Showing papers in "Dialogues in Clinical Neuroscience in 2007"

Frontal-subcortical circuitry and behavior.

Abstract: The neuropsychiatric manifestations of neurodegenerative diseases are closely linked to neurocircuitry defects. Frontal-subcortical circuits, in particular, are effector mechanisms that allow the organism to act on its environment In this paper, we present the three main frontal-subcortical circuits: the dorsolateral prefrontal circuit allows the organization of information to facilitate a response; the anterior cingulate circuit is required for motivated behavior; and the orbitofrontal circuit allows the integration of limbic and emotional information into behavioral responses. Impaired executive functions, apathy, and impulsivity are hallmarks of frontal-subcortical circuit dysfunction. A variety of other neuropsychiatrie disorders, such as Tourette's syndrome, Huntington's disease, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, schizophrenia, and mood disorders may result from disturbances that have a direct or indirect impact on the integrity or functioning of these loops.

Gender differences in cardiovascular disease and comorbid depression.

Abstract: Although gender is increasingly perceived as a key determinant in health and illness, systematic gender studies in medicine are still lacking. For a long time, cardiovascular disease (CVD) has been seen as a "male" disease, due to men's higher absolute risk compared with women, but the relative risk in women of CVD morbidity and mortality is actually higher. Current knowledge points to important gender differences in age of onset, symptom presentation, management, and outcome, as well as traditional and psychosocial risk factors. Compared with men, CVD risk in women is increased to a greater extent by some traditional factors (e.g., diabetes, hypertension, hypercholesterolemia, obesity), and socioeconomic and psychosocial factors also seem to have a higher impact on CVD in women. With respect to differences in CVD management, a gender bias in favor of men has to be taken into account, in spite of greater age and higher comorbidity in women, possibly contributing to a poorer outcome. Depression has been shown to be an independent risk factor and consequence of CVD; however, concerning gender differences, the results have been inconsistent. Current evidence suggests that depression causes a greater increase in CVD incidence in women, and that female CVD patients experience higher levels of depression than men. Gender aspects should be more intensively considered, both in further research on gender differences in comorbid depression, and in cardiac treatment and rehabilitation, with the goal of making secondary prevention more effective.

Influence of antidepressants on hemostasis

Abstract: Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), are widely used for the treatment of depression and anxious disorders. The observation that depression is an independent risk factor for cardiovascular mortality and morbidity in patients with ischemic heart disease, the assessment of the central role of serotonin in pathophysiological mechanisms of depression, and reports of cases of abnormal bleeding associated with antidepressant therapy have led to investigations of the influence of antidepressants on hemostasis markers. In this review, we summarize data regarding modifications of these markers, drawn from clinical studies and case reports. We observed an association between the type of antidepressant drug and the number of abnormal bleeding case reports, with or without modifications of hemostasis markers. Drugs with the highest degree of serotonin reuptake inhibition - fluoxetine, paroxetine, and sertraline - are more frequently associated with abnormal bleeding and modifications of hemostasis markers. The most frequent hemostatic abnormalities are decreased platelet aggregability and activity, and prolongation of bleeding time. Patients with a history of coagulation disorders, especially suspected or documented thrombocytopenia or platelet disorder, should be monitored in case of prescription of any serotonin reuptake inhibitor (SRI). Platelet dysfunction, coagulation disorder, and von Willebrand disease should be sought in any case of abnormal bleeding occurring during treatment with an SRI. Also, a non-SSRI antidepressant should be favored over an SSRI or an SRI in such a context. Considering the difficulty in performing platelet aggregation tests, which are the most sensitive in SRI-associated bleeding, and the low sensitivity of hemostasis tests when performed in case of uncomplicated bleeding in the general population, establishing guidelines for the assessment of SRI-associated bleeding complications remains a challenge.

