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Background Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) provided benefit for treatment-resistant depression (TRD) in open-label studies but failed in a recent randomized sham-controlled trial. Informed patient selection, based on reliable biomarkers, is needed to optimize outcome. We investigated if rostral anterior cingulate (rACC) glutamate/glutamine concentration could serve as a potential biomarker of response. Methods Sixteen adults with TRD (Major Depression; MDD = 14; Bipolar Depression; BD =2) underwent proton magnetic resonance spectroscopy using a short-echo proton spectroscopy with a voxel placed in the rACC, prior to DBS. Improvement in depression was assessed using the 17-item Hamilton Rating Scale for Depression (HDRS). Glutamate and glutamine concentrations at baseline in the rACC were examined in relation to clinical outcomes at six months. Results Lower baseline glutamate predicted significant reduction in HDRS scores in all TRD patients (p = 0.018), and predicted both HDRS reduction (p = 0.002) and 6-month response outcome in MDD-TRD patients (p = 0.013). Neither baseline glutamine nor glutamine/glutamate ratio significantly related to outcome or symptom improvement. Limitations Our study was limited by sample size, though it is large for a DBS study. We measured from a single voxel in the brain, so we cannot be certain our findings are specific to the rACC. Conclusions These preliminary results suggest that baseline rACC-glutamate concentration could serve as a response-predictive biomarker for SCC-DBS, particularly in patients with resistant major depression. If our findings are replicated and validated, rACC-glutamate may provide a basis to prospectively select TRD patients to improve likelihood of response to SCC-DBS.

Introduction Pre‐treatment blood oxygenation level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) has been used for the early identification of patients with major depressive disorder (MDD) who later respond or fail to respond to medication. However, BOLD responses early after treatment initiation may offer insight into early neural changes associated with later clinical response. The present study evaluated both pre‐treatment and early post‐treatment fMRI responses to an emotion processing task, to further our understanding of neural changes associated with a successful response to pharmacological intervention. Methods MDD patients who responded (n = 22) and failed to respond (n = 12) after 8 weeks of treatment with either citalopram or quetiapine extended release, and healthy controls (n = 18) underwent two fMRI scans, baseline (pre‐treatment), and early post‐treatment (one week after treatment commencement). Participants completed an emotional face matching task at both scans. Results Using threshold‐free cluster enhancement (TFCE) and non‐parametric permutation testing, fMRI activation maps showed that after one week of treatment, responders demonstrated increased activation in the left parietal lobule, precentral gyrus, and bilateral insula (all P, Patients diagnosed MDD who later went on to respond to medication showed robust BOLD increases after one week of treatment to an emotion processing task. There were no differences between responders, non‐responders and healthy controls at baseline, indicating that BOLD fMRI can be used to identify mediating markers of treatment response.

BackgroundMotivational deficits in people with schizophrenia (PSZ) are associated with an inability to integrate the magnitude and probability of previous outcomes. The mechanisms that underlie probability-magnitude integration deficits, however, are poorly understood. We hypothesized that increased reliance on “value-less” stimulus-response associations, in lieu of expected value (EV)-based learning, could drive probability-magnitude integration deficits in PSZ with motivational deficits.MethodsHealthy volunteers (n= 38) and PSZ (n=49) completed a reinforcement learning paradigm consisting of four stimulus pairs. Reward magnitude (3/2/1/0 points) and probability (90%/80%/20%/10%) together determined each stimulus’ EV. Following a learning phase, new and familiar stimulus pairings were presented. Participants were asked to select stimuli with the highest reward value.ResultsPSZ with high motivational deficits made increasingly less optimal choices as the difference in reward value (probability*magnitude) between two competing stimuli increased. Using a previously-validated computational hybrid model, PSZ relied less on EV (“Q-learning”) and more on stimulus-response learning (“actor-critic”), which correlated with SANS motivational deficit severity. PSZ specifically failed to represent reward magnitude, consistent with model demonstrations showing that response tendencies in the actor-critic were preferentially driven by reward probability. ConclusionsProbability-magnitude deficits in PSZ with motivational deficits arise from underutilization of EV in favor of reliance on value-less stimulus-response associations. Consistent with previous work and confirmed by our computational hybrid framework, probability-magnitude integration deficits were driven specifically by a failure to represent reward magnitude. This work reconfirms the importance of decreased Q-learning/increased actor-critic-type learning as an explanatory framework for a range of EV deficits in PSZ.

