Carlo Altamura

Dexamethasone suppression test in positive and negative schizophrenia

Fifty-four inpatients with a DSM-III diagnosis of schizophrenia were studied. Patients were divided into positive and negative subtypes of schizophrenia according to Andreasens criteria. Blood samples were obtained from all patients for 2 consecutive days to determine plasma cortisol concentrations before and after a single administration (1 mg, p.o.) of dexamethasone at 11 p.m. The results revealed a significant increase in plasma cortisol levels in schizophrenic patients, with 40% of the patients being nonsuppressors on the dexamethasone suppression test. A higher percentage (62.5%) of patients with the negative form of schizophrenia were nonsuppressors.

Substance-Induced Psychoses: A Critical Review of the Literature

Substances with psychotomimetic properties such as cocaine, amphetamines, hallucinogens and cannabis are widespread, and their use or abuse can provoke psychotic reactions resembling a primary psychotic disease. The recent escalating use of methamphetamine throughout the world and its association with psychotic symptoms in regular users has fuelled concerns. The use of cannabis and cocaine by young people has considerably increased over recent years, and age at first use has dramatically decreased. There is some evidence that cannabis is now on the market in a more potent form than in previous decades. Furthermore, a large number of studies have reported a link between adolescent cannabis use and the development of stable psychosis in early adulthood. The situation is further complicated by the high rates of concomitant substance use by subjects with a psychotic illness which, especially in young users with an early-phase psychotic disorder, can make diagnosis difficult. This paper reviews the literature concerning the properties of psychotogenic substances and the psychotic symptoms they can give rise to, and discusses the association between substance abuse and psychosis with particular emphasis on the differential diagnosis of a primary and substance-induced psychotic disorder. The findings of this review indicate that psychosis due to substance abuse is commonly observed in clinical practice. The propensity to develop psychosis seems to be a function of the severity of use and dependence. From a phenomenological point of view, it is possible to identify some elements that may help clinicians involved in differential diagnoses between primary and substance-induced psychoses. There remains a striking paucity of information on the outcomes, treatments, and best practices of substance-induced psychotic episodes.

Biological markers for anxiety disorders, OCD and PTSD – a consensus statement. Part I: Neuroimaging and genetics

Abstract Objectives: Biomarkers are defined as anatomical, biochemical or physiological traits that are specific to certain disorders or syndromes. The objective of this paper is to summarise the current knowledge of biomarkers for anxiety disorders, obsessive–compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). Methods: Findings in biomarker research were reviewed by a task force of international experts in the field, consisting of members of the World Federation of Societies for Biological Psychiatry Task Force on Biological Markers and of the European College of Neuropsychopharmacology Anxiety Disorders Research Network. Results: The present article (Part I) summarises findings on potential biomarkers in neuroimaging studies, including structural brain morphology, functional magnetic resonance imaging and techniques for measuring metabolic changes, including positron emission tomography and others. Furthermore, this review reports on the clinical and molecular genetic findings of family, twin, linkage, association and genome-wide association studies. Part II of the review focuses on neurochemistry, neurophysiology and neurocognition. Conclusions: Although at present, none of the putative biomarkers is sufficient and specific as a diagnostic tool, an abundance of high-quality research has accumulated that will improve our understanding of the neurobiological causes of anxiety disorders, OCD and PTSD.

Understanding the impact of persistent symptoms in schizophrenia: Cross-sectional findings from the Pattern study

BACKGROUNDnThe high societal burden of schizophrenia is largely caused by the persistence of symptoms and accompanying functional impairment. To date, no studies have specifically assessed the course of persistent symptoms or the individual contributions of positive and negative symptoms to patient functioning. The cross-sectional analysis of the Pattern study provides an international perspective of the burden of schizophrenia.nnnMETHODSnClinically stable outpatients from 140 study centers across eight countries (Argentina, Brazil, Canada, France, Germany, Italy, Spain and the United Kingdom) were assessed using clinical rating scales: Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Schizophrenia (CGI-SCH) Scale and the Personal and Social Performance (PSP) Scale. Additional measures included patient-reported outcomes, patient socio-demographic variables, living situation, employment and resource use.nnnRESULTSnOverall, 1379 patients were assessed and analyzed and had similar sociodemographic characteristics across countries, with 61.6% having persistent positive and/or negative symptoms. Positive and negative symptoms had been persistent for a mean of 9.6 and 8.9 years (SD: 8.8 and 9.6), respectively. Approximately 86% of patients had a functional disability classified as greater than mild. Patients with a higher PANSS Negative Symptom Factor Score were more likely to have a poorer level of functioning.nnnCONCLUSIONSnThis analysis examines individual contributions of persistent positive and negative symptoms on patient functioning in different countries. A high prevalence of patients with persistent symptoms and functional impairment was a consistent finding across countries. Longitudinal observations are necessary to assess how to improve persistent symptoms of schizophrenia and overall patient functioning.

