Reliability of the bicaudate parameter in the revealing of the enlarged lateral Ventricles in schizophrenia patients.

INTRODUCTION: In schizophrenia patients the lateral ventricle enlargement has mostly been reported in relationship with smaller cortical and/or subcortical brain volumes; and it has been observed that ventricular system growth may be a consequence of the smaller caudate nucleus volume. Bicaudate parameters have been used in the Alzheimer dementia and Huntington's chorea diagnosing in order to evaluate brain changes and the enlargement of the lateral ventricles. SUBJECTS AND METHODS: This study has been carried out on 140 patients out of which 70 patients (30 men and 40 women) who met the ICD 10 criteria for schizophrenia and 70 healthy controls (30 men and 40 women) matched on sex and age with the studied group. All of them underwent direct caudatometry and volume computation based on MRI scans. RESULTS: Except for the bicorporal line, for all the parameters were obtained the statistically highly significant differences between the examined and control groups. Significant correlation was established for the majority of bicaudate parameters and volumes of the caudate nuclei and lateral ventricles. DISCUSSION: Enlargement of the lateral ventricles is one of the most frequent MRI finding in schizophrenia patients. Ventricles are enlarging gradually and frontal horns are more affected than other parts. The increased volumes of the caudate nuclei signalized that ventricular enlargement is not the consequence of the caudate atrophy. CONCLUSION: Bicaudate parameters are reliable parameters for the quick orientation in order to assess the enlarged ventricles in schizophrenia patients.

sVCAM-1, sICAM-1, TNF-α and IL-6 levels in bipolar disorder type I: Acute, longitudinal and therapeutic implications.

OBJECTIVES: To explore the serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular cell adhesion molecule-1 (sICAM-1), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in patients with bipolar disorder (BD), with regard to acute episode characteristics, course of the disorder and treatment. METHODS: The study group consisted of 83 patients diagnosed with BD type I. The control group consisted of 73 healthy individuals, matched with the study group according to age, gender and body mass index. The serum levels of sVCAM-1, sICAM-1, TNF-α and IL-6 were measured by ELISA. RESULTS: Compared with healthy controls, significantly elevated levels of IL-6 and sICAM-1 and significantly lower levels of TNF-α and sVCAM-1 were identified in acute and remission phases of BD. The acute serum levels of sVCAM-1 were associated with the type and severity of acute mood symptoms as well as with course of illness characteristics. TNF-α was associated with duration of untreated disorder and type of treatment. CONCLUSIONS: BD is related to both acute and long-term alterations of immune mediators, including adhesion molecules. The potential immunomodulatory role of pharmacotherapeutic treatment is also to be considered in BD.

Effect of childhood general traumas on suicide attempt depends on TPH2 and ADARB1 variants in psychiatric patients.

Suicidal behavior has been associated with a deficient serotonin neurotransmission which is likely a consequence of individual genetic architecture, exposure to environmental factors and interactions of those factors. We examined whether the interaction of child abuse, TPH2 (tryptophan hydroxylase 2) variant rs4290270, affecting alternative splicing and editing of TPH2 pre-mRNAs, and ADARB1 (adenosine deaminase acting on RNA B1) variants rs4819035 and rs9983925 may influence the risk for suicide attempt in psychiatric patients. TPH2 rs4290270 was genotyped in 165 suicide attempters and 188 suicide non-attempters diagnosed with major depressive disorder, bipolar disorder and schizophrenia. Genotyping data for ADARB1 variants were taken over from our previous study. Child abuse before the age of 18 years was assessed using the Early Trauma Inventory-Self Report. Generalized linear models and backward selection were applied to identify the main and interacting effects of environmental and genetic factors, including psychiatric diagnoses, patients' gender and age as covariates. Childhood general traumas were independently associated with suicide attempt. Two-way interaction between TPH2 rs4290270 and general traumas revealed that TT homozygotes with a history of general traumas had an increased risk for suicide attempt. Three-way interaction of general traumas, TPH2 rs4290270 and ADARB1 rs4819035 indicated that the highest predisposition to suicide attempt was observed in individuals who experienced general traumas and were TT homozygote for rs4290270 and TT homozygote for rs4819035. Our findings suggest that the risk for suicide attempt in psychiatric patients exposed to an adverse childhood environment may depend on TPH2 and ADARB1 variants.

