Novel biomarker may distinguish neurological and psychiatric disorders

Neurodegenerative disorders

By Michael Woodhead

26 Jun 2019

Dr Dhamidu Eratne

A pilot study by Victorian neurologists has shown that Neurofilament Light (NfL) may be a useful biomarker to distinguish primary psychiatric disorders from neurodegenerative and neurological disorders.

Researchers at the Royal Melbourne Hospital have shown that cerebrospinal fluid (CSF) levels of NfL are significantly higher in patients with neurological disorders such as early-onset dementia compared to those with similar symptoms cause by  conditions such as depression and schizophrenia.

And since NfL levels in blood mirror those in CSF, this raises the possibility of a simple routine test that could be used to help in the diagnostic challenge of distinguishing Alzheimer’s disease from ‘pseudodementia’, they say.

In a retrospective study the researchers assessed NfL levels in the CSF of patients referred to a tertiary neuropsychiatry unit because with complex cognitive, neurological and psychiatric symptoms. The gold standard clinical diagnoses were for neurological and neurodegenerative disorders such as frontotemporal dementia in 77 patients and for psychiatric disorders such as schizophrenia and major  depressive disorder in 31 patients.

NfL was significantly higher in patients with neurological and neurodegenerative disorders (mean 3560pg/ml) compared to those with psychiatric disorders (mean 949pg/ml).

NfL had an area under the curve (AUC) of 0.94 for distinguishing between psychiatric and neurological disorders, which was significantly greater than for other potential biomarkers in CSF such as Aβ1-42 (0.34) P-tau (0.20) and T-tau (0.14). Using an optimal cut-off of 1332pg/ml would give a sensitivity of 0.87 and specificity of 0.90.

Writing in the Australian and NZ Journal of Psychiatry, lead study investigator Dr Dhamidu Eratne, a consultant neuropsychiatrist, said the pilot study pointed to the possible use of NfL as a test to accurately identify the underlying aetiology of neuropsychiatric symptoms, particular in younger patients who may have broader non-specific features.

Currently may such patients faced a ‘diagnostic odyssey’ involving multiple costly and invasive assessments and investigations, conflicting clinical opinions, misdiagnosis and inappropriate treatment.

“Thus, there remains a great need for biomarkers to help distinguish neurodegenerative from psychiatric disorders, allow for more precise and judicious use of resources, improve diagnostic accuracy, reduce diagnostic delay and improve outcomes for patients and families,” he wrote.

He noted that NfL was a component of the neuronal cytoskeleton, that is released into CSF during neuronal injury, with smaller amounts crossing the blood–brain barrier, and capable of being measured in blood.

“Moving from measuring NfL in CSF to a more straightforward blood test has the potential to dramatically transform the clinical assessment, care and treatment of patients with neuropsychiatric, neurological and neurocognitive symptoms and allow a much more precision-medicine approach with regard to other assessments, investigations and treatments in a broad range of settings, from primary care, to memory clinics, to hospital wards, to psychiatric settings,” he wrote.

Larger, prospective studies on plasma and CSF NfL are now underway, to define the clinical merit of this potential biomarker in patients presenting with neurocognitive and neuropsychiatric symptoms, he added.

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