Cannabinoids in health and disease

Abstract: Cannabis sativa L. preparations have been used in medicine for millenia. However, concern over the dangers of abuse led to the banning of the medicinal use of marijuana in most countries in the 1930s. Only recently, marijuana and individual natural and synthetic cannabinoid receptor agonists and antagonists, as well as chemically related compounds, whose mechanism of action is still obscure, have come back to being considered of therapeutic value. However, their use is highly restricted. Despite the mild addiction to cannabis and the possible enhancement of addiction to other substances of abuse, when combined with cannabis, the therapeutic value of cannabinoids is too high to be put aside. Numerous diseases, such as anorexia, emesis, pain, inflammation, multiple sclerosis, neurodegenerative disorders (Parkinson's disease, Huntington's disease, Tourette's syndrome, Alzheimer's disease), epilepsy, glaucoma, osteoporosis, schizophrenia, cardiovascular disorders, cancer, obesity, and metabolic syndrome-related disorders, to name just a few, are being treated or have the potential to be treated by cannabinoid agonists/antagonists/cannabinoid-related compounds. In view of the very low toxicity and the generally benign side effects of this group of compounds, neglecting or denying their clinical potential is unacceptable - instead, we need to work on the development of more selective cannabinoid receptor agonists/antagonists and related compounds, as well as on novel drugs of this family with better selectivity, distribution patterns, and pharmacokinetics, and - in cases where it is impossible to separate the desired clinical action and the psychoactivity - just to monitor these side effects carefully.

The role of circadian clock genes in mental disorders.

Abstract: The study of molecular clock mechanisms in psychiatric disorders is gaining significant interest due to data suggesting that a misalignment between the endogenous circadian system and the sleep-wake cycle might contribute to the clinical status of patients suffering from a variety of psychiatric disorders. Sleep disturbances in major depressive disorder (MDD) are characterized by increased sleep latency, poorer sleep efficiency reduced latency to the first rapid eye movement (REM) sleep episode, and early-morning awakening, but there is little data to indicate a role of circadian clock genes in MDD. There is also relatively little information regarding the role of clock genes in anxiety. In contrast, a significant amount of evidence gathered in bipolar disorder (BPD) patients suggests a circadian rhythm disorder, namely an advanced circadian rhythm and state-dependent alterations of REM sleep latency. Most research on the role of clock genes in BPD has focused on polymorphisms of CLOCK, but the lithium target GSK3 may also play a significant role. A circadian phase shift is also theorized to contribute to the pathophysiology of winter seasonal affective disorder (SAD). Certain allelic combinations of NPAS2, PER3, and BMAL1 appear to contribute to the risk of SAD. In chronic schizophrenia, disturbances of sleep including insomnia and reduced sleep efficiency have been observed. Genetic studies have found associations with CLOCK, PER1, PER3, and TIMELESS. Sleep and circadian changes associated with dementia due to Alzheimer's disease suggest a functional change in the circadian master clock, which is supported by postmortem studies of clock gene expression in the brain.

Quality of life in schizophrenic patients.

Abstract: In the last decades, there has been increased interest in the field of quality of life in mental disorders in general, and particularly in schizophrenia. In addition, the appearance of the atypical antipsychotic drugs (amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone) with different therapeutic and side-effect profiles, has promoted a greater interest in assessing the quality of life of schizophrenic patients. In this paper we will briefly summarize the difficulties in assessing quality of life in schizophrenic patients, as well as the results concerning their quality of life and the influence of psychopathology, especially negative and depressive symptoms, on it. We will also review data from recent clinical trials showing the impact ofantipsychotic treatments and their side effects upon quality of life.

Pharmacologic treatments for opioid dependence: detoxification and maintenance options.

Abstract: While opioid dependence has more treatment agents available than other abused drugs, none are curative. They can, however, markedly diminish withdrawal symptoms and craving, and block opioid effects due to lapses. The most effective withdrawal method is substituting and tapering methadone or buprenorphine, α-2 Adrenergic agents can ameliorate untreated symptoms or substitute for agonists if not available. Shortening withdrawal by precipitating it with narcotic antagonists has been studied, but the methods are plagued by safety issues or persisting symptoms. Neither the withdrawal agents nor the methods are associated with better long-term outcome, which appears mostly related to post-detoxification treatment. Excluding those with short-term habits, the best outcome occurs with long-term maintenance on methadone or buprenorphine accompanied by appropriate psychosocial interventions. Those with strong external motivation may do well on the antagonist naltrexone. Currently, optimum duration of maintenance on either is unclear. Better agents are needed to impact the brain changes related to addiction.

