Papers by Elizabeth Belanger
Schizophrenia Research, 2015
The recalcitrance of negative symptoms in the face of pharmacologic treatment has spurred interes... more The recalcitrance of negative symptoms in the face of pharmacologic treatment has spurred interest in understanding the psychological factors that contribute to their formation and persistence. Accordingly, this study investigated whether deficits in metacognition, or the ability to form integrated ideas about oneself, others, and the world, prospectively predicted levels of negative symptoms independent of deficits in neurocognition, affect recognition and defeatist beliefs. Participants were 53 adults with a schizophrenia spectrum disorder. Prior to entry into a rehabilitation program, all participants completed concurrent assessments of metacognition with the Metacognitive Assessment Scale-Abbreviated, negative symptoms with the Positive and Negative Syndrome Scale, neurocognition with the MATRICS battery, affect recognition with the Bell Lysaker Emotion Recognition Task, and one form of defeatist beliefs with the Recovery Assessment Scale. Negative symptoms were then reassessed one week, 9weeks, and 17weeks after entry into the program. A mixed effects regression model revealed that after controlling for baseline negative symptoms, a general index of neurocognition, defeatist beliefs and capacity for affect recognition, lower levels of metacognition predicted higher levels of negative symptoms across all subsequent time points. Poorer metacognition was able to predict later levels of elevated negative symptoms even after controlling for initial levels of negative symptoms. Results may suggest that metacognitive deficits are a risk factor for elevated levels of negative symptoms in the future. Clinical implications are also discussed.
Molecular Psychiatry, 2015
Worldwide, one person dies every 40 seconds by suicide, a potentially preventable tragedy. A limi... more Worldwide, one person dies every 40 seconds by suicide, a potentially preventable tragedy. A limiting step in our ability to intervene is the lack of objective, reliable predictors. We have previously provided proof of principle for the use of blood gene expression biomarkers to predict future hospitalizations due to suicidality, in male bipolar disorder participants. We now generalize the discovery, prioritization, validation, and testing of such markers across major psychiatric disorders (bipolar disorder, major depressive disorder, schizoaffective disorder, and schizophrenia) in male participants, to understand commonalities and differences. We used a powerful within-participant discovery approach to identify genes that change in expression between no suicidal ideation and high suicidal ideation states (n = 37 participants out of a cohort of 217 psychiatric participants followed longitudinally). We then used a convergent functional genomics (CFG) approach with existing prior evidence in the field to prioritize the candidate biomarkers identified in the discovery step. Next, we validated the top biomarkers from the prioritization step for relevance to suicidal behavior, in a demographically matched cohort of suicide completers from the coroner's office (n = 26). The biomarkers for suicidal ideation only are enriched for genes involved in neuronal connectivity and schizophrenia, the biomarkers also validated for suicidal behavior are enriched for genes involved in neuronal activity and mood. The 76 biomarkers that survived Bonferroni correction after validation for suicidal behavior map to biological pathways involved in immune and inflammatory response, mTOR signaling and growth factor regulation. mTOR signaling is necessary for the effects of the rapid-acting antidepressant agent ketamine, providing a novel biological rationale for its possible use in treating acute suicidality. Similarly, MAOB, a target of antidepressant inhibitors, was one of the increased biomarkers for suicidality. We also identified other potential therapeutic targets or biomarkers for drugs known to mitigate suicidality, such as omega-3 fatty acids, lithium and clozapine. Overall, 14% of the top candidate biomarkers also had evidence for involvement in psychological stress response, and 19% for involvement in programmed cell death/cellular suicide (apoptosis). It may be that in the face of adversity (stress), death mechanisms are turned on at a cellular (apoptosis) and organismal level. Finally, we tested the top increased and decreased biomarkers from the discovery for suicidal ideation (CADM1, CLIP4, DTNA, KIF2C), prioritization with CFG for prior evidence (SAT1, SKA2, SLC4A4), and validation for behavior in suicide completers (IL6, MBP, JUN, KLHDC3) steps in a completely independent test cohort of psychiatric participants for prediction of suicidal ideation (n = 108), and in a future follow-up cohort of psychiatric participants (n = 157) for prediction of psychiatric hospitalizations due to suicidality. The best individual biomarker across psychiatric diagnoses for predicting suicidal ideation was SLC4A4, with a receiver operating characteristic (ROC) area under the curve (AUC) of 72%. For bipolar disorder in particular, SLC4A4 predicted suicidal ideation with an AUC of 93%, and future hospitalizations with an AUC of 70%. SLC4A4 is involved in brain extracellular space pH regulation. Brain pH has been implicated in the pathophysiology of acute panic attacks. We also describe two new clinical information apps, one for affective state (simplified affective state scale, SASS) and one for suicide risk factors (Convergent Functional Information for Suicide, CFI-S), and how well they predict suicidal ideation across psychiatric diagnoses (AUC of 85% for SASS, AUC of 89% for CFI-S). We hypothesized a priori, based on our previous work, that the integration of the top biomarkers and the clinical information into a universal predictive measure (UP-Suicide) would show broad-spectrum predictive ability across psychiatric diagnoses. Indeed, the UP-Suicide was able to predict suicidal ideation across psychiatric diagnoses with an AUC of 92%. For bipolar disorder, it predicted suicidal ideation with an AUC of 98%, and future hospitalizations with an AUC of 94%. Of note, both types of tests we developed (blood biomarkers and clinical information apps) do not require asking the individual assessed if they have thoughts of suicide, as individuals who are truly suicidal often do not share that information with clinicians. We propose that the widespread use of such risk prediction tests as part of routine or targeted healthcare assessments will lead to early disease interception followed by preventive lifestyle modifications and proactive treatment.
Psychosis, 2014
ABSTRACT For many diagnosed with schizophrenia, increased self-awareness is associated with an in... more ABSTRACT For many diagnosed with schizophrenia, increased self-awareness is associated with an increase in distress. This link, however, does not appear to be consistent for all with schizophrenia and thus it may be that there are different factors that make one more likely to experience increased distress with increased awareness. The current study sought to explore whether having experienced trauma could be one such factor that influences the relationship between increased awareness and greater distress. We hypothesized that for those who have experienced childhood sexual abuse, increasingly complex understandings of themselves will be linked with heightened distress and symptoms of schizophrenia. This hypothesis was examined in two groups of outpatients diagnosed with schizophrenia, with one group reporting a traumatic event and another group who did not report this specific trauma. Correlation coefficients of the relationship between measures of awareness and PANSS symptom scores among the two groups were compared and supported this hypothesis, suggesting that increased awareness may be associated with increased distress particularly for those who have experienced trauma in their lives. These findings have several clinical implications, including the importance of understanding the protective role psychotic symptoms may play in the face of distress.
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Papers by Elizabeth Belanger