[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.

Plasma homocysteine levels in young male patients in the exacerbation and remission phase of schizophrenia.

High levels of homocysteine (Hcy) were suggested to contribute to the pathogenesis of schizophrenia. Recent investigations have shown that treatment with folic acid, vitamin B-12 and pyridoxine are effective in reducing Hcy levels while concomitantly reducing the score of positive and negative symptoms in schizophrenic patients. In addition to the availability of nutrients (mainly folate, vitamins B6 and B12), plasma Hcy concentrations are dependent on complex metabolic regulation that could be disrupted in schizophrenia. This study was designed to test the influence of disease activity on plasma Hcy levels. Plasma Hcy concentrations were measured in male chronic schizophrenic patients with a predominantly positive (SCH (+)) or predominantly negative (SCH (-)) syndrome in schizophrenia immediately upon admission to the hospital (exacerbation phase) and one month later (remission phase). During this period patients received antipsychotic medications without vitamin therapy. The effects of age, duration of illness, folate and B12 concentrations, as well as smoking and coffee consumption habits on the observed changes were evaluated. Age- and sex-matched subjects were included in the control group. In the control group plasma Hcy concentration was 8.75+/-1.84 micromol/L. In the exacerbation phase plasma Hcy concentrations were significantly increased both in SCH (+) (14.91+/-6.19 micromol/L) and SCH (-) groups (12.8+/-3.27 micromol/L). There was no difference in plasma Hcy concentrations between SCH (+) and SCH (-) patients. Serum folate and B12 concentrations were not significantly different in any of the investigated groups of subjects. The plasma Hcy concentrations could not be correlated with age, duration of illness, the score of positive symptoms or the concentration of folate and vitamin B12. A positive correlation was found between plasma Hcy level and score of negative symptoms in both groups of patients. No correlation was found between smoking or coffee consumption habits and plasma Hcy concentrations. All patients exhibited decreased plasma Hcy levels in the remission phase of the illness, with a mean decrease of 2.68+/-1.57 micromol/L. Folate and B12 levels did not differ in the exacerbation and remission phases of the illness. The significant decrease of plasma Hcy levels, without changes in folate and vitamin B12 concentrations in the remission phase of schizophrenia, could indicate an influence of a pathogenetic process involved in schizophrenia on Hcy metabolism.

Baseline temperature in an animal model of schizophrenia: long-term effects of perinatal phencyclidine administration.

Phencyclidine (PCP), a dissociative anaesthetic, acts as a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist. PCP is a psychostimulant capable of producing both positive and negative symptoms of schizophrenia, including cognitive dysfunction in normal humans. Perinatal phencyclidine administration to rats has been widely accepted as an animal model of schizophrenia. It has been known for a long time that schizophrenia patients may develop various thermoregulatory disturbances. The aim of this study was to assess the acute effects of phencyclidine administration on the temperature of newborn rats, the long-term effects on the baseline temperature of perinatal phencyclidine administration and the effects of a PCP challenge on the temperature of adult perinatally treated rats. The animals were treated on the 2nd, 6th, 9th and 12th postnatal (PN) days with either phencyclidine (10 mg/kg) or saline. The interscapular skin temperature was measured during the first 40 postnatal days and subsequently the colonic temperature until PN day 62. The immediate effect of phencyclidine administration to pups was a significant decrease of the body temperature, while the application of PCP to adult rats perinatally treated with either saline or PCP caused a significant increase of the baseline temperature. Perinatal phencyclidine administration to rat pups produced a long lasting effect on the baseline temperature. It can be concluded that the nature of the response to acute phencyclidine administration differs between newborn and adult rats. Further experiments are necessary in order to clarify the role of specific neurotransmitter systems in the changes of temperature regulation provoked by phencyclidine administration.

[Executive functions in young patients with unipolar depression].