The oxytocinergic system has been assumed to contribute to food intake, possibly via interactions with dopamine. However, so far, it is unknown whether oxytocin influences the underlying motivational behaviour towards food. In the present study, we used a food-based approach-avoidance task (AAT) in a randomised, placebo-controlled, double-blind, cross-over design to compare intranasal oxytocin with a placebo. In the AAT, participants pushed or pulled a joystick when images of foods with a high or low craving rating were presented, where differences in response times typically reflect approach and avoidance motivational biases towards positively and negatively valence stimuli, respectively. Thirty-three healthy male participants (age = 25.12 ± 3.51 years; body mass index = 24.25 ± 2.48 kg/m2 ) completed the two-session study, one with placebo and the other with oxytocin. We used mixed-effects models to investigate effects of treatment (oxytocin, placebo), response type (approach, avoid) and stimulus (high, low craving). The results showed that both approach and avoid responses tended to be faster for foods higher in craving compared to foods lower in craving. Most importantly, we did not observe any significant effects of oxytocin compared to placebo in motivational behaviour towards food. Our study demonstrates a general response bias towards foods with different craving values, which could have implications for future studies investigating food-related behaviour. We discuss possible explanations for the null effects of oxytocin and suggest further investigation of the relationship between oxytocin, dopamine and food-reward processing.

Elliot C Brown,1–3 Darren L Clark,1–3 Stefanie Hassel,1,2 Glenda MacQueen,1,2 Rajamannar Ramasubbu1–3 1Mathison Centre for Mental Health Research and Education, University of Calgary, Calgary, AB, Canada; 2Department of Psychiatry, University of Calgary, Calgary, AB, Canada; 3Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada Background: Differences in the thalamocortical system have been shown in patients with major depressive disorder (MDD). Given prior evidence of phenotypic heterogeneity by the age of onset in MDD, we examined whether differences in thalamocortical connectivity could identify biological subtypes of MDD defined by the age of illness onset. Methods: A total of 94 subjects including 20 early-onset (EO) MDD (onset, 18 years), 34 adult-onset (AO) MDD, and 40 healthy controls (HCs) underwent resting-state functional MRI. Blood-oxygen-level-dependent time courses were extracted from six cortical regions of interest (ROIs) consisting of frontal, temporal, parietal, and occipital lobes and precentral and postcentral gyri. Each ROI’s time course was then correlated with each voxel in thalamus, while covarying out signal from every other ROI. Results: The analysis of variance results showed significant main effects of group in frontal and temporal connectivity with thalamus. Group contrasts showed a right fronto-thalamic hypoconnectivity only in AO-MDD, but not in EO-MDD, when compared to HCs. However, direct comparison between EO-MDD and AO-MDD showed no differences. Furthermore, there was a right temporal–thalamic hyperconnectivity in both EO-MDD and AO-MDD patients relative to HCs. These results were not accounted for by sex, age, or illness burden. Conclusion: The age of illness onset may be a source of heterogeneity in fronto-thalamic intrinsic connectivity in MDD. Keywords: depression, age of onset, neuroimaging, thalamus, cortex, resting-state fMRI

Darren L Clark,1–4 Nithya Konduru,1 Anne Kemp,5 Signe Bray,6–8 Elliot C Brown,1–4 Bradley Goodyear,1,2,4,6 Rajamannar Ramasubbu1–4 1Department of Psychiatry, 2Department of Clinical Neuroscience, 3Mathison Centre for Mental Health Research and Education, 4Hotchkiss Brain Institute, University of Calgary, Calgary, 5School of Medicine, University of Alberta, Edmonton, 6Department of Radiology, 7Department of Pediatrics, University of Calgary, 8Child and Adolescent Imaging Research Program, Alberta Children’s Hospital, Calgary, AB, Canada Background: Early-onset major depressive disorder (EO-MDD), beginning during childhood and adolescence, is associated with more illness burden and a worse prognosis than adult-onset MDD (AO-MDD), but little is known about the neural features distinguishing these subgroup phenotypes. Functional abnormalities of the amygdala are central to major depressive disorder (MDD) neurobiology; therefore, we examined whether amygdala intrinsic connectivity (IC) can differentiate EO-MDD from AO-MDD in a cohort of adult MDD patients.Subjects and methods: Twenty-one EO-MDD (age of onset ≤18 years), 31 AO-MDD patients (age of onset ≥19 years), and 19 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (7 minutes). Amygdala seed-based resting-state functional connectivity was compared between groups.Results: AO-MDD patients showed loss of inverse left amygdala–left dorsolateral prefrontal cortex IC and increased inverse left amygdala–left inferior parietal IC, compared to both HCs and EO-MDD. EO-MDD showed a switch from inverse to positive IC with right dorsomedial prefrontal cortex, compared to HCs and AO-MDD. This effect was removed when we controlled for illness burden.Conclusion: Alterations in amygdala IC with the default-mode network were specifically related to EO-MDD, whereas amygdala IC with executive cognitive control regions was preferentially disrupted in AO-MDD. Increased illness burden, an important clinical marker of EO-MDD, accounted for its specific effects on amygdala IC. Brain imaging has the potential for validation of clinical subtypes and can provide markers of prognostic value in MDD patients. Keywords: major depressive disorder, onset age, resting-state functional connectivity, functional magnetic resonance imaging, biomarker, amygdala

