Andràs Tikàsz

Abnormal effective fronto-limbic connectivity during emotion processing in schizophrenia

Background: Schizophrenia is associated with core emotional dysfunctions. At the neural level, functional neuro‐imaging studies have highlighted fronto‐limbic alterations during emotion processing in schizophrenia, as well as impaired connectivity between the amygdala and the prefrontal cortex. However, the direction of the impaired fronto‐limbic connections remains largely unknown. To clarify this issue, we performed an effective connectivity study on emotion processing in schizophrenia. Methods: Forty‐one healthy individuals and 39 schizophrenia patients (DSM‐IV criteria) viewed negative, positive and neutral images during an fMRI session. Effective connectivity between significantly activated regions was examined using Granger causality and psychophysical interaction analyses. Results: Subjective ratings of emotionally neutral images were higher in schizophrenia patients than in controls. Across groups, significant activations were observed in the dorso‐medial prefrontal cortex (dmPFC) and the bilateral amygdala. The Granger connectivity from the right amygdala to the dmPFC was significantly reduced in schizophrenia patients, relative to controls, during the negative and neutral conditions. The Granger connectivity from the left amygdala to the dmPFC was significantly reduced in schizophrenia patients, relative to controls, during the positive condition. Discussion: The finding of a reduced lagged connectivity from the bilateral amygdala to the dmPFC in schizophrenia suggests that the bottom‐up mechanisms involved in the processing of highly arousing emotional stimuli are impaired in this disorder. The finding of an impaired lagged connectivity from the right amygdala to the dmPFC during the processing of emotionally neutral stimuli in schizophrenia is novel and may explain why these patients tend to confer emotional significance to irrelevant stimuli. HIGHLIGHTSActivations in the dmPFC and the amygdala (AMG) during emotion processing were observed across groups.Connectivity from the right AMG to the dmPFC was significantly reduced in schizophrenia patients during negative conditions.Connectivity from the left AMG to the dmPFC was significantly reduced in schizophrenia patients during positive conditions.Bottom‐up mechanisms involved in the processing of highly arousing emotional stimuli are impaired in schizophrenia patients.

Emotion processing in treatment-resistant schizophrenia patients treated with clozapine: An fMRI study

OBJECTIVES To examine the neural correlates of emotion processing in treatment-resistant patients with schizophrenia (SCZ-TR). METHODS Twenty-two SCZ-TR patients on clozapine, 24 schizophrenia patients on antipsychotics other than clozapine, and 39 healthy controls were scanned using functional neuroimaging while viewing positive, negative and neutral images. RESULTS Emotionally-laden images (positive and negative) elicited hyper-activations in the dorso-medial prefrontal cortex and left cerebellum in SCZ-TR patients, compared to the two other groups. Similarly, neutral images prompted hyper-activations in the cingulate gyrus in SCZ-TR patients, relative to the two other groups. CONCLUSIONS Treatment resistance is associated with neuro-functional hyper-activations in schizophrenia patients during emotion processing.

Cigarette Cravings, Impulsivity, and the Brain.

Craving is a core feature of tobacco use disorder as well as a significant predictor of smoking relapse. Studies have shown that appetitive smoking-related stimuli (e.g., someone smoking) trigger significant cravings in smokers impede their self-control capacities and promote drug seeking behavior. In this review, we begin by an overview of functional magnetic resonance imaging (fMRI) studies investigating the neural correlates of smokers to appetitive smoking cues. The literature reveals a complex and vastly distributed neuronal network underlying smokers’ craving response that recruits regions involved in self-referential processing, planning/regulatory processes, emotional responding, attentional biases, and automatic conducts. We then selectively review important factors contributing to the heterogeneity of results that significantly limit the implications of these findings, namely between- (abstinence, smoking expectancies, and self-regulation) and within-studies factors (severity of smoking dependence, sex-differences, motivation to quit, and genetic factors). Remarkably, we found that little to no attention has been devoted to examine the influence of personality traits on the neural correlates of cigarette cravings in fMRI studies. Impulsivity has been linked with craving and relapse in substance and tobacco use, which prompted our research team to examine the influence of impulsivity on cigarette cravings in an fMRI study. We found that the influence of impulsivity on cigarette cravings was mediated by fronto-cingulate mechanisms. Given the high prevalence of cigarette smoking in several psychiatric disorders that are characterized by significant levels of impulsivity, we conclude by identifying psychiatric patients as a target population whose tobacco-smoking habits deserve further behavioral and neuro-imaging investigation.

