Epilepsy affects between 1 and 2% of the world population. Drug refractoriness is common and about 40% of patients suffer from psychiatric disorders.

Knowing noradrenaline, dopamine, serotonin and substance P receptors’ role in hippocampi removed from people with temporal lobe epilepsy (TLE) with or without psychiatric comorbidity.

To assess whether there are differences in different neurotransmitters’ roles in TLE with or without psychiatric comorbidity.

TacMan real-time PCR assay to quantify the receptors’ mRNA in 48 TLE patients without (Epilepsy-24) or with psychosis (Psychosis-10) or depression (Depression-14) and 8 necropsies (Controls).

AD2A and AD2C showed differences and more expression in the Epilepsy group when compared with Control and Psychosis. AD2A showed significance in the Antiepileptic variable, a substance that activates AD2A in the hippocampus. AD2A and AD2C without difference for Epilepsy and Depression indicate a two-way relation or common pathogenesis between these illnesses; and their minor expression in the Psychosis group suggests different adrenergic mechanisms connected with psychosis and epilepsy. D2 showed a significant difference in the Psychiatric Diagnosis Subtype and Epileptic Seizures frequency, probably due to chronicity and number of depressive episodes. The role of 5-HT2A in TLE is indicated by its greater expression in the Epilepsy group when compared with the Control, with significance for the Epileptic Seizures frequency. No significant results were found for D4, 5-HT1A, 5-HT2C and NK1.

Prospective research with complementary methods (immunohistochemistry, in situ hybridization, electronic microscopy and neuroimaging) is suggested to identify, locate and visualize the receptors’ distribution.

Lipid rafts are specialized membrane microdomains enriched in cholesterol and sphingolipids and are important in the organization of receptor-protein complexes and the regulation of signaling.

Given the emerging significance of lipids with respect to receptor structure and activation, we investigated the role of lipid rafts and membrane cholesterol on D2 dopamine receptor (DAR) signaling. As the D2 DAR is the molecular target for all antipsychotic drugs, more information about its signaling may help refine therapeutics for schizophrenia.

D2 DAR constructs were expressed in HEK293T cells. Sucrose density fractionation resolved lipid rafts from other membrane components. Methyl-β-cyclodextrin (MCD) was used to deplete membrane cholesterol and to disrupt lipid rafts.

Detergent solubilization followed by sucrose gradient centrifugation resolved lipid rafts from heavier membrane fractions. The D2 DAR was equally distributed amongst both the lipid raft and heavier membrane fractions. Pretreatment with MCD, however, eliminated both lipid raft markers and the D2 DAR from lipid raft fractions, although the receptor was still found in heavier membrane fractions. We also found that MCD treatment abolished D2 DAR-mediated inhibition of cAMP accumulation. In contrast D1 DAR-stimulated cAMP accumulation was unaffected by MCD treatment.

Our current results show that the D2 DAR is distributed in multiple membrane microdomains, including cholesterol-rich lipid rafts. We found that extraction of cholesterol disrupted lipid rafts and also an eliminated D2 DAR-mediated signaling. Thus, we hypothesize that lipid rafts are critical for D2 DAR signaling to occur.

Perinatal exposure to alcohol (PEA) induces general developmental and specific neuropsychiatric disturbances in association with disturbed synaptic plasticity and functions of the amino acid neurotransmitter glutamate.

We were interested in effects of ethanol during the terminal neurodevelopmental differentiation on glutamatergic neurotransmission.

To establish an animal model based on vapor chamber exposure and to assess the expression of vGluT1, EAAT1 to 4, NMDA receptor (NR) subunits 1, 2A to D and NR binding with 3H-labeled MK 801.

After delivery, female Wistar Han outbred rats (N = 4) and their pups were exposed until postnatal day 8 (P8). At the age of 5 months, the animals were behaviorally characterized. Both, at P8 and after the testing we performed in situ-hybridizations receptor binding assays.

