Marek Susta

Depression, traumatic stress and interleukin-6

BACKGROUND Recent evidence indicates that various types of interactions between nervous and immune system are important in pathogenesis of depression. These findings show that a significant role in developing depression play pro-inflammatory cytokines that may mediate its psychological, and neurobiological manifestations. Great importance among these cytokine molecules plays interleukin-6 (IL-6). There is growing evidence that this inflammatory process related to depression may be influenced by psychological stress as well as organic inflammatory conditions. These findings suggest that specific influences related to traumatic stress and dissociation could be found in close relationship to increased level of cytokine IL-6. METHODS In the present study we have performed psychometric measurement of depression (BDI-II), traumatic stress symptoms (TSC-40) and dissociation (DES, SDQ-20), and immunochemical measure of serum IL-6 in 40 inpatients with unipolar depression (mean age 42.3+/-6.8). RESULTS The results show that IL-6 is significantly correlated to BDI-II (Spearman R=0.47, p<0.01), TSC-40 (Spearman R=0.32, p<0.05), SDQ-20 (Spearman R=0.34, p<0.05) but not to DES (Spearman R=0.25, p=0.11). CONCLUSION The findings of the present study indicate that increased level of IL-6 in depression could be directly related to symptoms of traumatic stress and somatoform dissociation.

EEG phase synchronization in patients with paranoid schizophrenia

Recent findings suggest that specific deficits in neural synchrony and binding may underlie cognitive disturbances in schizophrenia and that key aspects of schizophrenia pathology involve discoordination and disconnection of distributed processes in multiple cortical areas associated with cognitive deficits. In the present study we aimed to investigate the underlying cortical mechanism of disturbed frontal-temporal-central-parietal connectivity in schizophrenia by examination of the synchronization patterns using wavelet phase synchronization index and coherence between all defined couples of 8 EEG signals recorded at different cortical sites in its relationship to positive and negative symptoms of schizophrenia. 31 adult schizophrenic outpatients with diagnosis of paranoid schizophrenia (mean age 27.4) were assessed in the study. The obtained results present the first quantitative evidence indicating direct relationship between wavelet phase synchronization and coherence in pairs of EEG signals recorded from frontal, temporal, central and parietal brain areas and positive and negative symptoms of schizophrenia. The performed analysis demonstrates that the level of phase synchronization and coherence in some pairs of EEG signals is inversely related to positive symptoms, negative symptoms and general psychopathology in temporal scales (frequency ranges) given by wavelet frequencies (WFs) equal to or higher than 7.56 Hz, and positively related to negative symptoms in wavelet frequencies equal to or lower than 5.35 Hz. This finding suggests that higher and lower frequencies may play a specific role in binding and connectivity and may be related to decreased or increased synchrony with specific manifestation in cognitive deficits of schizophrenia.

Dissociative symptoms and interregional EEG cross-correlations in paranoid schizophrenia

Recent findings indicate that binding and synchronization of distributed activities are crucial for the mechanism of consciousness, and there is increased evidence that disruptions in feature binding produce disintegration of consciousness in schizophrenia. These data suggest that the disrupted binding and disintegration of consciousness could be related to dissociation, which is historically linked to Bleulers concept of splitting in schizophrenia. In the present study we aimed to investigate relations among electroencephalogram (EEG) activities of cortical sites and used psychometric measures of positive and negative schizophrenia symptoms (Positive and Negative Syndrome Scale) and the Dissociative Experiences Scale (DES) in 58 patients with paranoid schizophrenia. The results show statistically significant Spearman correlations of the DES with cross-correlation function in nine (of 16) EEG pairs. Positive symptoms display significant Spearman correlation with mean of cross-correlation function in only one EEG pair (F4-C4). Results of the Mann-Whitney test between patients with higher (DES > or = 30) and lower dissociation show statistically significant differences between the groups for cross-correlations in nine EEG pairs. The results of this study provide the first supportive evidence for a negative relationship between cross-correlation indices and symptoms of dissociation in schizophrenia.

Dissociation, cognitive conflict and nonlinear patterns of heart rate dynamics in patients with unipolar depression.

Recent findings in cognitive neuroscience indicate that activation of anterior cingulate cortex (ACC) is related to detecting cognitive conflict. Conflict related ACC activation elicits responses in central autonomic network which can be assessed by psychophysiological measures such as heart rate variability (i.e. beat to beat R-R intervals--RRI). Recent findings in neuroscience also suggest that cognitive conflict is related to specific nonlinear chaotic changes of the signal generated by the neural systems. The present study used Stroop word-colour test as an experimental approach to the study of cognitive conflict in connection with RRI measurement, psychometric measurement of dissociation (DES) and calculation of largest Lyapunov exponents in nonlinear data analysis of RRI time series in 40 patients with unipolar depression and 35 healthy controls. Significant correlation 0.58 (p<0.01) between largest Lyapunov exponents and DES found in depressive patients indicate that cognitive conflict related neural interference during conflicting Stroop task is closely related to dissociative processes. These results present first supportive evidence that degree of chaos could be related to dissociation.

