Cytokines, diabetes mellitus and psychopathology: a challenging combination.

OBJECTIVES: The aim of this study was to investigate the association of IL-6, IL-12, and TNF-α with trait and state psychological factors in type 2 diabetic patients. DESIGN: Patients were divided in two groups. Group A consisted of 86 controlled diabetic patients (HbA1c<7) and the Group B consisted of 45 uncontrolled diabetic patients (HbA1c ≥ 7). SETTINGS: During the initial phase of the study (T0), blood samples were taken for measuring IL-6, IL-12 and TNF-α serum levels as well as a battery of psychometric instruments. One year later (T1), the uncontrolled diabetic patients were re-evaluated with the use of the same psychometric instruments and with the identical blood analysis. RESULTS: The average values of tnf-α were significantly different among controlled (7.73 ± 5.51) and uncontrolled patients (9.29 ± 4.52) at a significance level of 5% (p=0.009). Controlled diabetic patients show a statistically significant relationship between IL-6 and neuroticism (rp=0.303, p=0.010), and between IL-12 and psychotism, (rsp=0.382, p=0.001). Controlled diabetic patients show a statistically significant relationship between IL-12 and the act out hostility (rsp=-0.307, p=0.009). The scores of the psychometric tests differ significantly between the first and second evaluation. Acting out hostility and the direction of hostility increased when HbA1c values fell below the threshold of 7, while the total hostility index, as well as all other scales, dropped when patients controlled their metabolic profile. CONCLUSIONS: The present results provide evidence that IL-6, IL-12 and TNF-α are closely related to the course and treatment of type 2 diabetes.

Using Electroencephalogram-Extracted Nonlinear Complexity and Wavelet-Extracted Power Rhythm Features during the Performance of Demanding Cognitive Tasks (Aristotle's Syllogisms) in Optimally Classifying Patients with Anorexia Nervosa.

Anorexia nervosa is associated with impaired cognitive flexibility and central coherence, i.e., the ability to provide an overview of complex information. Therefore, the aim of the present study was to evaluate EEG features elicited from patients with anorexia nervosa and healthy controls during mental tasks (valid and invalid Aristotelian syllogisms and paradoxes). Particularly, we examined the combination of the most significant syllogisms with selected features (relative power of the time-frequency domain and wavelet-estimated EEG-specific waves, Higuchi fractal dimension (HFD), and information-oriented approximate entropy (AppEn)). We found that alpha, beta, gamma, theta waves, and AppEn are the most suitable measures, which, when combined with specific syllogisms, form a powerful tool for efficiently classifying healthy subjects and patients with AN. We assessed the performance of triadic combinations of "feature-classifier-syllogism" via machine learning techniques in correctly classifying new subjects in these two groups. The following triads attain the best classifications: (a) "AppEn-invalid-ensemble BT classifier" (accuracy 83.3%), (b) "Higuchi FD-valid-linear discriminant" (accuracy 75%), (c) "alpha amplitude-valid-SVM" (accuracy 83.3%), (d) "alpha RP-paradox-ensemble BT" (accuracy 85%), (e) "beta RP-valid-ensemble" (accuracy 85%), (f) "gamma RP-valid-SVM" (accuracy 85%), and (g) "theta RP-valid-KNN" (accuracy 80%). Our findings suggest that anorexia nervosa has a specific information-processing style across reasoning tasks in the brain as measured via EEG activity. Our findings also contribute to further supporting the view that entropy-oriented, i.e., information-based features (the AppEn measure used in this study) are promising diagnostic tools (biomarkers) in clinical applications related to medical classification problems. Furthermore, the main EEG-specific frequency waves are extremely enhanced and become powerful classification tools when combined with Aristotle's syllogisms.

The association of the metabolic profile in diabetes mellitus type 2 patients with obsessive-compulsive symptomatology and depressive symptomatology: new insights.