Visual impairment and circadian rhythm disorders

Abstract: Many aspects of human physiology and behavior are dominated by 24-hour circadian rhythms that have a major impact on our health and well-being, including the sleep-wake cycle, alertness and performance patterns, and many daily hormone profiles. These rhythms are spontaneously generated by an internal "pacemaker" in the hypothalamus, and daily light exposure to the eyes is required to keep these circadian rhythms synchronized both internally and with the external environment. Sighted individuals take this daily synchronization process for granted, although they experience some of the consequences of circadian desynchrony when "jetlagged" or working night shifts. Most blind people with no perception of light, however, experience continual circadian desynchrony through a failure of light information to reach the hypothalamic circadian clock, resulting in cyclical episodes of poor sleep and daytime dysfunction. Daily melatonin administration, which provides a replacement synchronizing daily "time cue, " is a promising therapeutic strategy, although optimal treatment dose and timing remain to be determined.

The chronobiology and neurobiology of winter seasonal affective disorder

Abstract: This review summarizes research on the chronobiology and neurobiology of winter seasonal affective disorder (SAD), a recurrent subtype of depression characterized by a predictable onset in the fall/winter months and spontaneous remission in the spring/summer period. Chronobiological mechanisms related to circadian rhythms, melatonin, and photoperiodism play a significant role in many cases of SAD, and treatment of SAD can be optimized by considering individual differences in key chronobiological markers. Converging evidence also points to a role for the major monoamine neurotransmitters serotonin, norepinephrine, and dopamine in one or more aspects of SAD. Ultimately, as with other psychiatric illnesses, SAD is best considered as a complex disorder resulting from the interaction of several vulnerability factors acting at different levels, the various genetic mechanisms that underlie them, and the physical environment. Models of SAD that emphasize its potential role in human evolution will also be discussed.

Cocaine and amphetamine-like psychostimulants: neurocircuitry and glutamate neuroplasticity.

Abstract: Although the pharmacology of amphetamine-like psychostimulants at dopamine transporters is well understood, addiction to this class of drugs has proven difficult to deal with. The reason for this disconnection is that while the molecular mechanism of amphetamine action is critical to reinforce drug use, it is only the first step in a sequence of widespread neuroplastic events in brain circuitry. This review outlines the affect of psychostimulants on mesocorticolimbic dopamine projections that mediate their reinforcing effect, and how this action ultimately leads to enduring pathological neuroplasticity in glutamatergic projections from the prefrontal cortex to the nucleus accumbens. Molecular neuroadaptations induced by psychostimulant abuse are described in glutamate neurotransmission, and from this information potential pharmacotherapeutic targets are identified, based upon reversing or countermanding psychostimulant-induced neuroplasticity.

The phase shift hypothesis for the circadian component of winter depression

Abstract: The finding that bright light can suppress melatonin production led to the study of two situations, indeed, models, of light deprivation: totally blind people and winterdepressives. The leading hypothesis for winter depression (seasonal affective disorder, or SAD) is the phase shift hypothesis (PSH). The PSH was recently established in a study in which SAD patients were given low-dose melatonin in the afternoon/evening to cause phase advances, or in the morning to cause phase delays, or placebo. The prototypical phase-delayed patient as well as the smaller subgroup of phase-advanced patients, optimally responded to melatonin given at the correct time. Symptom severity improved as circadian misalignment was corrected. Orcadian misalignment is best measured as the time interval between the dim light melatonin onset (DLMO) and mid-sleep. Using the operational definition of the plasma DLMO as the interpolated time when melatonin levels continuously rise above the threshold of 10 pglmL, the average interval between DLMO and mid-sleep in healthy controls is 6 hours, which is associated with optimal mood in SAD patients.

Neuropsychiatry of Huntington's disease

Abstract: Psychiatric manifestations are an integral part of Huntington's disease. They may be divided into those syndromes which resemble idiopathic disorders, but for which HD patients may be particularly at risk, those constellations which are peculiar to HD and related conditions, such as the executive dysfunction syndrome, and those symptoms that can truly be regarded as nonspecific, such as delirium. Most of these problems are believed to arise from subcortical neuropathologic changes. Major depression is a common psychiatric diagnosis, but the executive dysfunction syndrome, a difficult-to-define condition characterized by often simultaneous apathy and disinhibition, may be even more widespread. There are no large controlled studies of psychiatric treatments in HD, but case series, anecdotal reports, and clinical experience indicate that many of these syndromes respond readily to treatment. Further study of the neuropsychiatry of HD may help to reveal the underpinnings of psychiatric conditions found in the general population.

