Functional magnetic resonance imaging (fMRI) is a neuroimaging technique increasingly used for both patient care and clinical research. This techniche provides a space-time high-resolution able to detect small changes in regional brain activation.Ojbectives: the aim of this study was to compare patterns of regional brain activation in patients with eating disorders (ED) and healthy volunteers during emotional stimulation.

A group of 13 young female ED outpatients was selected using DSM-IV criteria and 13 young healthy female volunteers with no significant differences in sociodemographic or environmental data. fMRI was used to examine the neural responses after visual stimulation with neutral and fearful images, taken from the IAPS (International Affective Picture System) and selected a region of interest (ROI) aproach to examine the function of the amygdala in emotional processing.Data processing and higher level analysis were carried out using FSL (fMRI's Software Library).

ED patients showed significantly greater rigth amygdala activation to the fearful images versus neutral images than healthy control subjects (p < 0.02)

A higher right amygdala response to processing of fearful stimuli was observed in ED patients compared to healthy volunteers. This emotional dysregulation in the affective response to unpleasant stimuli would correlate with a maladaptative response and therefore justify disruptive behaviours in this patients.

The abnormal connectivity between brain regions has been proposed to account for the physiopathology of psychoses. But which brains regions or which specific links could play the more important role for psychosis to emerge? This study looked at long range functional connectivity in a large sample of schizophrenic patients during resting state.

Forty-two patients with DSM-IV defined schizophrenia were recruited and compared to 57 controls. Participants took part to a 20 min resting state fMRI scan keeping eyes closed but remaining awake. The signal from the 78 Brodman areas was averaged between which a correlation coefficient was computed as the metric for functional connectivity. Patients and controls were compared using permutation test correcting for multiple testing.

The differences can be better described in terms of hub regions that are more disconnected with others than by specific links. The internal temporal, the temporal pole, the inferior temporal and the anterior cingulate regions were the most disconnected. The sensori-motor frontal and parietal regions were less clearly implicated and were correlated with chlorpromazine equivalent dose. There were no inter-hemispheric difference.

The temporal pole was the most differently connected between the two groups. This region is poorly know as there is no equivalent in the other primates. The internal temporal areas (essentially the enthorhinal cortex) were also much concerned in accordance with the limbic hypothesis of psychosis. Surprisingly the prefrontal regions were not involved probably because of the absence of a outward directed cognitive task.

In personal and in political context, we often evaluate the risk of certain conditions. Therefore, two principal psychological approaches are suggested: the analytical consideration and the intuitive estimation, both with according discriminative brain activation. We investigated the neural basis on which non-experts evaluated high risk of different environmental hazards for the society compared with respective low risk.

Twenty healthy subjects underwent functional magnetic resonance imaging while evaluating the risk of fifty more or less risky conditions presented as written terms. We analyzed brain activations during the individual estimations of ‘high’ against ‘low’ risk. Further, the individual brain activations associated with ‘negative’ versus ‘not negative’ emotional valence of the terms were analyzed.

Estimating hazards to be of high risk was associated with activation in medial thalamus, anterior insula, nucleus caudatus, posterior cingulate cortex and precuneus. These areas were not involved according to the analysis of the emotion ratings.

The results point to a substantial contribution of viscerosensitive areas to signal high risk and supports models of an intuitive “gut” feeling independent of the subjective emotional valence when estimating a high risk of environmental hazards.

The authors evaluated cerebral blood flow response in schizophrenia patients during face perception to test the hypothesis of diminished limbic activation related to emotional relevance of facial stimuli.

Thirteen patients with schizophrenia and 17 comparison subjects viewed facial displays of happiness, sadness, surprise, anger, fear, and disgust as well as neutral faces using the Japanese and Caucasian Facial Expressions of Emotion and Neutral Faces (Matsumoto and Ekman, 1988). Functional magnetic resonance imaging was used to measure blood-oxygen-level-dependent signal changes as the subjects alternated between tasks of discriminating sex with an interleaved reference condition.

The groups did not differ in performance on the task. Healthy participants showed activation in the bilateral fusiform gyrus, medial temporal structures, occipital lobe, and inferior frontal cortex relative to the baseline condition. The increase was greater these regions in the right hemisphere than those in the left hemisphere. In the patients with schizophrenia, minimal focal response in the right fusiform gyrus, medial temporal structures, and occipital lobe was observed for the facial perception task relative to the baseline condition. Contrasting patients and comparison subjects revealed voxels in the left medial temporal structures, occipital lobe in which the healthy comparison subjects had significantly greater activation.