OBJECTIVE: The aim of the present study was to explore the relationship between diabetes mellitus type 2, Obsessive- compulsive disorder (OCD) symptomatology and depressive symptomatology with the metabolic profile of diabetic patients. METHODS: One hundred and thirty-one diabetic patients were randomly selected. In the first assessment all participants completed the Zung Self Rating Scale (ZUNG) and the Maudsley O-C Inventory Questionnaire (MOCI). After 1 year, diabetic patients that were initially uncontrolled (n = 31) (HbA1c > 7) were re-evaluated by the same psychometric tools. From those 31 patients, 10 had managed to control their metabolic profile. RESULTS: In the first evaluation MOCI and the sub-scale of slowness were statistically related with the diabetic profile (controlled, HbA1c ≤ 7; uncontrolled, HbA1c > 7), with uncontrolled patients scoring significantly higher on the overall MOCI score and the factor of slowness of MOCI scale (P = 0.028). The analysis revealed a positive association between depressive symptomatology (P = 0.004) and obsessive-compulsive disorder symptomatology (P < 0.001) and the metabolic profile of the patients. In the second evaluation the patients that managed to control their metabolic profile scored lower in both ZDRS and MOCI, although these differences in scores failed to reach significance levels were indicative of a tendency. CONCLUSIONS: The present results provide initial evidence that diabetes mellitus type 2 is associated with obsessive-compulsive disorder symptomatology and depressive symptomatology.

Effects of wi-fi signals on the p300 component of event-related potentials during an auditory hayling task.

The P300 component of event-related potentials (ERPs) is believed to index attention and working memory (WM) operation of the brain. The present study focused on the possible gender-related effects of Wi-Fi (Wireless Fidelity) electromagnetic fields (EMF) on these processes. Fifteen male and fifteen female subjects, matched for age and education level, were investigated while performing a modified version of the Hayling Sentence Completion test adjusted to induce WM. ERPs were recorded at 30 scalp electrodes, both without and with the exposure to a Wi-Fi signal. P300 amplitude values at 18 electrodes were found to be significantly lower in the response inhibition condition than in the response initiation and baseline conditions. Independent of the above effect, within the response inhibition condition there was also a significant gender X radiation interaction effect manifested at 15 leads by decreased P300 amplitudes of males in comparison to female subjects only at the presence of EMF. In conclusion, the present findings suggest that Wi-Fi exposure may exert gender-related alterations on neural activity associated with the amount of attentional resources engaged during a linguistic test adjusted to induce WM.

Periodic Catatonia: Long-term Treatment With Lamotrigine: A Case Report.

Periodic catatonia is a rare form of catatonia, characterized by episodes occurring in a cyclic pattern with clinical features of combined stupor and excitement, with intervals of remission. Although periodic catatonia is not common, it is an urgent condition, requiring hospitalization for evaluation and treatment. The management of periodic catatonia is quite challenging, mainly because of the unknown pathophysiological mechanisms involved in the onset of this clinical entity, which are less clear than in other forms of catatonia. Although positive trials of several medications in the acute phase of periodic catatonia have been published, available literature concerning the prevention of recurrent catatonic episodes is scarce. Here, we present the case of a patient with periodic catatonia in which long-term treatment with lamotrigine appears to have acted prophylactically in reducing the occurrence and severity of new catatonic episodes. A better understanding of the mechanisms involved in the pathophysiology of periodic catatonia and increasing psychiatrists' and physicians' awareness of the presentation of this clinical entity could be of benefit in shedding light on the most appropriate treatment approach. However, further clinical studies are needed before any firm recommendations can be made.

Complexity analysis of the brain activity in Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) due to cognitive loads/demands induced by Aristotle's type of syllogism/reasoning. A Power Spectral Density and multiscale entropy (MSE) analysis.