Slow vs standard up-titration of paroxetine in the treatment of panic disorder: a prospective randomized trial.

Aim:u2002 Patients with panic disorder (PD) might be sensitive to the stimulating effects of selective serotonin reuptake inhibitors (SSRI), thus requiring low dosages at treatment initiation. The aim of the present study was to assess eventual differences in terms of effectiveness and tolerability between a slow up‐titration with paroxetine and a standard one.

Transcranial Direct Current Stimulation for Autistic Disorder

To the Editor: Autistic disorder (AD) is a complex neurodevelopmental disorder with an increasing prevalence (1). It has its onset in infancy and is characterized by impairments in multiple behavioral domains, including reciprocal social interaction, language, and variety of interests and activities. Thus far, no specific treatment for AD exists; individual goals may vary among patients and usually include a combination of therapies (2). Despite the existing treatments, AD remains a chronic and a highly disabling condition, causing a considerable economic impact on the community and emotional distress for patients and their families. Thus, new and more effective treatment options are urgently needed. In the past decade, brain stimulation techniques have yielded promising and encouraging outcomes for the treatment of resistant psychiatric disorders. Among these options, transcranial direct current stimulation (tDCS), a noninvasive, safe, and easy-touse technique for the focal modulation of cortical brain areas, has recently emerged as an effective and economical tool for treating major psychiatric disorders, such as depression and schizophrenia (3,4). This technique involves the application of spongy electrodes over the scalp, painlessly delivering a weak and direct electrical current to the cerebral cortex. Its therapeutic action has been linked to polarity-dependent neurophysiologic changes in the targeted brain areas, causing either increases (anodal stimulation) or decreases (cathodal stimulation) in cortical excitability (5,6). To the best of our knowledge, tDCS has never been used to treat AD patients. We describe the first case of a patient with AD, who, after undergoing a tDCS course, displayed a dramatic reduction in his behavioral abnormalities. Mr. P, who was first diagnosed with AD at age 2, is a 26-year old man with an IQ score of 30 on the Leiter International Performance Scale—Revised. He has undergone several psychosocial and pharmacologic interventions to reduce his highly disabling behavior—including risperidone, promazine, pericyazine, lorazepam, and chlordesmethyldiazepam at adequate doses—with no improvement. When tDCS was considered, he

Similar white matter changes in schizophrenia and bipolar disorder: A tract-based spatial statistics study

Several strands of evidence reported a significant overlapping, in terms of clinical symptoms, epidemiology and treatment response, between the two major psychotic disorders—Schizophrenia (SCZ) and Bipolar Disorder (BD). Nevertheless, the shared neurobiological correlates of these two disorders are far from conclusive. This study aims toward a better understanding of possible common microstructural brain alterations in SCZ and BD. Magnetic Resonance Diffusion data of 33 patients with BD, 19 with SCZ and 35 healthy controls were acquired. Diffusion indexes were calculated, then analyzed using Tract-Based Spatial Statistics (TBSS). We tested correlations with clinical and psychological variables. In both patient groups mean diffusion (MD), volume ratio (VR) and radial diffusivity (RD) showed a significant increase, while fractional anisotropy (FA) and mode (MO) decreased compared to the healthy group. Changes in diffusion were located, for both diseases, in the fronto-temporal and callosal networks. Finally, no significant differences were identified between patient groups, and a significant correlations between length of disease and FA and VR within the corpus callosum, corona radiata and thalamic radiation were observed in bipolar disorder. To our knowledge, this is the first study applying TBSS on all the DTI indexes at the same time in both patient groups showing that they share similar impairments in microstructural connectivity, with particular regards to fronto-temporal and callosal communication, which are likely to worsen over time. Such features may represent neural common underpinnings characterizing major psychoses and confirm the central role of white matter pathology in schizophrenia and bipolar disorder.

