The autonomic nervous system: sympathetic / parasympathetic nervous system

The autonomic nervous system (ANS) consists of two parts, the (more activating) sympathetic nervous system and the (more inhibiting) parasympathetic nervous system. These two systems form a dynamic balance.
The sympathetic and parasympathetic nervous systems are controlled by different regions of the brain. The sympathetic nervous system is activated by the paraventricular nucleus, the locus coeruleus and the ventrolateral medulla. The parasympathetic nervous system is controlled by the nucleus tractus solitarius, the dorsal motor nucleus of the vagus nerve and the nucleus ambiguus.
The autonomic nervous system is semi-autonomous, i.e. many reactions are controlled directly in the spinal cord without the involvement of the brain, while others are regulated by higher-level instances (hypothalamus, brain stem, limbic system).
The sympathetic and parasympathetic nervous systems are not rigidly connected like a seesaw, but can be active or passive independently of each other.
Most of the organs of fulfillment are connected to the sympathetic and parasympathetic nervous system via direct nerves. Control takes place preganglionically via acetylcholine and postganglionically via noradrenaline. Depending on the organ, both neurotransmitters have an inhibitory or stimulating effect.

In stressful situations, the sympathetic nervous system reacts by activating organs and increasing the heart rate, breathing and blood pressure. The consequences are increased alertness and increased flight behavior. The alpha-amylase level in saliva is considered a biomarker of the sympathetic nervous system.
The activity of the autonomic nervous system can be determined by measuring heart rate variability.

A meta-study of 55 studies on the VNS in ADHD found no influence of the VNS on ADHD in almost half of the studies. Nevertheless, stimulants and rewards do influence the VNS.¹
In ADHD, adrenaline levels are reduced and the parasympathetic nervous system is excessive and inflexible. The findings on the sympathetic nervous system in ADHD are inconsistent. ADHD medication can cause changes in the autonomic nervous system and almost balance the activity of the sympathetic and parasympathetic nervous systems.

• 1. Sympathetic nervous system (activating)
• 2. Parasympathetic nervous system, vagus (inhibitory)
• 3. Control of the sympathetic, parasympathetic and HPA axis
  • 3.1. Activation of the sympathetic nervous system
  • 3.2. Activation of the parasympathetic nervous system
• 4. Stress reaction of the autonomic nervous system
  • 4.1. Trigger
  • 4.2. Reaction
  • 4.3. Effect
• 5. Alpha-amylase as a biomarker of the autonomic nervous system
• 6. Measurement of the autonomic nervous system using heart rate variability (HRV)
• 7. Vegetative nervous system and ADHD
  • 7.1. Adrenaline levels reduced in ADHD
  • 7.2. Parasympathetic nervous system excessive and inflexible
  • 7.3. Inconsistent findings on the sympathetic nervous system in ADHD
    • 7.3.1. Attenuated sympathetic nervous system: 2 studies
    • 7.3.2. Sympathetic nervous system unchanged: 2 studies
    • 7.3.3. Sympathetic nervous system increased: 2 studies
• 8. Changes in the autonomic nervous system due to ADHD medication
• 9. Parasympathetic / sympathetic nervous system for other disorders

1. Sympathetic nervous system (activating)¶

The sympathetic nervous system promotes motivation, activates and alerts.
Its nerves lead from the brain stem to the thoracic and lumbar parts of the spinal cord.

The sympathetic nervous system is a network of the brain regions²

• PVN, paraventricular nucleus / nucleus paraventricularis
  • A nucleus of the hypothalamus
  • Produced
    • Oxytocin
    • Antidiuretic hormone (low)
    • CRH
• Locus coeruleus
  • Produces noradrenaline
• Ventrolateral medulla
  • Produces noradrenaline
  • Regulated
    • Arterial blood pressure
    • Breathing

The transmitter control of the sympathetic nervous system takes place preganglionically (up to the ganglion) via acetylcholine.
Binding to cholinoceptors:

• N-receptors (nicotinergic)

Transmitter control postganglionically (from the ganglion) is via noradrenaline.
Binding to adrenoreceptors:

• Alpha receptors
• Beta receptors

Graphic by : Sciencia58, CC BY-SA 3.0, File: The autonomic nervous system.png - Wikimedia Commons

2. Parasympathetic nervous system, vagus (inhibitory)¶

The parasympathetic nervous system inhibits motivation, calms and aids digestion.
Its nerves lead from the brain stem through the cranial nerves and the sacral area of the spinal cord through the spinal cord nerves.

