxidase activity in sensation-seeking bullfighters.

Abstract: In this study, we attempt to demonstrate an association between low platelet monoamine oxidase (MAO) activity, as assessed by isotopic methods, and the stable behavioral pattern of sensation- and risk-seeking of professional bullfighters. Sixteen professional bullfighters were studied and compared with a control group of 46 healthy control subjects who did not engage in risky jobs or activities. The group of bullfighters had significantly reduced platelet MAO activity compared with the control group (P<0.05). Bullfighters were shown to be significantly more extroverted and sensation-seeking than controls on various temperament scales. A predisposition to engage in risky activities (eg, bullfighting) and sensation-seeking could be partly conditioned by the presence of biological components of personality manifested by a significantly decreased platelet MAO activity.

Variability in Response to Clozapine: Potential Role of Cytochrome P450 1A2 and the Dopamine D4 Receptor Gene

Abstract: Clozapine is a prototype atypical antipsychotic drug and displays efficacy in 30% to 60% of schizophrenia patients who do not respond to traditional antipsychotics. There is considerable evidence supporting a concentration-response relationship for clozapine. A plasma clozapine concentration >200 to 420 ng/mL increases the probability of antipsychotic effects. Approximately 70% to 80% of variability in clozapine plasma concentration can be attributed to variability in cytochrome P450 1A2 activity. Measurement of caffeine metabolites in plasma or urine can be used as an in vivo index of cytochrome P450 1A2 activity, since caffeine is primarily eliminated by oxidative metabolism through this cytochrome P450 enzyme. Caffeine-based tests may contribute to individualization of clozapine dosages and optimization of its antipsychotic effects in schizophrenia patieents There are several lines of evidence suggesting the potential involvement of the dopamine D4 receptor in pharmacodynamic effects of clozapine. Clozapine has a 10-fold higher affinity for the dopamine D4 receptor in comparison to the D2 and the D3 receptors. Moreover, the free plasma fluid concentration of clozapine is comparable to its binding affinity for the D4 receptor in vitro. Blockade of the D4 receptor in the mesocorticolimbic region, a brain area implicated in the pathogenesis of schizophrenia, may contribute to efficacy of clozapine in negative symptoms. Moreover, the dopamine D4 receptor gene (DRD4) displays an unusual degree of genetic variation (polymorphism). In a recent preliminary study, investigated the (G)n mononucleotide repeat polymorphism within the first intron of the D4 gene in 50 schizophrenia patients refractory to traditional antipsychotics. These patients were prospectively followed for antipsychotic response during clozapine treatment. Analysis of variance found significant differences in antipsychotic response as demonstrated by mean change in Brief Psychiatric Rating Scale scores among the genotype panels for this polymorphism F[3,49]=4.1 (P=0.01). Future studies investigating the mechanistic basis of variability in response to clozapine should focus on both pharmacokinetic and pharmacodynamic factors.

Neuropathology in Tourette Syndrome

Abstract: The unique clinical presentation of Tourette syndrome (TS) and its symptomatic response to dopamine antagonists are widely cited as evidence for the central role of the limbic-motor interface in the pathophysiology of TS. Nonetheless, the true neuropathology of TS remains elusive, even though significant advances have been made in understanding complex interconnected circuitries within the limbic system and basal ganglia. Neuropathologic and neuroimaging studies—plagued by small samples, clinical heterogeneity, and a number of interpretative problems—are generally supportive of pathology within the orbitofrontal cortex, striatum, and their efferent projections in TS. The specific patterns of abnormalities vary widely across these studies, clouding attempts to define a unifying neuropathology for this disorder. Converging yet circumstantial evidence for frontal cortical, and basal ganglia pathology in TS comes also from studies infields ranging from neuroimmunology to neuropsychology, and from the clinical overlap between TS and disorders such as obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, and Sydenhams chorea. As a “model” neuropsychiatric disorder, TS has stimulated advances in several areas of neurobiology research, yet we still await a real understanding of its pathophysiology in order to move from empirically driven therapeutics to the development of targeted effective treatments.

Demographics, Prevalence, and Clinical Features of the Schizo-obsessive Subtype of Schizophrenia.