Neuropsychological deficits associated with unipolar depression are seen in a broad range of cognitive domains. Executive deficits may be prominent in depression. Investigation of executive functions in younger adult patients with unipolar depression has been the focus of our study. Twenty-two consecutively depressive inpatients (24-36 years) and 21 healthy control subjects, matched on age, gender, education and verbal IQ were included in the study. Neuropsychological tests for executive functions were applied to all subjects. Unipolar young depressives showed significantly reduced number of completed categories and more trials for completion of the first category on Wisconsin Card Sorting Test (WCST). No difference of tasks assessing the short-term memory, total errors on WCST, perseverative and non-perseverative errors, and of both phonemic and semantic conditions of verbal fluency was found between groups. The results suggested that unipolar depressives had specific cognitive style characterized by "negative cognitive set" (stronger negative reaction to negative feedback) and by failure to use negative feedback to improve their performance.

[Panic disorder--psychobiological aspects of personality dimensions].

INTRODUCTION: Attempts to understand the underlying mechanisms of association between psychological factors and panic disorder have been mostly based on psychodynamic description. Evidence of the importance of serotonergic (5-HT) system in panic disorder (PD), however, has substanti ally increased in recent years. OBJECTIVE: The objective of our study was to determine whether there was a specific personality profile of panic disorder patients and how it was related to possible neurobiological mechanisms underlying personality dimensions. PATIENTS AND METHODS: Sample consisted of 14 inpatients with ICD-X diagnosis of panic disorder and 34 healthy control subjects. Personality dimensions were assessed by Minnesota Multiphasic Personality Inventory (MMPI-201) and Tridimensional Personality Questionnaire (TPQ). To assess central 5-HT function, platelet monoamine-oxidase (MAO) activity was measured. RESULTS: In panic disorder group, higher scores of histrionic, depressive and hypochondriac subscales and significant increase of harm avoidance (HA) scale as well as low MAO activity were found. Negative correlation was established between MAO activity and psychopathic deviance MMPI scale. CONCLUSION: The obtained results might indicate a specific personality profile of patients with panic disorder, which is characterized by high neuroticism, fearfulness, inhibition, shyness and apprehensive worry. Low MAO activity and high HA scores possibly indicate underlying hyperserotonergic state. The observed correlation between personality traits and MAO activity provide additional support for the hypothesized functional relationship between underlying central monoaminergic activity and temperament traits associated with anxiety, depression and impulsivity.

[Neuropsychological profile of patients with bipolar depression in remission].

AIM: To determine if the patients with bipolar affective disorder, after the depressive phase, would exhibit cognitive impairment in remission. METHODS: Twenty-three euthymic patients with bipolar disorder were matched, on a case-by-case basis, to twenty-one healthy subjects in the control group, for the presence of the symptoms of depression. The patients and the control group were tested with a battery of neuropsychological tests. RESULTS: Impairments were found in the patients compared with the control group in tests of verbal learning and memory and in tests of executive function. Verbal learning and memory, as well as executive functions, did not correlate either with the clinical indices of patients, or with the demographic and baseline clinical measures of depression. CONCLUSION: Impaired verbal learning and memory and executive functions may represent a trait rather than the state variables in bipolar disorder.

Carbamazepine for acute psychosis with EEG abnormalities.

AIM: To investigate the efficacy of carbamazepine as adjuvant drug therapy in acute paranoid psychosis with associated EEG abnormalities, compared to sole antipsychotic treatment. METHODS: Eleven medication-naive patients, diagnosed with acute paranoid psychosis with associated EEG abnormalities, were divided into two treatment groups: sole fluphenazine group, with flexible dosing of 5-10 mg/day (n=6), and carbamazepine group (n=5) with the addition of carbamazepine (600 mg/day) to fluphenazine treatment. Clinical Global Impression (CGI), Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), and EEG were assessed on the baseline and after 6 weeks of treatment. Paired and two-tailed t-tests were used for statistical significance. RESULTS: All the patients showed significant improvement of mental state after 6 weeks of treatment with no significant differences in CGI, BPRS, and total SANS scores in relation to the therapy with carbamazepine. Nevertheless, after 6 weeks of the treatment, EEG findings were significantly better in carbamazepine group, in relation to the findings from the onset of the treatment, as well as in comparison to sole fluphenazine group. CONCLUSION: Although carbamazepine stabilized abnormal brain electrical activities it seemed that the associated EEG abnormalities were not significant for acute psychosis observed. These preliminary results suggested that there was no convincing evidence that carbamazepine was efficient as the augmentation of antipsychotic treatment for patients with both acute paranoid psychosis and EEG abnormalities.

