Is essential tremor a disorder of primary GABA dysfunction? Yes

Area of Science:

• Neuroscience
• Neurology
• Neurochemistry

Background:

• Essential tremor (ET) is a neurological disorder characterized by involuntary shaking.
• Neurochemical dysfunction, particularly in gamma-aminobutyric acid (GABA) neurotransmission, is implicated in ET.
• The 'GABA hypothesis' proposes that reduced GABAergic tone underlies ET pathophysiology.

Purpose of the Study:

• To review existing evidence supporting the GABA hypothesis of essential tremor.
• To examine findings from cerebrospinal fluid, pathology, genetics, animal models, imaging, computational models, and drug studies.
• To identify areas requiring further investigation, including the neurodegenerative nature of ET and cerebellar GABA activity.

Main Methods:

• Systematic review of studies investigating GABAergic function in essential tremor.
• Analysis of data from diverse research methodologies including biochemical, genetic, imaging, and preclinical studies.
• Consideration of both supporting and contradictory findings, as well as controversies.

Main Results:

• Evidence suggests a potential link between GABA dysfunction and essential tremor.
• The precise role of reduced GABAergic tone (primary cause, consequence of Purkinje cell dysfunction, or cell death) remains unclear.
• Controversies and negative study findings highlight the complexity of ET pathophysiology.

Conclusions:

• Further research is essential to confirm the neurodegenerative aspects of ET and reduced cerebellar GABA activity.
• Targeted therapies aimed at enhancing cerebellar GABA transmission warrant investigation.
• Elucidating the exact contribution of GABAergic dysfunction is crucial for understanding and treating essential tremor.