Laura M. Tully

The neural basis of theory of mind and its relationship to social functioning and social anhedonia in individuals with schizophrenia

Theory of mind (ToM), the ability to attribute and reason about the mental states of others, is a strong determinant of social functioning among individuals with schizophrenia. Identifying the neural bases of ToM and their relationship to social functioning may elucidate functionally relevant neurobiological targets for intervention. ToM ability may additionally account for other social phenomena that affect social functioning, such as social anhedonia (SocAnh). Given recent research in schizophrenia demonstrating improved neural functioning in response to increased use of cognitive skills, it is possible that SocAnh, which decreases ones opportunity to engage in ToM, could compromise social functioning through its deleterious effect on ToM-related neural circuitry. Here, twenty individuals with schizophrenia and 18 healthy controls underwent fMRI while performing the False-Belief Task. Aspects of social functioning were assessed using multiple methods including self-report (Interpersonal Reactivity Index, Social Adjustment Scale), clinician-ratings (Global Functioning Social Scale), and performance-based tasks (MSCEIT—Managing Emotions). SocAnh was measured with the Revised Social Anhedonia Scale. Region-of-interest and whole-brain analyses revealed reduced recruitment of medial prefrontal cortex (MPFC) for ToM in individuals with schizophrenia. Across all participants, activity in this region correlated with most social variables. Mediation analysis revealed that neural activity for ToM in MPFC accounted for the relationship between SocAnh and social functioning. These findings demonstrate that reduced recruitment of MPFC for ToM is an important neurobiological determinant of social functioning. Furthermore, SocAhn may affect social functioning through its impact on ToM-related neural circuitry. Together, these findings suggest ToM ability as an important locus for intervention.

A Pilot Study of Cognitive Training in Clinical High Risk for Psychosis: Initial evidence of cognitive benefit

Individuals at clinical high risk (CHR) for psychosis have cognitive deficits that are associated with functional impairment and psychosis conversion (Giuliano et al., 2012). Targeted cognitive training (TCT) (i.e., intense, progressively difficult practice of a cognitive skill) improves cognition and daily functioning in schizophrenia (Wykes et al., 2011). TCT has been proposed as a preventive intervention for CHR, but research is minimal and optimal training parameters, including dose, intensity, and setting, are unknown. Because prolonged duration of untreated CHR symptoms can compromise outcome, rapid treatment response is essential (Fusar-Poli et al., 2009). However, ambiguous risk status, psychosis-related stigma, and practical scheduling problems can reduce treatment motivation and compliance. Without pilot data to guide intervention development, the randomized-controlled trials necessary to show efficacy of cognitive training in CHRmay be unsuccessful. This study investigated the feasibility and potential behavioral benefits of 40 h/8 weeks of computer-based TCT in a single group of CHR participants. Cognitive and functional outcome were assessed with measures recommended for clinical trials, including the MATRICS Consensus Cognitive Battery (MCCB) and Global Functioning (GF): Role and Social scales (Cornblatt et al., 2007). Training performance was analyzed to: verify the relationship between training engagement and treatment outcome; identify an early predictor of treatment response; and evaluate intervention dose.

Neural activity to positive expressions predicts daily experience of schizophrenia-spectrum symptoms in adults with high social anhedonia.

