Beyond Bipolar: Neuroscience opens new diagnositic doors

For more than 10 years we have found ourselves awash in a “bipolar” tide. Quite like the times when Borderline Personality was the wastebasket diagnosis back in the 60's and 70's.

First of all let's cover some fun vocabulary. Drop these terms on your friends at a dinner party on Saturday night:

On so many second or third opinions in my office I find myself on the tail end of a long bipolar, phenotypic, surface conclusion that falls short of the mark. Phenotype is the surface of matters, the tip of the iceberg, to coin a phrase. Genotype is the crystalline structure of the berg below.

Increasingly we now look for patterns that are clinical and yet beyond phenotypic, and become, another new word: endophenotypic [check out this deep reference]. Endophenotypic patterns are more biologic but somewhere between what we see in the office and genetics. Bottom line, we have to think more deeply than simply cycles, moods and impulsivity.

Why? Who cares? Well many do. One impassioned and most interesting voice Philip Dawdy over at Furious Seasons has some excellent pieces on his experience with bipolar. And let me tell you a true story:

A bright 40 yo woman with depression and a cocaine problem came into my office on 2400mg/day of lithium with a bipolar diagnosis. She had a clear history of cognitive [thinking problems, ADD] dating back into early childhood, On lithium since early 20's. So now we have at least four diagnoses, treated for just one for about 20 years. Lithium level was running in a low normal range, .8 mEq/l.

Major historical tidbit: She had a serious head injury with loss of consciousness in about the third grade, began to have many problems in adolescence, began trials of many meds, settled on lithium, and it did help with her moods and anger. Stimulants as a child made her worse. Antidepressants made her worse. “Classic” bipolar history…, but:

SPECT scans revealed brain injury with temporal lobe dysregulation, ADD, depression, no hint of classic SPECT findings of bipolar. She had been treated phenotypically, just as I would have treated her in the past. Lithium is an effective drug for the correct application. Lithium helped the moods, but never diminished the focus and concentration issues, – and only minimally covered the depression.

But she had a big medical problem: her kidneys were failing following the years of lithium. During our work together, in less than a year, she lost one kidney, and then went into kidney failure with the remaining

. Her mother gave her a kidney, she recovered, and is medically doing quite well.

On the psych side: I did take her off the lithium, treated her for the brain injury/temporal lobe dysregulation with an antiepileptic [Trileptal], treated her ADD with a stimulant [Adderall] and her depression with an antidepressant [Effexor]. Years ago, without evidence, any of us would have missed those several additional problems.

After 2 years she is sober, did not recycle on antidepressant meds or stimulants, is focused, and covered medically. The patterns were there, underneath the surface, now identifiable with a functional look at her brain.

Temporal lobe injury is one of the three most frequently missed diagnoses in my career. More about the other two [ADD and Metabolic Disorders] later.

“Bipolar 1 and 2” do not tell us which part of the brain isn't functioning correctly. These two only hint at comorbidity subsets. Our system isn't wrong, it simply manifests the common problem associated with labels generally, it just doesn't drive the right set of questions. It's Aristotle's fault.

That simple observation is easily appreciated in the field as many researchers report more than 8 subsets of Bipolar, including documentation with PET imaging diminished serotonin 5HT1A receptor and clear comorbidity with ADD.

A true understanding of the pathophysiology of BD [Bipolar Disorder] must address its neurobiology at different physiological levels, i.e. molecular, cellular, systems, and behavioral. Abnormalities in gene expression undoubtedly underlie the neurobiology of the disorder at the molecular level and this will become evident as we identify the susceptibility and protective genes for BD in the coming years. [from NIMH article in 2003]

Neurobiology is more complex, and while we don't have all the answers, it's time to include the answers we do have.

See the next post: categorical thinking.