2026 ECNP Congress

PS03-3148

Late-onset psychosis and catatonia as early manifestations of C9orf72-associated frontotemporal dementia: diagnostic pitfalls and treatment implications

Yaren Uzel — R.S. Ilhan, F.G. Altunsu, B. Duman, K.C. Can, B. Colak, Y. Kir, S.Z. Tatli, R. Yilmaz, S. Erdogan, M. Araz, G. Cinar, B.B. Kanat, M.C. Saka · Ankara University School of Medicine, Department of Psychiatry, Ankara, Türkiye

2026 ECNP Congress

Introduction

Frontotemporal dementia (FTD), particularly C9orf72-associated forms, can initially present with prominent neuropsychiatric symptoms such as psychosis and catatonia, often preceding overt cognitive decline [1–3]. These early psychiatric manifestations are frequently misattributed to primary psychiatric disorders, leading to diagnostic delay and potentially inappropriate or harmful treatment strategies [3,4]. Increasing recognition of these atypical presentations is critical, particularly in late-onset cases, where distinguishing between primary psychiatric and neurodegenerative conditions remains clinically challenging. This case underscores the importance of considering neurodegenerative etiologies in late-onset psychiatric syndromes.

Case Presentation

A previously healthy 49-year-old woman presented with an 18-month history of progressive behavioral and cognitive decline, preceded by subtle, unrecognized impairments in language comprehension and communication. Clinical deterioration accelerated in the months prior to admission, with disinhibition, perseverative speech, stimulus-bound behaviors, and functional decline.

On examination, she was disoriented and demonstrated frontal release signs, notably a positive snout reflex, consistent with frontal lobe dysfunction, along with severe catatonia (Bush–Francis Catatonia Rating Scale: 34). Brain MRI revealed frontoparietal and hippocampal atrophy, while EEG was unremarkable. Cerebrospinal fluid (CSF) analysis showed mild pleocytosis (20 cells/mm³), with negative autoimmune and paraneoplastic antibody panels.

She was initially managed under the assumption of a primary psychotic disorder and received intramuscular zuclopenthixol acetate for agitation. This was followed by a marked worsening of catatonic and confusional symptoms, suggesting increased sensitivity to antipsychotic exposure. Benzodiazepine treatment provided only limited benefit. Electroconvulsive therapy (ECT) led to substantial improvement in catatonic features; however, disinhibited and perseverative behaviors persisted.

Given the atypical progression and paradoxical treatment response, further evaluation was undertaken. Genetic testing identified a pathogenic C9orf72 hexanucleotide repeat expansion (>116 repeats), confirming behavioral variant FTD [1,4]. The patient showed minimal response to subsequent antipsychotic treatments and died approximately one year after symptom onset, consistent with a rapidly progressive disease course.

Discussion

This case highlights key diagnostic pitfalls in late-onset psychiatric presentations. Progressive symptom evolution, early language impairment, frontal release signs, and paradoxical worsening following antipsychotic exposure strongly point toward an underlying neurodegenerative process rather than primary psychosis [2–4]. Patients with FTD may exhibit increased sensitivity to antipsychotics, with potential for clinical deterioration and adverse outcomes.

While catatonia may partially respond to ECT, persistence of behavioral and executive dysfunction should prompt reconsideration of the diagnosis and further neurological evaluation. Structural neuroimaging may be non-specific in early disease stages, and mild CSF pleocytosis does not exclude neurodegeneration, further complicating the diagnostic process. Accordingly, late-onset severe psychiatric syndromes warrant a comprehensive diagnostic work-up that includes both neurodegenerative and autoimmune etiologies, with particular consideration of genetic testing such as C9orf72 analysis [1,5].

Conclusions

Late-onset psychosis accompanied by catatonia, atypical features, or treatment resistance should raise strong suspicion for C9orf72-associated FTD. Frontal release signs, antipsychotic sensitivity, and partial response to ECT may serve as clinically meaningful indicators of underlying neurodegeneration. Early integration of genetic testing into the diagnostic process is essential to ensure accurate diagnosis, guide clinical management, and avoid potentially harmful treatment strategies [1,2,5].

References

  1. DeJesus-Hernandez M, et al. Neuron. 2011;72(2):245–256.
  2. Sha SJ, et al. Neurology. 2012;79(10):1002–1011.
  3. Kertesz A, et al. Cogn Behav Neurol. 2013;26(3):146–154.
  4. Rascovsky K, et al. Brain. 2011;134(9):2456–2477.
  5. Graus F, et al. Lancet Neurol. 2016;15(4):391–404.