The effects of fluoxetine on cognitive functions in animal model of Alzheimer's disease.

Cognitive impairment is the hallmark of progressive neurodegenerative process observed in Alzheimer's disease (AD). Acetylcholine (Ach) deficiency is considered to be one of major factors underlying cognitive dysfunction in AD. Several lines of evidence suggest that sigma receptor ligands can elevate Ach extracellular levels in prefrontal cortex rat brain. Since all selective serotonin reuptake inhibitors (SSRIs) show affinity for sigma receptors, it has been assumed that fluoxetine could improve cognition in AD. The aim of study was to investigate the effects of fluoxetine on learning and memory processes in experimental model of AD in rats. Experiments were carried out on adult male Wistar rats divided into three major groups: intact control, sham-operated and nucleus basalis-lesioned rats. Bilateral electrolytic lesions of nucleus basalis Meynert (NBM) (experimental model of AD) were made by 1 mA direct current passed through unipolar electrode for 30 sec. The behavioural test (active avoidance) was performed after recovery period of 10 days from the lesion. The effects of several doses of fluoxetine (3, 5 and 10 mg/kg) on these processes were investigated after 7 days of administration. The results showed that lesion of NBM in rats markedly impaired learning and memory processes compared with controls (intact and sham). Fluoxetine in 5 mg/kg daily doses significantly improved (p<0.05) these processes in lesioned animals. These findings suggest that fluoxetine could be useful as symptomatic therapy in the treatment of AD.

[Correlation of neurodevelopmental disorders in schizophrenia]. / Korelati poremecaja neurorazvoja kod shizofrenije.

Contemporary aetiopathogenetic considerations, based on neuro-imaging, genetic and developmental neurobiology studies, suggest neurodevelopmental origin of schizophrenia. Several lines of evidence including structural abnormalities on in vivo brain imaging, the excess of prenatal and obstetric complications and the association of congenital and minor physical anomalies with schizophrenia, strongly indicate the neurodevelopmental pathogenesis of schizophrenia. On the other hand, controversial concept of psychotic continuum suggests schizophrenia and depression sharing the same genetic contribution to the pathogenesis. If this would be the case, depression could also be considered as neurodevelopmental disorder. The aims of the study were to investigate the association between: a) pregnancy and birth complications (PBC), and b) minor physical anomalies (MPA) and schizophrenia or depression. Experimental groups consisted of 60 schizophrenic, 28 major depression patients and 30 healthy controls. All patients were diagnosed according to DSM-IV. Schizophrenic group was divided with regard to PANSS score into positive (n = 32) and negative form (n = 28) subgroups. PBC informations were gathered from maternal recall while MPA were examined by using Waldrop scale for adults. The results showed that negative and positive schizophrenic subgroups had significantly more PBC than depressive group (p < 0.05), as well than controls (p < 0.001; p < 0.05; respectively). There was nonsignificant trend for more PBC in negative than in positive subgroup. All schizophrenic patients had higher rates of MPA than depressives (p < 0.05). This trend for more MPA was not significant in comparison with healthy controls. These findings suggest that schizophrenia, especially its negative forms, could be considered as a member of the spectrum of neurodevelopmental disorders, which does not seem to be the case with depression. PBC and MPA could also be valuable in evaluation of risks for schizophrenia and possible predictive indicators of its development.