PEA-pubs showed a pronounced and highly significant retardation of body weight and length. Behavioral testing revealed no differences in locomotion and anxiety (open field and elevated plus maze) as well as T-maze-learning, but significantly impaired hippocampus-dependent spatial learning (MWM). We observed significant inductions of vGluT1, EAAT1, EAAT3, NR2A, 2B, 2C and 2D, as well as trends of increased NR1 mRNA. NR binding was found increased in hippocampus (P8) and parietal cortex (P8 and 5M).

The observed inductions of glial glutamate transporters validate previous in vitro data. Altered glutamatergic neurotransmission in general might be considered a molecular correlate of the learning deficit in our PEA model. This further supports the glutamatergic theory of PEA and suggests new targets for therapeutic interventions.

There is evidence that psychiatric diseases are accompanied by structural alterations in the human brain, partly reversible by pharmacological treatments. Several studies including Tost et al. (Nat.Neurosci.2010;13(8):920-2) investigated the effect of psychotropic drugs on neuronal plasticity pointing towards rapid pharmacologically induced brain grey matter variations, apart from already presumed slow structural changes within weeks. Here, we investigated the short-term (days) structural effects of SSRIs.

To identify structural changes of grey and white matter following 10d of oral administration (citalopram/escitalopram vs. placebo) in 18 healthy subjects investigated by magnetic resonance imaging (MRI) using voxel-based morphometry (VBM).

Study design: Randomized, cross-over, placebo-controlled, double-blind study.

Subjects: 18 healthy caucasian subjects (6 female 24.8 ± 2.5 years, 12 males 28.9 ± 6.7 years) MRI: 3 MRI scans/subject (3 Tesla scanner)

Treatment: 10d of oral medication intake of either 20 mg citalopram/d, 10 mg escitalopram/d or placebo in alternating order of administration

Data analysis: VBM, as implemented in SPM8.

Statistical analysis: analysis of variance (ANOVA, FWE corrected), post-hoc pair-wise comparisons.

ANOVA (grey matter: F(2,48) = 18.85, p < 0.05; white matter: F(2,48) = 17.79, p < 0.05) did not reveal suprathreshold clusters in grey or white matter.

This VBM-study does not support previous short-time (days) MR findings of pharmacologically-induced structural alterations in the brain, considering the lack of significant changes in grey and white matter volumes following 10d of SSRI administration. This divergence may be caused by dissent pharmacological effects of SSRIs compared to other psychotropic drugs.

Psychiatric Patients show abnormalities in volumes of several subcortical structures. Recently wider usage of automated segmentation methods in research of these abnormalities based on MR images has become possible. However manual segmentation is still considered to be the gold standard.

To compare differences in hippocampus volumes between manual segmentation and 2 packages for automatic segmentation (FSL and FreeSurfer).

To explore the overlap and differences between different segmentation methods used for segmentation of subcortical structures.

Structural MR brain scans were aquired from 98 subjects (53 schizophrenia patients, 45 controls). Volumes of left and right hippocampus were measured after manual, FreeSurfer and FSL segmentations. Differences between volumes from different methods were tested by the t-test (using R). In addition percent volume differences, Pearson correlations, Bland-Altman plots and Cronbach’s alpha were computed.

Both automatic methods yielded significantly larger hippocampal volumes than the manual segmentation. FreeSurfer volumes showed a higher correlation and lower percent volume difference with manual segmentation than FSL. Bland-Altman plots and Cronbach’s alpha showed only limited agreement between manual and both automatic methods.

Although volumes acquired by FreeSurfer appeared to be more related to manual segmentation, clear superiority of either of automatic methods could not be demonstrated. Therefore, all three methods seem to measure other aspects of hippocampus volume. An useful approach would be to compare effect-size of the difference between patients and healthy controls using different segmentation methods. We are currently pursuing this in a larger sample.

Converging evidence suggests alterations of neural activation in the basal ganglia to represent neural correlates of Major Depressive Disorder (MDD). While a previous study reported increases of functional connectivity in resting state activity between the caudate nuclei and the posterior cingulate cortex in acutely depressed patients, it remains unclear whether this finding persists during full remission once antidepressant treatment has been discontinued.

