Abstract
BackgroundAnxiety is a heterogeneous behavioral domain playing a role in a variety of neuropsychiatric diseases. While anxiety is the cardinal symptom in disorders such as panic disorder, co-morbid anxious behavior can occur in a variety of diseases. Stiff person syndrome (SPS) is a CNS disorder characterized by increased muscle tone and prominent agoraphobia and anxiety. Most patients have high-titer antibodies against glutamate decarboxylase (GAD) 65. The pathogenic role of these autoantibodies is unclear.Methodology/Principal FindingsWe re-investigated a 53 year old woman with SPS and profound anxiety for GABA-A receptor binding in the amygdala with (11)C-flumazenil PET scan and studied the potential pathogenic role of purified IgG from her plasma filtrates containing high-titer antibodies against GAD 65. We passively transferred the IgG fraction intrathecally into rats and analyzed the effects using behavioral and in vivo electrophysiological methods. In cell culture, we measured the effect of patient IgG on GABA release from hippocampal neurons. Repetitive intrathecal application of purified patient IgG in rats resulted in an anxious phenotype resembling the core symptoms of the patient. Patient IgG selectively bound to rat amygdala, hippocampus, and frontal cortical areas. In cultured rat hippocampal neurons, patient IgG inhibited GABA release. In line with these experimental results, the GABA-A receptor binding potential was reduced in the patient's amygdala/hippocampus complex. No motor abnormalities were found in recipient rats.Conclusion/SignificanceThe observations in rats after passive transfer lead us to propose that anxiety-like behavior can be induced in rats by passive transfer of IgG from a SPS patient positive for anti-GAD 65 antibodies. Anxiety, in this case, thus may be an antibody-mediated phenomenon with consecutive disturbance of GABAergic signaling in the amygdala region.
Highlights
Anxiety and fear are the leading symptoms in anxiety disorders such as panic disorder and phobias, which are thought to feature complex neurobiological underpinnings with both genetic as well as environmental factors
The PET scan analysis showing reduced 11C-FMZ binding potential in motor-premotor cortex was extended and we show that the binding potential was reduced in the limbic region, namely the amygdala and hippocampal complex (Figure 1; right: 1.80 vs. 2.1860.39, left: 1.58 vs. 1.9660.41, Stiff person syndrome (SPS) patient vs. control patients, means 6 SD)
Because the patient was clinically affected by profound anxiety, agoraphobia, and panic attacks, we focused on anxiety-like behavior in experimental rats receiving repetitive i.th. injections of purified patient IgG
Summary
Anxiety and fear are the leading symptoms in anxiety disorders such as panic disorder and phobias, which are thought to feature complex neurobiological underpinnings with both genetic as well as environmental factors. Stiff person syndrome (SPS), a rare and multi-facetted disorder of the central nervous system, is one of the neuropsychiatric disorders where anxious symptoms are found most frequently [1,2]. The anxious phenotype of the patients which often resembles agoraphobia and not rarely entails substance abuse, often leads to a misdiagnosis of a primary psychiatric disorder and must clearly be attributed to supraspinal pathology. This may be one reason why SPS remains still an underdiagnosed condition [6]. While anxiety is the cardinal symptom in disorders such as panic disorder, co-morbid anxious behavior can occur in a variety of diseases.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