long-acting olanzapine in maintenance therapy of schizophrenia: A study with plasma levels

Abstract Introduction. This prospective study was performed to evaluate clinical efficacy and tolerability of olanzapine long-acting injection (OLZ-LAI) and the relation between OLZ plasma level (PL) and the clinical outcome in maintenance therapy of schizophrenia. Material and methods. Twenty-five chronic schizophrenic outpatients with age ranging from 18 to 65 years were included in this 9-month study. Patients were given a dosage of either 210 or 300 or 405 mg of OLZ-LAI every 28 days. Patients were evaluated at baseline and every four weeks by Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Symptom Scale (PANSS); at the same time, PL of OLZ was determined. The metabolic profile (aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein, low-density lipoprotein, total cholesterol, and glucose levels) was analyzed every two months. Results. BPRS and total PANSS showed a statistically significant improvement from T2 with a clinical stabilization of psychopathological picture. PL ranged from 4.0 to 78.9 ng/ml (mean 20.59 ng/ml ± 14.66 standard deviation). The coefficient of variation of PLs was related to clinical stabilization. No post-injection delirium sedation syndrome occurred. Conclusions. Our data reveal the efficacy of OLZ-LAI in maintenance treatment of schizophrenia at lower dosages also in comparison with that of oral therapy. OLZ-LAI seems to be useful for guaranteeing constant PL of the drug. A lesser variation of PL was the most predictable factor associated with maintenance of clinical benefit.

Progressive disability and prefrontal shrinkage in schizophrenia patients with poor outcome: A 3-year longitudinal study

INTRODUCTIONnSchizophrenia is a severe disabling disorder with heterogeneous illness courses. In this longitudinal study we characterized schizophrenia patients with poor and good outcome (POS, GOS), using functional and imaging metrics. Patients were defined in accordance to Keefes criteria (i.e. Kraepelinian and non-Kraepelinian patients).nnnMETHODSn35 POS patients, 35 GOS patients and 76 healthy controls (H) underwent clinical, functioning and magnetic resonance imaging (MRI) assessments twice over three years of follow-up. Information on psychopathology, treatment, disability (using the World Health Organization Disability Assessment Scale II, WHO-DAS-2) and prefrontal morphology was collected. Dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) were manually traced.nnnRESULTSnAt baseline, subjects with POS showed significantly decreased right dorsolateral prefrontal cortex (DLPFC) white matter volumes (WM) compared to healthy controls and GOS patients (POS VS HC, p<0.001; POS vs GOS, p=0.03), with shrinkage of left DLPFC WM volumes at follow up (t=2.66, p=0.01). Also, POS patients had higher disability in respect to GOS subjects both at baseline and after 3years at the WHO-DAS-2 (p<0.05).nnnDISCUSSIONnOur study supports the hypothesis that POS is characterized by progressive deficits in brain structure and in real-life functioning. These are particularly notable in the DLPFC.

A review of altered biochemistry in the anterior cingulate cortex of first-episode psychosis

Relevant biochemicals of the brain can be quantified in vivo, non-invasively, using proton Magnetic Resonance Spectroscopy (¹H MRS). This includes metabolites associated with neural general functioning, energetics, membrane phospholipid metabolism and neurotransmission. Moreover, there is substantial evidence of implication of the frontal and prefrontal areas in the pathogenesis of psychotic disorders such as schizophrenia. In particular, the anterior cingulate cortex (ACC) plays an important role in cognitive control of emotional and non-emotional processes. Thus the study of its extent of biochemistry dysfunction in the early stages of psychosis is of particular interest in gaining a greater understanding of its aetiology. In this review, we selected ¹H MRS studies focused on the ACC of first-episode psychosis (FEP). Four studies reported increased glutamatergic levels in FEP, while other four showed preserved concentrations. Moreover, findings on FEP do not fully mirror those in chronic patients. Due to conflicting findings, larger longitudinal ¹H MRS studies are expected to further explore glutamatergic neurotransmission in ACC of FEP in order to have a better understanding of the glutamatergic mechanisms underlying psychosis, possibly using ultra high field MR scanners.