MAO and aggression

PreprintNon peer reviewe

Pharmacotherapy of Treatment-resistant Combat-related Posttraumatic Stress Disorder with Psychotic Features

Aim: To assess retrospectively the clinical effects of typical (fluphenazine) or atypical (olanzapine, risperidone, quetiapine) antipsychotics in three open clinical trials in male Croatian war veterans with chronic combat-related posttraumatic stress disorder (PTSD) with psychotic features, resistant to previous antidepressant treatment. Methods: Inpatients with combat-related PTSD were treated for 6 weeks with fluphenazine (n=27), olanzapine (n=28), risperidone (n=26), or quetiapine (n=53), as a monotherapy. Treatment response was assessed by the reduction in total and subscales scores in the clinical scales measuring PTSD (PTSD interview and Clinician-Administered PTSD Scale) and psychotic symptoms (Positive and Negative Syndrome Scale). Results: After 6 weeks of treatment, monotherapy with fluphenazine, olanzapine, risperidone, or quetiapine significantly decreased the scores listed in trauma reexperiencing, avoidance, and hyperarousal subscales in the clinical scales measuring PTSD, and total and subscales scores listed in positive, negative, general psychopathology, and supplementary items of the Positive and negative syndrome scale subscales, respectively, in patients with PTSD (P<0.001). Conclusion: PTSD and psychotic symptoms were significantly reduced after monotherapy with typical or atypical antipsychotics. As psychotic symptoms commonly occur in combat-related PTSD, the use of antipsychotic medication seems to offer another approach to treat a psychotic subtype of combat-related PTSD resistant to previous antidepressant treatment

Serotonin

Serotonin is a monoamine that could be found in plans, animals and human body. The homeostasis of serotonin is maintained by the series of interdependent processes that include synthesis, storage, transport and removal/degradation. In the human body serotonin is synthesized in two independent compartments that are separated by brain-blood barrier. The majority of serotonin is synthesized in enterochromaffin cells of the gastrointestinal tract, released in the blood stream and stored in blood platelets. About 5% of serotonin is synthesized in the brain within serotonergic neurons. As a neurotransmitter serotonin plays an important role in the regulation of physiological functions like body temperature, sleep, vomiting, sexuality, appetite, behaviour and cognitive functions such as learning and memory. The dysfunction of the serotonergic system has been implicated in the aetiology of a variety of psychiatric (depression, schizophrenia, alcoholism) and neurological (migraine, Alzheimer’s disease, epilepsy) disorders. Recent genetic association studies of the neuropsychiatric disorders have focused on functional polymorphisms i.e. DNA sequence variations that alter the expression and/or functioning of the gene product in the loci encoding different genes. Some of them are genes for tryptophan hydroxylase, serotonin transporter and serotonergic receptors

Serotonin

Serotonin is a monoamine that could be found in plans, animals and human body. The homeostasis of serotonin is maintained by the series of interdependent processes that include synthesis, storage, transport and removal/degradation. In the human body serotonin is synthesized in two independent compartments that are separated by brain-blood barrier. The majority of serotonin is synthesized in enterochromaffin cells of the gastrointestinal tract, released in the blood stream and stored in blood platelets. About 5% of serotonin is synthesized in the brain within serotonergic neurons. As a neurotransmitter serotonin plays an important role in the regulation of physiological functions like body temperature, sleep, vomiting, sexuality, appetite, behaviour and cognitive functions such as learning and memory. The dysfunction of the serotonergic system has been implicated in the aetiology of a variety of psychiatric (depression, schizophrenia, alcoholism) and neurological (migraine, Alzheimer’s disease, epilepsy) disorders. Recent genetic association studies of the neuropsychiatric disorders have focused on functional polymorphisms i.e. DNA sequence variations that alter the expression and/or functioning of the gene product in the loci encoding different genes. Some of them are genes for tryptophan hydroxylase, serotonin transporter and serotonergic receptors

BIOMARKERS OF DEPRESSION ASSOCIATED WITH COMORBID SOMATIC DISEASES

Depression is heterogeneous clinical entity with different clinical symptoms, that imply diverse biological underpinning, different molecular substrates and pathways. Besides different psychiatric comorbidities, depression is frequently interrelated with somatic diseases. Multi-morbidities, i.e. somatic diseases associated with depression, reduce quality of life, worsen clinical picture and increase mortality. The most frequent somatic diseases co-occurring with depression are cardiovascular and metabolic diseases. Vulnerable individuals will develop depression, and the goal in modern research and in precision/personalized medicine is to determine vulnerability factors associated with development of depression and to find easy available biomarkers of depression, especially comorbid with somatic diseases. This mini-review aimed to describe the latest published data (from 2015-20120) considering biomarkers of depression related to somatic diseases. Biomarkers related to inflammatory processes, atherosclerosis, imbalance of the hypothalamic-pituitary-adrenal axis, autonomic nerve system, sympathetic and parasympathetic nervous system, heart rate variability and endothelial dysfunction could improve the understanding of the underlying biological mechanisms of the common pathways of depression comorbid with somatic diseases. These targeted biomarkers might be used to reduce the symptoms, improve the treatment of these interrelated diseases, and decrease the morbidity and mortality

NEUROTRANSMITTER MEASURES IN THE CEREBROSPINAL FLUID OF PATIENTS WITH ALZHEIMER\u27S DISEASE: A REVIEW

Background: Alzheimer\u27s disease (AD) is a severe neurodegenerative disorder characterized by progressive cognitive and functional decline, as well as by a variety of neuropsychiatric and psychological symptoms and behavioral dysfunctions. Various studies proposed the role of different neurotransmitter systems not only in AD-related cognitive, but also psychotic symptoms and behavioral and emotional deficits. Due to the close proximity, pathological neurochemical changes in brain occurring in AD are likely to be reflected in the cerebrospinal fluid (CSF). The purpose of this review is to provide a summary of the CSF neurotransmitter correlates of AD in order to get further insights into the potential role of altered neurotransmitters in the pathophysiology of AD and to offer novel AD biomarkers. Methods: PubMed and MEDLINE data bases were searched for English-language articles by using "Alzheimer\u27s disease", "CSF" and "neurotransmitter" as primary terms. No time or article type constraints were applied. Moreover, the lists of references were searched manually for additional articles. Results: Changes in various correlates of cholinergic, monoaminergic and amino acid neurotransmitter systems, as well as neuropeptides, have been observed in CSF of AD patients. However, as the results of these studies have been controversial, the importance of CSF neurotransmitter parameters as potential biomarkers in AD remains quite unclear. The observed discrepancies could be bypassed by implementation of new sensitive methods, such as novel proteomics approaches that include protein separation techniques, mass spectroscopy and targeted multiplex panels of specific analytes. Conclusion: Although no individual CSF neurotransmitter correlate was demonstrated as suitable biomarker of AD, a combined profile of several CSF neurochemical parameters might show enhanced sensitivity and specificity and thus contribute to earlier and more accurate diagnosis of AD, crucial for application of effective treatments