2026 ECNP Congress

EP01-1003

When alcohol disinhibits: neurobiological mechanisms of paradoxical behavioral dysregulation and suicidal behavior in mania a potu

Luísa Figueiredo — M. Cunha, C. Eusébio, A. Fernandes, F. Lobo, D. Rodrigues, D. Cotovio, M. Martins · ULS Loures Odivelas, Psychiatry, Lisbon, Portugal

2026 ECNP Congress

Introduction

Mania a potu describes an acute psychotic state triggered by alcohol intoxication, characterized by paradoxical behavioral changes, psychomotor agitation, and affective dysregulation. Despite its 19th-century nosological origins, the phenomenon remains clinically relevant, with a lifetime prevalence of approximately 4% in individuals with alcohol dependence. Its recognition requires careful exclusion of delirium tremens, Wernicke encephalopathy, and primary mood disorder, a distinction with direct therapeutic implications. Atypical presentations, particularly those combining suicidal behavior with complete amnesia, are rarely described and pose significant diagnostic and management challenges.

Aims

This case report aims to: (1) describe an atypical presentation of mania a potu featuring suicidal behavior and complete episodic amnesia following reduced alcohol consumption; and (2) elucidate the underlying neurobiological mechanisms through integration of clinical findings and current literature on alcohol-related neurotoxicity and circuit dysfunction.

Methods

We present a 42-year-old woman with recurrent depressive disorder, prior detoxification from alcohol and benzodiazepines, and current polypharmacy (lithium, lamotrigine, quetiapine, propranolol, alprazolam), admitted following a suicide attempt by strangulation (GCS 6 on presentation; cervical abrasions; labial cyanosis). Diagnostic workup included full laboratory panel, brain MRI, and EEG. Differential diagnoses were systematically excluded based on clinical, neuroimaging, and electrophysiological criteria. Neurobiological correlates were examined through narrative review of peer-reviewed literature (PubMed, 2009–2025), focusing on GABAergic, glutamatergic, dopaminergic, serotonergic, and neuropeptidergic systems, and prefrontal-limbic circuitry.

Results

All investigations (MRI, EEG, laboratory workup) returned within normal limits, supporting a primary alcohol-induced etiology. The episode occurred after observed alcohol consumption, notably limited in quantity, with rapid behavioral deterioration and complete anterograde amnesia; psychomotor agitation resolved within 48 hours. Alcohol’s biphasic effect, initial stimulation during ascending blood alcohol levels followed by sedation during descending levels, is particularly pronounced in genetically susceptible individuals, explaining paradoxical agitation at low doses. Literature data indicate that rapidly ascending blood alcohol concentrations preferentially impair NMDA receptor-mediated hippocampal long-term potentiation, accounting for blackout phenomena; prevalence of alcohol-induced blackouts reaches 40–50% and is more strongly associated with rate of consumption than total amount ingested. Cortico-limbic dysregulation, specifically alcohol-induced disinhibition of amygdala reactivity combined with prefrontal executive impairment via NMDA receptor modulation, underlies paradoxical agitation and suicidal behavior. Neuropeptides including corticotropin-releasing factor and vasopressin further amplify aggressive responses, while alcohol-induced oxidative stress modulates dopaminergic and serotonergic tone in the hippocampus and limbic system, contributing to impulsivity and suicidality.

Conclusions

This case demonstrates that even modest alcohol intake can precipitate severe paradoxical responses in neurobiologically vulnerable individuals with psychiatric comorbidity and prior dependence. Simultaneous dysregulation across GABAergic, glutamatergic, dopaminergic, serotonergic, and neuropeptidergic systems, compounded by prefrontal-limbic circuit dysfunction, provides a mechanistic account of the full clinical triad: agitation, suicidal behavior, and amnesia. Clinicians should maintain a high index of suspicion for mania a potu in the differential diagnosis of acute behavioral deterioration, particularly in patients with complex psychiatric histories and substance use disorders, even when alcohol consumption appears limited. Early recognition of this entity is essential to avoid diagnostic delay, prevent misattribution to primary psychiatric disorders, and guide appropriate acute management.

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