OBJECTIVE: We aim to investigate whether EEG dynamics differ in adults with ASD (Autism Spectrum Disorders), ADHD (attention-deficit/hyperactivity disorder), compared with healthy subjects during the performance of an innovative cognitive task: Aristotle's valid and invalid syllogisms. We follow the Neuroanatomical differences type of criterion in assessing the results of our study in supporting or not the dual-process theory of Kahneman, 2011) (Systems I & II of thinking). METHOD: We recorded EEGs from 14 scalp electrodes in 30 adults with ADHD, 30 with ASD and 24 healthy, normal subjects. The subjects were exposed in a set of innovative cognitive tasks (inducing varying cognitive loads), the Aristotle's four types of syllogism mentioned above. The multiscale entropy (MSE), a nonlinear information-theoretic measure or tool was computed to extract features that quantify the complexity of the EEG. RESULTS: The dynamics of the curves of the grand average of MSE values of the ADHD and ASD participants was significantly in higher levels for the majority of time scales, than the healthy subjects over a number of brain regions (electrodes locations), during the performance of both valid and invalid types of syllogism. This result is seemingly not in accordance of the broadly accepted 'theory' of complexity loss in 'pathological' subjects, but actually this is not the case as explained in the text. ADHD subjects are engaged in System II of thinking, for both Valid and Invalid syllogism, ASD and Control in System I for valid and invalid syllogism, respectively. A surprising and 'provocative' result of this paper, as shown in the next sections, is that the Complexity-variability of ASD and ADHD subjects, when they face Aristotle's types of syllogisms, is higher than that of the control subjects. An explanation is suggested as described in the text. Also, in the case of invalid type of Aristotelian syllogisms, the linguistic and visuo-spatial systems are both engaged ONLY in the temporal and occipital regions of the brain, respectively, of ADHD subjects. In the case of valid type, both above systems are engaged in the temporal and occipital regions of the brain, respectively, of both ASD and ADHD subjects, while in the control subjects only the visuo-spatial type is engaged (Goel et al., 2000; Knauff, 2007). CONCLUSION: Based on the results of the analysis described in this work, the differences in the EEG complexity between the three groups of participants lead to the conclusion that cortical information processing is changed in ASD and ADHD adults, therefore their level of cortical activation may be insufficient to meet the peculiar cognitive demand of Aristotle's reasoning. SIGNIFICANCE: The present paper suggest that MSE, is a powerful and efficient nonlinear measure in detecting neural dysfunctions in adults with ASD and ADHD characteristics, when they are called on to perform in a very demanding as well as innovative set of cognitive tasks, that can be considered as a new diagnostic 'benchmark' in helping detecting more effectively such type of disorders. A linear measure alone, as the typical PSD, is not capable in making such a distinction. The work contributes in shedding light on the neural mechanisms of syllogism/reasoning of Aristotelian type, as well as toward understanding how humans reason logically and why 'pathological' subjects deviate from the norms of formal logic.

Differences in Performance of ASD and ADHD Subjects Facing Cognitive Loads in an Innovative Reasoning Experiment.

We aim to investigate whether EEG dynamics differ in adults with ASD (Autism Spectrum Disorders) and ADHD (attention-deficit/hyperactivity disorder) compared with healthy subjects during the performance of an innovative cognitive task, Aristotle's valid and invalid syllogisms, and how these differences correlate with brain regions and behavioral data for each subject. We recorded EEGs from 14 scalp electrodes (channels) in 21 adults with ADHD, 21 with ASD, and 21 healthy, normal subjects. The subjects were exposed in a set of innovative cognitive tasks (inducing varying cognitive loads), Aristotle's two types of syllogism mentioned above. A set of 39 questions were given to participants related to valid-invalid syllogisms as well as a separate set of questionnaires, in order to collect a number of demographic and behavioral data, with the aim of detecting shared information with values of a feature extracted from EEG, the multiscale entropy (MSE), in the 14 channels ('brain regions'). MSE, a nonlinear information-theoretic measure of complexity, was computed to extract a feature that quantifies the complexity of the EEG. Behavior-Partial Least Squares Correlation, PLSC, is the method to detect the correlation between two sets of data, brain, and behavioral measures. -PLSC, a variant of PLSC, was applied to build a functional connectivity of the brain regions involved in the reasoning tasks. Graph-theoretic measures were used to quantify the complexity of the functional networks. Based on the results of the analysis described in this work, a mixed 14 × 2 × 3 ANOVA showed significant main effects of group factor and brain region* syllogism factor, as well as a significant brain region* group interaction. There are significant differences between the means of MSE (complexity) values at the 14 channels of the members of the 'pathological' groups of participants, i.e., between ASD and ADHD, while the difference in means of MSE between both ASD and ADHD and that of the control group is not significant. In conclusion, the valid-invalid type of syllogism generates significantly different complexity values, MSE, between ASD and ADHD. The complexity of activated brain regions of ASD participants increased significantly when switching from a valid to an invalid syllogism, indicating the need for more resources to 'face' the task escalating difficulty in ASD subjects. This increase is not so evident in both ADHD and control. Statistically significant differences were found also in the behavioral response of ASD and ADHD, compared with those of control subjects, based on the principal brain and behavior saliences extracted by PLSC. Specifically, two behavioral measures, the emotional state and the degree of confidence of participants in answering questions in Aristotle's valid-invalid syllogisms, and one demographic variable, age, statistically and significantly discriminate the three groups' ASD. The seed-PLC generated functional connectivity networks for ASD, ADHD, and control, were 'projected' on the regions of the Default Mode Network (DMN), the 'reference' connectivity, of which the structural changes were found significant in distinguishing the three groups. The contribution of this work lies in the examination of the relationship between brain activity and behavioral responses of healthy and 'pathological' participants in the case of cognitive reasoning of the type of Aristotle's valid and invalid syllogisms, using PLSC, a machine learning approach combined with MSE, a nonlinear method of extracting a feature based on EEGs that captures a broad spectrum of EEGs linear and nonlinear characteristics. The results seem promising in adopting this type of reasoning, in the future, after further enhancements and experimental tests, as a supplementary instrument towards examining the differences in brain activity and behavioral responses of ASD and ADHD patients. The application of the combination of these two methods, after further elaboration and testing as new and complementary to the existing ones, may be considered as a tool of analysis in helping detecting more effectively such types of disorders.

