Abstract:The presence or absence of psychosis and the range of affective disturbance contribute to considerable heterogeneity within the DSM category of bipolar disorder and significant overlap between the DSM models for affective and psychosis spectrum disorders. The Psychosis and Affective Research Domains and Intermediate Phenotypes (PARDIP) project aims to isolate biomarkers within intrinsic neurophysiological activity that can segregate affective disturbance and psychosis within mental disorder, permitting progress toward more sophisticated and reliable differential diagnoses, early intervention, and targeted therapies. The current study investigated whether biomarkers for spectral power and connectivity within intrinsic neural activity can differentiate DSM diagnostic groups and healthy comparison subjects along the distinct and interacting domains of psychosis and affective symptoms. Frequency and connectivity analysis on resting-state EEG data from a sample of 155 bipolar probands with and without psychosis and 110 healthy controls revealed that low-frequency activity in the delta/theta (Δ/Θ) range was most significant. Elevated Δ/Θ power differentiated bipolar groups from healthy participants but not from each other. Power values correlated with clinical measures of greater childhood trauma, anxiety, and loss of functioning, consistent with previous research associating elevated low-frequency activity with affective disturbance and impaired cognition, and disordered mood with childhood trauma.Augmented Δ/Θ connectivity differentiated bipolar with psychosis from nonpsychotic bipolar and healthy controls, supporting recent findings identifying aberrant hyperconnectivity as a potential biomarker for psychosis. Antidepressant use correlated with elevated power and antipsychotic use correlated with elevated connectivity; both associations may be indicative of the underlying state for which the medications were prescribed.
Together, the double dissociation in the Δ/Θ bands supports the hypothesis that intrinsic neural activity may between the affective and psychosis domains in bipolar type one disorder, and challenge the DSM models for affective and psychosis spectrum disorders. The existence of distinct biomarkers for each dimension suggests that overlapping symptoms of varying severity represent a continuum of comorbidity rather than separate diagnoses. Email:[email protected]
What does research mean to you? To me, research is an attempt to peel back the curtains of existence in order to catch a glimpse of how life and the universe actually function and might possibly be explained. If the procession of stars in the sky and the arrangement of petals in a lotus can both be explained mathematically, why not also the exquisite and interacting patterns of activity within the human brain? And if we can begin to document and explain the measurable patterns within the brain, perhaps we might come closes to understanding how it functions and contributes to the human experience, and how we might offer early interventions and effective treatment to those who need and wish it most.
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Advice for Future Green Fellows
To students who are considering applying: Just do it. I have heard so many students say they aren’t sure if they should apply because they don’t think they’ll get in. To that logic, my response is: So? So what’s the worst that can happen? You’re not accepted, and you register for spring semester like usual. What’s the best that can happen? You’re granted the honor of a full-time research fellowship at a nationally respected biomedical graduate institution, and you have the chance to experience the real world of scientific research. At UT Southwestern, you’ll be exposed not only to the scientific process itself, but also the finer details of associating socially and professionally in a scientific academic atmosphere. Even the Green Fellowship application process itself will impart invaluable experience as you learn how to request and receive letters of recommendation, how to formulate and edit application essays, and how to keep a personal deadline. To me, there is no reason not to apply.
To fellows who’ve been accepted, I would share my favorite keys to excellent research: humble determination and unwavering curiosity. Becoming a wise and skilled scientist requires a lot of time and focus, and it’s important to pace yourself to remain attentive and patient through the lulls and frustrations that lie between moments of discovery. Sometimes I’m so excited I get goosebumps in the moments before I run a promising new series of calculations, but I pause to reflect that even the most favorable preliminary finding must be checked and rechecked, replicated and verified in order to be considered the result of good science. The most important part of this process is documenting and preserving everything. If test or calculation results appear inconclusive or unusable, save them anyway. I cannot count how many times what seemed like a loss turned out to be a victory. Also, don’t forget to back up your data completely and often. Finally, while I caution future fellows against getting too attached to preliminary findings, I think it’s also important to celebrate small victories. I have a small group of friends whom I trust with my research tales of woe and discovery. Having this kind of social support helps me keep a clear head at work. Having celebrated my findings and played through the possibilities and next steps with my friends, I feel I’m better prepared to do what it takes to critically examine my findings, and I find it easier to reject them and try again if those findings crumble under careful scrutiny.