The diagnostic value of serum UCHL-1 and S100-B levels in differentiate epileptic seizures from psychogenic attacks.

OBJECTIVE: To assess the value of postictal serum Ubiquitin C-terminal hydrolase (UCHL-1), a neuronal biomarker, and S100-B, a glial biomarker, levels, in differentiate epileptic seizures (ES) form psychogenic attacks. METHODS: In this analytical cross-sectional study, serum UCHL-1 and S100-B levels were measured within six hours of occurring seizure, in 43 patients with ES, 20 patients with psychogenic non-epileptic seizures (PNES) and 19 healthy individuals by electrochemiluminescence immunoassay. RESULTS: Both serum UCHL-1 and S100-B levels were significantly higher in patients with ES than PNES (P < 0.05) and controls (P < 0.01). PNES patients had significantly higher serum S100-B levels compared to controls (P < 0.01). There was a significant correlation between the serum UCHL-1 and S100-B levels in patients with ES (r = 0.46, P = 0.002). CONCLUSIONS: Our study showed that serum UCHL-1 level could be potentially used in differentiate ES from PNES (sensitivity 72%, specificity 59%). Serum S100-B level had lower value compared to UCHL-1 (AUC 0.68 for UCHL-1 v/s 0.59 for S100B). Post-seizure serum UCHL-1 and S100-B levels could be used in future studies to better understand the underlying mechanism of seizures and may offer as an adjunctive diagnostic test in differentiate ES from PNES.

Serum NT-pro CNP levels in epileptic seizure, psychogenic non-epileptic seizure, and healthy subjects.

PURPOSE: Epileptic seizure is the result of uncontrollable neural excitation in the brain. The C-type natriuretic peptide is a member of natriuretic peptide hormone family and is synthesized by brain and blood vessels in CNS. NT-pro CNP is an amino-terminal fragment of C-type natriuretic peptide and is more stable compared to its predecessor. In this study, we aimed to evaluate the role of NT-pro CNP in psychogenic non-epileptic seizures, epileptic seizures, and normal subjects. METHODS: Thirty-three patients with epilepsy and 43 patients with psychogenic non-epileptic seizures were enrolled in this study. The control group consisted of 28 healthy subjects. Post-ictal serum levels of NT-pro CNP were acquired from all participants. Statistically significant differences between patient groups and controls regarding serum levels of NT-pro CNP were sought. RESULTS: NT-pro CNP levels were significantly lower in the epilepsy group than the psychogenic non-epileptic seizure group and control group with no significant difference between the psychogenic non-epileptic seizure and control group (p < 0.05). CONCLUSION: Post-ictal serum NT-pro CNP levels were lower in epileptic seizures compared to psychogenic non-epileptic seizures as well as healthy controls. We think that such a difference is associated with C-type natriuretic peptide-related neural mechanisms such as altered microcirculation, increased brain-blood barrier permeability, and synaptic stabilization.

Serum GFAP level: A novel adjunctive diagnostic test in differentiate epileptic seizures from psychogenic attacks.

PURPOSE: There has been increasing interest in the use of different biomarkers to help distinguish psychogenic from epileptic seizures, in patients presenting acutely with seizure-like events. In the present study, we measured serum glial fibrillary astrocytic protein (GFAP) levels in patients presenting with such events who were subsequently diagnosed as epileptic seizures (ESs) or psychogenic non-epileptic seizures (PNESs) and compared GFAP levels obtained with those found in healthy subjects. METHODS: Sixty-three patients with seizures (43 with ES and 20 with PNES), and 19 healthy subjects participated in the study. Venous blood samples were obtained within the first 6 h after seizures and serum GFAP levels were measured by protein quantification (ELIZA kit) with an electrochemical luminescence immunoassay. RESULTS: Serum GFAP levels were significantly higher in patients with ES compared to PNES or healthy controls. A cut-off point of 2.71 ng/ml was found optimally to differentiate ES from PNES (sensitivity 72%, specificity 59%). CONCLUSION: Our study suggests that post-seizure serum GFAP levels could be used in future studies better to understand the underlying mechanism of seizures and may offer as an adjunctive diagnostic test in differentiating ES from PNES.

The effect of long-term melatonin supplementation on psychosomatic disorders in postmenopausal women.

