Irritability in pre-clinical Huntington's disease

Area of Science:

• Neuroscience
• Psychiatry
• Genetics

Background:

• Irritability is a key feature of pre-symptomatic Huntington's disease (HD), but experimental data is limited.
• Irritability in HD is linked to impulsivity and aggression, involving brain regions like the orbitofrontal cortex (OFC) and amygdala.

Purpose of the Study:

• To investigate neuronal processing differences in pre-symptomatic Huntington's disease gene carriers (PSCs) during an emotional feedback task.
• To explore the neural basis of disrupted emotion processing in early HD stages.

Main Methods:

• Functional magnetic resonance imaging (fMRI) was used to scan 16 PSCs and 15 controls during a visual task with negative feedback.
• Participants identified the larger of two squares, receiving feedback about their or their partner's performance.

Main Results:

• While task performance and reported irritation were similar, fMRI revealed differences in brain activation between PSCs and controls.
• PSCs showed weaker inverse functional coupling between the amygdala and OFC compared to controls.
• Amygdala activation during negative feedback was not positively correlated with task-induced irritation in PSCs, unlike in controls.

Conclusions:

• PSCs exhibit disrupted emotion processing circuits, characterized by attenuated modulation of emotional status.
• These early neural dysfunctions may contribute to the later emergence of psychiatric symptoms, including irritability, in Huntington's disease.