Daniel Fulford

Motivational deficits in individuals at-risk for psychosis and across the course of schizophrenia

Motivational impairment is a critical factor that contributes to functional disability in schizophrenia and undermines an individuals ability to engage in and adhere to effective treatment. However, little is known about the developmental trajectory of deficits in motivation and whether these deficits are present prior to the onset of psychosis. We assessed several components of motivation including anticipatory versus consummatory pleasure (using the Temporal Experience of Pleasure Scale (TEPS)), and behavioral drive, behavioral inhibition, and reward responsivity (using the Behavioral Inhibition Scale/Behavioral Activation Scale (BIS/BAS)). A total of 234 participants completed study measures, including 60 clinical high risk (CHR) participants, 60 recent-onset schizophrenia participants (RO), 78 chronic schizophrenia participants (SZ) and 29 healthy controls (HC) age matched to the CHR group. CHR participants endorsed greater deficits in anticipatory pleasure and reward responsivity, relative to HC comparison participants and individuals diagnosed with schizophrenia. Motivational deficits were not more pronounced over the course of illness. Depressed mood was uniquely associated with impairments in motivation in the CHR sample, but not the schizophrenia participants. The results suggest that CHR individuals experience multiple contributors to impaired motivation, and thus multiple leverage points for treatment.

Pushing and Coasting in Dynamic Goal Pursuit Coasting Is Attenuated in Bipolar Disorder

In an experience-sampling study, we tested the influence of goal progress on subsequent effort toward that goal among persons with bipolar disorder (BD) and among control subjects without BD. We hypothesized, overall, that unexpectedly low progress toward a goal would lead to an increase in subsequent effort toward that goal, and unexpectedly high progress would lead to a decrease in effort (permitting effort to be shifted to another goal). Drawing on literature relating BD to elevated goal-approach sensitivity, we hypothesized that persons with BD would be less responsive to unexpectedly high progress than would control subjects. Participants answered questions three times a day, for 21 days, about three goals. The results of the study confirmed our overall hypothesis. In addition, although the reactions of persons with BD did not differ from the reactions of control subjects after lower-than-expected goal progress, persons with BD decreased effort toward goals significantly less than did control subjects after better-than-expected goal progress.

Modeling the role of negative symptoms in determining social functioning in individuals at clinical high risk of psychosis

A priority for improving outcome in individuals at clinical high risk (CHR) is enhancing our understanding of predictors of psychosis as well as psychosocial functioning. Social functioning, in particular, is a unique indicator of risk as well as an important outcome in itself. Negative symptoms are a significant determinant of social functioning in CHR individuals; yet, it is unclear which specific negative symptoms drive functional outcome and how these symptoms function relative to other predictors, such as neurocognition and mood/anxiety symptoms. In a sample of 85 CHR individuals, we examined whether a two-factor negative symptom structure that is found in schizophrenia (experiential vs expressive symptoms) would be replicated in a CHR sample; and tested the degree to which specific negative symptoms predict social functioning, relative to neurocognition and mood/anxiety symptoms, which are known to predict functioning. The two-factor negative symptom solution was replicated in this CHR sample. Negative symptom severity was found to be uniquely predictive of social functioning, above and beyond depression/anxiety and neurocognition. Experiential symptoms were more strongly associated with social functioning, relative to expression symptoms. In addition, experiential symptoms mediated the relationship between expressive negative symptoms and social functioning. These results suggest that experiences of motivational impairment are more important in determining social functioning, relative to affective flattening and alogia, in CHR individuals, thereby informing the development of more precise therapeutic targets. Developing novel interventions that stimulate goal-directed behavior and reinforce rewarding experiences in social contexts are recommended.

Emotion perception and quality of life in bipolar I disorder.

BACKGROUND Across two studies we examined the role of emotion perception as a correlate of quality of life and occupational functioning in bipolar I disorder. METHOD In Study 1, we tested a multifactorial model of quality of life and occupational functioning, including the role of emotion perception and other established correlates of functional outcomes, among 42 participants diagnosed with bipolar I disorder. In Study 2, participants diagnosed with bipolar I disorder and age- and gender-matched controls completed an affect recognition task and a quality of life measure. RESULTS Across both studies, emotion perception related to functional outcomes. In Study 1, self-rated emotion perception explained unique variance in subjective well-being after controlling for illness characteristics, education, and executive function. In Study 2, a behavioral measure of facial affect recognition accuracy was related to quality of life, even after controlling for illness severity. LIMITATIONS Limitations include the use of a cross-sectional design, relatively small sample sizes, and the focus on only one aspect of social cognition. CONCLUSIONS Findings indicate that emotion perception may protect quality of life in bipolar disorder. This dimension may help predict important outcomes and, with further research, could serve as a potential treatment target.

The Double-Edged Sword of Goal Engagement: Consequences of Goal Pursuit in Bipolar Disorder

A series of studies suggest that bipolar disorder is related to high sensitivity to incentives and that incentive sensitivity (or sensitivity of the approach system) can predict the course of mania. Incentive sensitivity in bipolar disorder seems to be related to two processes: a tendency to invest in difficult-to-attain goals and an over-reactivity to cues of goal progress versus thwarting. Both of those processes appear relevant to symptom generation. Hence, bipolar disorder seems related to a greater emphasis on reaching goals and also a problematic reactivity to reaching those highly desired goals. We suggest directions for treatment development focused on these issues in goal regulation.