Visual hallucinatory syndromes: past, present, and future.

Abstract: In 1936, two clinical rewiews, one by de Morsier, the other by L'Hermitte and de Ajuriaguerra, formulated an approach to visual hallucinations that continues to this day. Breaking with previous traditions, the papers championed visual hallucinations as worthy of study in their own right, de-emphasizing the clinical significance of their visual contents and distancing them from visual illusions. De Morsier described a set of visual hallucinatory syndromes based on the wider neurological and psychiatric context, many of which remain relevant today; however, one - the Charles Bonnet Syndrome - sparked 70 years of controversy over the role of the eye. Here, the history of visual hallucinatory syndromes and the eye dispute is reviewed, together with advances in perceptual neuroscience that question core assumptions of our current approach. From a neurobiological perspective, three syndromes emerge that relate to specific dysfunctions of afferent cholinergic and serotonergic visual circuitry and promise future therapeutic advances.

Depression and cardiovascular comorbidity.

Abstract: Depression has long had a popular link to cardiovascular disease and death. However, only during the last 15 years has scientific evidence supporting this common wisdom been available. Beginning in the early 1990s, there began to accumulate community-based epidemiological evidence that medically healthy, depressed patients followed for long periods of time were at increased risk of both cardiovascular disease and cardiac death. In the mid-1990s, evidence appeared to indicate that depression following a heart attack increased the risk of death. It is now apparent that depression aggravates the course of multiple cardiovascular conditions. There are two major unanswered questions. One is whether treating depression will reduce the risk of cardiovascular disease and death. Here, preliminary, but not definitive, evidence suggests that the serotonin reuptake inhibitors may be useful. The other unanswered question regards the mechanisms that underlie this link between depression and cardiovascular disease. There is strong evidence linking platelet activation, autonomic activity and inflammatory markers to both depression and heart disease, but why these links exist is far less clear.

Neuropsychiatric consequences of cardiovascular medications

Abstract: The use of cardiovascular medications can have a variety of neuropsychiatric consequences. Many cardiovascular agents cause higher rates of fatigue and sedation than placebo, and case reports of medication-induced mood syndromes, psychosis, and cognitive disturbances exist for many cardiovascular drugs. Depression has been associated with P3-blockers, methyldopa, and reserpine, but more recent syntheses of the data have suggested that these associations are much weaker than originally believed. Though low cholesterol levels have been associated with depression and suicide, lipid-lowering agents have not been associated with these adverse effects. Finally, cardiovascular medications may have beneficial neuropsychiatric consequences; for example, the use of clonidine in patients with attention deficit-hyperactivity disorder, the use of prazosin for patients with post-traumatic stress disorder; and the use of propranolol for performance anxiety and akathisia.

Historical and cultural aspects of man's relationship with addictive drugs

Abstract: Our taste for addictive psychoactive substances is attested to in the earliest human records. Historically, psychoactive substances have been used by (i) priests in religious ceremonies (eg, amanita muscaria); (ii) healers for medicinal purposes (eg, opium); or (iii) the general population in a socially approved way (eg, alcohol, nicotine, and caffeine). Our forebears refined more potent compounds and devised faster routes of administration, which contributed to abuse. Pathological use was described as early as classical Antiquity. The issue of loss of control of the substance, heralding today's concept of addiction, was already being discussed in the 17th century. The complex etiology of addiction is reflected in the frequent pendulum swings between opposing attitudes on issues that are still currently being debated, such as: is addiction a sin or a disease; should treatment be moral or medical; is addiction caused by the substance; the individual's vulnerability and psychology, or social factors; should substances be regulated or freely available.

A history of chaos theory.

Abstract: Whether every effect can be precisely linked to a given cause or to a list of causes has been a matter of debate for centuries, particularly during the 17th century when astronomers became capable of predicting the trajectories of planets. Recent mathematical models applied to physics have included the idea that given phenomena cannot be predicted precisely although they can be predicted to some extent in line with the chaos theory Concepts such as deterministic models, sensitivity to initial conditions, strange attractors, and fractal dimensions are inherent to the development of this theory, A few situations involving normal or abnormal endogenous rhythms in biology have been analyzed following the principles of chaos theory This is particularly the case with cardiac arrhythmias, but less so with biological clocks and circadian rhythms.