Predictive value of sICAM-1 and sVCAM-1 as biomarkers of affective temperaments in healthy young adults.

BACKGROUND: Affective temperaments are intermediate phenotypes for major affective disorders and are reported to have a neuroimmune etiopathogenesis. Here we investigated the role of soluble intercellular cell adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in affective temperaments and mood symptoms in healthy adults. METHODS: Healthy adults (n=94) were screened for psychiatric disorders using the nonpatient version of the Structured Clinical Interview for DSM-IV-I and II. Subjects with medical conditions associated with changes in inflammatory response were excluded, deriving the final sample (n=68). Affective temperaments were evaluated with Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire (TEMPS-A). State mood symptoms were assessed using the Young Mania Rating Scale and Montgomery-Åsberg Depression Rating Scale. Serum sICAM-1 and sVCAM-1 levels were measured using enzyme-linked immunosorbent assay. RESULTS: After adjusting for confounders (age, gender, BMI, and smoking habits), a high negative correlation between depressive and irritable temperament TEMPS-A scores and sVCAM-1 levels was detected. Although we identified no association between sICAM-1 levels and affective temperament scores, sICAM-1 was related to the state severity of manic symptoms. In a multiple linear regression model, sVCAM-1 remained a significant predictor of depressive but not irritable temperament scores. LIMITATIONS: The temperaments were estimated on the basis of self-report questionnaire. CONCLUSIONS: Our findings suggest that sVCAM-1 is related to affective temperaments, and it is a trait marker for liability to mood disorders. This relationship between alterations in cellular adhesion and affective temperament may be important for vulnerability to affective disorders.

The Efficacy and Safety of Antipsychotic Medications in the Treatment of Psychosis in Patients with Parkinson's Disease.

Psychotic symptoms are present in up to 50% of patients with Parkinson's disease. These symptoms have detrimental effects on patients' and caregivers' quality of life and may predict mortality. The pathogenesis of psychotic symptoms in Parkinson's disease is complex, but the use of dopaminergic medications is one of the risk factors. The treatment of psychotic symptoms in Parkinson's disease is complicated due to the ability of antipsychotic medications to worsen motor symptoms. The efficacy of clozapine in the treatment of psychosis in patients with Parkinson's disease has been confirmed in several clinical trials; however, the adverse effects and the necessity of blood count monitoring are the reasons why the use of this drug is challenging. The studies on safety and efficacy of other antipsychotics conflicting results. The use of antipsychotics in these patients is also associated with increased mortality. Psychotic symptoms in Parkinson's disease per se are also proven predictors of mortality. Thus it is necessary to treat psychotic symptoms but the choice of an antipsychotic should be based on careful risk/benefit assessment. Pimavanserin as a novel therapeutic option with more favorable adverse effects profile is now available for this indication, but careful postmarketing monitoring is necessary to establish the true picture of this drug's long-term safety and efficacy.

Tryptophan Hydroxylase 1 Variant rs1800532 is Associated with Suicide Attempt in Serbian Psychiatric Patients but does not Moderate the Effect of Recent Stressful Life Events.

Tryptophan hydroxylase 1 (TPH1) gene, coding for serotonin synthesizing enzyme, and recent stressful life events (SLEs) have been commonly associated with suicidal behavior. TPH1 has been also hypothesized to be involved in stress-response mechanisms. The aim of this study was to assess TPH1 variant rs1800532 and its possible interaction with recent SLEs as risk factors for suicide attempt (SA) in Serbian psychiatric patients, including 165 suicide attempters and 188 suicide nonattempters. rs1800532 and recent SLEs were independently associated with SA, while rs1800532 did not moderate the effect of recent SLEs on SA vulnerability among Serbian psychiatric patients.