The effects of intranasal oxytocin in opioid-dependent individuals and healthy control subjects: a pilot study

RationaleThere has been an explosion of research on the potential benefits of the social neuropeptide oxytocin for a number of mental disorders including substance use disorders. Recent evidence suggests that intranasal oxytocin has both direct anti-addiction effects and pro-social effects that may facilitate engagement in psychosocial treatment for substance use disorders.ObjectivesWe aimed to assess the tolerability of intranasal oxytocin and its effects on heroin craving, implicit association with heroin and social perceptual ability in opioid-dependent patients receiving opioid replacement therapy (ORT) and healthy control participants.MethodsWe performed a randomized, double-blind, placebo-controlled, within- and between-subjects, crossover, proof-of-concept trial to examine the effects of oxytocin (40 international units) on a cue-induced craving task (ORT patients only), an Implicit Association Task (IAT), and two social perception tasks: the Reading the Mind in the Eyes Task (RMET) and The Awareness of Social Inference Test (TASIT).ResultsOxytocin was well tolerated by patients receiving ORT but had no significant effects on craving or IAT scores. There was a significant reduction in RMET performance after oxytocin administration versus placebo in the patient group only, and a significant reduction in TASIT performance after oxytocin in both the patient and healthy control groups.ConclusionsA single dose of intranasal oxytocin is well tolerated by patients receiving ORT, paving the way for future investigations. Despite no significant improvement in craving or IAT scores after a single dose of oxytocin and some evidence that social perception was worsened, further investigation is required to determine the role oxytocin may play in the treatment of opioid use disorder.Clinical Trial RegistrationMethadone Oxytocin Option. ClinicalTrials.gov identifier: NCT01728909

Development of the treatment attitudes questionnaire in bipolar disorder

Despite the success of pharmacotherapy in the management of bipolar disorder, as many as one-half of those in treatment discontinue their medication over time. Currently, no self-report measure is available that predicts treatment engagement in bipolar disorder. The goal of the current study was to develop a measure of awareness of symptoms and attitudes toward treatment among those with bipolar disorder. Sixty-six participants diagnosed with bipolar I disorder on the SCID completed the Treatment Attitudes Questionnaire (TAQ) and were then followed for up to 2 years to assess symptom levels. Medication data were available for 37 participants. Analyses of the TAQ were conducted to examine reliability, predictors of subscales, and how well scores predicted medication and symptom levels over time. Results indicate that previous episodes of depression, but not episodes of mania, correlated with increased scores on the Insight and the Enjoyment of Mania subscales. Scores on the Nonbiological Attributions subscale predicted lower levels of lithium as well as increased depressive symptoms over time. Although the current study includes limited measurement of treatment engagement and a small sample size, this easily administered scale may help treatment planning for those with bipolar disorder.

Differentiating risk for mania and borderline personality disorder: The nature of goal regulation and impulsivity.

Researchers and clinicians have long noted the overlap among features and high comorbidity of bipolar disorder and borderline personality disorder. The shared features of impulsivity and labile mood in both disorders make them challenging to distinguish. We tested the hypothesis that variables related to goal dysregulation would be uniquely related to risk for mania, while emotion-relevant impulsivity would be related to risk for both disorders. We administered a broad range of measures related to goal regulation traits and impulsivity to 214 undergraduates. Findings confirmed that risk for mania, but not for borderline personality disorder, was related to higher sensitivity to reward and intense pursuit of goals. In contrast, borderline personality disorder symptoms related more strongly than did mania risk with threat sensitivity and with impulsivity in the context of negative affect. Results highlight potential differences and commonalities in mania risk versus borderline personality disorder risk.

Negative Generalization and Symptoms of Anxiety Disorders.

The tendency to generalize from a single failure to ones entire self-worth is an important correlate and predictor of depression. Despite conceptual overlap between cognitive biases in anxiety and depression, little research has examined whether negative generalization relates to anxiety symptoms. We examined associations of negative generalization with symptoms of several anxiety disorders, above and beyond its association with lifetime symptoms of depression, among 248 undergraduates. After controlling for lifetime symptoms of major depression, negative generalization was significantly correlated with symptoms of each anxiety disorder tested, most notably generalized anxiety and social phobia.

Symptom assessment in early psychosis: The use of well-established rating scales in clinical high-risk and recent-onset populations

Symptom assessment in early psychosis research typically relies on scales validated in chronic schizophrenia samples. Our goal was to inform investigators who are selecting symptom scales for early psychosis research. We described measure characteristics, baseline scores, and scale inter-relationships in clinical-high-risk (CHR) and recent-onset psychotic disorder (RO) samples using the Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, Scale for the Assessment of Positive Symptoms, and Scale for the Assessment of Negative Symptoms; for the CHR group only, we included the Scale of Prodromal Symptoms. For investigators selecting symptom measures in intervention or longitudinal studies, we also examined the relationship of symptom scales with psychosocial functioning. In both samples, symptom subscales in the same domain, across measures, were moderately to highly intercorrelated. Within all measures, positive symptoms were not correlated with negative symptoms, but disorganized symptoms overlapped with both positive and negative symptoms. Functioning was significantly related to negative and disorganized, but not positive, symptoms in both samples on most measures. Findings suggest strong overlap in symptom severity ratings among the most common scales. In recent-onset samples, each has strengths and weaknesses. In CHR samples, they appear to add little information above and beyond the SOPS.