Autonomic nervous system in psychiatry

1. AUTONOMIC NERVOUS SYSTEM - By Dr. SRIRAM. R

2. This topic can be discussed under three sub-headings Introduction Evolutionary aspects of ANS Importance of ANS in psychiatry

3. INTRODUCTION

4. The autonomic nervous system (ANS or visceral nervous system or involuntary nervous system) is the part of the peripheral nervous system that acts as a control system functions largely below the level of consciousness. Controls visceral functions, including heart rate, digestion, respiratory rate, salivation, perspiration, pupillary dilation, micturition (urination), sexual arousal, breathing and swallowing

5. In the brain… ANS is located in the medulla oblongata in the lower brainstem. The medulla's major ANS functions include respiration (the respiratory control center, or " rcc "), cardiac regulation (the cardiac control center, or " ccc "), vasomotor activity (the vasomotor center or " vmc "), and certain reflex actions (such as coughing, sneezing , vomiting and swallowing). Those are then subdivided into other areas and are also linked to ANS subsystems and nervous systems external to the brain.

6. The hypothalamus, just above the brain stem, acts as an integrator for autonomic functions, receiving ANS regulatory input from the limbic system to do so. The ANS is divided into three main sub-systems: the parasympathetic nervous system (PSNS), sympathetic nervous system (SNS), and the enteric nervous system (ENS)

7. SNS is often considered the "fight or flight" system, while the PSNS is often considered the "rest and digest" or "feed and breed“ system . In many cases, PSNS and SNS have "opposite" actions. A more modern characterization is that the sympathetic nervous system is a " quick response mobilizing system " and the parasympathetic is a " more slowly activated dampening system ", but even this has exceptions, such as in sexual arousal and orgasm, wherein both play a role.

8. Subdivisons of the ANS The sympathetic division has thoracolumbar “outflow”, meaning that the neurons begin at the thoracic and lumbar (T1-L2/3 ) portions of the spinal cord. The parasympathetic division has craniosacral “outflow”, meaning that the neurons begin at the cranial nerves (Cranial nerves III, VII, IX, and X) and sacral (S2-S4) spinal cord. Efferent pathway is 2 neuron - the preganglionic neuron must first synapse onto a postganglionic neuron before innervating the target organ.

9. SYMPATHETIC DIVISION The sympathetic division ( thoracolumbar outflow) consists of cell bodies in the lateral horn of the spinal cord ( intermediolateral cell columns) from T1 to L2/3. These cell bodies are GVE (general visceral efferent) neurons and are the preganglionic neurons. There are several locations upon which preganglionic neurons can synapse for their postganglionic neurons:

10. Paravertebral ganglia (3) of the sympathetic chain (these run on either side of the vertebral bodies) 1 . cervical ganglia (3) 2 . thoracic ganglia (12) and rostral lumbar ganglia (2 or 3) 3 . caudal lumbar ganglia and pelvic ganglia Prevertebral ganglia (celiac ganglion, aorticorenal ganglion, superior mesenteric ganglion, inferior mesenteric ganglion) Chromaffin cells of the adrenal medulla (this is the one exception to the two-neuron pathway rule: the synapse indirectly efferent onto the target cell bodies)

11. These ganglia provide the postganglionic neurons from which innervation of target organs follows. Examples of splanchnic (visceral) nerves are: Cervical cardiac nerves & thoracic visceral nerves, which synapse in the sympathetic chain Thoracic splanchnic nerves (greater, lesser, least), which synapse in the prevertebral ganglion Lumbar splanchnic nerves, which synapse in the prevertebral ganglion Sacral splanchnic nerves, which synapse in the inferior hypogastric plexus These all contain afferent (sensory) nerves as well, known as GVA (general visceral afferent) neurons.

12. STRESS RESPONSE SYSTEM The Locus Ceruleus in the brainstem is the "start" button for the fight or flight system. It releases norepinephrine /noradrenalin anytime stress of any kind is detected. All of this takes place in the limbic system. This triggers the amygdala which triggers the hypothalamus. The amygdala prompts feelings of anxiety and fear. The hypothalamus then releases CRH, which stimulates the pituitary. The pituitary release ACTH to stimulate the adrenal glands. The adrenal glands release adrenalin and cortisol .