Interpersonal and social rhythm therapy: an intervention addressing rhythm dysregulation in bipolar disorder.

Abstract: Bipolar disorder is characterized by frequent recurrences, often related to noncompliance with drug treatment, stressful life events, and disruptions in social rhythms. Interpersonal and social rhythm therapy (IPSRT) was designed to directly address these problem areas. This article discusses the circadian basis of IPSRT and the importance of stable daily routines in the maintenance of the euthymic state, as well as the two large controlled trials which empirically support this intervention. The authors discuss the advantages of IPSRT as an acute intervention, as well as a prophylactic treatment for both bipolar I and II disorder. Using a case example, the authors describe how IPSRT is implemented in a clinical setting, detailing the therapeutic methods and processes involved.

The daily timing of gene expression and physiology in mammals

Abstract: Mammalian behavior and physiology undergo daily rhythms that are coordinated by an endogenous circadian timing system. This system has a hierarchical structure, in that a master pacemaker, residing in the suprachiasmatic nucleus of the ventral hypothalamus, synchronizes peripheral oscillators in virtually all body cells. While the basic molecular mechanisms generating the daily rhythms are similar in all cells, most clock outputs are cell-specific. This conclusion is based on genome-wide transcriptome profiling studies in several tissues that have revealed hundreds of rhythmically expressed genes. Cyclic gene expression in the various organs governs overt rhythms in behavior and physiology, encompassing sleep-wake cycles, metabolism, xenobiotic detoxification, and cellular proliferation. As a consequence, chronic perturbation of this temporal organization may lead to increased morbidity and reduced lifespan.

Hypertension, cognitive decline, and dementia: an epidemiological perspective.

Abstract: Hypertension is a known risk factor for stroke, and thus for vascular dementia However, recent large observational studies have suggested that high blood pressure may also play a role in Alzheimer's disease The mechanisms linking hypertension to Alzheimer's disease remain to be elucidated, but white matter lesions seen on cerebral magnetic resonance imaging appear to be a good marker of this association It is not yet clearly established whether lowering blood pressure reduces the risk of white matter lesions and dementia, so large trials dealing with this question are eagerly awaited These future trials could confirm the hope that, by lowering blood pressure, we may have a preventive treatment for dementia This issue is of major importance, as the number of cases of dementia is expected to rise

Neural basis of reward and craving--a homeostatic point of view.

Abstract: Here, it is argued that the interoceptive system, which provides information about the subjects internal state and is integrated in the insular cortex, and not the subcortical ventral striatum, is the critical neural substrate for reward-related processes. Understanding the internal state of the individual, which is processed via this system, makes it possible to develop new interventions that are aimed at treating reward-dysfunction disorders, ie, substance and alcohol dependence. Although the ventral striatum is important for signaling the degree to which rewarding stimuli are predicted to occur, this system alone cannot account for the complex affective, cognitive, and behavioral phenomena that occur when individuals come into contact with potentially rewarding stimuli. On the other hand, the interoceptive system is able to make connections between all cortical, subcortical, and limbic systems to orchestrate a complex set of responses. Craving and urges are among the most notable responses, and may have important functions to preserve homeostasis.

Psychiatric manifestations of neurologic disease: where are we headed?

Abstract: Neuropsychiatry represents a field of medicine situated at the crossroads of neurology and psychiatry, and deals with the interface of behavioral phenomena driven by brain dysfunction. Psychiatric symptoms are highly prevalent in these conditions, are a major source of disability and diminished quality of life, and potentially represent the target of treatment interventions that stand to significantly decrease the suffering they generate. In this article, the disease paradigm is explained, with particular attention to its role as an organizing principle for the field. Specific diseases including traumatic brain injury, stroke, Parkinson's disease, Alzheimer's disease, multiple sclerosis, and epilepsy are explored in relation to the presentation of multiple psychiatric phenotypes in each, associations with underlying brain pathology, and existing treatment approaches. Finally the article explores the inherent complexities in this area of research and proposes a framework for future work based on the understanding of phenomenology and associated risk factors, the involvement of the rapidly advancing field of neuroscience, and targeted treatment development to serve as a road map for advancement in the field..

Common genetic factors for depression and cardiovascular disease.

