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

People with ADHD 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

Theory of Mind impairments correlate neurophysiologically with increased gray matter volume in the bilateral amygdala and hippocampus in people with ADHD as in those without. EEG studies found statistically significantly higher electrophysiological activity during ToM tasks in the frontal, temporal, parietal and occipital lobes in people with ADHD.¹³