Impaired activation was seen in patients with schizophrenia for detection of facial attributes such as sex. Impairment in the medial temporal structure such as amygdale may lead to misunderstanding of social communication and may underlie difficulties in social adjustment experienced by people with schizophrenia.

There is significant overlap between the cortical network involved in fearful face perception and regional abnormalities identified in patients with bipolar disorder. The primary aim of this study was to measure effective connectivity arising from Dynamic Causal Modelling (DCM) to identify differences within this network in a group of patients with bipolar disorder and controls during an affective processing task.

Functional MRI was used to record brain activations from 52 euthymic patients with bipolar disorder and 44 healthy controls engaged in a fearful versus neutral facial affect recognition task. We used Bayesian model selection to identify the best model of effective connectivity, as well as a random-effects analysis. Additionally, the endogenous connections and modulatory influences were extracted and further analyzed.

Within the network subserving fearful facial affect recognition, patients with bipolar disorder demonstrated reduced connectivity from the inferior occipital gyrus to the fusiform gyrus compared to healthy controls. Furthermore this connection when modulated by fear showed a reduction in strength in patients with bipolar disorder.

Bipolar disorder was associated with deficits early in the processing of facial affect suggesting the possibility of perceptual abnormalities being associated with the disorder.

Dr Frangou was supported by a NARSAD Independent Investigator Award

It is an unsettled issue in the literature, under which nosological group depersonalization disorder (DPD) should be subsumed.

We measured clinical traits in DPD patients that had previously been implicated in DPD.

Investigated were N = 9 patients with DPD and N = 12 normal controls. To establish the diagnosis of DPD, ICD-10 criteria and cut-off values (CDS > 70) were included. Clinical traits were measured with internationally established psychiatric taxons. Implicit fMRI tasks inducing three steps of happy and sad facial expressions were run, and clinical trait scores were correlated with brain activation in each emotion category.

Significant differences in the regression slopes for the two groups were observed for somatization in the right temporal operculum (happy) and ventral striatum bilaterally (sad). Discriminative regions for depression were the right middle frontal gyrus (happy) and left amygdala (sad). For dissociation, discriminative regions were the left pulvinar (happy) and left parahippocampal gyrus (sad). For state anxiety, discriminative regions were the left ventrolateral prefrontal cortex (happy) and left ventrolateral cortex (sad)(different locations). For trait anxiety, discriminative regions were the right caudate head (happy) and left retrosplenial cortex (sad).

Our results endorse the notion that depersonalization disorder patients show multifaceted clinical traits, but do not justify any bias for a certain nosological category. The differential regions ascertained by regression during emotion processing comparing to normal controls reflect substantial deviations in DPD for clinical trait processing in the brain.

The current study elucidates the relations between alexithymia and brain activation towards happy and sad emotional stimulation in Depersonalization Disorder (DPD). We hypothesized that various facets of the alexithymia construct are differentially related to single neural structures characterizing abnormal emotion processing in DPD.

Investigated were N = 9 patients with DPD and N = 12 normal controls. To establish the diagnosis of DPD, ICD-10 and scale cut-off values (CDS > 70) were included. Alexithymia was measured using the Toronto Alexithymia Scale (TAS-20). Implicit fMRI tasks inducing three steps of happy and sad facial expressions were run, and clinical trait scores were correlated with brain activation in each emotion category.

Significant positive correlations for alexithymia levels in DPD patients were in the right hypothalamus (happy, r = 0.60, p < 0.00001) and right retrosplenial cortex (sad, r = 0.78, p < 0.00001). The prominent regions for alexithymia levels in normal controls were instead in the left cerebellum (happy, r = 0.71, p < 0.00001) and right ventrolateral cortex (sad, r = 0.89, p < 0.00001). Significant differences in the regression slopes for the two groups were observed in the left putamen (happy, average Δr = 0.86, p < 0.0255) and in the left dorsal ACC (sad, average Δr = 0.87, p < 0.0087).

The present results suggest that the alexithymia trait is related to specific brain regions dependent on emotion. DPD patients recruit different brain regions compared to normal controls in alexithymia.

To identify alterations in neural networks for visual motion perception and pursuit tracking and their interrelationship in schizophrenia, and secondarily to evaluate their comparability to findings in psychotic bipolar disorder.