Different psychosomatic disorders are observed in postmenopausal women. The decrease of estrogen production is believed to be the main cause of their severity. It is nowadays evident that the decreased melatonin release in women at this age who suffer from postmenopausal disorders might also contribute to the severity of the symptoms. The aim of the study was to evaluate the effect of melatonin supplementation on female hormones release and the alteration in climacteric symptoms. The study included 60 postmenopausal women, aged 51 - 64 years, who were randomly allotted into two equal groups. Group I was recommended placebo (2 x 1 tablet) and Group II - melatonin (3 mg in the morning and 5 mg at bedtime) for 12 months. Serum levels of 17ß-estradiol, follicle-stimulating hormone (FSH), melatonin and urinary 6-sulfatoxymelatonin (aMT6s) excretion as well as Kupperman Index (KI) and body mass index (BMI) were determined before the start and at 12 months after placebo or melatonin administration. In Group I only the value of KI slightly decreased (28.4 ± 2.9 versus 25.6 ± 3.8 points, P = 0,0619). In Group II - KI decreased from 29.1 ± 2.9 to 19.7 ± 3.1 points (P < 0.001) and BMI from 30.9 ± 2.9 to 28.1 ± 2.3 kg/m2 (P < 0.05). Melatonin supplementation failed to change significantly the serum concentration of female reproductive hormones 17ß-estradiol and FSH. We conclude that melatonin supplementation therapy exerts a positive effect on psychosomatic symptoms in postmenopausal women and can be recommended as the useful adjuvant therapeutic option in treatment of these disorders.

[Lipid profile and psychometric traits in patients with psychosomatic disorders and chronic cerebral ischemia]. / Lipidnyi spektr krovi i psikhometricheskie pokazateli u patsientov s psikhosomaticheskoi patologiei i khronicheskoi ishemiei golovnogo mozga.

AIM: To explore the correlation of serum cholesterol and triglycerides with psychometric traits in patients with psychosomatic disorders and chronic cerebral ischemia (CCI). MATERIAL AND METHODS: One hundred and ten patients with CCI, aged from 46 to 76 years, were examined. Total cholesterol and triglycerides were measured in the blood. A battery of tests for assessment of cognitive functions and neurotic traits was used. RESULTS: The level of cholesterol was higher in patients with post-infarction cardiosclerosis (PICS) compared to patients with CCI without psychosomatic disorders but did not differ from that in patients with gastric ulcer (GU). The level of triglycerides was higher in both groups with psychosomatic disorders, patients with PICS had higher levels compared to patients with GU. No differences between total cholesterol and triglycerides and assessment of cognitive functions in patients of different age were observed. CONCLUSION: Patients with psychosomatic disorders had lower cognitive function and higher level of neuroticism. Results of regression analysis indicate that blood contents of cholesterol and triglycerides can be considered as a prognostic factor for cognitive decline.

Lactate as a diagnostic marker in transient loss of consciousness.

PURPOSE: The diagnostic classification of disorders of consciousness is often challenging, particularly the distinction between epileptic and non-epileptic seizures. The aim of the study was to examine serum lactate as a diagnostic marker of transient loss of consciousness. METHOD: Serum lactate levels in blood samples drawn within 2h of the event were compared retrospectively between patients with generalized tonic-clonic seizures (n=195) and patients with other seizures (syncopes [n=52], psychogenic non-epileptic seizures [n=17], and complex focal seizures [n=37]), respectively. RESULTS: Serum lactate in patients with generalized tonic-clonic seizures was significantly (p<0.001, Mann-Whitney-U test) increased in comparison to other forms of seizure incidences. The area under the ROC-curve was 0.94 (95% CI 0.91-0.96). For a cut-off concentration of 2.45mmol/l, the sensitivity was 0.88 and the specificity 0.87. CONCLUSIONS: Serum lactate levels in the acute diagnosis were an excellent biomarker for the discrimination of generalized seizures from psychogenic non-epileptic and syncopal events, corroborating its importance for the standard work-up of acute disturbances of consciousness.

Antinociceptive fatty acid patterns differ in children with psychosomatic recurrent abdominal pain and healthy controls.