Borderline Personality Disorder (BPD) is characterized, among other symptoms, by interpersonal dysfunction and difficulties in empathizing. According to Simulation Theory empathy is linked to the activity of the mirror neuron system (MNS). Mu-rhythm desynchronization, as reflected in a suppression of electroencephalographic alpha-frequency bands (8-13Hz) provides a non-invasive electrophysiological window into MNS function. Here, we analyzed mu-desynchronization in twenty-two patients with BPD and twenty-three matched healthy controls in a reward and punishment-sensitive action observation task. In addition, we examined empathy using the Interpersonal Reactivity Index. BPD patients and controls did not differ with regard to mu-desynchronization when the entire time course was compared. However, differences in mu-suppression between groups occurred after the goal of the action became discernible. Correlations between mu-suppression and empathy ratings emerged only in controls, but not in the patient group. These findings suggest that BPD patients do not have a generalized impairment in MNS activity, though associations with contextual factors seem plausible.

Subcallosal cingulate (SCC) deep brain stimulation (DBS) is a promising therapy for treatment-resistant depression (TRD), but response rates in open-label studies were not replicated in a large multicenter trial. Identifying biomarkers of response could improve patient selection and outcomes. We examined SCC metabolic activity as both a predictor and marker of SCC DBS treatment response. Brain glucose metabolism (CMRGlu) was measured with [18F] FDG-PET at baseline and 6 months post DBS in 20 TRD patients in a double-blind randomized controlled trial where two stimulation types (long pulse width (LPW) n = 9 and short pulse width (SPW) n = 11) were used. Responders (n = 10) were defined by a ≥48% reduction in Hamilton Depression Rating Scale scores after 6 months. The response rates were similar with five responders in each stimulation group: LPW (55.6%) and SPW (44.5%). First, differences in SCC CMRGlu in responders and non-responders were compared at baseline. Then machine learning analysis was performed with a leave-one-out cross-validation using a Gaussian naive Bayes classifier to test whether baseline CMRGlu in SCC could categorize responders. Finally, we compared 6-month change in metabolic activity with change in depression severity. All analyses were controlled for age. Baseline SCC CMRGlu was significantly higher in responders than non-responders. The machine learning analysis predicted response with 80% accuracy. Furthermore, reduction in SCC CMRGlu 6 months post DBS correlated with symptom improvement (r(17) = 0.509; p = 0.031). This is the first evidence of an image-based treatment selection biomarker that predicts SCC DBS response. Future studies could utilize SCC metabolic activity for prospective patient selection.

Background Electroconvulsive therapy (ECT) can lead to rapid and effective responses in major depressive disorder (MDD). However, the precise neural mechanisms of ECT for MDD are still unclear. Previous work has confirmed that thalamocortical circuits play an important role in emotion and cognition. However, the relationship between mechanisms of ECT for MDD and thalamocortical connectivity has not yet been investigated. Method Thalamocortical functional connectivity analysis was performed on resting-state functional magnetic resonance imaging (fMRI) data collected from 28 MDD patients both pre- and post-ECT treatment, as well as 20 healthy controls. The cortex was parceled into six regions of interest (ROIs), which were used as seeds to assess the functional connectivity between the cortex and each voxel in the thalamus. Then, functional connectivity between the identified thalamic subregions and the rest of the brain was quantified to better localize thalamocortical connectivity related to ECT. Structural connectivity among the functionally abnormal regions was also determined using probabilistic tractography from diffusion tensor imaging (DTI) data. Results There was decreased parietal cortex–left pulvinar and left pulvinar–bilateral precuneus functional connectivity in post-ECT MDD patients, compared to pre-ECT MDD patients. Furthermore, functional connectivity strength of parietal cortex–left pulvinar and left pulvinar–bilateral precuneus was negative correlation with verbal fluency test scores in post-ECT MDD patients. No significant change was found in structural connectivity analysis. Limitations The sample size of our study was not large. Conclusion Our findings implicate that the specific abnormalities in thalamocortical circuit may be associated with cognitive impairment induced by ECT.

Social stimuli grab our attention. However, it has rarely been investigated how variations in attention affect the processing of social stimuli, although the answer could help us uncover details of social cognition processes such as action understanding. In the present study, we examined how changes to bottom-up attention affects neural EEG-responses associated with intentional action processing. We induced an increase in bottom-up attention by using hypnosis. We recorded the electroencephalographic μ-wave suppression of hypnotized participants when presented with intentional actions in first and third person perspective in a video-clip paradigm. Previous studies have shown that the μ-rhythm is selectively suppressed both when executing and observing goal-directed motor actions; hence it can be used as a neural signal for intentional action processing. Our results show that neutral hypnotic trance increases μ-suppression in highly suggestible participants when they observe intentional actions. This suggests that social action processing is enhanced when bottom-up attentional processes are predominant. Our findings support the Social Relevance Hypothesis, according to which social action processing is a bottom-up driven attentional process, and can thus be altered as a function of bottom-up processing devoted to a social stimulus.