To investigate patterns of functional coupling between the basal ganglia and cortical regions during resting-state conditions.

To determine whether increases of functional connectivity between caudate nuclei, putamen, and pallidum with cortical regions, in particular the cingulate cortex, pertain during remission of MDD.

Forty-three remitted depressed (rMDD) patients and thirty-five healthy controls were recruited at Medical University of Vienna, Vienna, Austria, and performed a six minute resting-state fMRI scan. Seed time series were extracted from the preprocessed data using individual masks for the basal ganglia and correlated with all nodes in a surface based analysis using FreeSurfer, AFNI and SUMA. The resulting correlation coefficients were then Fisher-transformed, group results were determined by comparing group mean smoothed z-scores with a two-sample t-test.

Increased resting-state functional connectivity was revealed between basal ganglia and cingulate as well as prefrontal cortex in the rMDD group compared to healthy controls.

Our preliminary results revealed increased functional coupling between the basal ganglia and wide parts of the cingulate and prefrontal cortex to possibly represent a specific neural pattern during remission of MDD.

A growing body of research now documents a specific pattern of brain activation during emotional tasks in patients with social phobia. Furthermore, recent studies indicate that non-clinical participants show a similar pattern of responses. Clinical and physiological data from literature highlight that social anxiety is associated with difficulties in emotional managing. However, much less is known about the part of alexithymia in social phobia, as far as clinical and infra-clinical (high shyness) approaches are concerned.

Four hundred undergraduate university students were screened with an anxiety and social phobia questionnaire. Forty participants, with low and high levels of social phobia, were then included according to a dimensional approach. Each participant underwent a comprehensive psychiatric evaluation that included a structured clinical interview for current and past psychiatric disorders and psychometric scales, including the Liebowitz Social Anxiety Scale (LSAS) and the Toronto Alexithymia Scale (TAS-20). Participants were asked to make gender discrimination choices when viewing faces that showed happiness, fear, anger, sadness, neutral expressions or distractors while in a 3 Tesla fMRI scanner.

As expected, social phobia trait was correlated with TAS-20 scores, and specifically in “difficulties identifying feelings”. Brain activations showed an evolutionary pattern response in correlation with social phobia and alexithymia concerning limbic regions (amygdala and insula). Social phobia trait seems to be particularly receptive to anger faces.

Our findings support the hypothesis that alexithymia play a major role in social anxiety disorder. Identifying feelings could explain alexithymic functioning in social phobia, clinically and physiologically.

The request of diagnostic imagining techniques, such as CT, is sometimes necessary when working in the emergency service as a psychiatrist. Common circumstances that need CT are altered level of consciousness, absence of psychiatric history, sudden beginning of the symptoms or visual hallucinations.

To study the profitability of the cranial CT for patients with psychiatric symptoms in the Emergency Service.

Retrospective review of the cranial CT was made to patients who presented psychiatric symptoms in the Emergency Service of our hospital from November 2009 to July 2010 using Hospital Ramon Cajal’s history software.

We collected a total of 94 patients.-Sex: there were no important differences, 45,7% were women and 53,3% were men. -Age: < 18 years (3,2%), 18–30 years (12,8%), 31–40 (7,4%), 41–50 (26,6%), 51–60 (17%), 61–70 (14,9%), >71 (18,1%) Cause of consulting: The most frequent cause of consulting was “behavior disorder” (35,1%) and psychotic symptoms (14,9%). Other causes were altered level of consciousness and neurological symptoms.

Image findings: It stands out that up to a 63,8% of the patients had no significant radiological findings. The most frequent diagnosis (26,6%) was cortical-subcortical atrophy, followed by vascular cerebral illness in 9,6%.

Diagnosis: 20,2% were diagnosticated of psychotic disorder, 11,7% neurological disorder and 10,6% dementia.

1. - Only in 6,4% of the cases the image results were indispensable to reach a correct diagnosis.

2. - Cranial CT requests should not be made routinely and guides should be followed more strictly.