Untreated first-episode patients with schizophrenia (N=24) and psychotic bipolar disorder (N=13), and 20 matched healthy participants performed a passive visual motion processing task and a pursuit eye tracking task, which patients have been shown to perform as well as healthy subjects, during functional neuroimaging. Available subjects were retested after four weeks, during which both patient groups received second generation antipsychotics.

During the motion processing task, neither patient group showed reduced activation in V5, but activations in its projection fields in posterior parietal cortex were reduced in both groups. Pursuit related neural activation in both patients groups was not reduced in sensorimotor systems, but was enhanced in anterior intraparietal sulcus and insula. In schizophrenia, activation was also enhanced in dorsolateral prefrontal cortex and dorsomedial thalamus. Greater V5 activation during passive motion processing predicted greater activation in posterior parietal cortex during pursuit in healthy individuals but not in patients. The only significant change at follow-up was decreased anterior cingulate activation during pursuit in schizophrenia.

Reduced transfer of visual motion information to parietal association cortex may compromise information about target speed and tracking error needed for sensorimotor transformations during pursuit tracking in psychotic disorders. Enhanced activation of a prefrontal-thalamo-parietal network during pursuit tracking in schizophrenia may represent compensation for this deficit.

The diagnostic boundaries of social anxiety disorder (SAD) are still controversial and recent evidence suggests that the condition could be better understood as a continuum of severity, rather than a strictly circumscribed entity. Current neuroanatomical theories on SAD support the involvement of limbic structures in its pathophysiology, with an emphasis on the amygdala. Thus, the objective of this study was to investigate the hypothesis of volumetric alterations in the amygdala of subjects in different points of the social anxiety spectrum.

The sample consisted of patients with generalized SAD (n=17), subthreshold SAD (increased social anxiety without avoidance; n=13), and healthy controls (n=15). Participants underwent structural magnetic resonance scans and the volume of the bilateral amygdala was manually determined.

Significantly greater volumes of bilateral amygdala were found in socially anxious individuals. Amygdala volumes of subthreshold SAD participants fell between the values found for generalized SAD and healthy controls.

Individuals suffering from SAD have greater amygdala volumes compared to controls and this difference seems to be in agreement with the theoretical conception of SAD as a severity continuum and not as a circumscribed nosological entity.

Recent studies have identified DAAO as a probable susceptibility gene for schizophrenia and bipolar disorder. However, little is known about how this gene may affect brain function to increase vulnerability to these disorders.

The present investigation examined the impact of DAAO genotype on brain function in patients with schizophrenia, patients with bipolar I disorder and healthy volunteers.

We tested the hypotheses that the high-risk variant of DAAO would be associated with altered prefrontal function and functional connectivity in schizophrenic and bipolar patients.

We used functional magnetic resonance imaging to measure brain responses during a verbal fluency task in a total of 121 subjects comprising 40 patients with schizophrenia, 33 patients with bipolar I disorder and 48 healthy volunteers. We then used statistical parametric mapping (SPM) and psycho-physiological interaction (PPI) analyses to estimate the main effects of diagnostic group, the main effect of genotype and their interaction on brain activation and functional connectivity.

In schizophrenic patients relative to bipolar patients and controls, the high-risk variant of DAAO was associated with lower deactivation in the left precuneus and greater activation in the right calcarine and posterior cingulate gyrus during task performance. In addiction, these areas expressed altered functional connectivity with the rest of the brain in schizophrenic patients relative to bipolar patients and controls.

Our results suggest that genetic variation in DAAO has a significant impact on brain function and provide preliminary evidence for a disease-specific pattern of gene action in specific brain regions.

Deficits of social cognition are a relevant predictor of functioning and outcome. Several studies have found that euthymic bipolar patients perform worse in social cognition tasks than healthy controls. Some data show a higher relapse risk in bipolar patients with concomitant mentalization deficits. However, relatively little is known about the neurobiological base of these deficits.

12 euthymic bipolar I patients and 14 age- and IQ-matched healthy controls underwent event-related functional MRI study while performing 15 irony, and 15 control tasks (auditory stimulus) in the scanner. Both within group (irony versus control task) and random effects between group analyses were performed on fMRI data.