Various studies have suggested that auditory deviance detection is organized in a hierarchical manner with ascending levels of complexity. Event-related potentials (ERP) are considered to reflect different cortical processing stages. In the current electroencephalographic study, we employed an auditory sequence oddball paradigm to investigate different levels of cortical auditory processing and the contribution of neuronal habituation and prediction error mechanism to N1 and Mismatch Negativity (MMN). Our findings suggest that N1 reflects a lower cortical process primarily involved in the encoding of simple physical features and is thus mainly modulated by neuronal attenuation and not complex top-down mechanisms. By analyzing within-sequence signal differences, we divided the MMN into distinct subcomponents reflecting different hierachical levels of auditory processing. We determined a “first-order” MMN that reflects the processing of simple deviant features (such as frequency) and “higher-order” MMNs that occur at regularity violation of complex patterns or unexpected inputs that do not allow further predictions. In our source localization analysis, both the primary auditory cortex and left IFG were primarily involved in the detection of simple, physically deviant features, while the right IFG was associated with the processing of novel, unexpected auditory inputs and the ACC with regularity violation of known patterns. Summarizing, our results might contribute to a better understanding of the different complexities of neuronal habituation and prediction error mechanisms at different levels of cortical auditory processing.

Individuals from across the psychosis spectrum display impairments in reinforcement learning. In some individuals, these deficits may result from aberrations in reward prediction error (RPE) signaling, conveyed by dopaminergic projections to the ventral striatum (VS). However, there is mounting evidence that VS RPE signals are relatively intact in medicated people with schizophrenia (PSZ). We hypothesized that, in PSZ, reinforcement learning deficits often are not related to RPE signaling per se but rather their impact on learning and behavior (i.e., learning rate modulation), due to dysfunction in anterior cingulate and dorsomedial prefrontal cortex (dmPFC). Twenty-six PSZ and 23 healthy volunteers completed a probabilistic reinforcement learning paradigm with occasional, sudden, shifts in contingencies. Using computational modeling, we found evidence of an impairment in trial-wise learning rate modulation (α) in PSZ before and after a reinforcement contingency shift, expressed most in PSZ with more severe motivational deficits. In a subsample of 22 PSZ and 22 healthy volunteers, we found little evidence for between-group differences in VS RPE and dmPFC learning rate signals, as measured with fMRI. However, a follow-up psychophysiological interaction analysis revealed decreased dmPFC-VS connectivity concurrent with learning rate modulation, most prominently in individuals with the most severe motivational deficits. These findings point to an impairment in learning rate modulation in PSZ, leading to a reduced ability to adjust task behavior in response to unexpected outcomes. At the level of the brain, learning rate modulation deficits may be associated with decreased involvement of the dmPFC within a greater RL network.

Aim Neuroimaging-based multivariate pattern-recognition methods have been successfully used to develop diagnostic algorithms to distinguish patients with major depressive disorder (MDD) from healthy controls (HC). We developed and evaluated the accuracy of a multivariate classification method for the differentiation of MDD and HC using cerebral blood flow (CBF) features measured by non-invasive arterial spin labeling (ASL) MRI. Methods Twenty-two medication-free patients with the diagnosis of MDD based on DSM-IV criteria and 22 HC underwent pseudo-continuous 3-D-ASL imaging to assess CBF. Using an atlas-based approach, regional CBF was determined in various brain regions and used together with sex and age as classification features. A linear kernel support vector machine was used for feature ranking and selection as well as for the classification of patients with MDD and HC. Permutation testing was used to test for significance of the classification results. Results The automatic classifier based on CBF features showed a statistically significant accuracy of 77.3% (P = 0.004) with a specificity of 80% and sensitivity of 75% for classification of MDD versus HC. The features that contributed to the classification were sex and regional CBF of the cortical, limbic, and paralimbic regions. Conclusion Machine-learning models based on CBF measurements are capable of differentiating MDD from HC with high accuracy. The use of larger study cohorts and inclusion of other imaging measures may improve the performance of the classifier to achieve the accuracy required for clinical application.

Previous studies reported attenuated cortisol reactivity as one explanation for poor social functioning in schizophrenia. Recent research has demonstrated that both glucocorticoid and oxytocin systems are central to stress regulation. Here, we studied the associations between basal oxytocin, stress-induced cortisol levels, and social functioning and social support in schizophrenia. A mock job interview was used as an ecologically-valid social stressor in 32 schizophrenia patients. Blood samples were taken before and after stress induction to assess basal oxytocin and cortisol levels. In addition social functioning and social support scales were collected. Patients were divided into cortisol responders and non-responders according to percentage change following stress induction. Our findings revealed a possible subgroup of patients who did not exhibit attenuated cortisol responses. Importantly, cortisol responders had generally better social functioning, but perceived social support was not different between groups. There was also no evidence of a relationship between cortisol and oxytocin. This study highlights the heterogeneity of cortisol responses to stress in a schizophrenia population, and the importance of the relationship between social functioning and cortisol reactivity. These findings could be relevant when considering therapeutic interventions that manipulate endocrinology in order to improve real-world functioning. Ruhr University Research School - TUBITAK (The Scientific and Technological Research Council of Turkey) foreign researcher fellowship Ruhr University Research School funded the costs for the biochemical kits. Dr Brown was funded by a TUBITAK (The Scientific and Technological Research Council of Turkey) foreign researcher fellowship for the partial duration of this study. There are no conflicts of interest. WOS:000454972600148 29960725 Q2

