Is it in your DNA? Subthreshold Bipolar Disorder and Precision Medicine
Bipolar disorder is one of the most commonly misdiagnosed conditions in psychiatry, affecting approximately 1-4% of the global population and carrying one of the highest mortality rates of any psychiatric condition. For many patients, the journey to getting a bipolar diagnosis can take over a decade – with some people even reporting waits of up to 15 to 20 years, moving between different diagnoses and treatments before finally understanding the driver of their symptoms. This delay can be extremely challenging, leaving many people confused, frustrated and without the support or treatment they need to manage their symptoms and improve their quality of life.
But what if a simple genetic test could remedy this situation? Fortunately, our understanding of bipolar disorder is evolving, and with it, the way doctors are able to approach diagnostics and treatment. New developments, including genetic testing, support the early identification of bipolar disorder and the delivery of truly personal psychiatric care.
So, why has bipolar disorder remained so hard to diagnose for so long? What is subthreshold bipolar disorder, and why is it being missed? What is precision medicine and is it a bipolar disorder treatment? And what should you do if you suspect you might have a bipolar type disorder?
Why is bipolar disorder misdiagnosed so often?
It’s fair to assume that a high risk profile combined with notable prevalence in the global population would prompt swift, accurate diagnosis of bipolar disorder – yet the average UK patient still waits 9.5 years for the correct diagnosis.
In that time, you may have received other diagnoses and treatment for conditions such as depression or anxiety. Indeed, a huge population is being treated incorrectly, with one UK primary care study finding an adjusted prevalence of unrecognised bipolar disorder in patients presenting with depression of 10%.
Why is bipolar disorder being misdiagnosed such a concern?
Interim treatment received by misdiagnosed bipolar patients often involves antidepressants. However, the prescription of antidepressants without mood stabilisation actually carries a documented risk of mood destabilisation and triggering states of rapid cycling – defined as four or more distinct mood episodes within a twelve-month period. Rapid cycling is also associated with greater severity, worse functioning and a higher risk of suicide – being characterised by deep lows alongside impulsivity and risky behaviour.
Bipolar symptoms can overlap with those of depression, anxiety disorders, ADHD, complex trauma and personality disorders, making it extra tricky to identify. Without a biological marker to distinguish one condition from the other, diagnosis relies entirely on clinical history and present evaluation.
The lapse in time between the onset of symptoms and finally receiving the correct diagnosis leaves many patients suffering for significantly longer than necessary – and creates the conditions for bipolar to grow more resistant to treatment when it is identified.
During this time, you may experience relationships degrading, see careers derailed, and lose your ability to truly enjoy life. In other words, there are heavy personal and social costs to diagnostic delays.
Fortunately, we apply innovative diagnostic tools at The London Psychiatry Centre to break this cycle, and help you get the answers and support you deserve.
What is subthreshold bipolar disorder?
Before exploring subthreshold bipolar, it may help you to understand the full spectrum of bipolar type disorders, as the distinctions between each type are meaningful – and often misunderstood. For more information on bipolar I and bipolar II, see The London Psychiatry Centre’s dedicated bipolar page.
When you think of bipolar disorder, you probably picture dramatic swings between mania and severe depression. However, there is another type of bipolar disorder – which doesn’t meet the criteria for bipolar I or bipolar II – known as subthreshold bipolar disorder, or unspecified bipolar disorder. Subthreshold bipolar disorder is clinically defined as four or more affective episodes in a year, ranging from depression to mania and hypomania. Consultant Psychiatrist Dr Andy Zamar clarifies that “many patients who go on to be diagnosed with subthreshold bipolar report states of depression with a kind of washing machine cycle of rapid thoughts.”
What does subthreshold bipolar disorder actually look like?
Because subthreshold bipolar symptoms don’t present as the textbook highs and lows of bipolar I or II, it’s often mistaken for depression, anxiety, or a personality disorder. If you’ve been struggling with your mood for a long time and still have no answers, the following may resonate.
