Brain Training in Clinical High Risk for Psychosis
The devastating personal and societal consequences of schizophrenia have mobilized a world-wide effort to improve early detection, and early, preventive intervention for individuals at risk for psychosis. Early detection research illustrates a ‘clinical high risk’ (CHR) state that precedes frank psychosis and is characterized by attenuated (i.e. mild) psychotic symptoms, brief psychotic experiences, or genetic vulnerability with functional decline. Neural abnormalities and associated cognitive deficits that are characteristic of schizophrenia are evident, though less severe, in CHR, and deteriorate as illness progresses. Approximately 36% of CHR develop psychosis within three years (Fusar-Poli et al., 2013; Fusar-Poli et al., 2012) and CHR with worse neurocognitive deficits have higher probability of conversion, indicating neurocognition as a biomarker of psychosis risk (Fusar-Poli et al., 2012; Giuliano et al., 2012). Development and implementation of early intervention in psychosis faces numerous challenges. Psychosis-related treatments have significant costs with unclear benefits for CHR. Anti-psychotic medications have negative side-effects and long-term health consequences (Ho, Andreasen, Ziebell, Pierson, & Magnotta, 2011) and it is not clear that anti-psychotics reduce sub-threshold positive symptoms or prevent psychosis. Most CHR individuals never develop psychosis, yet continue to experience cognitive deficits and functional disability (Addington et al., 2011) which anti-psychotic medications do not improve. Moreover, without appropriate context, stigma associated with psychosis can cause unintended adverse consequences from psychosocial interventions focused, specifically, on psychosis-risk (Park, Bennett, Couture, & Blanchard, 2013; Vauth, Kleim, Wirtz, & Corrigan, 2007). The right intensity of psychosocial interventions is also difficult to gauge since ambiguity of risk status in CHR may compromise motivation for long-term treatment. Furthermore, anti-psychotic medications and most psychosocial interventions do not target the neural deterioration and related cognitive deficits that appear to be a potent underlying cause of transition to psychosis.
Funding: National Institute of Mental Health (R01 MH105246)
Optimizing Social Cognition in Psychosis
Schizophrenia and related psychotic disorders are severe, chronic mental illnesses that affect more than two million individuals in the U.S. (Reiger et al 1993). The healthcare burden attributable to psychotic disorders is estimated at $62 billion annually (McEvoy 2007; Rupp and Keith 1993), and is expected to grow as many treatment programs fail to successfully re-integrate these individuals into the larger society. These costs are largely incurred by the functional impairments in living, work, and everyday function, which are an essential diagnostic feature of the illness (APA 2013), found in many patients with psychotic disorders (Albert N et al 2011). These poor functional outcomes are manifested by the high rates of unemployment, poor social and community functioning, reduced capabilities for independent living, and a generally reduced quality of life (Albert N et al 2011; Corrigan, Hirschbeck, and Wolfe 1995).
Importantly, recent studies have now compellingly shown that these fundamental deficits in functional ability in psychotic disorders are largely attributable to pervasive and enduring impairments in social cognition (SC): the perception, interpretation and processing of social information. Individuals with a psychotic disorder exhibit deficits in all core domains of SC: emotion perception (the recognition of facial and vocal affect), social cue perception (the ability to detect and comprehend cues in a social context), theory of mind (the mental capacity to infer one’s own and others’ mental states), attributional style (attribution of causes of events to the self, to others, or to factors in the environment), and empathy (the ability to share, understand and appropriately react to the emotional states of others). Notably, impairments in each of these domains have been shown to have a significant impact on functional outcome in psychotic disorders.
Funding: Posit Science Corporation on behalf of the National Institute of Mental Health (R44 MH091793 PSC-1004-14)
Cognitive Control of Emotion in Bipolar I Disorder
Difficulty with emotion regulation is a central feature of Bipolar Disorder that is not only apparent during mood episodes but also persists in between episodes and contributes to the onset, chronicity, and severity of illness. Successful emotion regulation requires cognitive control of emotion (CCE), the ability to control emotions and the influence of emotions on behavior. CCE is dependent on the coordinated activity of at least two neural systems: 1) the cognitive control network, which includes the lateral prefrontal and superior parietal cortex, and supports a variety of skills (e.g. attention, inhibition, working to memory) to control and manipulate information from multiple sensory domains; and 2) the emotion processing network, which includes the amygdala, insula, and ventral striatum, and supports the experience, expression, and perception of emotion. CCE consists of several processes in which the cognitive control network modulates neural response in emotion processing regions to control the impact of emotion on experience and behavior. Poor recruitment of frontoparietal control functions when processing negative emotional stimuli (measured with fMRI) prospectively predicts mood and behavioral problems after an interpersonal conflict in daily life (Hooker et al 2000). Together the data suggests that compromised CCE capacity makes a person more vulnerable to experiencing negative psychological consequences after a stressful event (e.g., Hooker et al 2010; Hooker et al 2013; Tully et al 2014).
Children and adults with bipolar disorder have deficits on both behavioral and neural measures of CCE (Phillips and Swartz 2014). Typical CCE tasks require identifying a target stimuli (e.g. word, facial expression, etc.) while inhibiting irrelevant or conflicting emotional information. During such tasks, people with bipolar disorder have difficulty controlling the distracting influence of irrelevant emotional information. These behavioral deficits are associated with neural abnormalities in both cognitive control and emotion processing neural systems; these abnormalities are characterized, primarily, by abnormally low activity in the cognitive control network, particularly the lateral prefrontal cortex, and abnormally high activity in emotion processing regions, particularly the amygdala and ventral striatum. Bipolar disorder is also associated with abnormalities in structural elements of these neural systems, including abnormal gray matter volume and white matter tracks. Research suggests that deficits in CCE and related neural networks are an underlying cause of symptoms that are characteristic of bipolar disorder, including emotional lability, extreme mood states, and disinhibited behavior (reviewed in Phillips and Swartz 2014 and Wegbbreit et al. 2014). These findings point to CCE as a clinically relevant and scientifically tractable treatment target for bipolar disorders.
Funding: Ryan Licht Sang Bipolar Foundation and the Brain and Behavior Research Foundation