BACKGROUND: People with schizophrenia (PSZ) can suffer from a reduced tendency to engage in goal-directed behavior, with these impairments often being associated with motivational deficit severity (e.g. amotivation, avolition). Previous work suggests that reductions in goal-directed behavior can be driven by an inability to represent the value of rewards (1) or impairments in adaptive instrumental learning, potentially related to abnormal signaling of reward prediction errors (2). Whether a compromised ability to seek out new information under uncertainty may contribute to deficits in goal-directed behavior, however, has received little attention. Here, we investigated uncertainty-driven exploration and associated neural responses during an explore/exploit paradigm. METHODS: 24 healthy volunteers (HV) and 26 PSZ performed a three-option slot machine task in a 3T MRI environment (based on Daw et al. (3)). During a stable phase (150 trials), reward payout for every machine fluctuated (sd=10), and one machine consistently was the optimal choice (i.e. the highest expected value). During a volatile phase (150 trials), reward payouts for every machine fluctuated (sd=10) and every 25 trials another machine would become the optimal choice. In the latter phase, participants had to actively sample from all three machines to maximize the total amount of accumulated reward. RESULTS: All participants made less optimal choices during the volatile, compared to the stable, phase (t=8.58, p

Introduction Understanding the biological underpinnings of unipolar (UD) and bipolar depression (BD) is vital for avoiding inappropriate treatment through the misdiagnosis of bipolar patients in their first depressive episode. One plausible way to distinguish between UD and BD is to compare EEG brain dynamics to identify potential neurophysiological biomarkers. Here we aimed to test group differences in EEG power, cordance and coherence values between UD and BD. Methods Twenty-five bipolar and 56 unipolar depression patients were recruited. Sociodemographic and clinical variables were collected in addition to resting state EEG. Data was analyzed with multivariate and repeated analyses of variance where parametric assumptions were met. Results Accordingly, we did not find any differences in the EEG absolute power and frontal asymmetry indexes between UD and BD. Regarding cordance, significant group differences were observed in the right theta cordance values (p=0.031). Regarding coherence, BD patients (as compared to UD) exhibited greater central–temporal theta (p=0.003), and parietal–temporal alpha (p=0.007) and theta (p=0.001) coherence. Lastly, less alpha coherence in BD was present at right frontal–central (p=0.007) and central inter-hemispheric (p=0.019) regions. Conclusions Our results demonstrate that EEG cordance and coherence values have potential to discriminate between UD and BD. The loss of temporal synchronization in the frontal interhemispheric and right sided frontolimbic neuronal networks may be a unique feature that distinguishes between BD and UD.

BACKGROUND: The current study was designed to test the hypothesis that motivational deficits in schizophrenia (SZ) are tied to a reduced ability to differentially signal gains and instances of loss-avoidance in the brain, leading to reduced ability to form adaptive representations of expected value. METHODS: We administered a reinforcement learning paradigm to 27 medicated SZ patients and 27 controls, in which participants learned three probabilistic discriminations. In regions of interest in reward networks identified a priori, we examined contrasts between trial-types with different expected values (Expected Gain – Non-monetary, e.g.), and between outcomes with the same prediction error valence but different experienced values (Gain – Loss-avoidance outcome, Miss – Loss outcome, e.g.). RESULTS: Both whole-brain and regions-of-interest analyses revealed that schizophrenia patients showed reduced differentiation between Gain and Loss-avoidance outcomes in dorsal anterior cingulate cortex and bilateral anterior insula. That is, SZ patients showed reduced contrasts between positive prediction errors of different objective values in these areas. Furthermore, we observed significant correlations between [Gain – Loss-avoidance outcome] contrasts in ventral striatum and ratings for Avolition/Anhedonia, and between [Expected Gain – Non-monetary] contrasts in ventral striatum and ventromedial prefrontal cortex. CONCLUSIONS: These results provide further evidence for intact prediction error signaling in medicated schizophrenia patients, especially with regard to loss-avoidance. By contrast components of frontostriatal circuits appear to show reduced sensitivity to the absolute valence of expected and experienced outcomes, suggesting a mechanism by which motivational deficits may emerge.

Background: In previous work (Gold et al., 2012), we found that, in the context of a reinforcement learning (RL) task, patients with schizophrenia (SZ) were more likely to subjectively value gains and instances of loss-avoidance similarly, although instances of loss-avoidance were objectively neutral. This finding was most true of avolitional SZ patients and was attributed to maladaptive representations of expected value (EV), in the presence of intact signaling of reward prediction errors (RPEs). In the current study, using fMRI, we investigated the neural basis of this phenomenon, hypothesizing that SZ patients would exhibit aberrant neural signals related to value-signaling in frontostriatal loops, rather than attenuated RPE signals.