Early auditory-evoked potentials in body dysmorphic disorder: An ERP/sLORETA study.

Body dysmorphic disorder (BDD) is characterized by excessive preoccupation with imagined or slight physical defects in appearance. BDD is associated with cognitive impairments (attention, visual processing). Our study aims to evaluate the early neural responses (N100, P200) to prepulse inhibition (PPI) and prepulse facilitation (PPF), to investigate attentional processing of BDD in the auditory domain. Fifty-five adults took part: 30 BDD patients and 25 healthy controls. We compared their brain responses to PPI and PPF by analyzing global field power (GFP), event-related potentials (ERPs) and their respective sources. BDD exhibited reduced N100 amplitudes compared to healthy controls in response to the startle tone elicited by both PPI and PPF, potentially suggesting impaired allocation of attention. Interestingly, the lower the GFP at the N100, the higher the BDD severity. Source reconstruction analysis showed reduced activation for BDD during the N100 time window in PPI. Scalp responses and source activations in PPI were decreased overall compared to PPF, confirming the gating effect of PPI. We provided evidence that the N100 may serve as an electrophysiological marker of BDD, predicting its severity. Our study demonstrated the potential of using ERPs combined with behavioural PPI and PPF protocols to advance our understanding of BDD pathophysiology.

Test-retest reliability of brain oscillations in a prepulse inhibition and facilitation paradigm: effects of gender in healthy humans.

There is a growing interest in assessing the reliability of electroencephalographic (EEG) measures in clinical and research settings. Prepulse inhibition (PPI: representing attentional modulation) and facilitation (PPF: reflecting selective attention) paradigms have been used to study inhibitory function and selective attention, respectively. However, to date, little has been known with regards to the stability of brain oscillatory activity during PPI and PPF. We investigated the stability of event-related EEG oscillations during PPI and PPF in healthy humans over two monthly sessions. Power spectral densities were analysed at traditional frequency bands (delta, alpha, beta sub-bands, and gamma). We assessed test-retest reliability by calculating intraclass correlation coefficients (ICCs, absolute agreement definition) and examined potential effects of gender. The results showed good-to-excellent reproducibility of EEG power (both in PPI and PPF) over all frequency bands (ICCs > 0.75), except for delta (ICCs < 0.75), with alpha exhibiting the highest repeatability performance. In addition, females showed reduced reliability compared to males in both PPI and PPF, possibly attributed to menstrual cycle phase across our female participants. Overall, our findings suggest that brain oscillatory activity can be test-retest reliable, while gender needs to be controlled with caution. Finally, event-related EEG oscillations during both PPI and PPF could provide a complementary tool to study psychopathology in clinical practice.

Changes in LORETA and conventional patterns of P600 after steroid treatment in multiple sclerosis patients.

