[Show abstract][Hide abstract] ABSTRACT: It is assumed that stress-related changes in the endocrine and immune systems are key mediators involved in the development of diseases associated with posttraumatic stress disorder (PTSD). Evidence suggests that those changes might be related to the duration of PTSD. The aim of our study was to investigate the differences in selected endocrine- and immune-related variables between PTSD patients and control subjects, and whether these differences persist over time.
We assessed 39 Croatian war veterans with PTSD and 25 healthy volunteers (civilians without traumatic experience), all men, at two time points separated by 5.6 years (median; interquartile range: 5.4-6.3). Cortisol and prolactin levels were measured by radioimmunoassays while interleukin-6 and tumor necrosis factor-α were determined by enzyme-linked immunosorbent assays. Immune function was assessed by in vitro natural killer cell cytotoxicity (NKCC). Lymphocyte counts, immunophenotype and intracellular glucocorticoid receptor expression in various lymphocyte subsets were determined by three-color flow cytometry.
At the first assessment, moderate to large effect size estimates of differences between patients and controls were observed for most of the measured variables. Only prolactin levels and lymphocyte counts remained significantly elevated in PTSD patients at the second assessment with low to moderate effect size estimates of differences between patients and controls in other variables.
Observed endocrine- and immune-related changes in PTSD over time may depend on the duration of the allostatic load posed by the disorder and its impact on interactions between the endocrine and immune systems involved in stress response.
[Show abstract][Hide abstract] ABSTRACT: Several abnormalities, including lower histamine levels in brain, elevated serum histamine and degeneration of histaminergic neurons in tuberomammillary nucleus, were described in the histaminergic system of patients with Alzheimer's disease (AD). Histamine is a central neurotransmitter with several functions in brain including regulation of memory, cognition, locomotion, and is degraded in part by histamine N-methyltransferase (HNMT). A common Thr105Ile polymorphism within HNMT gene results in decreased enzyme activity. The Thr105Ile polymorphism was associated with Parkinson's disease, essential tremor, attention-deficit hyperactivity disorder (ADHD), asthma and alcoholism, thus we tested possible association of HNMT functional polymorphism with AD. We have tested 256 AD cases and 1190 healthy controls of Croatian origin. Thr105Ile polymorphism was determined by TaqMan RT-PCR Genotyping Assay and EcoRV digestion. Prevalence of functional HNMT polymorphism among all tested groups was similar and frequency of less active Ile105 variant was 11.5% among AD patients and 13.4% for healthy controls (p=0.26, X(2)=1.25). Our results indicate lack of the association of HNMT Thr105Ile functional polymorphism with Alzheimer's disease.
[Show abstract][Hide abstract] ABSTRACT: The reduction of hippocampal volume was frequently reported in schizophrenia, but not in bipolar disorder. This volume reduction is associated with clinical features of schizophrenia, in particular with working and verbal memory impairments. Schizoaffective disorder, as a specific disorder sharing clinical features of both schizophrenia and bipolar disorder is rarely analyzed as a separate disorder in neurobiological studies. The aim of this study was to compare hippocampal volumes in separate groups of patients with schizophrenia, schizoaffective and bipolar disorder. Hippocampal volumes were estimated using high resolution magnetic resonance imaging in 60 subjects, 15 subjects in each patient and one healthy volunteer (control) group. There were no significant differences in hippocampal volume between bipolar disorder and control group. Hippocampal volume was statistically significantly reduced in the group of patients with schizophrenia and schizoaffective disorder, compared to either bipolar disorder or control group, thus supporting the hypothesis that hippocampal volume reduction could be considered as a possible neurobiological basis for clinical aspects of schizophrenia and schizoaffective disorder associated with working and verbal memory impairment.