AIM: Stress is considered to trigger psychosomatic recurrent abdominal pain (RAP), but the mechanism behind the pain is unclear. Because the essential fatty acids, omega-6 and omega-3, are involved in pain, by regulating lipid mediators, we analysed the fatty acid patterns in children with RAP compared to healthy children. METHODS: This was a cross-sectional study of plasma phospholipid fatty acids in 22 consecutively included children with RAP, aged six to 16 years, at an outpatient clinic specialising in RAP. The controls were 100 healthy children previously reported on and analysed in the same laboratory. RESULTS: The children with psychosomatic RAP showed higher mean concentrations of saturated fatty acids than the controls (49.0 mol% versus 47.4 mol%) but lower mean levels of polyunsaturated fatty acids (38.6 mol% versus 39.9 mol%). Omega-3 fatty acids were lower in children with psychosomatic RAP, resulting in higher ratios of linoleic to alpha-linolenic acids (p < 0.001) and arachidonic to eicosapentaenoic acids (p = 0.01), despite a lower concentration of arachidonic acid in children with RAP (p < 0.01). CONCLUSION: The results suggested an imbalance between nociceptive omega-6 fatty acids and antinociceptive omega-3 fatty acids in psychosomatic RAP. Further studies, including lipid mediators and oxidative products, are necessary to confirm an association.

Psychological insulin resistance in type 2 diabetes patients regarding oral antidiabetes treatment, subcutaneous insulin injections, or inhaled insulin.

BACKGROUND: "Psychological insulin resistance" (PIR) is an obstacle to insulin treatment in type 2 diabetes, and patients' expectations regarding alternative ways of insulin delivery are poorly understood. SUBJECTS AND METHODS: PIR and beliefs regarding treatment alternatives were analyzed in patients with type 2 diabetes (n=532; mean glycated hemoglobin, 68±12 mmol/mol [8.34±1.5%]) comparing oral antidiabetes treatment, subcutaneous insulin injections, or inhaled insulin. Questionnaires were used to assess barriers to insulin treatment (BIT), generic and diabetes-specific quality of life (Short Form 36 and Problem Areas in Diabetes, German version), diabetes knowledge, locus of control (Questionnaire for the Assessment of Diabetes-Specific Locus of Control, in German), coping styles (Freiburg Questionnaire of Illness Coping, 15-Items Short Form), self-esteem (Rosenberg Self-Esteem Scale, German version), and mental disorders (Patient Health Questionnaire, German version). Patients discussed treatment optimization options with a physician and were asked to make a choice about future diabetes therapy options in a two-step treatment choice scenario. Step 1 included oral antidiabetes drugs or subcutaneous insulin injection (SCI). Step 2 included an additional treatment alternative of inhaled insulin (INH). Subgroups were analyzed according to their treatment choice. RESULTS: Most patients perceived their own diabetes-related behavior as active, problem-focused, internally controlled, and oriented toward their doctors' recommendations, although their diabetes knowledge was limited. In Step 1, rejection of the recommended insulin was 82%, and in Step 2, it was 57%. Fear of hypoglycemia was the most important barrier to insulin treatment. Patients choosing INH (versus SCI) scored higher regarding fear of injection, expected hardship from insulin therapy, and BIT-Sumscore. CONCLUSIONS: The acceptance of insulin is very low in type 2 diabetes patients. The option to inhale insulin increases the acceptability for some but not the majority of patients.

[Analysis of infringements of exchange processes in combatatnts with psychosomatic disorders in the period after participation in operations].

Analysis of clinical and biochemistry blood test parameters was conducted. It was revealed that metabolic disorders with predomination of catabolic reactions are typical for combatatnts who took part in military actions. So, the blood serum glucose value in the patients group is higher than in the control group. Military men with psychosomatic disorders are characterized by the decrease of cholesterol and triglycerides. The obtained data is supported by the results of model analysis of posttraumatic stress disorders in animals.

[C reactive protein in women with coronary heart disease and its association with depression]. / C-reaktives Protein bei Frauen mit koronarer Herzkrankheit und Zusammenhange mit Depressivitat.