Abstract: There is increasing knowledge regarding the considerable comorbidity between depression and cardiovascular disease, which are two of the most common disorders in developed countries. The associated vulnerability is not unidirectional, as the presence of cardiovascular disease can also influence mood states. Although this may be the result of psychological factors, common biological mechanisms, including genetic ones, are thought to be responsible for this interaction; we can thus question whether variations in genes could be predisposing factors. Regarding the multiple interactions in the mechanisms between depression and cardiovascular system disorders, e.g., dysfunctions in the hypothalamic-pituitary-adrenocortical and sympathoadrenal axis and the response to stress, the importance of the serotonergic and immune systems, or the impact on the renin-angiotensin system, several candidate genes are being investigated. However, despite the interest in unraveling the potential susceptibility genes for both disorders, most available studies have so far dealt with the impact of polymorphisms in relation to either depression or cardiovascular disease. A few recent studies have now examined the effects of gene-gene or gene-environment interactions, and are investigating the impact of "depression-related" variants on cardiac response to stress. The first promising results were obtained with the serotonin transporter, and it may be hypothesized that this polymorphism interacts via the impact of the S allele on depression and via the effect of the L allele on platelet activation. However, the role played by various other candidate genes remains to be determined, especially regarding the question as to whether they are indicative of common pathophysiological mechanisms, or for identifying a subgroup of patients with somatic disorders that are more closely related to psychiatric symptoms.

Neuropsychiatric manifestations of depression in multiple sclerosis: neuroinflammatory, neuroendocrine, and neurotrophic mechanisms in the pathogenesis of immune-mediated depression

Abstract: Evidence suggests that depression in multiple sclerosis (MS) is largely biologically mediated by some of the same processes involved in the immunopathogenesis of this neurologic disease. In particular, the increase in proinflammatory cytokines, activation of the hypothalamic-pituitary-adrenal (HPA) axis, and reduction in neurotrophic factors that occur in MS may each account for the increased rate of depression seen in MS. The possible contributions of these neuroinflammatory, neuroendocrine, and neurotrophic mechanisms suggest a diverse array of novel treatment strategies for depression, both in the context of inflammatory conditions as well as in idiopathic depression. Furthermore, if such processes in MS play a causative role in the pathogenesis of depression, and depression in turn has affects on neurophysiological processes related to immune function, then treatment of depression might have a positive effect on MS disease progression. This makes treating MS depression a neuropsychiatric imperative.

Neuropsychiatric manifestations in CADASIL.

Abstract: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL) is an inherited small-artery disease of mid-adulthood caused by mutations of the NOTCH3 gene. The disease is responsible for widespread white-matter Iesions associated with lacunar infarctions in varinus subcortical areas. The disease is responsible for migraine with aura and ischemic strokes, and is associated with various degrees of cognitive impairment and with mood disturbances. CADASIL is considered as a unique model to investigate what is known as "subcortical ischemic vascular dementia. "Recent data suggest that the number of lacunar infarctions and severity of cerebral atrophy are the main magnetic resonance imaging markers associated with cognitive and motor disabilities in this disorder. Mood disturbances are reported in 10% to 20% of patients, most often in association with cognitive alterations. Their exact origin remains unknown; the presence of ischemic lesions within the basal ganglia or the frontal white matter may promote the occurrence of these symptoms. Further studies are needed to better understand the relationships between cerebral lesions and both cognitive and psychiatric symptoms in this small-vessel disease of the brain.

Tourette's syndrome: clinical features, pathophysiology, and therapeutic approaches.

Abstract: Tourette's syndrome (TS) is a disorder characterized by simple and complex motor tics, vocal tics, and frequently obsessive-compulsive symptoms, its onset occurs before the age of 21. Typically, TS shows a waxing and waning course, but a chronification of the tics, even during later life, is often observed, TS mainly occurs in boys, and shows genetic heritability with differing penetrance. The pathological mechanism is still unclear. Neuroanatomical and neuroimaging studies, as well as effective treatment using antipsychotics, suggest that a disturbance of the dopaminergic system in the basal ganglia plays an important role in the pathogenesis of TS, Several possibly causative mechanisms of the disturbed dopaminergic neurotransmission are discussed, with the main emphasis on the-infection-triggered- inflammatory immune process, Extrapyramidal movement disorders are known to occur as a symptom of poststreptococcal disease, such as in Sydenham's chorea. Cases of childhood TS are proposed to be caused by such a post-streptococcal mechanism, being part of a spectrum of childhood neurobehavioral disorders termed pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS), The overlap between TS and PANDAS is discussed, and a critical view of the PANDAS concept is presenter], The therapeutic implications of the different pathological mechanisms are described, taking into consideration not only the acute or chronic natures of different infections, but also an autoimmune process, Moreover, therapeutic strategies using typical and atypical antipsychotics, and also experimental therapies such as repetitive transcranial magnetic stimulation and deep brain stimulation, are critically discussed.