Collegium antropologicum 01/2011; 35:249-252. · 0.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction and aim:
Posttraumatic stress disorder (PTSD) is associated with increased medical morbidity, particularly from the autoimmune and cardiovascular diseases. Changes in the endocrine and immune system are key mediators in this process. The aim of our study was to investigate weather hormones (cortisol and prolactin), proinflammatory cytokines (interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)), components of HPA-axis (lymphocyte expression of glucocorticoid receptor (GR)), immune function (natural killer cell cytotoxicity) and peripheral blood percentages of various lymphocyte subpopulations (T cells, helper T cells, cytotoxic T cells, B cells and natural killer cells) change in patients with posttraumatic stress disorder over time.
49th International Neuropsychiatric Pula Congress, Pula, Croatia; 06/2009
[Show abstract][Hide abstract] ABSTRACT: Suvremeno liječenje anksioznih poremećaja uključuje psihofarmakološko liječenje, psihoterapiju i druge oblike liječenja, samostalno ili u kombinaciji. Za liječenje socijalne fobije mnogi smatraju da najbolje rezultate daje kombinacija psihološkog i farmakološkog tretmana, kao prvi izbor u liječenju paničnog poremećaja koriste se antidepresivi iz skupine selektivnih inhibitora ponovne pohrane serotonina (SIPPS), dok su to kod općeg anksioznog poremećaja antidepresivi iz skupine SIPPS i SNRI. Iako su na raspolaganju sigurni i učinkoviti lijekovi za sve anksiozne poremećaje, i nadalje je bitno svakog bolesnika adekvatno i što prije dijagnosticirati, te procijeniti koja je terapijska strategija za njega najbolja
[Show abstract][Hide abstract] ABSTRACT: Kako bi se dijagnosticirao neki od anksioznih poremećaja – generalizirajući anksiozni poremećaj, agorafobija, socijalna fobija, panični poremećaj ili opsesivno-kompulzivni poremećaj – potrebno je utvrditi prisutnost klinički značajne anksioznosti koja se javlja kontinuirano više mjeseci (opći anksiozni poremećaj), u definiranim situacijama (fobija), epizodično u paničnim napadajima (panični poremećaj) i prisutnost opsesivnih i prisilnih misli u razdoblju od najmanje sat vremena dnevno (opsesivno-kompulzivni poremećaj). Anksioznost mora biti primarna, a diferencijalno dijagnostički treba isključiti druge psihičke poremećaje, druge tjelesne bolesti i lijekove koji mogu imati simptome anksioznosti kao nuspojavu
[Show abstract][Hide abstract] ABSTRACT: Depressive disorders are among the most frequently reported mental disorders with the current prevalence of 5 to 10%, lifetime prevalence of up to 18%, and lifetime risk of 20 to 30%. According to the Global Burden of Disease Study for 96 most frequent diseases, based on DALYs for all ages, unipolar depressive disorder ranks fourth and it is anticipated to rank second in 2020. Based on YLDs (Years Lived with Disability), unipolar depressive disorder, with 11.9%, is the most frequent cause of disability. In 2002, Croatia recorded 3 755 hospitalizations and 136 272 days of hospital treatment due to depressive disorders. Consequently, depressive disorders rank third in the group of mental disorders by the number and duration of hospitalization and they account for 9.7 and 7.6%, respectively. In the period from 1995 to 2002, both the total hospitalization number and rate and the hospitalization number and rate by gender showed an increasing trend with some oscillations. The hospitalization rate in 1995, 1996, 1999 and 2002 was 54.6, 88.1, 75.7, 89.4 and 84.6/100 000, respectively. The number of hospitalizations of women was higher than that of men (1.4-2.5:1). The hospitalization rate for both genders was the highest in the age group of 40 to 59. Depressive disorders represent one of public health priorities. Based on projections, the programs for mental health protection should be intensified.