Impairments in social functioning commonly seen in schizophrenia are thought to be mediated by deficits in the domains of social cognition. Some previous research has explored how social cognitive skills and psychotic symptoms are associated with social functioning, however these associations are still under debate. The main aim of this study was to investigate the relationship between different domains of social cognition and psychotic symptomatology, and also to look at the relationships with individual subdomains of social functioning within a clinically stable schizophrenia population. 45 outpatients were recruited and symptoms were assessed with the PANSS, and measures of emotion processing, affective and cognitive theory of mind (ToM), mental state reasoning attributional biases, and social functioning were taken. A correlational analysis was performed with the data. Following this, a regression analysis was used to reveal which domains of social cognition best predicted psychotic symptoms. In this stable group of patients, our results support the suggestion of a likely distinction between affective and cognitive components of ToM. The study also demonstrated that ToM and mental state reasoning were the best predictors of psychotic symptoms. Here we reveal that cognitive ToM had the most widespread relationship with social functioning, across multiple subdomains, while only some specific subdomains of social functioning correlated with other domains of social cognition and symptomatology. Further to this, positive symptoms were associated with much fewer subdomains of social functioning than negative and general symptoms. These findings imply that different aspects of social functioning may be served by different domains of social cognition and symptomatology. (C) 2014 Elsevier Inc. All rights reserved.

Die Gruppe der Schizophrenien umfasst heterogene psychopathologische Syndrome, die oft mit neurokognitiven Störungen und niedrigem psychosozialen Funktionsniveau assoziiert sind. Empirische Studien legen nahe, dass viele mit Schizophrenie assoziierte Symptome auf Störungen der sozialen Kognition bzw. metakognitive Störungen zurückgeführt werden können. Diese Konzepte beziehen sich auf die Fähigkeit, soziale Signale wahrnehmen und interpretieren, eigene und psychische Zustände Anderer reflektieren und dieses Wissen flexibel in sozialen Interaktionen und zur Problemlösung einsetzen zu können. Der vorliegende Artikel gibt eine Übersicht über sozial-kognitive und metakognitive Defizite bei Schizophrenien und wie über das Training dieser Kernkompetenzen das psychosoziale Funktionsniveau von Patienten mit Schizophrenie verbessert werden kann. Bei Schizophrenien sind soziale Kognition und Metakognition eng mit dem psychosozialen Funktionsniveau verbunden, zum Teil jedoch auch abhängig von neurokognitiven Fähigkeiten. Sozial-kognitives bzw. metakognitives Training kann zur Verbesserung des psychosozialen Funktionsniveaus beitragen, möglicherweise aber in Abhängigkeit vom Lernpotential und der Motivation der Patienten. Zukünftige Studien sollten untersuchen, welche Subtypen innerhalb des Schizophrenie-Spektrums am ehesten von sozial-kognitivem und metakognitivem Training profitieren können und welche Gruppen ggf. zusätzlich neurokognitives Training benötigen, um das psychosoziale Funktionsniveau zu verbessern.

The term “schizophrenia” refers to a debilitating group of disorders that usually results in a severely impaired quality of life (QoL). Symptomatology appears to have a substantial role in determining QoL, although the relationship between QoL and specific psychotic symptoms is still unclear and has demonstrated mixed results. Due to the intrinsic importance of social functioning in QoL, and the mediating effect of social cognition on social functioning, the aim of this study was to try to investigate QoL in schizophrenia, not only in terms of symptomatology, but also in consideration of potential neurocognitive and social cognitive contributing factors. Methods Twenty-eight clinically stable patients with schizophrenia performed a broad range of neurocognitive and social cognitive assessments, and also participated in a semi-structured interview of QoL, assessing four partially independent subdomains of QoL. A stepwise regression model was used to determine the best predictors of QoL, and additionally a mediator analysis was performed to test for the mediating power of social cognition on QoL. Results Negative symptoms, intelligence, executive functioning and social cognition all had some power in predicting QoL in schizophrenia. Though most interestingly, mental state reasoning was specifically found to be most strongly related with the Intrapsychic Foundation subdomain of QoL, whereas neurocognition and symptom severity were associated with other subdomains of QoL. Conclusions The association between mental state reasoning and the more “internal” aspects of QoL in schizophrenia may reflect a specific role for social cognition in introspective and subjective judgments of one's own QoL, whereas neurocognition and negative symptomatology may be more predictive of the external or extrinsic aspects of QoL. In conclusion, social cognitive skills appear to play a crucial role in the experience of one's own subjective well-being, which could help to explain previous inconsistencies in the literature investigating QoL in schizophrenia.