Neutrophil-to-lymphocyte ratio predicting suicide risk in euthymic patients with bipolar disorder: Moderatory effect of family history.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has been independently related to bipolar disorder (BD) and factors associated with suicidal risk. The aim of our study was to explore the relationship between NLR and suicide risk in euthymic BD patients. We also sought to propose a model of interaction between NLR and stress-diathesis factors, leading to suicidal risk in BD. METHODS: The study group consisted of 83 patients diagnosed with BD (36 suicide attempters; 47 suicide non-attempters), compared to the healthy control group (n=73) and matched according to age, gender, and body mass index (BMI). NLR was measured according to the complete blood count. Mood symptoms have been assessed by Young Mania Rating Scale and Montgomery-Asberg Depression Rating Scale. Early trauma and acute stress were evaluated by Early Trauma Inventory Self Report-Short Form and List of Threatening Experiences Questionnaire, respectively. Suicide risk has been assessed by Suicide Behaviors Questionnaire-Revised (SBQ-R). RESULTS: Significant correlation was found between NLR and SBQ-R score. The main effects of suicide attempts on NLR, after covarying for confounders, were observed, indicating increased NLR in BD suicide attempters compared to healthy controls. We found significant moderatory effects of family history on NLR relationship to suicidal risk, with NLR being significant positive predictor of suicidal risk only in the patients with positive family history of suicide attempts. CONCLUSIONS: The results suggest an enhancing effect of positive family history of suicide attempts on predictive effect of NLR on suicide risk. Our data support the idea that immune markers can predict suicide attempt risk in BD, but only in the subpopulation of BD patients with family history of suicide attempts. This could lead to prevention in suicide behavior in the patient population at particular risk of suicide.

Role of sICAM-1 and sVCAM-1 as biomarkers in early and late stages of schizophrenia.

Schizophrenia (SZ) is a neuroprogressive disorder presenting with biochemical, functional, and structural changes, which differ from early to late stages of the illness. We explored the differences in serum levels of soluble intercellular cell adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) between early and late stages of SZ, in regard to clinical characteristics and treatment application. Serum levels of sICAM-1 and sVCAM-1 were measured in 80 patients with SZ (40 early stage; 40 late stage), and compared with 80 healthy controls, matched by age, gender, body mass index, and smoking habits with each SZ group. Serum levels of sICAM-1 and sVCAM-1 were measured using ELISA. The severity of psychopathology was assessed using the Clinical Global Impression Scale and five-factor Positive and Negative Symptoms in Schizophrenia Scale. After adjustment for confounders, we noticed normal levels of sICAM-1 in the early stage, and elevated levels of sICAM-1 in the late stage of SZ. sVCAM-1 levels were decreased in both stages of SZ. Higher sICAM-1 levels have been related to more pronounced cognitive deficit and excitement symptoms in the early stage of SZ and to favorable characteristics of treatment application in both stages. SZ is associated with changes in the levels of adhesion molecules that vary from early to late stages of the illness. This implies that the concept of biochemical staging is applicable in SZ, at least for markers of cellular adhesion.

Burnout of Formal Caregivers of Children with Cerebral Palsy.

BACKGROUND: Burnout syndrome is under-researched within caregivers (CGs) of children with cerebral palsy. The primary aim was to determine the burnout level of formal CGs of children with cerebral palsy (G1) and to compare it with a control group (G2) of professional pediatric nurses, and second, to correlate the level of depression and anxiety with the burnout level. METHOD: In a total sample of 60 CGs, the Maslach Burnout Inventory Human Services Survey (MBI-HSS), consisting of three structural units - emotional exhaustion (MBIEE) subscale, depersonalization (MBI-DP) subscale and personal accomplishment (MBI-PA) subscale - was used to measure burnout. The Beck Anxiety Inventory (BAI) was used for the assessment of anxiety, and the Beck Depression Inventory (BDI) for depression. RESULTS: A significant difference was shown on the MBI-EE subscale and on the BDI test (p<0.05), in both cases higher scores were obtained by G1. High burnout was observed in all subscales, on the MBI-EE subscale registered 50% of CGs in G1, and 17% in control G2. Correlation of the MBI-EE subscale with BDI and BAI tests was highly significant (p<0.01). CONCLUSIONS: These findings indicate the need for future research aimed at formulating preventive strategies for caregivers' mental health. Better care for caregivers would provide them with better professional satisfaction, and consequently would lead to better care for patients.