Abstract: The schizo-obsessive subtype of schizophrenia has been proposed to describe the condition of patients with chronic psychotic disorders and prominent obsessive-compulsive (OC) symptoms. These patients differ from others with schizophrenia not only in their psychopathology, but perhaps also in their prognosis and pharmacotherapeutic response. Potent serotonin reuptake blockers, such as clomipramine, fluvoxamine, and fluoxetine, in conjunction with antipsychotics, can prove helpful in improving these patients' OC symptoms. The current study to access the demographics, prevalence, and clinical features of the schizo-obsessive subtype included established outpatients with a principal diagnosis of schizophrenia or schizoaffective disorder treated at a large urban public hospital. More than 50% of the hospital's psychiatric population is Hispanic. The Modified Maudsley Obsessive Compulsive Inventory (MMOCI) was used to identify prominent compulsive symptoms. Of the 52 patients who fulfilled the specific screening criteria, 17 (33%) also had prominent OC symptoms. Surprisingly, there was a statistical trend (P=0.06) for Hispanic patients to meet our threshold for the schizo-obsessive subtype. The MMOCI proved to be an adequate and efficient self-rated screening tool. The prevalence of the schizo-obsessive subtype, especially among Hispanic patients, highlights the importance for mental health professionals working with this population to identify and appropriately treat this group of patients.

From Gilles de la Tourette's Disease to Tourette Syndrome: A History

Abstract: Over the past century researchers have attributed the symptoms that today are labeled as Tourette syndrome to various etiologies. Although most investigators have accepted Gilles de la Tourette's initial description of a symptom complex of tics and involuntary vocalizations, most have rejected his claim that “tic disease” resulted from hereditary degeneration. Subsequent investigators have offered an array of contradictory etiological explanations including viewing these symptoms as a subset of choreas, a result of insufficient inhibition, a failure to control infantile habits, a sequel to encephalitis and other infections, or the result of unconscious psychosexual childhood conflict. With the advent of effective pharmacologic treatments in the 1960s, psychiatrists, often urged on by the parents of afflicted children, began to insist that the disorder resulted from organic factors, most likely connected to transmission of the neurotransmitter dopamine and signaling in the basal ganglia. Since the 1970s, research has focused on a variety of possible organic substrates, but disputes over which symptoms to include in the syndrome's phenotype continue to constrain efforts to locate its etiology.

Predictors of therapeutic response to treatments for depression: a review of electrophysiologic and dichotic listening studies.

Abstract: There are few clinical or biologic predictors of response to treatments for depression. This article reviews growing evidence that electrophysiologic and neurocognitive measures of brain function may be of value as predictors of therapeutic response to antidepressants. Initial studies using dichotic listening, quantitative electroencephalography, or event-related brain potential measures have found differences between treatment responsive and nonresponsive subgroups of depressed patients. The neurophysiologic basis for these differences and the potential clinical utility of electrophysiologic and dichotic predictors of treatment outcome remain to be determined in future studies.

Psychosocial treatments for social phobia.

Abstract: Increasing recognition of the prevalence and impairment associated with social phobia has spurred the development of effective psychosocial treatments for this disorder. Exposure-based interventions have the most empirical support. This article applies the tripartite model of anxiety to social phobia, describes state-of-the-art psychosocial treatments, and highlights studies on the comparative and combined efficacy of psychological and pharmacologic treatments. Clinical issues related to treatment implementation, limitations of extant psychosocial interventions, and suggestions for future research are also discussed.

Neurocognitive Deficits and Recovery in Chronic Alcohol Abuse

Abstract: The excessive and chronic use of alcohol is associated with a variety of neurocognitive changes in a substantial number of detoxified alcoholics. These deficits extend across a wide variety of neuropsychological domains and can be observed over a period of months following detoxification. Furthermore, they are seen in both male and female alcoholics, despite the fact that female alcoholics often have shorter drinking histories. Although these deficits are widely observed, there is considerable heterogeneity both within and across studies. Currently, the sources of this variability are only poorly understood. In this article, we review these neurocognitive and neurophysiological deficits, their pattern of recovery, potential contributing or confounding factors, and some of the clinical implications of these findings.

Anxiety and the blues after breast cancer: how common are they?

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

The shyness spectrum.

Abstract: Debate continues regarding the relationship between shyness and social phobia. Some have proposed that this relationship is best understood by adopting a spectrum approach where increasing levels of shyness eventually merge into the clinical disorder of social phobia. This paper begins to explore the validity of this spectrum by reviewing similarities and differences between shyness and social phobia and investigating how shyness relates to social phobia subtypes. This paper will also explore precursors to social phobia, namely childhood behavioral inhibition.