Impairments in the mirror neuron system (MNS) have been implicated as a possible underlying neurological basis for deficits in higher-level social cognition in schizophrenia. Previous work testing this hypothesis has used the electroencephalographic mu rhythm as an index of MNS activity, with studies showing mixed results. Here we investigated the role that reward plays in modulating the mu rhythm, and its association with empathy and emotional mental state reasoning. A group of schizophrenia patients and a healthy control group completed an action observation paradigm in which they watched actions that were financially rewarding, punishing, or neutral. Patients showed intact reward-related modulation of the mu rhythm, and greater mu suppression was associated with greater negative symptoms. There was also a trend for reduced mu suppression in patients. Furthermore, both empathy and emotional mental state reasoning were associated with the degree of mu suppression, but only in healthy controls. These findings confirm the association between the mu suppression and high-level social cognition. It is possible that schizophrenia patients utilize different cognitive routes to infer mental states. The demonstration that reward influences the degree of mu suppression in schizophrenia patients may help to account for previous conflicting findings in the literature.

Objective: Recent studies in patients with Bipolar Disorder (BD) have revealed problems in emotion recognition, specifically for negative emotions, which have been subsequently related to amygdala activity. Previously, the prosocial neuropeptide oxytocin has been shown to be one hormone that alters emotion perception capacities and modulates amygdala response. Accordingly, the aim of this study was to see if plasma oxytocin levels have specific effects on predicting emotion recognition patterns in BD. Methods: Twenty-eight remitted BD patients were recruited for this study and the Vienna Emotion Recognition Task was given. In addition, blood samples were collected for plasma oxytocin analysis. Results: Strong associations were found between fearful emotions and basal oxytocin levels, which were supported by a stepwise regression analysis. Patients with higher levels of basal oxytocin also exhibited greater recognition of fearful emotions. Conclusions: The relationship between recognition of fearful faces and individual endogenous oxytocin levels may contribute to explaining individual differences in social functioning and amygdala dysfunction in BD.

Background The Iowa Gambling Task (IGT; Bechara et al., 1994) has frequently been used to assess risky decision making in clinical populations, including patients with schizophrenia (SZ). Poor performance on the IGT is often attributed to reduced sensitivity to punishment, which contrasts with recent findings from reinforcement learning studies in schizophrenia. Methods In order to investigate possible sources of IGT performance deficits in SZ patients, we combined data from the IGT from 59 SZ patients and 43 demographically-matched controls with data from the Balloon Analog Risk Task (BART) in the same participants. Our analyses sought to specifically uncover the role of punishment sensitivity and delineate the capacity to integrate frequency and magnitude information in decision-making under risk. Results Although SZ patients, on average, made more choices from disadvantageous decks than controls did on the IGT, they avoided decks with frequent punishments at a rate similar to controls. Patients also exhibited excessive loss-avoidance behavior on the BART. Conclusions We argue that, rather than stemming from reduced sensitivity to negative consequences, performance deficits on the IGT in SZ patients are more likely the result of a reinforcement learning deficit, specifically involving the integration of frequencies and magnitudes of rewards and punishments in the trial-by-trial estimation of expected value.

Objective: Recent studies in patients with Bipolar Disorder (BD) have revealed problems in emotion recognition, specifically for negative emotions, which have been subsequently related to amygdala activity. Previously, the prosocial neuropeptide oxytocin has been shown to be one hormone that alters emotion perception capacities and modulates amygdala response. Accordingly, the aim of this study was to see if plasma oxytocin levels have specific effects on predicting emotion recognition patterns in BD. Methods: Twenty-eight remitted BD patients were recruited for this study and the Vienna Emotion Recognition Task was given. In addition, blood samples were collected for plasma oxytocin analysis. Results: Strong associations were found between fearful emotions and basal oxytocin levels, which were supported by a stepwise regression analysis. Patients with higher levels of basal oxytocin also exhibited greater recognition of fearful emotions. Conclusions: The relationship between recognition of fearful faces and individual endogenous oxytocin levels may contribute to explaining individual differences in social functioning and amygdala dysfunction in BD.

Background: There is a rapidly amassing body of evidence suggesting that reinforcement learning may be impaired in schizophrenia (SZ). Reinforcement learning not only depends on the ability to signal reward prediction errors (RPEs), but also on the ability to modulate the impact that RPEs have on learning, especially in a volatile environment. Here, we investigated the ability of individuals with SZ to use RPEs to rapidly update their decision-making strategies and the neural correlates thereof.