[Show abstract][Hide abstract] ABSTRACT: This article shows the classification of antidepressants that is mainly based on their historical development: from classical (tricylic and tetracyclic) non-selective antidepressants and monoamine oxidase inhibitors (MAOIs) to selective serotonin reuptake inhibitors (SSRIs) and antidepressants with dual action. The theories of neuroplasticity have been only mentioned since they are not widely used in pharmacotherapy. As this text is intended for Croatian physicians, a detailed description of antidepressants mainly includes the drugs registered in Croatia. Of course, this neither reflects the authors’ opinion about the efficacy or tolerability of unregistered antidepressants nor does it mean that they would not like to have some of these drugs available for their patients. As far as its practical implementation is concerned, this article can also serve as a manual of pharmacotherapy for depressed patients. The need for individual and rational approach and the following principles should be considered: the treatment of patients with mild to moderate depression falls within the responsibility of general practitioners, while the treatment of patients with serious depression and suicidality falls within the responsibility of psychiatrists. Therapeutically resistant patients should be referred to relevant subspecialists. The treatment of depression is primarily carried out with antidepressants. In addition to antidepressants, it is often important to coadminister sedatives/hypnotics because some time is needed for antidepressants to start acting in order to avoid sleepless nights and thus alleviate suffering and increase patient compliance.
[Show abstract][Hide abstract] ABSTRACT: Depressive disorders are currently one of the most frequent mental diseases whose incidence has been continuously increasing since the last century. Epidemiological studies show that every fifth woman and every tenth man has experienced at least one serious depressive episode in a lifetime. In addition to the loss of joie de vivre, the WHO data show that depressive disorders are one of the most frequent causes of incapacity for work worldwide. The abovementioned leads to the conclusion that depression has actually become a public health problem. On the other hand, some ten years ago only psychiatrists treated depression. However, due to its increasing prevalence, general practitioners and family physicians have become first-line physicians in the treatment of depression. Consequently, practical treatment guidelines are needed in everyday work.
[Show abstract][Hide abstract] ABSTRACT: Pharmacogenetics, and particularly pharmacogenomics, are new scientific disciplines whose initial results hold promise that the homogeneous groups with respect to the expected therapeutic response will be recognized among people suffering from depression, which would enable its more efficient treatment. It is clear that the therapeutic response is a result of complex genetic effects, and not only of one gene. Therapeutic response is affected not only by genetic polymorphisms, but also by variations in gene expression and post-translational modifications of proteins under the influence of numerous factors, e.g. dose, food, interactions with other substances. Although pharmacogenetic or even pharmacogenomic studies alone are not expected to completely elucidate the variability in the therapeutic response, the establishment of at least some causes of this variability, which is under a direct genetic influence, would significantly contribute to a more reliable assessment of expected therapeutic response and considerably increase a currently low share of patients responding to antidepressant therapies. For the most part, the variability in the therapeutic response can be explained only by further transcriptomic and proteomic research that is, currently, in the early phase of development.
[Show abstract][Hide abstract] ABSTRACT: Clinical investigations and clinical practice are oriented on finding efficacious antidepressants with side-effect profile that would not influence the patients’ quality of life. The patients should be warned of the possibility of side-effects’ occurence in order to recognize and treat these side effects as soon as possible. Extrapyramidal side-effects (EPS) including parkinsonism, dystonia, akathisia and tardive dyskinesia as the most difficult manifestation of EPS, can occure during therapy with antidepressants. Also, weight gain, different metabolic changes, changes in electrocardiogram and cardiovascular changes, as well as sexual sideeffects can occure during therapy with antidepressants. In older patients antidepressants should be used in lower doses, titrated as slow as possible and regularly monitored.
[Show abstract][Hide abstract] ABSTRACT: Dementia is characterised with multiple cognitive deficits which include memory impairment. It is most common in the elderly. The prevalence is around 1% in the age of 60 and increases twice every five years. Inhibitors of acetylcholinesterase are used in the treatment of Alzheimer’s disease (AD) presently. Most common side-effects in therapy with inhibitors of acetilcholinesterase are gastrointestinal side-effects, tiredness, headache and dizziness. Agressiveness and agitation are present in 80% of AD cases. Benzodiazepines, mood stabilizers and antipsychotics are aproved in these cases. Two thirds of patients suffering from dementia have depressive symptoms. The prevalence of depressive simptoms in patients with AD is 25-30%. Treatment with antidepressants is necessary in these cases and the first line of treatment are selective serotonine reuptake inhibitors. Beside clinical examination, it is very important to take into consideration hetheroanamnesis obtained from the members of the family and caregivers. Neuropsychological estimation, as well as the scales of general clinical estimation, are good indicators for efficacy of the therapy. Based on this, decisions for further therapeutical procedures are made.