OBJECTIVE: The P600 component of event-related potentials (ERPs) reflecting the 'rule-governed sequence of information processing', has been associated with multiple sclerosis (MS)-related cognition. The present study aimed at examining the effects of methylprednisolone treatment in MS patients on cognition as reflected by the low-resolution brain electromagnetic tomography (LORETA) of the P600 as well as its conventional constituents (amplitudes and latencies) recorded during a working memory (WM) test. METHOD: A paired LORETA comparison was performed in the P600 component of ERPs elicited during a (WM) test in 18 MS patients suffering from the relapsing-remitting form, before and after 1 week treatment with methylprednisolone. The P600 component was also evaluated in 16 healthy controls matched to the patients on age and educational level. RESULTS: When pre- and post-treatment recordings of LORETA were compared all patients as a group showed significantly different patterns of current density activation located at right frontal lobe. The treatment was accompanied by an increase of the amplitude of P600 at the right frontoparietal area. In the post-treatment phase the patients exhibited significant improvement of the memory performance as compared to themselves before treatment. As a result both the P600 amplitudes and memory performance at post-treatment were closer to those exhibited by normal controls. CONCLUSION: These findings support the notion that steroid treatment in relapsing-remitting MS patients, may exert a beneficial effect in 'rule-governed sequence of information processing'.

Acute mobile phone effects on pre-attentive operation.

There is a debate whether electromagnetic field (EMF) emitted by mobile phones (MP) have an effect on cognitive functions. Since the auditory P50 component of event-related potentials (ERPs) reflects pre-attentive processing and working memory (WM) operation, the present study was designed to investigate whether the exposure to MP-EMF affects the patterns of the P50 component of ERPs elicited during a WM test. The P50 elicited during a WM task and evoked by two warning stimuli low and high frequency (500 and 3000 Hz) has been assessed in 19 normal subjects (10 women and 9 men) both without and with exposure to a 900 MHz signal, emitted by a dipole antenna placed near the subjects. Results showed that the presence of MP-EMFs induced statistically significant increase in the amplitude of P50 evoked by the low frequency stimuli, at Fp1 and O1 electrode leads as compared to themselves without MP-EMF exposure. In contrast the exposure to MP-EMFs revealed statistically significant decrease of the amplitude of P50 evoked by the high frequency stimuli, at Fp1 electrode lead as compared to themselves without MP-EMF exposure. These findings provide evidence that the MP-EMF emitted by mobile phone affect pre-attentive information processing as it is reflected in P50 evoked potential. The basis of such an effect is unclear, although several possibilities exist and call for potential directions of future research.

Excessive weight gain after remission of depression in a schizophrenic patient treated with risperidone: case report.

BACKGROUND: The use of atypical antipsychotics in schizophrenic patients has been associated with a risk of weight gain. Similarly, recovery from depression is often followed by improved appetite, greater food intake and potential increase in weight. CASE PRESENTATION: A Caucasian 33-year-old schizophrenic female patient was being treated with 6 mg/day of risperidone and 15 mg/day of clorazepate. She developed depressive symptomatology and 40 mg/day of fluoxetine was gradually added to her treatment regimen for about 9 months. After the remission of depression, and the discontinuation of fluoxetine, she experienced an increase in appetite and subsequently excessive weight gain of 52 kg. Re-administration of fluoxetine did not reverse the situation. The patient developed diabetes mellitus, which was successfully controlled with metformin 1700 mg/day. The addition at first of orlistat 360 mg/day and later of topiramate 200 mg/day has helped her to lose a significant part of the weight gained (30 kg). CONCLUSION: The case suggests a probable association between the remission of depressive symptomatology and weight gain in a schizophrenic patient.

Abnormal auditory N400 in a case of zolpidem dependence, during a working memory test.

Zolpidem is a GABA (A) agonist, which is indicated for the short-term management of insomnia. Recent research provide evidence suggesting that zolpidem produces spatial working memory (WM) deficits and dependence; however, the underlying mechanisms of these effects are unknown. Since the auditory N400 component of event-related potentials (ERPS) is considered as an index of memory use of context processing, the present study focused on N400 waveform of ERPs elicited during a WM task in a case suffering from zolpidem dependence. The patterns of N400 waveform of this case were compared to the patterns obtained from healthy controls. This comparison revealed that zolpidem dependence is accompanied by reduced amplitudes located at posterior brain areas and diffuse prolongation of N400. These findings may indicate that zolpidem dependence manifests alterations with regard to the memory use of context processing, involving or affecting a wide-ranging network of the brain's structures.