The parasympathetic nervous system is a network of the brain regions²

• NTS, nucleus tractus solitarius
  • Controls
    • Taste perception (“taste nucleus”)
    • Respiratory reflex
    • Gag reflex
    • Emetic reflex
• DMX, nucleus dorsalis nervi vagi, dorsal motor nucleus of the vagus nerve
  • Part of the medulla oblongata
• NA, Nucleus ambiguus
  • Part of the medulla oblongata

Transmitter control of the parasympathetic nervous system is carried out preganglionically (up to the ganglion) and postganglionically (from the ganglion) by acetylcholine.

Binding to cholinoceptors

• N-receptors (nicotinergic)
• M receptors (muscarinergic)

3. Control of the sympathetic, parasympathetic and HPA axis¶

The hypothalamus and brain stem moderate the actions of the sympathetic and parasympathetic nervous system in order to keep the body’s constantly changing conditions in what is known as homeostatic equilibrium.

While the HPA axis is controlled by neurotransmitters and hormones (endocrine), the autonomic nervous system is controlled neuronally (electrically). This is why the response of the autonomic nervous system is much faster.

3.1. Activation of the sympathetic nervous system¶

• Amygdala →
  and
• Intralimbic cortex →
  • → Nucleus of the solitary tract →
    • → Locus coeruleus →
      • → Sympathetic nervous system
    • → ventrolateral medulla →
      • → Sympathetic nervous system
    • → Hypothalamus (there: paraventricular nucleus) →
      • → Sympathetic nervous system
• Dorsomedial hypothalamus →
  • → Hypothalamus (there: paraventricular nucleus) →
    • → Sympathetic nervous system

Source³

3.2. Activation of the parasympathetic nervous system¶

• Stria terminalis (there: anterior bed nucleus) →
  • → Hypothalamus (there: paraventricular nucleus) →
    • → dorsal motor nucleus of the vagus nerve →
      • → Parasympathetic nervous system
  • → Nucleus of the solitary tract →
    • → dorsal motor nucleus of the vagus nerve →
      • → Parasympathetic nervous system
    • → Nucleus ambiguus →
      • → Parasympathetic nervous system
• Prelimbic cortex →
  • → Nucleus ambiguus →
    • → Parasympathetic nervous system

Source³

4. Stress reaction of the autonomic nervous system¶

4.1. Trigger¶

• Great effort
• Emotional stress
• Severe pain
• Severe fluid deficiency

4.2. Reaction¶

Noradrenaline activates other organs of the body via the sympathetic nervous system.
Adrenaline is released by the adrenal medulla.

• Increased heart rate
  (noradrenaline and adrenaline via β1 receptors)
• Accelerated breathing
  (noradrenaline and adrenaline via β2 receptors)
• Increase in blood pressure
  (noradrenaline and adrenaline via alpha1 and β receptors)
• Pupil dilation
• Increased supply of oxygen-rich blood to the skeletal muscles in preparation for the fight or flight response
• Noradrenaline and adrenaline reduce the blood supply to currently unimportant organs via β3 receptors
  • Intestine
  • Skin (reduce the risk of bleeding in the event of injury / combat, increase body heat)
• Stimulation of the liver to release energy-rich glucose
• Sweat glands activated (cold sweat)
• Stimulation of the adrenal gland
  Strengthening the alert status by
  • Increased release of adrenaline
  • Increased release of noradrenaline

4.3. Effect¶

• Increased alertness
• Increased flight behavior
• Increased energy consumption

A similar effect appears to exist in the central nervous system (brain and spinal cord), where the PFC is the “digestive” organ that is boosted by moderate levels of norepinephrine and shut down by high levels of norepinephrine, while the sensorimotor and affective regions of the brain are boosted by higher levels of norepinephrine.⁴

5. Alpha-amylase as a biomarker of the autonomic nervous system¶

Just as cortisol, the last hormone of the HPA axis, is a highly measurable biomarker of the HPA axis (e.g. in saliva), the alpha-amylase level reflects the reactivity of the sympathetic nervous system.⁵⁶

Both biomarkers can be easily measured in saliva.