Bipolar patients were significantly compromised in their ability to appropriately answer irony tasks. Bipolar patients showed a reduced activation in right cingulate, right anterior paracingulate cortex, right precuneus, left superior parietal lobule, left hippocampus, left insula in comparison to healthy controls. However, bipolar patients brain activation was significantly increased in the left inferior frontal gyrus, left superior temporal gyrus, and left secondary somatosensory cortex.

The findings of this neuroimaging study suggest that euthymic bipolar patients are restricted in their ability to mentalize fully. They show less activation in brain regions involved in mental imaginery, emotional processing and self-representation. Therefore, bipolar patients have difficulties in understanding others’ intentions and emotions, which impacts on interpersonal relationships and the functional outcome.

Serotonergic neurotransmission plays a key role in seasonal changes of mood and behaviour. Higher serotonin transporter availability in healthy human subjects in times of lesser light has been reported in recent studies. Furthermore, seasonal alterations of postsynaptic serotonin-1A receptors have been suggested by a recent animal study. Following that, this study aimed at identifying seasonal alterations of serotonin-1A receptor binding in the living human brain.

Thirty-six healthy, drug-naïve subjects were investigated using PET and the specific tracer [carbonyl-11C]WAY-100635. Regional serotonin-1A receptor binding (5-HT1A BPND) was related to the individual exposure to global radiation. Furthermore, the subjects were divided into two groups depending on individual exposure to global radiation, and the group differences in regional 5-HT1A BPND were determined.

Correlation analysis controlled for age and gender revealed highly significant positive correlations between regional postsynaptic 5-HT1A BPND and global radiation accumulated for 5 days (r=.32 to .48, p=.030 to .002). Highly significant differences in 5-HT1A BPND binding between subjects with low compared to high exposure to global radiation were revealed (T=-2.63 to -3.77, p .013 to .001). 20% to 30% lower 5-HT1A BPND was found in the subject group exposed to lower amount of global radiation.

Seasonal factors such as exposure to global radiation influence postsynaptic serotonin-1A receptor binding in various brain regions in healthy human subjects. In combination with seasonal alterations in serotonin turnover and 5-HTT availability revealed in recent studies, our results provide an essential contribution of molecular mechanisms in seasonal changes of human serotonergic neurotransmission.

Irony is a form of speech used to convey feelings in an indirect way. Patients with schizophrenia demonstrated an impaired irony processing, associated with poor theory of mind.

We used fMRI to examine neural circuitry underlying deficits in understanding irony in schizophrenia.

11 right-handed patients with paranoid schizophrenia and 11 right-handed healthy subjects were studied. Participants were asked to listen short scenarios. The 15 irony condition consisted an ironic statement, and the 15 control condition was physical causality. We used an event-related design. Every scenario started with a two sentences long context, followed by a 2-4 s (jittered) inter-stimulus interval. The third, critical ironic sentence appeared next, and finally a simple yes/no comprehension question followed. Between trials an inter-trial interval of 5-7 s (jittered) were used.

The schizophrenic group performed significantly worse in the irony condition than the control group (p=0.0008). Ironic statements resulted in significant activations in the left inferior frontal gyrus (IFG) and insula, right superior and medial frontal gyrus, left postcentral gyrus, posterior division of right superior and left middle temporal gyrus, left lingual gyrus, left cuneus and right inferior parietal lobule in the schizophrenic group. The control group showed significantly greater activity in the left IFG and insula compared to the schizophrenic group.

Among schizophrenic patients we found a significant underactivation in the left IFG and insula during irony comprehension, which may contribute to the impairements of social behavior in schizophrenia.

Schizophrenia is characterized by marked disturbances of cognitive functions. One core finding is a memory dysfunction. Recently, this has been attributed to impaired hippocampus function that is crucial in comparing new to known information. Hippocampal novelty detection triggers activity of neurons in the ventral tegmental areal (VTA) to which it is reciprocally connected.

Here, we examined whether neuronal activation during the detection of novel information is impaired in these structures.

We investigated novelty detection using an fMRI oddball face paradigm with repeated novel oddballs (1-4 repetitions) in 25 patients (12 female, mean age 26 years) suffering from paranoid-hallucinatory schizophrenia and 25 healthy controls (12 female, mean age 25 years).

Schizophrenia patients, relative to control subjects, showed impaired patterns of activation in mediotemporal areas, including the hippocampus, as well as in VTA/ Substantia Nigra during novelty detection. Furthermore, the activity related to detection of previously novel but repeatedly presented stimuli shows an altered adaptation in the patients.