OBJECTIVES: Depression is associated with increased risk and poor outcome of coronary heart disease (CHD), though the mechanisms are largely unknown. Low-grade inflammation offers a possible biological pathway, which has been confirmed in men but not in women. METHODS: We studied the association of C reactive protein (CRP), a biomarker of inflammation, with depressive symptoms in 292 women with CHD and 300 healthy age-matched controls, considering confounder variables (BMI, age, HDL cholesterol, triglycerides, menopausal status). CRP was measured by a high sensitivity assay. RESULTS: In the overall sample no significant association was found between depressive symptoms and CRP, whereas in the control group women with 2 or more versus 0-1 depressive symptoms showed heightened CRP (p = 0.005); there was no significant difference in CRP levels between CHD patients with 0-1 versus 2 or more depressive symptoms. Women with CHD had higher serum levels of CRP and more depressive symptoms than did controls. CONCLUSIONS: Contrary to men and healthy controls there was no link between CRP and depressive symptoms in women with CHD. More research is needed on how the harmful effects of depression are mediated, especially in women.

[Psychophysiological signs of hyperuricemy in military personnel].

It was shown that concentration of uric acid in blood is dependent on person's neurotic type. People combining high working potential, assertions and work concentration with continuous hypersympathycotonia exhibit psychosomatic predisposition and are at risk of cardiovascular pathology. Neuromuscular relaxation and cognitive-behavior training can be recommended to prevent cardiovascular disorders.

Common laboratory measures of global health may not be suited to assess, discriminate or predict chronic stress effects on biological systems.

BACKGROUND: There is a longstanding discussion that prolonged psychological stress can have negative somatic effects, especially in respect to endocrinological and immunological changes. Yet, the clinical significance of these findings is still unclear. Patients with prolonged stress should show more signs and symptoms of related illnesses. AIM: The question we like to answer in this study is: are laboratory measures of global health suited to assess, discriminate or predict chronic psychological stress effects on biological systems? METHODS: Included were 50 inpatients who were suffering from post-traumatic embitterment disorder (PTED), a condition that causes persistent and intense psychological distress. They were compared with a group of 50 matched control patients with unselected psychosomatic disorders but no immediate stress and strain. Gender distribution and age were the same in both samples because of the matching (60% women; mean age: 49 years). PTED patients had an average duration of illness of 31.7 (±35.5) months. In the SCL-90 they showed an average GSI score of 1.13 (±0.55) compared with 0.74 (±0.50) in the controls, as indicator of their increased psychological strain. Between groups, we compared the results of 24 laboratory tests, which can be seen as indicators of functioning of all important body systems. RESULTS: There was no significant difference in the results of laboratory tests between groups and especially no indicators for different rates of immunological or inflammatory illnesses. CONCLUSION: Laboratory measures of global health may not be suited to assess, discriminate or predict psychological chronic stress effects on important biological systems.

Decreased serum BDNF levels in patients with epileptic and psychogenic nonepileptic seizures.

OBJECTIVE: Neurotrophins promote neurogenesis and help regulate synaptic reorganization. Their dysregulation has been implicated in a number of neurologic and psychiatric disorders. Previous studies have shown decreased levels of brain-derived neurotrophic factor (BDNF) in the serum of patients with psychiatric disorders such as major depressive disorder (MDD) and conversion disorder (CD). In human patients with temporal lobe epilepsy, there is an increase in both BDNF mRNA and protein levels in surgically resected hippocampi compared to controls. One study of children with epilepsy has found normal to increased serum BDNF levels compared to controls. Plasma [corrected] BDNF levels have not been investigated in adult patients with epileptic seizures (ES). We hypothesized that BDNF would differentiate between ES and psychogenic nonepileptic seizures (PNES). METHODS: We assessed plasma [corrected] BDNF immunoreactivity in 15 patients with ES, 12 patients with PNES, and 17 healthy volunteers. Plasma [corrected] BDNF levels were measured using an enzyme-linked immunoassay. RESULTS: Healthy controls showed higher BDNF levels (4,289 ± 1,810 pg/mL) compared to patients with PNES (1,033 ± 435 pg/mL) (p < 0.001). However, unexpectedly, healthy controls also showed higher levels of BDNF compared to patients with ES without comorbid MDD (977 ± 565 pg/mL) (p < 0.001). CONCLUSIONS: Unlike children, adults with epilepsy appear to have decreased levels of plasma [corrected] BDNF. Reduced plasma [corrected] BDNF levels can be used to differentiate adult patients with ES or PNES from healthy controls. Further human studies are needed to better understand the pathophysiology explaining the decreased plasma [corrected] BDNF levels found in epilepsy and in PNES.