Anterior cingulate hyperactivations during negative emotion processing among men with schizophrenia and a history of violent behavior.

Background Evidence suggests a 2.1–4.6 times increase in the risk of violent behavior in schizophrenia compared to the general population. Current theories propose that the processing of negative emotions is defective in violent individuals and that dysfunctions within the neural circuits involved in emotion processing are implicated in violence. Although schizophrenia patients show enhanced sensitivity to negative stimuli, there are only few functional neuroimaging studies that have examined emotion processing among men with schizophrenia and a history of violence. Objective The present study aimed to identify the brain regions with greater neurofunctional alterations, as detected by functional magnetic resonance imaging during an emotion processing task, of men with schizophrenia who had engaged in violent behavior compared with those who had not. Methods Sixty men were studied; 20 with schizophrenia and a history of violence, 19 with schizophrenia and no violence, and 21 healthy men were scanned while viewing positive, negative, and neutral images. Results Negative images elicited hyperactivations in the anterior cingulate cortex (ACC), left and right lingual gyrus, and the left precentral gyrus in violent men with schizophrenia, compared to nonviolent men with schizophrenia and healthy men. Neutral images elicited hyperactivations in the right and left middle occipital gyrus, left lingual gyrus, and the left fusiform gyrus in violent men with schizophrenia, compared to the other two groups. Discussion Violent men with schizophrenia displayed specific increases in ACC in response to negative images. Given the role of the ACC in information integration, these results indicate a specific dysfunction in the processing of negative emotions that may trigger violent behavior in men with schizophrenia.

Emotionally Neutral Stimuli Are Not Neutral in Schizophrenia: A Mini Review of Functional Neuroimaging Studies.

Reliable evidence shows that schizophrenia patients tend to experience negative emotions when presented with emotionally neutral stimuli. Similarly, several functional neuroimaging studies show that schizophrenia patients have increased activations in response to neutral material. However, results are heterogeneous. Here, we review the functional neuroimaging studies that have addressed this research question. Based on the 36 functional neuroimaging studies that we retrieved, it seems that the increased brain reactivity to neutral stimuli is fairly common in schizophrenia, but that the regions involved vary considerably, apart from the amygdala. Prefrontal and cingulate sub-regions and the hippocampus may also be involved. By contrasts, results in individuals at risk for psychosis are less consistent. In schizophrenia patients, results are less consistent in the case of studies using non-facial stimuli, explicit processing paradigms, and/or event-related designs. This means that human faces may convey subtle information (e.g., trustworthiness) other than basic emotional expressions. It also means that the aberrant brain reactivity to neutral stimuli is less likely to occur when experimental paradigms are too cognitively demanding as well as in studies lacking statistical power. The main hypothesis proposed to account for this increased brain reactivity to neutral stimuli is the aberrant salience hypothesis of psychosis. Other investigators propose that the aberrant brain reactivity to neutral stimuli in schizophrenia results from abnormal associative learning, untrustworthiness judgments, priming effects, and/or reduced habituation to neutral stimuli. In the future, the effects of antipsychotics on this aberrant brain reactivity will need to be determined, as well as the potential implication of sex/gender.