Background Schizophrenia is a debilitating mental disorder that presents impairments in neurocognition and social cognition. Several studies have suggested that the etiology of schizophrenia can be partly explained by oxidative stress. However, our knowledge about the implications of oxidative stress on illness-related cognitive deficits is still far from being clear. The aim of this work was to study the role of oxidative stress molecules on social cognition and neurocognition in patients with schizophrenia. Methods We assessed the peripheral levels of several molecules associated with oxidative stress, namely nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), homocysteine, superoxide dismutase (SOD) and neurotrophin 4/5 (NT4/5), in forty–one patients with schizophrenia and forty-three healthy participants. A battery of tests to measure neurocognition and social cognition was also administered to the schizophrenia group. Results We found that the schizophrenia group presented substantially higher levels of oxidative stress than the control group, as revealed by elevated quantities of the pro-oxidants NO and MDA, and decreased levels of the antioxidants GSH, SOD and NT4/5. Interestingly, the levels of NT4/5, which have been shown to have antioxidant effects, correlated with executive functioning, as measured by two distinct tests (WCST and TMT). However, social cognition and symptom severity were not found to be associated with oxidative stress. Conclusions We propose a protective role of NT4/5 against oxidative stress, which appears to have a potentially beneficial impact on neurocognition in schizophrenia.

Exciting new research has revealed that the administration of oxytocin can improve empathetic abilities, increase trustworthiness and other attachment-related behaviors, and reduce social anxiety in both healthy and some clinical populations. A growing body of work has explored the potential therapeutic benefit of oxytocin for improving deficits in social cognition in schizophrenia. The aim of this chapter is to review the current state of this work, including current limitations and issues for future work.

While deficits in metacognition have been observed in schizophrenia (SZ), it is less clear whether these are specific to the disorder. Accordingly, this study compared metacognitive abilities of patients with schizophrenia and bipolar disorder (BD) and examined the degree to which neurocognition contributed to metacognitive deficits in both groups. Participants were 30 patients with SZ and 30 with BD. Metacognitive capacity was measured using the Metacognition Assessment Scale Abbreviated (MAS-A). This scale comprises four domains: self-reflectivity, understanding others׳ minds, decentration and mastery. Verbal memory, executive functioning and symptoms were concurrently assessed. Group comparisons revealed that SZ patients had greater deficits in metacognitive self-reflectivity, which correctly classified 85.2% of patients with SZ in a logistic regression. Self-reflectivity and understanding others׳ minds were related to verbal memory and executive functioning in the SZ group, but not in the BD group. Furthermore, greater positive and general psychotic symptoms were associated with poorer metacognition in SZ. Results suggest SZ involves unique deficits in the ability to self-reflect and that these deficits may be uniquely linked with neurocognition.

With the contribution of social neuroscience in neuropsychiatry, a large body of literature has suggested that schizophrenia is a product of a dysfunction in the ‘social brain’. The rising interest in the field of social neuroscience has provided an instrumental foundation for understanding how the social brain may be going wrong in schizophrenia, and how neurobiologic abnormalities may help to explain deficits in social cognition. So far, work using animal disease models and neuroimaging in patients has already made progress in uncovering some of the neurobiologic factors related to social cognitive deficits in schizophrenia. This chapter will summarize the work to date in this area, while also raising some crucial unresolved issues in this field by taking a critical view on the literature, and making future suggestions for research.

Kuzu, Duygu (Arel Author), Patients with schizophrenia suffer from dysfunctional social behaviour. Social approach and avoidance (AA) has been associated with motor responses, as the affective valence and gaze direction of facial stimuli can bias push and pull motor tendencies. The aim of this study was to investigate the role of endogenous oxytocin in social AA behaviour in schizophrenia. Basal plasma oxytocin levels were collected from 28 patients who were then given a joystick-based Approach-Avoidance Task (AAT). Reaction times were recorded and AAT effect scores calculated for responses to happy and angry faces, which either had direct or averted gaze. Individual differences in basal oxytocin had a significant relationship with AAT responses, and patients with higher levels of oxytocin tended to avoid angry faces more. Furthermore, greater avoidance of angry faces was correlated with more severe psychotic (positive and general) symptoms and greater paranoia. This suggests that the endogenous effects of oxytocin may be specific to the interpretation of negative threatening emotions in schizophrenia patients, and also provides evidence that psychotic symptoms and paranoia can impact on social AA behaviour by heightening threat avoidance.

Patients with anxiety spectrum disorders are a highly heterogeneous group, requiring new therapeutic strategies and individualized treatment monitoring. Today, there is a growing interest for implementing biological approaches to clinical practice in psychiatry. Quantitative EEG is an excellent tool in this regard, though it has been widely underestimated when compared to recent neuroimaging techniques. In this case series, we presented four cases with a different diagnosis of anxiety spectrum disorder and evaluated their qEEG changes before and after the treatment. In addition, we also calculated the so-called EEG cordance values as an index of cerebral perfusion and cingulate cortex activity. According to the results, there appears to be an increase in the frontal beta and theta band in our cases, which has responded to treatment. In regards to the cordance values, we found that there was a reduction in the prefrontal regions up to %38 percent following the treatment. Based on previous studies, this may also indirectly suggest reduction in the cingulate cortex activity. The possible implications of these findings were discussed. Taken together, this case series highlighted the potential use of qEEG power values, normative z-scores and cordance values in treatment response monitoring of anxiety spectrum disorders.