Somatised affective disorders and functional neurological symptoms in outpatient neurology practice: neurobiological mechanisms and positive differential diagnosis

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Background: Functional neurological disorder (FND) and somatised (“masked”) anxiety–depressive syndromes are among the most common yet under-recognised presentations in outpatient neurology, frequently mimicking structural or peripheral nervous system disease in the absence of any lesion on neuroimaging or electrophysiological testing. Methods: Narrative review of the clinical and neuroimaging literature on FND and somatised affective disorders, synthesising evidence on neurobiological mechanisms, DSM-5-TR positive diagnostic criteria, and neuroplasticity-based treatment, illustrated by an index case managed in outpatient practice. Results: FND accounts for a substantial share of new outpatient neurology presentations, most consistently estimated at approximately 6% of new referrals, with functional and psychological symptom categories collectively representing a larger share of the referral base. Neuroimaging evidence implicates dysregulated connectivity between the amygdala and medial prefrontal cortex within the default-mode and salience networks, hypothalamic–pituitary–adrenal axis hyperactivation associated with reduced hippocampal volume, and impaired descending serotonergic–noradrenergic pain modulation. Anxiety symptoms frequently precede the motor onset of Parkinson disease by several years. Diagnosis rests on DSM-5-TR positive clinical signs of incongruence — including the Hoover sign and the tremor entrainment test — rather than on exclusion alone. In the illustrative case, a 36-year-old woman with an 8-month history of persistent postural-perceptual dizziness (PPPD) and migratory limb paraesthesia, with unremarkable neuroimaging and laboratory work-up, achieved a 50% symptom reduction at 4 weeks and full remission at 12 weeks following duloxetine titrated to 60 mg/day combined with cognitive behavioural therapy (CBT). Conclusion: Positive-criteria diagnosis of FND and masked depression, followed by multidisciplinary neuroplasticity-oriented treatment combining serotonin–noradrenaline reuptake inhibition with CBT, reduces iatrogenic risk and unnecessary investigation while offering an effective route to remission in outpatient neurology practice.