Unipolar Or Bipolar Disorder- The Million Dollar Question

Unipolar or Bipolar DisorderOne of the most common questions in clinical practice posed by colleagues and patients alike is “Is this Bipolar (Bipolar Disorder) Or Unipolar Disorder (Depression)?”
In a recent ANZJP article, the authors Malhi and Porter start the article with the following quote To the befuddlement of physicists, the universe is expanding; in fact it is accelerating apart at an unbelievable rate ………….While the implications of this are profound, the time frame involved means there is little chance of any direct impact on human kind as we know it. In contrast, another kind of expansion is affecting our lives here and now and also seems to have no end in sight; the diagnostic expansion of bipolarity.” (Malhi and Porter, 2014)

So How Do We Approach This Issue?
Let’s take a page from Scott Peck (Psychiatrist and author of The Road less Traveled); “Abandon the urge to simplify everything, to look for formulas and easy answers, and to begin to think multidimensionally, to glory in the mystery and paradoxes of life, not to be dismayed by the multitude of causes and consequences that are inherent in each experience — to appreciate the fact that life is complex.”
Based on the above advice,  let’s look at what depression and mania look like in the brain.

Adapted and Modified from Stahl's Essential Psychopharmacology

Adapted and Modified from Stahl’s Essential Psychopharmacology

Adapted and Modified from Stahl’s Essential Psychopharmacology

Considering the pathways and, at a minimum,  taking into account three neurotransmitters (NE, Serotonin and Dopamine) out of others (Glutamate, GABA, Acetylcholine etc ), simple mathematics tells us that if there are 10 pathways involved and you had to pick three pathways (r) from a choice of 10 pathways (n) the number of permutations is equal to 120. Add on top the neurotransmitters and the possible permutations and combinations increase significantly. In patient terms, imagine you have one patient with decreased dopamine in the frontal lobe and increased dopamine in the limbic system whilst another patient may have reduced serotonin and dopamine in the limbic system and increased dopamine in frontal lobe; add on other neurotransmitters and a different combination arises and the list goes on and on…. , I’m sure you get the point.

What’s the Solution?
Even to the untrained eye, the above images scream out loud that it is extremely difficult to lump the disorders into Unipolar and Bipolar Disorder. The variables that influence these pathways, notwithstanding the permutations and combinations of the pathways involved, show us that an alternative approach is required in treatment. Take one example (See diagram below); A patient presenting with depressed mood at one point (in this case let’s say due to decreased frontal dopamine and noradrenaline) may very easily have mixed features (racing thoughts, psychomotor agitation, irritability etc.) due to increased dopamine in the limbic system which from a treatment perspective will require treatment of his mood state by increasing dopamine in frontal lobe and reduction of racing thoughts, agitation and irritability by reducing dopamine in the limbic system through either dopaminergic blockade (antipsychotic-mood stabilisers like D2-5HT2 blockers) or mood stabiliser GABA potentiators that indirectly have an inhibitory effect on limbic dopamine.

Similarly, depression can occur due to dysregulation of serotonin in the limbic system. It is therefore not surprising that terms like bipolar depression, mixed affective states, atypical depression, major depression with mixed features, cyclothymia, rapid cycling have proliferated to explain these permutations and combinations. My answer to patients (especially if they present with no clear cut symptoms of mania or depression) is that the human brain is far too complex to box people into categories. I put forward a diagnostic label as I am required to for treatment, but focus on explaining what may be happening in the brain based on the above pathways and linking those to their symptoms and etiology (formulation). Treatment then proceeds by neuromodulation and identifying modifiable biological and psychological factors.

Don’t Forget to Know Your Way Around
It is important to remember that the causes of neurotransmitter dysregulation may be due to a multitude of reasons (e.g. thyroxine deficiency, Vit B12 deficiency, frontal injury, vascular factors etc.). For example, if the person is deficient in serotonin due to a deficiency in essential elements required in the production of serotonin (e.g. Zinc, Mg, B6 ) or if substances that are required for enhancing sensitivity of serotonin on 5HT receptors are deficient (e.g. Thyroid hormone) then prescribing SSRI’s may not do much as there may not be enough serotonin or in the second case , the receptors are not sensitive enough for the serotonin to act. It’s like getting to know the neighbourhood laneways.  If you don’t know them well, you won’t be able to help someone who can’t find their way.

What Would Einstein Do?
We can take a page about problem solving from Einstein “If I had an hour to solve a problem (e.g unipolar or bipolar), I’d spend 55 minutes thinking about the problem (causes and pathways involved) and 5 minutes thinking about solutions (treatment).”  (brackets are my insertions) . The take home message here is to spend time deciphering the problem. The solution is the end product once the problem is well understood. The issue of causality is particularly important because depression and bipolar disorder can present due to a range of causes and although the same pathways are affected, the causes may be different. Think of the pathways as a system of interconnected roads. These roads may be blocked by road blocks, falling boulders, flooding, road damage etc. A single broad brush approach will not solve the different problems; in some cases it may even be dangerous. The same applies to disorders of the brain. The key is to understand what is affecting these pathways; if it is a neurotransmitter abnormality then psychiatric medications may help. If however it is an alternate issue other treatments may be required as we saw here and here.
Solving such a conundrum in clinical practice requires going back to a basic problem solving approach. Listen, Gather information, Build a hypothesis based on possible causality and Test the hypothesis. The article is not intended to deter from diagnosis, but to understand the limitations of a label. A human being is much too complex to explain in a single diagnosis. “Ask not what disease the person has but what person the disease has”. (Osler)
So the next time you come across this question, it may be OK to step outside the poles.

1. Malhi, G. S., & Porter, R. J. (2014). Are ‘buy-polar’forces and ‘try-polar’thinking expanding bipolarity?. Australian and New Zealand Journal of Psychiatry, 48(8), 697-700.
2. Rege, S., & Hodgkinson, S. J. (2014). Anti-neuronal antibodies associated with a first episode of mania. Australian and New Zealand Journal of Psychiatry
3. Gomez-Bernal, G. J., & Bernal-Perez, M. (2007). Vitamin B12 deficiency manifested as mania: a case report. Primary care companion to the Journal of clinical psychiatry, 9(3), 238.

This article is written by Dr Sanil Rege. Sanil is a Consultant Psychiatrist in private practice on the Mornington Peninsula and co-founder of psychscene.com. He is pursuing an MBA at the Melbourne Business School. You can follow him on Google+

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