Although the deviations of brain volume deficits in sporadic and familial first-episode schizophrenia patients (FEP) had been presented, the difference of brain asymmetries remained unidentified.

To assess the potential differences of volumetric asymmetries of gray matter (GM) and white matter (WM) between groups.

To find out the different injury alteration of sporadic FEP and familial FEP.

42 sporadic and 30 familiar drug-naïve FEP with and 72 matched normal controls (NC) were recruited. Participants were assessed with neuropsychological tests and scanned by a 3.0T MRI to obtain T1-weighted and DTI images. Lateralization distribution maps of GM and WM volume were generated by employing optimized voxel-based morphometry. The asymmetries were analyzed by comparing calculating Laterality Index (LI) voxel by voxel.

All three groups showed similar overall brain torque. Familiar FEP have more regional extensive GM asymmetry brain lesions compared to sporadic FEP. There was no shared regional lesion between two groups. LIGM and LIWM in right superior temporal were negatively correlated. Significant negative correlations were also found between LIGM of left superior parietal lobule and LIWM of right superior parietal lobule, and between LIGM of right inferior parietal lobule and LIWM of left inferior parietal lobule. The asymmetry in distinct brain regions were related to cognitive deficits especially in the domains of language and memory.

The two patient groups had different alteration in injuries of brain asymmetry. Familiar FEP has more GM extensive asymmetry brain region, which may correlate with their high genetic burdens.

Emotional regulation is a crucial aspect of adaptive behaviour and social interaction, and is often disrupted in a range of psychiatric disorders.

In the past decade, neuroimaging studies have identified key components of the neural networks that underpin emotional processing during facial affect recognition. Although these networks are extremely interconnected, current evidence points to the ventral prefrontal cortex (VPFC) as having a pivotal role in emotional regulation.

We were particularly interested in specifying the functional interrelationships of VPFC with component network regions and in exploring potential modulation by the valence of the facial affect.

Functional magnetic resonance imaging (fMRI) data were obtained from 40 healthy individuals during a facial affect recognition task involving fearful, sad and angry facial expressions. Within the networks engaged by the task, we used Dynamic Causal Modelling (DCM) to measure effective connectivity followed by Bayesian Model Selection to identify the model best model fitting our data and Bayesian Model Averaging to analyze the endogenous connections and the modulatory influence of affect.

Processing of all three facial expressions engaged the visual cortex, fusiform gyrus, amygdala and VPFC. DCM analysis showed that the connection between the visual cortex and the VPFC plays a more important role in the recognition of facial emotions than other regions.

We provide evidence for the central role of a valence independent increase in visual cortical and VPFC coupling during the processing of facial affect.

182 patients with epilepsy aged 18–55 years observed recurrently for 5–9 years. Etiologically epilepsy was symptomatic (n = 108), idiopathic (n = 26) and cryptogenic (n = 48). Remission for ≥2 year period was set in 67% cases.

Digital EEG performed on 19 channels and analyzed in spectral and period metric regimen.

Brain mapping (digital EEG) revealed organic brain damage patterns (1–4 Digital EEG signs) in 81.9% of cases: 86.1% for symptomatic, 69.2% for idiopathic, 79.2% for cryptogenic epilepsy among patients with acute phase of disease. When remission achieved EEG patterns exposition decreased dramatically - from 81.9% to 9.8%.

The data obtained fits the hypothesis that activity of epilepsy defined by mean of Digital EEG. These characteristics of the brain’ functional state are very sensible and neurologists have possibility to take into account this information while prescribing or depriving anticonvulsants.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disease characterized by symptoms of inattention, hyperactivity, and impulsivity.

Current accounts of ADHD postulate the existence of at least two different but not mutually exclusive ADHD endophenotypes: those characterized by cognitive executive function (“cool EF”) abnormalities, presumably produced by dysfunctions in dopaminergic mesocortical branches; and those characterized by abnormalities in reward management processes (also know as “hot EF”), which are thought to result from alterations in dopaminergic mesolimbic circuits.