In schizophrenia, the Hippocampus-VTA-loop displays a dysregulated activity pattern during novelty detection that is crucial for encoding into long-term memory. As this loop is mainly governed by dopaminergic neurotransmission these results underline the pivotal pathophysiological role of mesolimbic dopaminergic dysregulation in the pathophysiology of memory dysfunction in schizophrenia.

Recent research has shown that adiponectin levels in patients with schizophrenia vary similar to the general population. Moreover, antipsychotic medication may influence adiponectin levels, independent of metabolic parameters. We hypothesise different antipsychotics might vary in their effect on adiponectin levels independent of BMI and metabolic syndrome (MetS) status.

113 patients, with similar baseline demographic and metabolic characteristics, received either risperidone (n=54) or olanzapine (n=59). They were followed prospectively for 12 weeks. Adiponectin levels as well as general metabolic parameters were measured at baseline, 6 weeks and 12 weeks.

We observed a significant treatment by time interaction, showing an adiponectin increase in the risperidone treated patients and an adiponectin decrease in olanzapine treated patients. This effect was independent of BMI and the presence/absence of the metabolic syndrome. There was a significant association between fall in adiponectin and increase in waist circumference in the Olanzapine treated group (Figure 1).There was no change in HOMA-IR as a measure of insulin resistance in either group.

We observed a differential effect of antipsychotic treatment (risperidone vs olanzapine) on adiponectin levels over time, independent of BMI (and MetS) suggesting an effect of olanzapine on adipose tissues, similar to what has been observed in animals models. The effects on adiponectin levels may partly explain the increased rates of obesity with Olanzapine.

Quantify the burden of chronic insomnia characterized by nighttime awakenings (CINA) among diabetes patients.

Database analyses of National Health and Wellness Survey, an annual cross-sectional study of U.S. adults. Data were collected across the U.S. through self-administered, Internet-based questionnaires. Patients included in this study self-reported physician-diagnosed diabetes. From this cohort, subjects were categorized as CINA patients if they experienced nighttime awakenings, but did not experience difficulty falling asleep or sleep apnea. Controls did not experience sleep difficulties, sleep apnea, or symptoms of insomnia in the past twelve months. Outcomes included resource utilization in the past six months, work productivity and activity impairment as measured by validated WPAI questionnaire, and summary scores of the SF-8. Regression models were developed to assess independent effects of CINA on outcomes, adjusting for demographics and physical and psychiatric comorbidity.

Among diabetes patients, 150 experienced CINA; 2,437 experienced no insomnia (projected 0.56MM adults with CINA and diabetes). After adjustments, diabetes patients with CINA had 1.9 (p< 0.001) more provider visits, 11.8% (p=0.013) greater work impairment (among full-time employed) 17.0% (p< 0.001) greater activity impairment, and SF-8 physical and mental summary scores that were 5.2 and 5.2 (p< 0.001 for both) points lower than those without insomnia, a projected $33MM in direct costs and a loss of nearly six weeks of work productivity per year.

Among patients with diabetes, CINA in relative isolation was associated with a significant negative impact on healthcare utilization and its associated costs, work productivity, and health-related quality of life.

Increased levels of high-sensitivity CRP have been associated with e.g. major depression, chronic stress and obesity. The purpose of the present study was to investigate the association between generalized anxiety disorder and hsCRP.

The study sample consisted non-smoking women who were living in the town of Turku or nearby and had taken part in the longitudinal Health and Social Support Study (the HeSSup Study) in 1998 and 2003. Of these 312 women the address was unknown for 82, 230 were contacted and 153 subjects responded (67%), 18 (8%) refused to take part and 19 (8%) were excluded. All 116 participants signed and returned the informed consent. The MINI neuropsychiatric interview was used for diagnostics and blood samples were drawn for the analyses of hsCRP and cytokines.

The range mean of hsCRP-level was 1.7 mg/l (range: 0.17 -30.9 mg/l). The mean of BMI was 25.3 (SD=5.0, 17.3-50.8). There was an inverse correlation between GAD and BMI (rho= -0.19, p< 0.05). The odds for a person with GAD diagnosis to have high CRP was 0.37-fold (0.14-0.88), an increased IFN-G-1 0.74 -fold(0.61-0.90) an increased TNF-alfa 1.31-fold (1.01-1.71). Adding BMI to the multivariate analysis did not render the results insignificant.

We found a significant inverse correlation between immunity markers and GAD.