You can find out more about alpha-amylase in ADHD and its interaction with cortisol at ⇒ α-Amylase in ADHD And ⇒ Correlation between alpha-amylase and cortisol.

6. Measurement of the autonomic nervous system using heart rate variability (HRV)¶

The activity of the autonomic nervous system, in particular the parasympathetic nervous system, can be measured non-invasively by measuring heart rate variability. This results in interesting approaches to diagnostics and therapy.
⇒ Heart rate variability (HRV) in ADHD

7. Vegetative nervous system and ADHD¶

A meta-study on the autonomic nervous system in ADHD found⁷

• 2 studies reported a reduced sympathetic tone
• 7 studies reported lower sympathetic reactivity to task demands / stress
• 1 study reported reduced vagal tone

There was no evidence of altered task-related parasympathetic reactivity.

7.1. Adrenaline levels reduced in ADHD¶

Adrenaline is usually measured in the urine.
The basic functions of adrenaline: ⇒ neurotransmitters Neurotransmitters - messenger substances.

• A high adrenaline level correlates with faster decisions and fewer errors in cognitive tests in unstressed individuals, while a reduced adrenaline level correlates with slower decisions and higher error rates.⁸
• In a boring, under-stimulating task, (unstressed) subjects with higher adrenaline levels performed better than those with lower adrenaline levels. In contrast, subjects with lower adrenaline levels performed better in a demanding, overstimulating task.⁸
• Young men (average age 24) who showed a higher increase in noradrenaline and adrenaline in response to stress were more efficient in tests. This effect was even stronger for adrenaline than for noradrenaline.⁹
• Subjects whose adrenaline levels increased during an attention test compared to the waiting time achieved better results.¹⁰
• Children whose adrenaline levels increased during an arithmetic test compared to a passive situation performed better in the test than children who did not react with an adrenaline increase.¹¹
• The subjective perception of stress correlates linearly with the level of adrenaline in healthy test subjects.¹²
• The adrenaline level (but not the noradrenaline level) in stressful situations tends to decrease with the feeling of control and manageability of those affected.¹³
• The adrenaline release of the sympathetic adrenal gland is significantly reduced in children with aggressiveness, motor restlessness and concentration difficulties under stress and without stress. Hyperactive boys show a significantly lower adrenaline release under stress as well as outside stress than those not affected. Low sympathetic-adrenal reactivity is discussed as a risk factor and susceptibility indicator for social and / or profound behavioral disorders.¹⁴
• People with depressive tendencies show a lower adrenaline stress response to acute stress than those who are not affected.¹⁵

7.2. Parasympathetic nervous system excessive and inflexible¶

A small study found in unmedicated children with ADHD:¹⁶

• Increased arousal of the parasympathetic nervous system
• Methylphenidate shifted the autonomic balance of children with ADHD towards normal values, but did not reach the comparative values of non-affected children
• MPH inhibits the normal response of the autonomic nervous system to a cognitive challenge.
• Methylphenidate appears to alter / suppress the normal stress response

Another study found differences in parasympathetic activity (PRS) in children with ADHD.¹⁷
Children with ADHD showed an inflexible, equally strong increase in PRS at

• Negative emotions
• Positive emotions
• Suppression of an activity
• Induction of an activity

Children without ADHD, on the other hand, showed

• Negative emotions: PRS increased more strongly
• Positive emotions: PRS less elevated
• Suppression of an activity: PRS more elevated
• Induction of an activity: PRS less elevated

A replication study confirmed the rigid pattern of increased PRS in children with ADHD, and also found an increased sympathetic nervous system response. The changes in the sympathetic nervous system in ADHD correlated with disorders of emotion reactivity, while the deviations in the parasympathetic nervous system correlated with disorders of emotion regulation.¹⁸

A study on children with and without ADHD found no significant differences in the resting activity or reactivity of the respiratory sinus arrhythmia (RSA). However, each correlated with the other regardless of ADHD status:¹⁹

• Reduced prosocial behavior with
  • Lower RSA value at rest
  • Lower reactive RSA decline
• Emotion regulation problems with
  • Increased reactive RSA decline to incentives.