The aim of the present study is to assess brain activity during “cool EF” and “hot EF” in adults with ADHD and to identify the neurobiological and behavioral interrelation between the each of the processes.

Sample: 19 control subjects and 19 ADHD adults, naïve.

In order to assess “cool EF”, we employed a paradigm assessing inhibition response, the Go-noGo task. A reward paradigm was used to assess hot EF functions.

Preliminary results are in line with previous functional magnetic resonance imaging showing reduced ventro-striatal activation during reward anticipation in ADHD. In addition, results derived form the inhibition response paradigm are also in agreement with neuroimaging and lesion studies, appointing the right inferior frontal cortex as a key region for inhibition processing.

Our results indicate the existence of alterations in cool EF and hot EF as reflected by abnormal activity in dopaminergic mesocortical and dopaminergic mesolimbic circuits. These findings underline the importance of taking into account both “cool EF” and “hot EF” in order to understand the neurobiology of ADHD.

Regional alterations of serotonergic neurotransmission and functional activation in the amygdalar region of patients with major depression are underpinning its important role in affective disorders. In this study we used fMRI and PET to describe functional and molecular alterations associtated with an astrocytoma in the left amygdalar region in a patient with organic depressive disorder compared to control subjects.

The serotonin-1A (5-HT1A) receptor binding (BPND) was quantified with PET (30 frames, 90 min, 4.4 mm FWHM) in 36 subjects using the radioligand [carbonyl-11C]WAY-100635, and a reference tissue model (MRTM2). In fMRI (3T, EPI inplane resolution 1.6*2.7 mm, 10 AC-PC orientated slices, ST = 3 mm, TE/TR = 31/1000 ms), 32 participants performed emotion discrimination and sensorimotor control tasks. Statistical analysis with SPM5 and unpaired t-tests were performed on molecular and functional data separately.

The astrocytoma was delineated in the serotonin-1A receptor distribution showing (p < 0.01, uncorrected) regional BPND decrease. The ipsilateral thalamus and bilateral habenula regions displayed (p < 0.001; uncorrected) BPND increase. The fMRI data showed significantly (p < 0.05; uncorrected) reduced activation in the affected amygdalar region, ipsilateral fusiform gyrus, bilateral orbitofrontal cortex and temporal regions and increased activation in the contralateral temporal pole.

Lower serotonin-1A receptor binding in the left amydala region reflects the glial provenance of the tumor. The increased receptor binding in the habenulae might be associated with altered monoaminergic neurotransmission and depressive symptoms according to the influence of the habenulae on monoaminergic nuclei. The functional data demonstrate neuroplastic changes beyond affected areas and might indicate compensatory mechanisms.

Mechanisms contributing to the development and maintenance of obesity remain to be elucidated especially regarding the interaction between appetite regulating hormones and mesolimbic reward circuits. Leptin was recently suggested to attenuate dopamine release in mesolimbic reward pathways. We now test the functional relevance assessing whether leptin plasma concentration affects the BOLD-response following the presentation of food cues.

21 obese and 23 normal weight subjects were investigated. Visual food cues and neutral stimuli were presented in a block design during fMRI. Blood-samples were collected immediately prior to the scan to assess plasma leptin concentration. Using linear regression analyses, the association between BOLD response to food cues and the body mass index (BMI) as well as plasma leptin concentration was examined.

Food-cues elicited activation of large cortical and subcortical networks, whereas only in obese patients food cues activated the left ventral and right dorsal striatum. Mean plasma concentration of leptin was significantly increased in obese subjects compared to normal weight controls. We found a significant positive correlation between the food cue-induced BOLD signal change in the ventral striatum and leptin plasma concentration. Furthermore, ventral and dorsal striatum BOLD response to food cues was significantly positive associated with the body mass index (BMI).

These findings suggest a physiological role of the satiety factor leptin in modulating responsivity of reward pathways towards food cues. Altered homeostatic feedback regulation of the mesolimbic brain reward circuit might explain the inability of obese patients to adapt their food intake according to physiologically needs.