[Volumetric analysis of gray matter, white matter and cerebrospinal fluid space in schizophrenia]. / Volumetrijska analiza sive mase, bele mase i prostora cerebrospinalne tecnosti u shizofreniji.

Schizophrenia is characterized by diffuse brain abnormalities, some of them involving volumes of three intracranial compartments: gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF). Novel methods, such as Statistical Parametrical Mapping, provide an automated means of comparing structural features across high quality MRI scans and the measurement based on the principles of voxel based morphometry. For the purposes of the present study, we selected sex balanced group of young adults with recent onset illness to assess the effects of the illness on the volumes of compartments and also to minimize the effects of chronicity, medication, sex and aging. Sixty-four subjects were selected from a larger sample (inclusion criteria: age range 18-31). Thirty-one had DSM IV diagnosis of schizophrenia or schizoaffective disorder, 33 were controls. T1 weighted MRI images were acquired on two scanners (1.5T both): a) fast gradient echo sequence, FLASH, 40 msec repetition time, 5 ms echo time, 40 degree flip angle and b) turbo gradient echo, 12 msec repetition time, 4 msec echo time, 20 degree flip angle, 1 excitation). The resulting data set consisted of: a) 128 consecutive slices with 1.17 mm thickness and 256 x 256 pixels per slice and b) 160 consecutive slices of 1 mm thickness and 256 x 256 pixels per slice. All 64 images were processed by ANALZYE, and normalized and segmented by SPM99. Following the automatic segmentation of the images into the three intracranial compartments, volumetry was performed based on the principles of voxel analysis. Results were expressed relative to whole brain volume, and MANOVA analyses were performed to correct the confounding effects of MRI acquisition center differences and age difference between diagnostic groups. Young adults with recent onset schizophrenia had 6% reduction in GM volume and 14% increase in the volume of CSF, after all confounders were included into analyses (MANCOVA: p = 0.006 and 0.0002, respectively). No significant changes in WM volume were evident. In comparison to a few similar studies published recently, all results yielded similar scores regarding effects of recent onset illness and young adult population, thus confirming the reliability of the procedure. In conclusion, global neuropil reduction was discussed as a consequence of the cortical neurodevelopmental disgenesis. It was suggested that neuropil reduction i.e. synaptic and dendritic changes were to induce functional abnormalities and the expression of schizophrenia.

Substrate kinetics of erythrocyte membrane Na,K-ATPase and lipid peroxides in schizophrenia.

Previous studies have shown decreased erythrocyte membrane (EM) Na,K-ATPase activity in chronic patients suffering from schizophrenia (SCH). There are no data about changes at the onset of psychosis and enzyme kinetics. Increased lipid peroxidation could be responsible for alterations in Na,K-ATPase activity. Substrate kinetics pattern of EM Na,K-ATPase and levels of lipid peroxides in plasma and erythrocytes were measured in (1) patients with first episode of psychosis (n=20) before medication and after the first 3 weeks of treatment, (2) chronic medicated schizophrenic patients (n=52) in the exacerbation phase, and (3) age- and sex-matched control subjects (n=30). All patients were assigned to groups with predominantly positive or predominantly negative symptoms on the basis of their scores on Positive and Negative Syndrome Scale (PANSS). In first-episode patients with predominantly negative symptoms before treatment, uncompetitive inhibition of Na,K-ATPase was noticed. The first-episode patients with predominantly positive symptoms had increased enzyme catalytic activity. After 3 weeks of treatment, activities were normalized in both groups. Among chronic patients, uncompetitive inhibition was found only in patients with predominantly negative symptoms. Plasma lipid peroxides (thiobarbituric acid-reactive substances [TBARS]) were elevated in both groups of patients with first episode of psychosis. Despite the presence of peroxidative injury indicative for the loss of membrane phospholipid essential fatty acids, the activities of Na,K-ATPase differ between SCH (+) and SCH (-) patients.