Creativity in psychopharmacotherapy - the bright side of face of psychiatric god Janus.

This paper discusses about challenges to psychopharmacotherapy, evidence-based psychopharmacology, creative psychopharmacology, creativity and dopamine, creative-rational polypharmacy as a paradigm for creativity in psychopharmacotherapy, and about polypharmacy classification as a good, bad and ugly By stimulating the patient to participate in the creative and artistic process we effect on his optimal identification with the role of the sick person. Through creation, imagination and visualization patients can recognize their own reservoir of inner healing and create a healthier new identity. Psychopharmacotherapy can prevent the deterioration of creativity affecting the quality of life and personal recovery. It may also affect the goals and aspirations of patients as well as the way in forming strategies of their realization.

Descartes and His Peculiar Sleep Pattern.

Rene Descartes (1596-1650) was a mathematician, philosopher, and scholar, whose work set a foundation for modern science. Among other interests, he focused on locating the "core and the seat of the soul" and concluded that the pineal gland was such a structure. Recent scientific findings validate Descartes' deep interest in pineal gland, appreciating its role as part of the circadian rhythm system. On the other hand, the biographical information suggests that Descartes had an aberration of the circadian rhythm (delayed sleep phase). Coincidentally, this meant that one of the most important things in his private life and one of the most significant areas of his research intersected in an overlooked way.

Cannabis and psychosis revisited.

The association between cannabinoids and psychosis has been known for almost a thousand years, but it is still speculated whether cannabis use may be a contributory cause of psychosis, that is, whether it may precipitate schizophrenia in those at risk. In this paper, we will briefly present the data from individual longitudinal studies in the field, together with the factors that are considered important for the association of cannabis abuse and occurrence of schizophrenia and prevention opportunities in the target population. The reviewed studies clearly suggest that cannabis abuse predicts an increased risk for schizophrenia, particularly in young adults. They underline both the need to create adequate prevention measures and consequently avoid the occurrence of the disease in the young at risk. Particular attention should be additionally devoted toward encouraging the young presenting with psychotic symptoms to stop or, at the very least, reduce the frequency of cannabis abuse. The issues are undoubtedly to be addressed by the health care system in general.

Joint effect of ADARB1 gene, HTR2C gene and stressful life events on suicide attempt risk in patients with major psychiatric disorders.

OBJECTIVES: Adenosine to inosine RNA editing, serotonin 2C receptor (HTR2C), and stressful life events (SLEs) have all been implicated in suicidal behaviour. We examined the main and moderating effects of RNA editing (ADAR, ADARB1) and HTR2C genes, childhood trauma (CT), recent SLEs and psychiatric disorders as contributors to suicide attempt (SA) vulnerability. METHODS: Study included 165 suicide attempters and 188 suicide non-attempters, all diagnosed with one of major psychiatric disorders. CT and recent SLEs were assessed using Early Trauma Inventory-Self Report and List of Threatening Experiences Questionnaire, respectively. Selected ADAR and ADARB1 tag-variants, and HTR2C rs6318 were pre-screened for association with SA, while generalized linear models and backward selection were applied to identify individual and interacting SA risk factors. RESULTS: ADARB1 rs9983925 and rs4819035 and HTR2C rs6318 were associated with SA. The best minimal model found emotional abuse, recent SLEs, rs9983925 and rs6318 as independent SA risk factors, and general traumas as a factor moderating the effect of psychiatric disorders and emotional abuse. CONCLUSIONS: SA vulnerability in psychiatric patients is related to the joint effect of ADARB1 and HTR2C variants, the existing mood disorder and the cumulative exposures to a various childhood and recent stressful experiences.

Transcranial electric stimulation for intraoperative motor evoked potential monitoring: dependence of required stimulation current on interstimulus interval value.