Gender related differences on the EEG during a simulated mobile phone signal.

The present study investigated the gender-related influence of electromagnetic fields (EMF), similar to that emitted by mobile phones, on brain activity. Ten women and nine men performed a short memory task (Wechsler test), both without (baseline) and with exposure to a 900 MHz signal. The EEG energy of the total waveform and the alpha, beta, delta and theta; rhythms were calculated from the recordings of 15 scalp electrodes. Baseline EEG energy of males was greater than that of females, while exposure to EMF decreased EEG energy of males and increased that of females. Memory performance was invariant to EMF exposure and gender influences. These findings indicate that EMF may exert a gender-related nfluence on brain activity.

Long-term abstinence syndrome in heroin addicts: indices of P300 alterations associated with a short memory task.

Attentional deficits have been implicated in the pathophysiology of opioid addicts. The P300 component of event-related potentials (ERPs) is considered as a manifestation of attentional operations. The authors' goal was the comparison of P300 elicited during a short memory test between subjects with prolonged heroin abstinence and current heroin users as well as healthy controls. The P300 component was evaluated during the anticipatory period of a short memory task in 20 patients characterized by a past history of opioid dependence (6 months abstinence), in 18 current heroin users and in 20 healthy comparison subjects, matched for age, sex and educational level. Abstinent heroin addicts exhibited significant reduction of P300 amplitude at central frontal region, relative to the other two groups. The findings are discussed in connection to the aim of identifying psychophysiological indices, addressing issues in opioid use disorders, and suggest that knowledge about cognitive operations, such as those reflected by P300 component, could provide further insight into psychophysiological mechanisms underlying the long-term abstinence state of heroin addicts.

Psychophysiological correlates of patients with delusional misidentification syndromes and psychotic major depression.

BACKGROUND: Psychotic major depression (PMD) and delusional misidentification syndromes (DMS) exhibit cognitive deficits. Since the P300 component of event-related potentials (ERPs) provides valuable information concerning cognition, we studied this component of ERPs in DMS and PMD patients. METHODS: Nine patients with DMS, 15 patients with PMD, and 11 healthy controls, matched for age, sex and educational level, were tested using the auditory P300 component of ERPs. RESULTS: Both patient groups showed significant reductions in P300 amplitude at the right frontal region, while DMS group showed significant attenuation of the P300 amplitude at the right parietal area. P300 latency was significantly prolonged in the central midline brain region in the DMS group. LIMITATIONS: The smallness of the sample size and the hypothetical post-hoc assignation of psychological function to regional activation. CONCLUSION: PMD and DMS patients may share similar psychophysiological alterations connected to the right frontal region, mediating automatic processes, while DMS are associated with dysfunction of effortful mechanisms and allocation of attentional resources involving the interhemispheric and right parietal circuitry.

Abnormal P600 in obsessive-compulsive disorder. A comparison with healthy controls.

Recently, the P600 component of the event-related potential (ERP), a waveform that is thought to be generated and/or modulated by the anterior cingulate gyrus and basal ganglia has been considered as an index of second pass-parsing processes of information processing, having much in common with working memory (WM) operation. Moreover, dysfunction of these brain structures as well as WM deficits have been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). The present study is focused on P600 elicited during a WM test in OCD patients compared with healthy controls. Twenty drug-free OCD patients and an equal number of normal subjects matched for age, sex and educational level were studied via a computerized version of the Wechsler digit span test. Auditory P600 was measured during the anticipatory period of this test. The patient group, as compared with healthy controls, showed significantly enhanced amplitudes of P600 at the right temporoparietal area and prolonged latencies at the right parietal region. Moreover, the memory performance of patients was significantly impaired. These findings may indicate that OCD patients manifest abnormal aspects of second pass-parsing processes of information processing as they are reflected by P600 amplitudes and latencies.