Introductions

Current state of assessment tools in bipolar disorder

• There are many screening tools for mania/bipolar disorder, but they are not all well-known and clinicians may not feel confident selecting a tool and/or administering it
  • Youngstrom et al. (2015)^[1] multivariate meta-analysis of discriminative validity of caregiver, youth, and teacher rating scales of PBD (free full text) is a good step toward better understanding the available tools, so that an efficient measure can be selected
    • The results show that caregiver report produces significantly larger effects than youth or teacher report.\
    • Three top performing measures are public domain and freely available on Wikipedia
• Screening tools are helpful for narrowing clinical hypotheses, but are not appropriate for diagnosis. Structured (or semi-structured) interviews are important in order to improve the accuracy of diagnosis
  • Two key obstacles to the accurate diagnosis of bipolar disorder are the episodic nature of the illness and high rates of comorbidity. [Semi]Structured interviews are more likely to pick-up on both
• Once the clinical data (screening measures, interview, family history, etc) are collected, clinicians tend to combine this information in their heads to arrive at a diagnosis. Research has consistently shown that this method results in less accurate diagnostic decisions, relative to using actuarial methods to combine data
  • The nomogram is a quick, and easy, way to combine clinical data and arrive at the probability that an individual has bipolar disorder (or other diagnosis of interest)

Opportunities for assessment research

Distinct reward signaling in mood disorders

There is evidence that, especially in the context with unipolar depression, there is reduced activity in the reward-related brain area of the brain. However, this same brain anomaly is not seen in those who are just experiencing general stress-related depression. On the other side, a manic brain shows an over activation in this area. Risk for major depression vs bipolar disorder characterized by extreme and opposite profiles of reward signaling (Alloy, Nusslock, & Boland, 2016; Nusslock & Alloy, in press; Nusslock, Walden, & Harmon-Jones, 2015; Nusslock et. al, 2014).

But, can we use this data as a predictor of bipolar before they develop bipolar symptoms? Alloy, Young, Damme,...Nusslock, (in prep) suggests that, yes, we can! In this study they find that those with the elevated activation in these reward centers in the brain have a higher risk of developing bipolar disorder in the future. Why? Those with bipolar disorder engage the cortex in the way that amplifies (over amplifies) the interaction between the cortex and subcortical cortex of rewards. Essentially, the brain is on reward overdrive instead of reward cruise-break.

Brain stress test (discussion)

Is there a way to stress the brain in a way that can show us if there are those abnormalities that indicate higher risk for mania and depression? In our conversation, we looked at the promises, pitfalls, and challenges of using biomarkers to facilitate diagnosis?

• Something that needs to be better validated are the psychometric properties of this kind of test before we can start making claims and justifying the cost of the scan.
• What are the brain scan differences of adult bipolar patients and pediatric bipolar patients? And if we are going to use brain stress tests to see if the brain exhibits the abnormalities, what are the developmentally appropriate stresses?
• What happens to those who have those activated areas in the brain, but don't want to be treated for the mania, because they don't find it impairing? What is the cost-benefit analysis for them?
• Similarly, what about those that have this elevated activity, but haven't been diagnosed with bipolar disorder and haven't experienced a manic episode yet? It is similar to the dilemma of whether it is better or worse for someone to find out that they have a gene that increases their risk of breast cancer, but they don't have breast cancer yet. The discussion continued with early intervention and the benefits and cons of early interventions.
• There is also the issue that, using brain scans as diagnostic tools in general, the "normal" brain may not be representative of the actual "normal" brain. Example: say a person has a slightly higher than normal thyroid activity, but their thyroid activity has always been at that level, unchanging, and has not presented any problems. So this "higher than normal" activity, is actually "normal" activity for this person.
• Is it feasible to have a team of neuroscientists and statisticians at every clinic to review these brain scans and come up with diagnostic likelihoods?
• There are stigma challenges, challenges linking brain regions to brain systems (and brain systems to physical behaviors), and phenomenology does not map onto biology.
• Take home point, regardless, is that we are not at the point that we can do this. It is difficult to subject children to these scans and get reliable results since adolescents, in general, have more activated brains that may be normal for them, but "manic" for adults. Additionally, we would want better sensitivity and specificity, considering the extremely negative outcomes in misdiagnosing bipolar disorder.

Dr. Nusslock: ideally, some day, a child comes into the clinic with concerns of depression or bipolar. After getting the family history and psychiatric history, it becomes aware that there is a family history of bipolar disorder. After gathering this data, a cost-benefit analysis is run to see if it is appropriate to get a brain stress test scan done, keeping in mind that this is a tool and not a diagnosis.

Training the future (discussion)

How are we supposed to master all the domains of clinical neuroscience while still being a student with all the responsibilities of a student?

• You cannot be an expert in everything. You need a that will support you. Collaborations and teamwork is absolutely critical, not only as a student, but also as a faculty.
• Your research needs to be a priority, and you need to follow the field and your research frequently. This is a fast paced environment with new discoveries and new changes being made every day.
• You choose one, and you stick with it. Don't be a jack of all trades (doing coursework, doing clinical training, taking on learning multiple new techniques at the same time). It may not be fun for a little while, but you will have a strong skill set that will make you an expert in a particular area that another team may need. You go to that team with your skill, and there you can start learning a different skill. So sequential learning is key.
• Post-docs: start thinking about it 2 years before graduating. Look into training grants. Look to work on a faculty member's RO1 or PO1 so you can be working on a team, getting publications, gaining skills, etc for multiple years... Write an NRSA (which requires a two year maturation period anyways, so look for a lab to work for multiple years in)
• How do you find that faculty member to mentor with? Go to conferences, make connections, and tell your story. Doing this takes time, which is why you want to start 2 years before graduating.