Sensitization, epileptic-like symptoms and local synchronization in patients with paranoid schizophrenia

Recent findings indicate that changes in synchronization of neural activities underlying sensitization and kindling could be more comprehensively understood using nonlinear methods. With this aim we have examined local synchronization using novel measure of coarse-grained information rate (CIR) in 8 EEG signals recorded at different cortical areas in 44 patients with paranoid schizophrenia. The values of local synchronization that could reflect sensitization related changes in EEG activities of cortical sites were then related to psychometric measures of epileptic-like symptoms and positive and negative schizophrenia symptoms (PANSS). While no significant correlations between CIR and positive and negative symptoms have been found, statistically significant relationships described by Spearman correlation coefficients between CIR indices and results of LSCL-33 have been observed in 7 (of 8) EEG channels (r in the range from 0.307 to 0.374, p<0.05). Results of this study provide first supportive evidence for the relationship between local synchronization measured by CIR and epileptic-like symptoms in schizophrenia.

Diagnosis and management of central hypersomnias

Central hypersomnias are diseases manifested in excessive daytime sleepiness (EDS) not caused by disturbed nocturnal sleep or misaligned circadian rhythms. Central hypersomnias includes narcolepsy with and without cataplexy, recurrent hypersomnia, idiopathic hypersomnia, with and without long sleep time, behaviorally induced insufficient sleep syndrome, hypersomnia and narcolepsy due to medical conditions, and finally hypersomnia induced by substance intake. The Epworth Sleepiness Scale is a subjective tool mostly used for EDS assessment, while the Multiple Sleep Latency Test serves as an objective diagnostic method for narcolepsy and idiopathic hypersomnias. As for symptomatic therapy of EDS, the central nervous system stimulants modafinil and methylphenidate seem to work well in most cases and in narcolepsy and Parkinson’s disease; sodium oxybate also has notable therapeutic value.

Traumatic Stress, Dissociation, and Limbic Irritability in Patients with Unipolar Depression Being Treated with SSRIs

Recent evidence suggests that stressful experiences may be related to deficits in inhibitory functions and temporolimbic epileptic-like activity. The latter may produce psychosensory seizure-like symptoms that may also appear in nonepileptic conditions. This study assesses whether the increased presence of the seizure-like symptoms in 113 unipolar depressive patients treated with SSRIs is associated with significantly more severe symptoms of depression, traumatic stress, and dissociation in comparison with 86 healthy controls. Results indicate that seizure-like symptoms in depressive patients have significant association with depression, symptoms of dissociation, and traumatic stress. This association suggests that processess generating seizure-like symptoms may be related to symptoms of depression, traumatic stress, and dissociation.

An increase in substance misuse rather than other mental disorders has led to increased forensic treatment rates in the Czech Republic

It is suggested that limited access to appropriate care forces psychiatric patients towards forensic treatment or to the prison system. According to our data, the number of prisoners, the number of hospitalized psychiatric patients (from 1987 to 2007), the number of court ordered forensic treatments in the Czech Republic (from 1991 to 2007), and the rate of people in psychiatric and sex offender forensic treatment has remained constant. However, an increase (162%) in number of treatments imposed for abusing illicit drugs did occur during this period. This increase contributed to the correlation between both the number of sentences given for protective treatment and the number of all sentenced persons (Pearson cor. 0.647, p < 0,001) and the number of prisoners (Pearson cor. 0.798, p < 0,001). The analysis of all admissions to a forensic facility from a catchment area of 1,260,318 inhabitants shows no increase in number of admission between 2002 and 2007. The same data prove that the number of patients ordered to psychiatric and sexology treatment remained steady and did not reflect changes in the number of prisoners or number of hospitalized patients. This could be explained by a high number of psychiatric hospitalizations protecting the patients from deteriorating to criminal behaviour.

Dissociative States and Chaotic Patterns of Electrodermal Activity During Associative Experiment

A dynamic concept of schizophrenia linked to the theory of dissociated complexes was experimentally demonstrated by Jung in “The Psychology of the Dementia Praecox”. According to him, during schizophrenia the psyche is split-off into a plurality of autonomous complexes and the whole personality is pathologically disintegrated. This pathological disintegration is frequently observed in schizophrenic associations that display “chaotic randomness”. The “chaotic randomness” does not mean a true randomness because schizophrenic associations are not without underlying order and causality. An important aspect of schizophrenic dissociation is an extreme subjective sensitivity. These two signs of schizophrenic associations are analogical to known characteristics of chaotic nonlinear dynamical systems. The hypothesis tested in the present study is that neural chaos, calculated from electrodermal activity (EDA), during rest and word-association process is more prominent in schizophrenic patients compared to healthy controls. To test the hypothesis we have measured EDA during the experiment performed in 25 schizophrenic patients and 21 healthy control subjects. Results of nonlinear and statistical analysis indicate that the neural chaos characterized by positive largest Lyapunov exponents during rest and the word-association process is significantly higher in the schizophrenic patients. These data suggest that pseudo-randomness of schizophrenic associations and increased sensitivity related to dissociative states might be linked to the chaotic neural dynamics.

CHAOTIC PATTERNS OF AUTONOMIC ACTIVITY DURING HYPNOTIC RECALL

Chaoticneural dynamics likely emerge in cognitive processes and may present time periods that are extremely sensitive to influences affecting the neural system. Recent findings suggest that this sensitivity may increase during retrieval of stressful emotional experiences reflecting underlying mechanism related to consolidation of traumatic memories. In this context, hypnotic recall of anxiety memories in 10 patients, simultaneously with ECG measurement was performed. The same measurement was performed during control cognitive task in 8 anxiety patients and 22 healthy controls. Nonlinear data analysis of ECG records indicates significant increase in the degree of chaos during retrieval of stressful memory in all the patients. The results suggest a role of chaotic neural dynamics during processing of anxiety-related stressful memories.