Psychosomatic symptoms as biomarkers: transcending the psyche-soma dichotomy.

Following the advancement in understanding dynamical systems, the author presents a novel metaphor of psychosomatic symptoms as low-dimensional biomarkers. This metaphor, which transcends the old binary of psyche-soma, resonates with classical psychoanalytic concepts and with Matte-Blanco's idea of repetition as indicative of dimensionality reduction. The relevance of this metaphor for explanation, diagnosis, and treatment is illustrated through a case study of a male patient suffering from hyperprolactinemia.

Aging males' symptoms in relation to the genetically determined androgen receptor CAG polymorphism, sex hormone levels and sample membership.

Late-onset hypogonadism describes the co-occurrence of a range of physical, psychological and sexual symptoms in aging men, with the implication that these symptoms are caused by androgen deficiency. Previous investigations examined mostly population samples and did not take into account the testosterone modulating effects of the genetically determined CAG repeat polymorphism (CAGn) of the androgen receptor (AR) gene. This is the first study which investigates aging male symptoms (AMS) in relation to the genetically determined androgen receptor CAG polymorphism, estradiol and testosterone levels in men > or =50 years of age in a healthy population sample (n=100), outpatients of an andrological department (n=76) who presented with sexual and "aging male" symptoms and a psychosomatic/psychiatric sample (n=120) who presented with various psychological and medically unexplained somatic complaints. Although the population sample was significantly older than the two patient groups, they reported significantly fewer AMS and had higher testosterone levels and shorter CAG repeats of the AR. Regression analysis revealed influences of CAGn on the AMS global score and the psychological and somatic subscale only in the two patient samples, while testosterone had some impact on the sexual subscale. Our results suggest that the so-called aging male symptoms show a certain association to androgenicity, but that they are rather unspecific and of multifactorial origin. Other factors contributing to AMS need further clarification.

[Psychoemotional and humoral changes in patients with combined reflux disorders].

AIM: To investigate disorders of psychoemotional functions, humoral regulation (substance P) and duodenal motility (DM) in patients with combined refluxes for their differential correction. MATERIAL AND METHODS: A total of 60 patients with gastroesophageal and duodenogastric refluxes were examined. RESULTS: Patients with reflux disorders had more frequent and severe neurotic reactions. Humoral changes are associated with characteristics of psychoemotional regulation. The risk of subnormal levels of the substance P rises substantially in changes in the scales of anxiety, neurotic depression, hysterical reaction and autonomic disorders. Segmental duodenal motility regresses with lowering of plasmic levels of substance P. CONCLUSION: Patients with combined reflux disorders have psychoemotional disorders, abnormal humoral regulation and duodenal motility necessitating a differential approach to treatment of such patients.

Serum creatine phosphokinase is helpful in distinguishing generalized tonic-clonic seizures from psychogenic nonepileptic seizures and vasovagal syncope.

OBJECTIVE: Distinguishing epileptic generalized tonic-clonic seizures (GTCS) from either psychogenic nonepileptic seizures (PNES) or vasovagal syncope (VVS) is important. In this study, we investigated the use of postictal serum creatine phosphokinase (CPK) concentrations in distinguishing between these events. METHODS: Patients admitted to the Neurology Ward at Namazi Hospital in Shiraz, Iran, with an attack of transient loss of consciousness and abnormal movements witnessed by a neurologist were studied. We categorized the patients into three groups: 20 patients with GTCS, 22 with VVS, and 20 with PNES. A group of 20 normal healthy individuals were included in the study as the control group. Serum CPK concentration was measured 12-15 h after the attack in all patients and at one time in the control group. A P value less than 5% was considered significant. RESULTS: There were no significant differences between the four groups with respect to age and sex. Mean CPK concentrations statistically significantly differed between the four groups, with higher levels in patients with GTCS (P=0.0001). Serum CPK concentration had a sensitivity of 75% and specificity of 86% for the diagnosis of GTCS. CPK concentration was above 160 mg/dl in 75% of patients with GTCS, 15% of patients with PNES, 13.6% of patients with VVS, and 15% of the control group (P=0.0001). The PNES, VVS, and control groups did not statistically significantly differ with respect to CPK concentrations. CONCLUSION: In patients with a recent loss of consciousness and abnormal movements, serum CPK concentration is a useful, practical, and relatively accurate parameter to assist in the differentiation of epileptic seizures from either VVS or PNES.