STUDY OBJECTIVE: To evaluate the relationship between stimulus intensity by constant current transcranial electric stimulation and interstimulus interval (ISI) for eliciting muscle motor evoked potentials (MEPs) in three different hand muscles and the tibialis anterior muscles. PATIENTS/MATERIAL AND METHODS: We tested intraoperatively different monophasic constant current pulses and ISIs in 22 patients with clinically normal motor function. Motor thresholds of contralateral muscle MEPs were determined at 0.5 milliseconds (ms) pulse duration and ISIs of 1, 2, 3, 4, 5, and 10 ms using a train of 2, 3, and 5 monophasic constant current pulses of 62 to 104 mA before craniotomy and after closure of the dura mater. RESULTS: The lowest stimulation threshold to elicit MEPs in the examined muscles was achieved with a train of 5 pulses (ISI: 3 ms) before craniotomy, which was statistically significant compared with 2 pulses (ISI: 3 ms) as well as 3 pulses (ISIs: 3 and 10 ms). An ISI of 3 ms gave the lowest motor thresholds with statistical significance compared with the ISIs of 4 ms (2 pulses) and of 1 ms (3 pulses). All current intensity (mA) and ISI (ms) relationship graphs had a trend of the exponential function as y = a + bx + c ρ (x), where y is intensity (mA) and x is ISI (ms). The minimum of the function was determined for each patient and each muscle. The difference was statistically significant between 3 and 5 pulses before craniotomy and between 3 and 5 pulses and 2 and 5 pulses after closure of the dura mater. CONCLUSION: In adult neurosurgical patients with a normal motor status, a train of 5 pulses and an ISI of 3 ms provide the lowest motor thresholds. We provided evidence of the dependence of required stimulation current on ISI.

The life and work of Ksenija Atanasijevic (1894-1981)--psychology and anthropology as the inevitability and necessity of philosophy.

Ksenja Atanasijevic (1894-1981) was the first woman in Serbia to obtain a Ph.D. in philosophy. Going through numerous psychological metamorphoses in her lifetime and confronted with numerous challenges, Ksenija Atanasijevic developed a specific philosophical-psychological system of consolation prominently featuring the concepts of happiness, bliss, moderation, courage and wisdom. Modifying the original teachings of Democritus and Epicurus, Ksenija Atanasijevic developed a distinctive anthropology based on confrontation with but equally the overcoming of obstacles, both internal (spiritual) as well as external ones. The philosopheress developed a reflexive and indeed metaphysical defensive psychotherapeutical skill at the root of which was cleansing the soul, as well as dedication to the realm of fancy, fantasy and imagination. Ksenija Atanasijevic also had precious literary talent which was best expressed in her analyses of the poetry and prose of great Serbian writers (Pandurovic, Njegos, Nastasijevic, etc.). It is quite certain that this, with Anica Savic-Rebac, definitely greatest Serbian philosopheress, through personal suffering, creative solitude and shrouded desperation built an utterly authentic and harmonious system of philosophical comfort.

Volumetric analysis of amygdala, hippocampus, and prefrontal cortex in therapy-naive PTSD participants.

OBJECTIVE: In our study we have hypothesized that volume changes of amygdala, hippocampus, and prefrontal cortex are more pronounced in male posttraumatic stress disorder participants. MATERIAL AND METHODS: We have conducted a study of 79 male participants who underwent MRI brain scanning. PTSD diagnosis was confirmed in 49 participants. After MRI was taken all scans were software based volume computed and statistically processed. RESULTS: We found that left amygdala is the most significant parameter for distinction between PTSD participants and participants without PTSD. There were no significant differences in volumes of hippocampi and prefrontal cortices. Roc curve method outlined left amygdala AUC = 0.898 (95% CI = 0.830-0.967) and right amygdala AUC = 0.882 (95% CI = 0.810-0.954) in the group of PTSD participants which makes both variables highly statistically significant. CONCLUSION: The present investigation revealed significant volume decrease of left amygdala in PTSD patients. Concerning important functions of the amygdala and her neuroanatomical connections with other brain structures, we need to increase number of participants to clarify the correlation between impared amygdala and possible other different brain structures in participants with PTSD.

Polysomnographic sleep patterns in depressive, schizophrenic and healthy subjects.