[Show abstract][Hide abstract] ABSTRACT: Economic estimation of consequences of disturbed mental health and of research in which therapeutic outcome is compared with invested funds has often been met in professional and scientific literature, along with the increase of available possibilities in pharmacotherapy of psychiatric disorders. This review presents more important research work in economic sequelae of psychiatric disorders, trends in use of psychopharmaca, principles of conducting pharmacoeconomic investigations, and the possibilities of their practical application.
[Show abstract][Hide abstract] ABSTRACT: We have tried to explain some general facts and newer aspects of clinical trials. Clinical trials are classified as those based on the phases of clinical development of a particular drug and as those based on the type and goal of the trial itself. There are numerous contact points between trials according to type and according to phases, but differences exist as well. Despite the omnipresent detailed information to the patients about the aims and ways of performing the investigations, and independent evaluations by professional and ethical principles in current studies, several ethical dilemmas regarding the clinical trials performance in psychiatry are still present.
[Show abstract][Hide abstract] ABSTRACT: The frequency and length of admissions over 50 years were analyzed in a sample of 10.268 schizophrenic patients according to ICD-10 subtypes of schizophrenia. The lowest yearly hospitalization frequencies during the risk period were observed in simple, catatonic, unspecified and hebephrenic schizophrenia. When the total sample was analyzed, unspecified schizophrenia exhibited a significantly higher length of hospitalization than paranoid and undifferentiated/other schizophrenia. However, after the exclusion of continuous hospitalizations, unspecified schizophrenia, in severe contrast, was identified as the subtype with lowest admission length. This indicates the need for further research in order to explore the homogeneity of that diagnostic category, i.e. whether unspecified schizophrenia encompasses two subgroups with significantly different courses. Despite the fact that paranoid schizophrenia is generally considered as having the best course and prognosis, this subtype did not have the lowest frequency, nor length of hospitalization. A weak, but significant, negative correlation was observed between admission rate and the length of hospitalization for the total sample, and particularly in the paranoid and residual schizophrenia subtypes. In conclusion, subtypes of schizophrenia differ both in hospitalization rate and length of admission. The introduction of additional factors such as age at onset, gender, subtype presented at initial course of disorder or subtype stability during further analyses could help to identify groups that are more homogenous in their course, prognosis, and, possibly, etiology.
[Show abstract][Hide abstract] ABSTRACT: Benzodiazepines are generally well tolerated, have relatively few side-effects, and are efficacious in treatment of anxious and related disorders. Because benzodiazepines are effective hypnotics they are used in treatment of sleep disorders. Benzodiazepines are also efficacious as myorelaxant agents or anticonvulsants, and are widely used for diminishing withdrawal syndrome. They are also used as intravenous anesthetics. Pharmacokinetic features of particular benzodiazepine determine their indication for use. Despite wide use of benzodiazepines, their primary indication remains for anxiety disorders in particular generalized anxiety disorder and panic disorder. This medication is relatively nontoxic and safer than other medication of similar effect, and when taken in overdose rarely lethal. The most common side-effect of these medications is unwanted daily sedation, and most problematic side-effect is dependence, which can develop in many patients on chronic treatment. Also another significant problem is the discomfort caused by the withdrawal syndrome. Because of all this the use of benzodiazepines should be very rational, i. e. they should be prescribed only when indicated, the lowest possible dose should be administered for as short time as possible. If possible the therapy of anxious states should not be longer than 4 weeks in continuum, and the therapy for insomnia should be sporadic.