Tom Ronan

Originally submitted for the Hugh Platt Foundation essay prize. The case described has been anonymised.

The topic for the 2020 competition was ‘Tiny test, huge impact’ – an essay drawing on experience of a patient encounter which illustrates the impact a pathology result can have on a patient and their family.

Christine never got on with her neighbours. They always had the TV on too loud, and always left their bins out too long. Common quibbles amongst neighbours – but in the last few months the disputes have begun to escalate.

“They’ve really got it in for me,” she says.

The satellite dish next door, ostensibly for picking up TV signals, is really being used to record her thoughts. Christine is sure of this. She can also hear them talking about her all hours of the day. Even when she is out at the supermarket, their voices come through crystal clear.

Richard, her husband, becomes concerned about her increasingly bizarre beliefs and behaviours, and reaches out for help. A variety of people come to the house in succession, but Christine doesn’t want to take the tablets they give her. She thinks the police should be involved, not a mental health team.

“It’s not in my head, I promise. I’m not safe with them next door.”

Things eventually come to a head, and Christine is detained under the Mental Health Act. As the ward junior doctor, it is my job to clerk her in. She is understandably terrified by the whole process, and I do my best to allay some of her fears. As well as listening to her story and observing her mental state, I perform a full physical examination and take a blood sample. She looks at me with suspicion when I mention the blood tests, wondering if this too is part of the conspiracy against her. Christine will only deteriorate further without treatment, and the blood tests that I request play a vital role in her recovery. As a team, we cannot safely prescribe psychotropic medications without monitoring certain biochemical and haematological parameters. We also need to rule out some physical causes of her presentation.

Her electrolytes are neatly in range and her thyroid is ticking along nicely. A urinary drug screen is positive only for the benzodiazepines we have been giving her. Her CT head is pristine. She has no infective symptoms and her inflammatory markers are plumb normal.

Christine’s husband asks to speak in private – he wants to know her test results. With her permission, I relay the results. They are all negative. “This confirms our initial suspicions,” I tell him. “Christine has developed a mental illness, something we call psychosis.” He asks if this could be the start of schizophrenia, like Christine’s uncle has. I say yes, and he only gives a slow nod in reply, his face suspended in worry. We discuss what these words mean, what treatments are available, what the future might hold.

Richard has done some research online, and was holding out hope for an organic cause. Labels like psychosis and schizophrenia still carry huge stigma. Organic causes are often perceived as more treatable than their functional counterparts, but many people with functional psychoses respond well to antipsychotic medications. We can only proceed safely with these treatments once laboratory testing has ruled out some common causes of organically-driven psychosis and delirium.

Decades of research have sought out biomarkers for schizophrenia. A number of genes¹, blood markers² and brain regions³ have been implicated, but there is no specific and sensitive test used in routine clinical practice⁴. A surprisingly large number of common illnesses are diagnosed in this way, generally relying on clinical rather than laboratory testing – think of migraine, asthma, or Bell’s palsy.

When a histopathologist clinches a cancer diagnosis, or a microbiologist pins down the guilty pathogen in a septic patient, the material impacts of pathology results are obvious to all. There are defined, structural lesions for doctors to locate and confirm. With that slither of stained sample on a microscope slide, entire lives can change. In one eventuality, there are sighs of relief, false scares, reassurances given. In another there are tears, hugs, condolence cards, major operations, and gruelling chemotherapy regimes.

At a surface level, psychiatry and pathology seem like polar ends of medical practice; the chin-stroking and soul-searching shrink pitted against the clean-cut precision of laboratory science. But whatever the speciality, medicine is full of grey areas and ambiguities. Endocrine tissue biopsies pose a particular challenge, as the line between benign and malignant morphologies can be notoriously blurred. Pathologists often have no choice but to return an indeterminate result, leaving patients in limbo. Whether on the pathologist’s slide, or the psychiatrist’s couch, the subjects of the medical gaze do not always give up their secrets with ease.

Negative results can have nuanced effects. On the one extreme, a low troponin level gives us strong confidence that we are not facing an acute myocardial infarction⁵. Conversely, we have quickly learned that a negative Covid-19 swab is no guarantee that a patient is clear of the virus⁶. When clinical suspicion is high, a negative swab will have little impact on our management plan. Somewhere in the middle, diagnoses like systemic lupus erythematosus require a careful synthesis of evidence sources, with specificities and sensitivities carefully weighed and balanced⁷. And in some cases, including Christine’s, we use the weight of negative evidence to assure us that an organic cause is absent, and that our functional diagnosis is therefore correct.

Christine is less bothered by her neighbours these days. She still gets a little suspicious, and can hear their voices from time to time, but her once florid psychosis is now well controlled. She had a rocky road to recovery, with two other antipsychotics never quite fully controlling her symptoms. She now takes clozapine, meaning she needs weekly blood tests to track her leucocyte counts. As in the initial stages of her treatment, we rely on these laboratory tests to ensure we can treat her safely. Most importantly, Christine now feels safe in her own home. As doctors, what better impact can we hope to have?

References

1.    Henriksen, M. G., Nordgaard, J. & Jansson, L. B. Genetics of Schizophrenia: Overview of Methods, Findings and Limitations. Front. Hum. Neurosci. 11, (2017).

2.    Lai, C.-Y. et al. Biomarkers in schizophrenia: A focus on blood based diagnostics and theranostics. World J. Psychiatry 6, 102–117 (2016).

3.    Wheeler, A. L. & Voineskos, A. N. A review of structural neuroimaging in schizophrenia: from connectivity to connectomics. Front. Hum. Neurosci. 8, (2014).

4.    Prata, D., Mechelli, A. & Kapur, S. Clinically meaningful biomarkers for psychosis: A systematic and quantitative review. Neurosci. Biobehav. Rev. 45, 134–141 (2014).

5.    Reichlin, T. et al. One-Hour Rule-out and Rule-in of Acute Myocardial Infarction Using High-Sensitivity Cardiac Troponin T. Arch. Intern. Med. 172, 1211–1218 (2012).

6.    Wang, W. et al. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA 323, 1843–1844 (2020).

7.    Aringer, M. et al. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol. 71, 1400–1412 (2019).

8.    Rao, S. N. & Bernet, V. Indeterminate thyroid nodules in the era of molecular genomics. Mol. Genet. Genomic Med. n/a, e1288.