Blood viscosity and inflammation in first-episode and acute exacerbations of schizophrenia: A case-control study with healthy controls

Introduction: Elevated proinflammatory status and alterations in blood flow, both of which are associated with the pathophysiology of schizophrenia, may be linked with an increased risk of cardiovascular diseases. However, such a relationship at different acute stages of schizophrenia has not been evaluated. We aimed to examine whether blood viscosity and systemic inflammatory status varied between first-episode schizophrenia (FES) and acute exacerbations of schizophrenia. Methods: Fifty-two patients with FES, 69 schizophrenia patients with acute exacerbation (S-AE) and 56 healthy controls (HC) were included in the study. Whole blood viscosity (WBV) was calculated according to de Simone’s formula at low and high shear rates (LSR and HSR). Systemic immune-inflammation index (SII) and systemic inflammatory response index (SIRI) were calculated from hemogram screening data at admission. Results: When adjusted for age, WBV at both LSR and HSR were significantly decreased in both FES and S-AE groups compared to HCs. Systemic inflammatory response index was significantly higher in FES patients than in the S-AE and HC groups. Total cholesterol (TC) and WBV at HSR were correlated in patients. Total cholesterol predicted WBV at LSR in patients with FES whereas other independent variables including age and SIRI did not. Conclusion: Both first and subsequent episodes of schizophrenia are associated with reduced blood viscosity. Increased inflammatory status may not fully explain such a relationship. Extrapolation of hemorheological characteristics in schizophrenia may help to stratify cardiovascular risk and reflect the pathophysiological process in the early and later stages of schizophrenia

Inhibition of prandial and waterspray-induced rat grooming by 8-OH-DPAT

The effects of 8-OH-DPAT treatment on rat grooming behaviour, elicited either prandially or in response to spraying with water were investigated. Dose (≤0.1 mg/kg s.c.) response studies employed momentary time sampling over 30 or 60 min with behaviour being scored in one of 6 or 7 (depending on food availability) mutually exclusive categories (feeding, active, scratching, face-grooming, body grooming, genital-grooming and resting) at 15 s intervals. In non-deprived rats, tested with wet mash available, feeding and activity frequencies were increased, but resting and total grooming were inhibited by 8-OH-DPAT. Face-, body- and genital-grooming occurred at higher levels than scratching, but all categories were reduced with reductions in scratching occurring at a lower dose (0.01 mg/kg). Misting rats with a fine water spray selectively increased body grooming and decreased activity without altering feeding, while 8-OH-DPAT increased feeding and reduced face-, body- and genital-grooming, without affecting already low levels of scratching. In misted rats, tested without food, 8-OH-DPAT reduced face-, body- and genital-grooming and increased resting. These results confirm i) that the water spray technique is a useful method for increasing grooming and ii) that 8-OH-DPAT has a suppressant effect on grooming independent of response competition from enhanced feeding

Psychopharmacology

Psychopharmacology is the scientific study of the effects drugs have on mood, sensation, thinking, and behavior. Particularly it concerns the use of medications in the treatment of mental disorders. The goal of this chapter is to define the major classes of psychotropic drugs, introducing general pharmacological concepts, explaining the different mechanisms of action and the main clinical applications of the drugs used to treat psychiatric disorders. Psychotropic drugs are commonly categorized according to their major clinical applications: antidepressants, anxiolytics, antipsychotics, and mood stabilizers. However, almost every drug used in psychiatry has multiple therapeutic roles and many clinical applications. For example, SSRIs are considered the first-line pharmacological treatment for several disorders, such as depressive disorders, anxiety disorders, and OCD. Similarly, antipsychotics are indicated as first-choice drugs for psychotic disorders, but many guidelines recommend their use, in combination with mood stabilizers, also in the treatment of acute mania

Behavioral and synaptic circuit analysis in models of neuropsychiatric disorders: Dissecting the in vivo role of the postsynaptic density proteins nArgBP2 and Shank3 using genetic engineered mice

Dissertation presented to obtain the Ph.D degree in BiologyUnderstanding how discrete genes affect neuronal biology, synaptic function and, ultimately, behavior is a major goal in neuroscience. Not surprisingly, genes believed to be involved in human psychiatric and developmental brain disorders garner the most attention due to the likelihood that their disruption will promote salient changes in neurobiological functions. They also promise to nurture further understanding of relevant biomedical questions. Using the mouse as a model organism accelerates this discovery process because the species is amenable to manipulation at the genetic level, allowing for the orthologous recreation of human mutations. Simultaneously, our understanding of murine behavioral outputs can now be linked to particular endophenotypes reminiscent of human disorders.(...)Apoio financeiro da FCT e do FSE no âmbito do Quadro Comunitário de Apoio (SFRH/BD/15855-2005

Doctor of Philosophy

dissertationDepressive disorders (DD) are a leading cause of disability worldwide and display diverse symptoms including anhedonia, melancholia, decreased concentration, sleep and appetite disturbances, and suicidal thoughts and acts. Current available medications are still ineffective for more than 30% of patients, suggesting DD are multi-faceted heterogeneous disorders. Despite intense research, as yet there are no widely used biological diagnostic tests for DD. Since DD are likely a manifestation of both genetic and environmental factors, gene expression of peripheral blood leukocyte allows for a non-invasive means to evaluate trait- and state-dependent neurophysiological dysregulation. In this dissertation, we employed real-time quantitative polymerase chain reaction (qPCR) to evaluate differences between healthy controls and patients with medication-refractory depression, for a panel of candidate genes previously implicated in depression as well as novel genes implicated in related neurological disorders. Chapter 1 begins with an overview of the multiple domains involved in depression and of previous literature findings evaluating protein and gene expression. Chapter 2 describes one of our studies of gene expression of a small panel of 14 genes involved in the immune and stress response in 19 patients with medication-refractory depression, before and following symptom improvement, compared to 20 healthy controls. We found that patients displayed trait- and state-dependent dysregulation in immune cytokines IL-10 and IL-6, transcription factor NFkB1, the serotonin receptor HTR1D, GABAA modulator DBI, and the adrenergic receptors ADR2A and ADRB1. Furthermore, the dopamine receptor DRD4, the glucocorticoid receptor NR3C1, and SULT1A1 displayed acute changes following treatment, though no differences were observed Pretreatment. In Chapter 3, we describe another gene expression study with results using a larger sample size (42 patients and 38 controls) and an expanded gene panel (46 genes) that includes candidate genes from diverse biological pathways. In this study, we found upregulation of IL-10 and IL-6 as well as dysregulation in the amyloid precursor protein, neuregulin-1, and several ion channels that have roles in anxiety, pain, and fatigue. Finally, Chapter 4 summarizes results from both studies and discusses future research into promising biomarkers and novel mechanisms of depression