Psychopathology in Substance Use Disorder Patients with and without Substance-Induced Psychosis

Background. Substance-induced psychotic disorder (SIPD) is a diagnosis constructed to distinguish substance-induced psychotic states from primary psychotic disorders. A number of studies have compared SIPD persons with primary psychotic patients, but there is little data on what differentiates substance use disorder (SUD) individuals with and without SIPD. Here, we compared psychopathology, sociodemographic variables, and substance use characteristics between SUD patients with and without SIPD. Methods. A retrospective chart review was conducted on newly admitted patients at a rehabilitation centre between 2007 and 2012. Results. Of the 379 patients included in the study, 5% were diagnosed with SIPD (n = 19) and 95% were diagnosed with SUDs without SIPD (n = 360). More SIPD patients reported using cannabis and psychostimulants, and fewer SIPD patients reported using alcohol than SUDs patients without SIPD. SIPD patients scored higher on the “schizophrenia nuclear symptoms” dimension of the SCL-90R psychoticism scale and exhibited more ClusterB personality traits than SUD patients without SIPD. Discussion. These data are consistent with previous studies suggesting that psychopathology, substance type, and sociodemographic variables play important role in the development of SIPD. More importantly, the results highlight the need for paying greater attention to the types of self-reported psychotic symptoms during the assessment of psychotomimetic effects associated with psychoactive substances.

Increased spinal pain sensitization in major depressive disorder: A pilot study

Although patients suffering from major depressive disorder (MDD) often complain from painful symptoms, the relationship between experimental pain processes and depression has yet to be clearly characterized. Only recently have studies employing temporal summation (TS) paradigms offered preliminary insight into the co-occurrence of pain and depression. This study sets out to evaluate the contribution of spinal and supraspinal processes in pain sensitization in MDD using a TS paradigm. Thirteen volunteers with no psychiatric disorders (controls) and fourteen MDD subjects were included in the analysis. Low-(0.14Hz) and high-(1Hz) frequency intermittent stimulations of the sural nerve were used to induce TS. Spinal pain sensitization was quantified by measuring the change in the amplitude of the nociceptive-specific flexion reflex (NFR) response, and supraspinal pain sensitization was obtained by measuring change in subjective pain rating, from the low- to high-frequency stimulation condition. We found an increased sensitization in the NFR response (p<0.05) in MDD subjects in the high-frequency condition, which did not translate into an increase of their subjective responses. However, we found a positive association between spinal sensitization and painful somatic symptoms in MDD subjects. Together, these results suggest increased spinal pain sensitization in MDD, which might explain the high prevalence of painful somatic symptoms in these patients.

Reduced dorsolateral prefrontal cortex activation during affective Go/NoGo in violent schizophrenia patients: An fMRI study

We investigated the influence of anger processing on cognitive control in male schizophrenia patients presenting violent behaviors. We recruited 23 patients without and 24 patients with (SCZ+V) a history of violent behaviors, as well as 22 healthy non-violent men. Participants were administered an affective (angry-neutral faces) Go/NoGo task while undergoing functional magnetic resonance imaging. We found a reduced activation in the dorsolateral prefrontal cortex in SCZ+V patients specifically when inhibiting a response while viewing angry faces. These results show an inability of SCZ+V to recruit a core region of the (inhibitory) cognitive control network in the context of anger.

History of Suicide Attempt Is Associated with Reduced Medial Prefrontal Cortex Activity during Emotional Decision-Making among Men with Schizophrenia: An Exploratory fMRI Study

Despite the high prevalence of suicidal ideas/attempts in schizophrenia, only a handful of neuroimaging studies have examined the neurobiological differences associated with suicide risk in this population. The main objective of the current exploratory study is to examine the neurofunctional correlates associated with a history of suicide attempt in schizophrenia, using a risky decision-making task, in order to show alterations in brain reward regions in this population. Thirty-two male outpatients with schizophrenia were recruited: 13 patients with (SCZ + S) and 19 without a history of suicidal attempt (SCZ − S). Twenty-one healthy men with no history of mental disorders or suicidal attempt/idea were also recruited. Participants were scanned using fMRI while performing the Balloon Analogue Risk Task. A rapid event-related fMRI paradigm was used, separating decision and outcome events, and the explosion probabilities were included as parametric modulators. The most important finding of this study is that SCZ + S patients had reduced activations of the medial prefrontal cortex during the success outcome event (with parametric modulation), relative to both SCZ − S patients and controls, as illustrated by a spatial conjunction analysis. These exploratory results suggest that a history of suicidal attempt in schizophrenia is associated with blunted brain reward activity during emotional decision-making.