The role of carbon dioxide (and intracellular pH) in the pathomechanism of several mental disorders. Are the diseases of civilization caused by learnt behaviour, not the stress itself?

The role of carbon dioxide (CO2) is underestimated in the pathomechanism of neuropsychiatric disorders, though it is an important link between psyche and corpus. The actual spiritual status also influences respiration (we start breathing rarely, frequently, irregularly, etc.) causing pH alteration in the organism; on the other hand the actual cytosolic pH of neurons is one of the main modifiers of Ca2+-conductance, hence breathing directly, quickly, and effectively influences the second messenger system through Ca2+-currents. (Decreasing pCO2 turns pH into alkalic direction, augments psychic arousal, while increasing pCO2 turns pH acidic, diminishes arousal.) One of the most important homeostatic function is to maintain or restore the permanence of H+-concentration, hence the alteration of CO2 level starts cascades of contraregulation. However it can be proved that there is no perfect compensation, therefore compensational mechanisms may generate psychosomatic disorders causing secondary alterations in the "milieu interieur". Authors discuss the special physico-chemical features of CO2, the laws of interweaving alterations of pCO2 and catecholamine levels (their feedback mechanism), the role of acute and chronic hypocapnia in several hyperarousal disorders (delirium, panic disorder, hyperventilation syndrome, generalized anxiety disorder, bipolar disorder), the role of "locus minoris resistentiae" in the pathomechanism of psychosomatic disorders. It is supposed that the diseases of civilization are caused not by the stress itself but the lack of human instinctive reaction to it, and this would cause long-lasting CO2 alteration. Increased brain-pCO2, acidic cytosol pH and/or increased basal cytosolic Ca2+ level diminish inward Ca2+-current into cytosol, decrease arousal--they may cause dysthymia or depression. This state usually co-exists with ATP-deficiency and decreased cytosolic Mg2+ content. This energetical- and ion-constellation is also typical of ageing-associated and chronic organic disorders. It is the most important link between depression and organic disorders (e.g. coronary heart disease). The above-mentioned model is supported by the fact that H+ and/or Ca2+ metabolism is affected by several drugs (catecholemines, serotonin, lithium, triaecetyluridine, thyroxine) and sleep deprivation, they act for the logically right direction.

[Psychosomatic concept of hyperthyroidism-Graves type--behavioral and biochemical characteristics].

INTRODUCTION: In this study we test the hypothesis that specific behavioral and biochemical vulnerabilities characterize individuals with hyperthyroidism-Graves type, one of the classically cited "psychosomatic disorders". MATERIAL AND METHODS: The sample included 24 subjects with Graves disease and 34 controls. All participants were evaluated for personality and temperament characteristics and for platelet MAO activity. A smaller group of panic disorder patients was tested with the same set of measures to ensure a validity of the study, especially regarding results on personality tests. RESULTS: Individuals with hyperthyroidism had lower platelet MAO activity and higher scores on histrionic (Hy), depressive (D) and hypochondriac (H) subscale on the MMPI-201 than normal controls. Their TPQ temperament scores were characterized by high Harm Avoidance, whereas other temperament traits were average. Platelet MAO activity was inversely correlated with the MMPI-201 psychopatic deviance scale (Pd) and positively correlated with the TPQ Reward Dependence scale. CONCLUSIONS: Our results provide support for the psychosomatic concept of Graves' disease. Personality features, temperament traits, and platelet MAO activity of hyperthyroid individuals are different from those in normal controls and correspond to those observed in anxiety disorders. We propose that the observed behavioral and biochemical similaritites between hyperthyroid and anxiety disorder patients represent an equicausality phenomenon, where the same underlying heritable factors, such as variable central monoaminergic activity coupled with temperament-related susceptibility to stress, facilitate phenotypic manifestation of a number of psychosomatic and psychialric disorders--including Graves disease. The observed correlations between personality traits and MAO activity provide support for the hypothesized functional relationship between the underlying central monoaminergic activity and temperament traits associated with anxiety, depression, and impulsivity.