Outpatient Long-term Intensive Therapy for Alcoholics (OLITA): a successful biopsychosocial approach to the treatment of alcoholism

Abstract: Alcohol dependence is a frequent, chronic, relapsing, and incurable disease with enormous societal costs. Thus, alcoholism therapy and research into its outcome are of major importance for public health. The present article will: (i) give a brief overview of the epidemiology, pathogenesis, and treatment outcomes of alcohol dependence; (ii) introduce the basic principles of outpatient long-term therapy of alcohol-dependent patients; and (iii) discuss in detail process-outcome research on Outpatient Long-term intensive Therapy for Alcoholics (OLITA). This successful biopsychosocial approach to the treatment of alcoholisms shows a 9-year abstinence rate of over 50%, a re-employment rate of 60%, and a dramatic recovery from comorbid depression, anxiety disorders, and physical sequelae. The outcome data are empirically based on treatment processes that have proven high predictive validity and give concrete information about where to focus the therapeutic efforts. Thus, process-outcome research on OLITA can serve for the development of new therapeutic guidelines on adapting individual relapse prevention strategies.

Neuropsychiatric consequences of coronary artery bypass grafting and noncardiovascular surgery

Abstract: This paper rewiews findings regarding short- and long-term neuropsychiatnc consequences of coronary artery bypass grafting (CABG) and noncardiac surgery. Stroke is one of the potentially most serious complications of CABG; studies have identified some demographic and medical risk factors. Short-term neuropsychological deficits are common after CABG, but have been similarly documented in noncardiac surgery patients, and may therefore not be specific to this procedure. Neuropsychological deficits in some cognitive areas may persist over time. Patients with depression before surgery are likely to have persistent depression afterwards. Also, depression does not account for the cognitive decline after CABG. Conflicting findings, and the possible methodological limitations of current published studies, are presented and discussed.

Association study of T102C 5-HT(2A) polymorphism in schizophrenic patients: diagnosis, psychopathology, and suicidal behavior.

Abstract: The objective of this study was to examine the association between the serotonin (5-HT)2A gene polymorphism (102T/C) and suicidal behavior in schizophrenic inpatients. We studied 129 subjects who met the diagnostic criteria for schizophrenia according to a structured clinicai interview (MINI-PLUS), Patients underwent a semistructured interview to assess suicide attempt history and its characteristics, in addition, at least one close relative of the patient was interviewed to assess prohand and family suicidal behavior. Healthy controls were students and hospital staff members free of psychiatric and medical illness. Genotypes were determined after polymerase chain reaction amplification of the region of 5-HT2A/T102C containing the polymorphic site and digestion with the restriction enzyme Hpall, We found no association between suicidal attempt history and suicide attempt characteristics and genotypic or aileie frequencies. Suicidal behavior was also not associated with demographic or psychopathological characteristics. These results suggest that the S-HT2A gene polymorphism (102T/C) is not involved in genetic susceptibility to suicidal behavior, but further studies in a larger sample are needed.

Frontotemporal dementia to Alzheimer's disease.

Abstract: Behavioral manifestations may dominate the clinical picture of the frontal variant of frontotemporal dementia (fv-FTD) for a long time before the appearance of true cognitive deficits. On the other hand, a deficit in the episodic memory domain represents the main manifestation of Alzheimer's disease (AD), Many behavioral disorders have been described in the clinical course of both FTD and AD; however, apathy and personality changes characterize frontal dementias, while depression dominates in AD, at least in the earlier stages. Depending on the distribution of neural damage, different patterns of noncognitive manifestations may be expected in different subtypes of FTD, Recent research on the social cognition deficit in FTD has offered new insights into the relationship between cognition and behavior, suggesting that some aspects of the behavioral changes in dementia may be generated by impairment in this domain.