Neuroimaging Studies in Tourette Syndrome.

Abstract: Tourette syndrome (TS) is a complex neurobehavioral disorder principally characterized by motor and vocal tics. However, features of obsessive-compulsive and attention-deficit/hyperactivity disorders are often present. The basal ganglia and associated brain structures have been implicated in the pathophysiology of TS, as well as in these related conditions. Specifically, it is believed that the neuroanatomically and functionally defined basal ganglia thalamocortical loops are involved in TS. These loops are composed of a sequence of connections originating in the cortex and passing in series through the striatum (caudate and putamen), globus pallidus, and thalamus before returning to the cortical areas of origin. This review concentrates on the neuroimaging findings in Ts, particularly as they relate to alterations in components of the basal ganglia thalamocortical circuits. These neuroimaging data suggest that the major abnormalities in TS involve striatal or cortical dysfunction, as well as dysfunction of dopaminergic systems that regulate basas ganglia neurotransmission.

Understanding the Genetic Basis of Obsessive-Compulsive Disorder

Abstract: Genetic study holds potential for understanding the etiology of a number of serious psychiatric disorders. In the case of obsessive-compulsive disorder (OCD), many investigators agree that there is a strong genetic component to its development. In this article, we review the scientific evidence gleaned from different types of studies that has led to a better understanding of the nature of the inherited factors in OCD.

The psychiatry of Tourette syndrome

Abstract: Tourette syndrome (TS) has been conceptualized as a psychological problem, a neurological problem, and more recently a neurobehavioral problem. Each conceptual model has had an impact on how persons with TS view themselves and how practitioners view individuals with TS, as well as an impact on what both clinicians and patients expect from diagnosis and treatment. This article reviews the common comorbid psychiatric disorders and their relationship to TS, and discusses how the evolving conceptions of TS have impacted psychologically on persons with tics and TS, as well as on the providers who treat them.

Trazodone Augmentation in OCD: A Case Series Report.

Abstract: Based on previous evidence that trazodone may have antiobsessional properties, the authors assessed trazodone augmentation of selective serotonin reuptake inhibitor (SSRI) therapy in five cases of obsessive-compulsive disorder. All patients showed symptomatic improvement after trazodone was added to treatment with various SSRIs, and in many cases, trazodone also improved the tolerability of SSRI therapy.

Clinical Experience With Transdermal Nicotine Patch in Tourette Syndrome

Abstract: Stemming from the finding that nicotine potentiates haloperidol-induced catalepsy in rats, nicotine in the form of nicotine gum and as transdermal nicotine patch (TNP) has been used in open-label studies to obtund motor and vocal tics of children (age≥8 years, weighi≥25 kg), adolescents, and adults. Reduction of tics was seen during chewing of nicotine gum; the improvement lasted no longer than 1 hour after chewing. With a TNP in subjects who were not responding well to a variety of dopamine blockers, with some also receiving clonidine or a variety of selective serotonin reuptake inhibitors, motor and vocal tics were obtunded 45% over baseline in 85% of 35 subjects within 30 minutes to 3 hours after TNP application. Moreover, the relief of symptoms with a single 7-mg TNP, remaining on the skin for 24 hours, persisted for a variable period of time ranging from 1 to 120 days with an average of 10±2 days. Application of a second TNP for 24 hours when symptoms began to return resulted in a similar reduction in tic severity and frequency, which persisted an average of l3±3 days. Nicotine alone, without D 2 blockers, was successful in reducing premonitory urges to tic. After follow-up of 3 to 5 years, 19 of 35 patients continued to use the TNP in gradually decreasing frequency and with gradual reduction in dose of D 2 blockers. However, 16 patients (45%), as they grew into middle adolescence, discontinued use of the TNP, stating that they objected to the nausea induced by the patch. There was no evidence of habituation to nicotine. Side effects were not life threatenting; the most disturbing side effect was nausea, appearing 1 to 4 hours after the application of the patch and lasting 1 to 3 hours. There was no change in blood pressure; pulse rate increased from 5 to 10% within 3 hours but returned to baseline after 24 hours. Unsolved problems using TNP are mentioned and a putative mechanism for nicotine effectiveness in Tourette syndrome is briefly discussed.