BACKGROUND: Sleep disorders are frequent symptoms described in psychiatric patients with major depression and schizophrenia. These patients also exhibit changes in sleep architecture measured by polysomnography (PSG) during sleep. The aim of the present study was to identify potential biomarkers to facilitate diagnosis based on PSG measurements. SUBJECTS AND METHODS: Thirty (30) patients with schizophrenia, 30 patients with major depression and 30 healthy control subjects were investigated in the present study. All subjects underwent PSG measurements for a minimum time of 8 hours according to the criteria of Rechtscahffen & Kales (1968). We tested the potential of multiple sleep variables to predict diagnosis in different groups by using linear discriminant analysis (LDA). RESULTS: There were significant differences in PSG variables between healthy control subjects and psychiatric patients (total sleep time, sleep latency, number of awakenings, time of awakening after sleep onset, REM 1 latency, REM 1 and index of endogenous periodicity). Importantly, LDA was able to predict the correct diagnosis in 88% of all cases. CONCLUSIONS: The presented analysis showed commonalities and differences in PSG changes in patients with major depressive disorder and in patients with schizophrenia. Our results underline the potential of PSG measurements to facilitate diagnostic processes.

Type D personality in patients with coronary artery disease.

BACKGROUND: During the past decade studies have shown that Type D personality is associated with increased risk of cardiac events, mortality and poor quality of life. Some authors suggested that depression and Type D personality have substantial phenomenological overlap. SUBJECTS AND METHODS: The sample consisted of non-consecutive case series of seventy nine patients with clinically stable and angiographically confirmed coronary artery disease (CAD), who had been admitted to the Clinic of Cardiology, University Clinical Centre, from May 2006 to September 2008. The patients were assessed by the Type-D scale (DS14), The Beck Depression Inventory (BDI), and provided demographic information. Risk factors for CAD were obtained from cardiologists. RESULTS: The findings of our study have shown that 34.2% patients with CAD could be classified as Type D personality. The univariate analysis has shown that the prevalence of Type D personality was significantly higher in individuals with unstable angina pectoris and myocardial infarction (MI) diagnoses (p=0.02). Furthermore, some components of metabolic syndrome were more prevalent in patients with Type D personality: hypercholesterolemia (p=0.00), hypertriglyceridemia (p=0.00) and hypertension (p=0.01). Additionally, the distribution of depression in patients with a Type D personality and a non-Type D personality were statistically significantly different (p=0.00). CONCLUSION: To our knowledge, this study is the first one to describe the prevalence and clinical characteristics of the Type D personality in patients with CAD in this region of Europe. We have found that the prevalence of Type D personality in patients with CAD is in concordance with the other studies. We also have found that Type D personality and depression are two distinctly different categories of psychological distress.

The role of C-Fos protein, somatostatin and neuropeptide Y in the pathogenesis of ischemic brain injuries based on animal model of cerebral ischemia.

The aim of this study was to define all the areas of changes in expression of nuclear c-Fos protein (c-Fos), cytoplasmic somatostatin (SS) and neuropeptide Y (NPY) in rat brain during experimental ischemia. Using the immunohistochemical method, brain mapping (based on the atlas by Paxinos & Watson) of immunoreactivity for c-Fos, SS and NPY in 39 rats, was studied in telencephalon, diencephalon and midbrain after resistant and transitory ischemia. The first experimental group (R group) was exposed to resistant ischemia by occlusion (10 minutes) of four vessels according to the Pulsinelli method. The second group was first exposed to transitory (4 minutes) ischemia (preconditioning) and, after 72 hours, to total ischemia as in the R group. There was a statistical difference between the R and T group in the c-Fos reaction, especially in the parietofrontal cortex, anterior amygdaloid area, claustrum, reuniens nucleus and suprachiasmatic nucleus. The dominant immunohistochemical reactivity was found for c-Fos protein, and the most reactive in terms of co-localization of c-Fos with SS and NPY was periventricular area of hypothalamus. The mapping showed that both, phylogenetically new as well as phylogenetically older brain structures reacted immunohistochemically. The results of our study, regarding the impact of preconditioning with a short period of ischemia on c-Fos activity and co-localization of c-Fos with SS and NPY immunoreactivity, showed the need for future studies of brain neuropeptides related to regional and time effects, and indicated brain structures which may require pharmacological targeting to achieve neuroprotective level of proto-oncogene activity in populations at risk.