Social anhedonia (SA), the diminished pleasure from social relationships, is a prominent characteristic of the vulnerability and manifestation of schizophrenia disorder. However, SA can develop for multiple reasons and little is known about its neural basis; these 2 issues hinder the utility and sensitivity of SA as a marker of schizophrenia pathology. This study investigated whether lateral prefrontal cortex (LPFC) deficits in social reward processing are associated with both SA and other schizophrenia-spectrum symptoms. During functional MRI (fMRI), a community sample of healthy adults (N = 30) with high and low SA viewed positive, negative, and neutral facial expressions. Afterward, participants completed an online daily diary in which they rated schizophrenia-spectrum symptoms and occurrence of interpersonal conflict each day for 21 days. Compared with low SA, high SA participants had less ventral (V)LPFC activity to positive versus neutral expressions. In addition, participants with a combination of high SA and low VLPFC activity to positive versus neutral expressions had worse daily diary ratings of schizophrenia-spectrum symptoms, including worse cognition, paranoia, motivation/productivity, and vigor/positive affect (i.e., psychomotor activation). Finally, among high SA participants, VLPFC activity predicted the daily relationship between distress from interpersonal conflict and symptom-severity; specifically, high SA participants with low VLPFC activity had worse paranoia on days of high conflict distress. These findings indicate that VLPFC deficits in positive emotion are associated with both SA and other schizophrenia-spectrum symptoms and that understanding the interaction of SA, VLPFC function, and social stress could facilitate the use of SA in the prevention and treatment of schizophrenia.

Impaired executive control of emotional information in social anhedonia

We examined the executive control of emotional information and its relationship to social functioning in individuals at risk for schizophrenia, defined by high social anhedonia (SA). Using the same structure as the Attentional Network Test (ANT), we developed a measure of executive control of emotional information (ANT-Emotion) in which subjects identify the direction of an arrow flanked by irrelevant angry or neutral faces. Subjects completed the ANT, ANT-Emotion, and the Social Adjustment Scale, Self-Report (SAS-SR), a measure of social functioning. While there were no group differences in the alerting, orienting, and executive control networks assessed by the ANT, high SA individuals exhibited a specific impairment in the executive control of emotional information. High SA individuals also reported poorer social functioning. However, executive control of emotional information did not mediate the relationship between SA and social functioning. These findings indicate that, in high-risk populations, the impaired ability to inhibit emotional information allows negative affective stimuli to exert inappropriate influence on cognitive processes. These results are consistent with studies indicating similar findings in schizophrenia patients, suggesting that impaired inhibition of negative emotion may be part of the liability for the disorder.

Social impairment in schizophrenia: New approaches for treating a persistent problem

Purpose of review Deficits in social cognition are an important determinant of social functioning in schizophrenia, a core feature of the illness that persists despite treatment. Recent research in neuroplasticity-based therapeutics shows that neural systems supporting core cognitive skills improve after targeted cognitive training, suggesting that social cognition, and concomitant social functioning, may be improved by targeting the neural systems supporting social cognition. However, the success of this approach depends on the extent to which the social brain is malleable. We review the neural effects of training programs focused on improving social cognition in healthy, schizophrenia, and other clinical samples. Recent findings The current literature suggests that the neural mechanisms underlying social cognition show neuroplastic changes after behavioral training and these neural changes confer concomitant benefits to social cognition and social behavior. Most research in schizophrenia has focused on emotion recognition, and although emotion recognition training has behavioral and neural benefits for schizophrenia, more advanced social cognitive processes need to be examined. Summary The data suggest that targeting neural systems underlying social cognition through socially focused behavioral interventions may improve social functioning impairments in schizophrenia. Questions remain regarding how to optimize training, which should be addressed in future work.

Lateral prefrontal cortex activity during cognitive control of emotion predicts response to social stress in schizophrenia.

LPFC dysfunction is a well-established neural impairment in schizophrenia and is associated with worse symptoms. However, how LPFC activation influences symptoms is unclear. Previous findings in healthy individuals demonstrate that lateral prefrontal cortex (LPFC) activation during cognitive control of emotional information predicts mood and behavior in response to interpersonal conflict, thus impairments in these processes may contribute to symptom exacerbation in schizophrenia. We investigated whether schizophrenia participants show LPFC deficits during cognitive control of emotional information, and whether these LPFC deficits prospectively predict changes in mood and symptoms following real-world interpersonal conflict. During fMRI, 23 individuals with schizophrenia or schizoaffective disorder and 24 healthy controls completed the Multi-Source Interference Task superimposed on neutral and negative pictures. Afterwards, schizophrenia participants completed a 21-day online daily-diary in which they rated the extent to which they experienced mood and schizophrenia-spectrum symptoms, as well as the occurrence and response to interpersonal conflict. Schizophrenia participants had lower dorsal LPFC activity (BA9) during cognitive control of task-irrelevant negative emotional information. Within schizophrenia participants, DLPFC activity during cognitive control of emotional information predicted changes in positive and negative mood on days following highly distressing interpersonal conflicts. Results have implications for understanding the specific role of LPFC in response to social stress in schizophrenia, and suggest that treatments targeting LPFC-mediated cognitive control of emotion could promote adaptive response to social stress in schizophrenia.