Common symptoms of subthreshold bipolar include:
- Low mood as your baseline – punctuated by periods of elevation that fall short of full mania
- Irritability and mood swings that won’t go away
- Difficulty maintaining focus, motivation or routine
- Disrupted sleep patterns that may shift with your mood state
- Making decisions you regret later: increased impulsivity or risk-taking during periods of high mood
- Social withdrawal, fatigue and low self-worth during depressive phases
- A general sense of instability that doesn’t respond to antidepressants
If this feels familiar, you’re not alone – and you may be surprised to hear that subthreshold bipolar disorder is estimated to affect between 55-60% of all bipolar cases. Despite this, NICE – the regulatory body that sets clinical standards and treatment guidelines in the UK – makes no specific recommendations for the assessment or management of subthreshold bipolar presentations at present. This leaves a significant gap in care, and it’s one that we endeavor to address.
What is causing mood instability? The science behind subthreshold bipolar
Zamar et al. (2022) found that the brain’s ability to activate and use thyroid hormones is frequently compromised in people with bipolar disorder, due to mutations in two specific enzymes, and deficiencies in the protein that transports active thyroid hormone into brain tissue.
In plain terms: even if your blood thyroid levels appear normal, your brain may not be receiving the thyroid hormone it needs to stabilise your mood. This can explain why after years of treatment, recovery wasn’t possible: the underlying, biological triggers were never accounted for.
This particular thyroid malfunction is identified through targeted genetic testing for bipolar disorder at The London Psychiatry Centre, where these findings have been observed in at least 90% of bipolar spectrum disorder cases. Our findings suggest that the thyroid is a core yet consistently ignored feature of subthreshold bipolar disorder – and crucially, it is treatable.
Precision medicine for bipolar disorder: The Zamar Protocol ® explained
This is where treatment finally becomes personal. Dr Andy Zamar, Consultant Psychiatrist at The London Psychiatry Centre, developed The Zamar protocol® (Precision guided high-dose thyroid hormones and rTMS protocol). This precision medicine approach to bipolar spectrum disorder, starts with genetic testing to identify the thyroid irregularities described above.
If these are confirmed, the treatment combines High Dose Thyroid Hormones – a targeted thyroid hormone replacement that addresses the deficiency at the root of mood instability – with repetitive Transcranial Magnetic Stimulation (rTMS). rTMS is a non-invasive neuromodulation treatment that supports mood stabilisation without bringing on side effects commonly associated with psychiatric medication. And the results are striking. The combined protocol achieved 96.4% full remission in a published cohort study, turning broad treatment into a precisely targeted one – and achieving outcomes that compare favourably to any existing bipolar disorder treatment.
Importantly, The Zamar Protocol® (Precision guided high-dose thyroid hormones and rTMS protocol) is reported to be safe and well-tolerated – and has produced results in patients where standard bipolar medication failed. It is currently the only evidence-based treatment for subthreshold bipolar disorder.
What is precision psychiatry — and could it solve the bipolar diagnosis crisis?
For the first time, a targeted biological explanation for treatment-resistant mood instability is not just possible – it is available at The London Psychiatry Centre. If you’ve tried many medications without sustained relief, our assessment offers something that no previous pathway could: a diagnosis built around your personal biology rather than by process of elimination.
It’s now possible to home in on the biological mechanism behind your mood instability – and to treat it directly, from the outset. The research behind this is growing fast, and points toward a future in which the average bipolar disorder patient will no longer wait nearly a decade for appropriate treatment.
If you experience treatment-resistant depression, persistent mood instability and other symptoms associated with subthreshold bipolar disorder, our expert team is here to provide answers.
At The London Psychiatry Centre, our clinicians offer expert assessment and evaluation for bipolar spectrum disorders, including genetic testing for mental health and access to The Zamar Protocol ® (Precision guided high-dose thyroid hormones and rTMS protocol) for eligible patients, where appropriate. Contact us on 020 7580 4224 or info@psychiatrycentre.co.uk to book a consultation.
You have likely spent long enough searching for an explanation. The right one may finally be within reach.
