Social phobia - neurophysiological correlates

Mice that repeatedly experienced aggression from conspecifics developed a lifelong social phobia. This could be remedied by:

• Elimination of BDNF in the VTA / nucleus accumbens pathway¹
• Permanent administration of antidepressants (fluoxetine)¹
• Single administration of ketamine, but less Rabastinel²
  • This also indicates the importance of BDNF in socially triggered stress

BDNF withdrawal in the VTA / nucleus accumbens pathway appears to have an antidepressant effect,^{34 5} , while conversely in the hippocampus BDNF administration has an antidepressant effect, antidepressants slowly increase BDNF in the hippocampus and ketamine rapidly increases BDNF in the hippocampus.⁶

Abnormalities in the social reward circuitry appear to contribute to the social deficit in ASD.
The social reward circuit consists mainly of:⁷

• basolateral amygdala (blA)
• Nucleus accumbens (Nac)
• dorsal anterior cingulate cortex (dACC)
• Hypothalamus
• Midbrain

ASD sufferers show reduced activity in the reward circuit blA / Nac.⁸
An increase in 2-arachidonoylglycerol (2-AG, an endocannabinoid signal) appears to reduce presynaptic glutamate release in the blA / Nac signaling pathway. This alleviated social avoidance in Shank3-/- model mice.⁹
Vitamin D deficiency correlated with a reduced expression of cannabinoid receptors in the spinal cord and of 2-AG in the intestine of mice.¹⁰
Vitamin D receptors are found almost everywhere in the brain, including in the brain regions of the social reward circuit.
It is possible that vitamin D modulates the amount of 2-AG in the blA-Nac circuit and thus the ASD symptom of social withdrawal⁷

A lack of empathy is an important characteristic of ASD and impairs social functions.
The ACC-blA circuit, among others, is involved in emotional empathy.¹¹
Children with ASD show reduced connectivity between the amygdala and ACC, the extent of which correlated with the degree of social deficits.¹²
Like almost all brain regions, blA and ACC also express vitamin D receptors and vitamin D deficiency correlated with a thinner ACC.
It is possible that vitamin D deficiency could affect the morphology of the ACC and thus contribute to a lack of emotional empathy.⁷