Respiratory sinus arrhythmia (RSA) consists of oscillatory increases and decreases in heart rate during the respiratory cycle. It represents parasympathetic / vagal effects on the heart. The RSA is thought to represent neuronal traffic through the vagus nerve²⁰. The vagus nerve is thought to represent a physiological mechanism for the rapid acceleration and deceleration of cardiac output in response to environmental (including social) demands.²¹

7.3. Inconsistent findings on the sympathetic nervous system in ADHD¶

The cardiac pre-ejection period (PEP) is a systolic time interval mediated by the sympathetic nervous system (SNS) that encompasses the depolarization of the left ventricle until the start of blood ejection into the aorta (the time from the start of electrical stimulation of the left ventricle (start of the Q-wave in the ECG) until the opening of the aortic valve). PEP represents mesolimbic dopamine reactivity, particularly during the reward response.²² A longer PEP is a marker for reduced activity of the sympathetic nervous system, even if this can also be influenced by other factors.²³

7.3.1. Attenuated sympathetic nervous system: 2 studies¶

A study of 2,209 participants found a correlation between inattention and a prolonged pre-ejection period (PEP), suggesting a weakened sympathetic nervous system in relation to inattention.²⁴ A small study also found an underarousal of the sympathetic nervous system in unmedicated children with ADHD¹⁶

7.3.2. Sympathetic nervous system unchanged: 2 studies¶

One study found no deviations of the sympathetic nervous system in ADHD¹⁷
A study of children with and without ADHD found no significant differences in resting activity or reactivity of the cardiac pre-ejection period (PEP). However, each correlated with the other regardless of ADHD status:¹⁹

• Behavioral problems and aggression with
  • Extended PEP at rest
  • Reduced PEP reactivity to incentives
    Sympathetic nervous system is increased:
    In contrast, another study found an increased sympathetic nervous system response in children with ADHD. The changes in the sympathetic nervous system in ADHD correlated with disorders of emotion reactivity, while the deviations in the parasympathetic nervous system correlated with disorders of emotion regulation.¹⁸

7.3.3. Sympathetic nervous system increased: 2 studies¶

In ADHD, HRV is reduced and the sympathetic nervous system is overactivated.²⁵ Together with reduced cardiac-linked parasympathetic activity and reduced HRV, this is a non-invasive marker for prefrontal hypoactivity and ADHD.²⁶

Further studies found evidence of an increased sympathetic nervous system in comorbid externalizing disorders

One study found a significant reduction in electrodermal activity in adolescents with ADHD with and without comorbid conduct disorder, which is consistent with the lower perception of anxiety in impulsivity. An attenuated PEP response to reward was only found in adolescents with ADHD and comorbid conduct disorder, not in ADHD alone.²⁷ Further studies also indicate that reduced reward reactivity of the mesolimbic dopaminergic system is reflected in attenuated PEP signals to reward and correlates particularly with aggressive externalizing behaviour ^{28 2930}
Two studies that found reduced heart rate variability to rewards in ADHD did not differentiate between ADHD and comorbid externalizing disorders.³¹³²

8. Changes in the autonomic nervous system due to ADHD medication¶

A study on adolescents with ADHD found reduced activity of the sympathetic and parasympathetic nervous system compared to those not affected. This difference was almost equalized by a slow-release MPH preparation.³³

9. Parasympathetic / sympathetic nervous system for other disorders¶

Borderline personality disorder showed an increased sympathetic tone with and without comorbid ADHD, which was reflected in larger pupils than in the control subjects.³⁴