Impaired cognitive control mediates the relationship between cortical thickness of the superior frontal gyrus and role functioning in schizophrenia

Structural abnormalities in the lateral prefrontal cortex (LPFC) are well-documented in schizophrenia and recent evidence suggests that these abnormalities relate to functional outcome. Cognitive control mechanisms, reliant on the LPFC, are impaired in schizophrenia and predict functional outcome, thus impaired cognitive control could mediate the relationship between neuroanatomical abnormalities in the LPFC and functional outcome. We used surface-based morphometry to investigate relationships between cortical surface characteristics, cognitive control, and measures of social and role functioning in 26 individuals with schizophrenia and 29 healthy controls. Results demonstrate that schizophrenia participants had thinner cortex in a region of the superior frontal gyrus (BA10). Across all participants, decreased cortical thickness in this region related to decreased cognitive control and decreased role functioning. Moreover, cognitive control fully mediated the relationship between cortical thickness in the superior frontal gyrus and role functioning, indicating that neuroanatomical abnormalities in the LPFC adversely impact role functioning via impaired cognitive control processes.

The 2nd Schizophrenia International Research Society Conference, 10-14 April 2010, Florence, Italy: summaries of oral sessions.

The 2nd Schizophrenia International Research Society Conference, was held in Florence, Italy, April 10-15, 2010. Student travel awardees served as rapporteurs of each oral session and focused their summaries on the most significant findings that emerged from each session and the discussions that followed. The following report is a composite of these reviews. It is hoped that it will provide an overview for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research.

Cognitive-Processing Biases in Individuals High on Perceived Criticism

A considerable literature now shows that perceived criticism (PC) predicts clinical outcomes transdiagnostically. Recent work has begun to identify potential mechanisms underlying PC’s connection to clinical outcomes. For example, anomalies have been found in neural processing when individuals who rate their key relatives as highly critical listen to criticism. To explore whether high-PC individuals are also characterized by other processing abnormalities, we examined cognitive processing in a sample of community participants (N = 76) high or low on PC. We measured the executive control of attention when these two groups of individuals processed emotional information and interpreted acoustically presented ambiguous words. High-PC individuals showed impaired executive control of negative emotional information relative to low-PC individuals. They also made more negative interpretations of ambiguous words. These findings indicate that PC is associated with underlying vulnerabilities that may predispose individuals to develop psychopathology.

The Next Big Thing in Child and Adolescent Psychiatry: Interventions to Prevent and Intervene Early in Psychiatric Illnesses

The last two decades have marked tremendous progress in our ability to prevent and intervene early in psychiatric illnesses. The interventions described in this article range from established, empirically-supported treatments to creative interventions early in their development and deployment. Some of these interventions are low-technology programs delivered in social settings (such as schools), and some rely on sophisticated emerging technologies such as neuroimaging. This article reviews 4 preventative interventions: 1) The use of structural brain imaging to identify children at risk for familial depression who are most likely to benefit from preventative cognitive behavioral therapy 2) The Good Behavior Game, a school based program that, when implemented in 1st grade classrooms, cut the incidence of substance use disorders in students in half when those students were 19 years old, 3) The SPARX video game, which has the potential to be an accessible, appealing, and cost-effective treatment for the thousands of teens affected by mild to moderate depressive disorders, and 4) Intensive psychosocial treatments which can reduce the progression of from the ultra high risk state to the first episode psychosis by 50% over 12 months. All of these interventions have tremendous potential to reduce the suffering and disability caused by psychiatric illness to both children and adults.