13. FUNCTION OF SNS Diverts blood flow away from the gastro-intestinal (GI) tract and skin via vasoconstriction Blood flow to skeletal muscles and the lungs is enhanced (by as much as 1200% in the case of skeletal muscles) Dilates bronchioles of the lung, which allows for greater alveolar oxygen exchange Increases heart rate and the contractility of cardiac cells ( myocytes ), thereby providing a mechanism for enhanced blood flow to skeletal muscles Dilates pupils and relaxes the ciliary muscle to the lens, allowing more light to enter the eye and far vision Provides vasodilation for the coronary vessels of the heart Constricts all the intestinal sphincters and the urinary sphincter Inhibits peristalsis Stimulates orgasm

14. PARASYMPATHETIC DIVISON The parasympathetic division ( craniosacral outflow ) consists of cell bodies from one of two locations: the brainstem(Cranial Nerves III, VII, IX, X) or the sacral spinal cord (S2, S3, S4). These are the preganglionic neurons, which synapse with postganglionic neurons in these locations:

15. Parasympathetic ganglia of the head: Ciliary (Cranial nerve III), Submandibular (Cranial nerve VII ), Pterygopalatine (Cranial nerve VII), and Otic (Cranial nerve IX ) In or near the wall of an organ innervated by the Vagus (Cranial nerve X) or Sacral nerves (S2, S3, S4 ) These ganglia provide the postganglionic neurons from which innervations of target organs follows. Examples are: The postganglionic parasympathetic splanchnic (visceral) nerves The Vagus Nerve, which wanders through the thorax and abdominal regions innervating, among other organs, the heart , lungs, liver and stomach

16. FUNCTIONS OF PSNS Promotes a "rest and digest" response, promotes calming of the nerves return to regular function, and enhances digestion The parasympathetic nerves dilate blood vessels leading to the GI tract, increasing blood flow (this is important following the consumption of food, due to the greater metabolic demands placed on the body by the gut) The parasympathetic nervous system can also constrict the bronchiolar diameter when the need for oxygen has diminished Dedicated cardiac branches of the vagus and thoracic spinal accessory nerves impart parasympathetic control of the heart (myocardium) During accommodation, the parasympathetic nervous system causes constriction of the pupil and contraction of the ciliary muscle to the lens, allowing for closer vision The parasympathetic nervous system stimulates salivary gland secretion, and accelerates peristalsis, mediating digestion of food and, indirectly, the absorption of nutrients I nvolved in the erection of genital tissues via the pelvic splanchnic nerves 2–4. S timulating sexual arousal

17. Neurotransmitters and pharmacology At the effector organs, sympathetic ganglionic neurons release noradrenaline ( norepinephrine ), along with other cotransmitters such as ATP , to act on adrenergic receptors, with the exception of the sweat glands and the adrenal medulla: Acetylcholine is the preganglionic neurotransmitter for both divisions of the ANS, as well as the postganglionic neurotransmitter of parasympathetic neurons. Nerves that release acetylcholine are said to be cholinergic.

18. In the parasympathetic system, ganglionic neurons use acetylcholine as a neurotransmitter to stimulate muscarinic receptors . At the adrenal medulla, there is no postsynaptic neuron. Instead the presynaptic neuron releases acetylcholine to act on nicotinic receptors. Stimulation of the adrenal medulla releases adrenaline (epinephrine) into the bloodstream, which acts on adrenoceptors , producing a widespread increase in sympathetic activity.

19. EVOLUTIONARY ASPECTS OF ANS

20. SOCIAL ENGAGEMENT SYSTEM Focuses only on the neural regulation of the striated muscles of the face and head and the specific autonomic functions mediated by the myelinated vagus . Conceptualized to emphasize a system that has a common neural substrate composed of several cranial nerves that develop embryologically together.

21. The social engagement system has a control component in the cortex (upper motor neurons) that regulates brainstem nuclei (i.e . lower motor neurons controlling special visceral efferent pathways) to control: eyelid opening (e.g . looking) facial muscles (e.g . emotional expression) ; middle-ear muscles (e.g . extracting human voice from background noise) ; muscles of mastication ( e.g.ingestion ) ; laryngeal and pharyngeal muscles ( e.g.vocalization and language) ; and head-turning muscles (e.g . social gesture and orientation)

22. The social nervous system functions from birth and rapidly develops to support communication with the environment. For example, when a healthy infant encounters the caregiver’s face, the infant will attempt to engage via facial expression and vocalizations. The infant may use vocalizations (cry) and facial expressions (grimace) to signal negative states to the caregiver. Or , to signal more positive states, a wide-eyed, smilinginfant would attempt to elicit positive vocalizations and smiles from the caregiver.

23. POLYVAGAL THEORY D erived from investigations of the evolution of the autonomic nervous system. 1. Evolution has modified the structures of the autonomic nervous system. 2. The mammalian autonomic nervous system retains vestiges of phylogenetically older autonomic nervous systems. 3. Emotional regulation and social behavior are functional derivatives of structural changes in the autonomic nervous system due to evolutionary processes. 4 . In mammals, the autonomic nervous system response strategy to challenge follows a phylogenetic hierarchy, starting with the newest structures and, when all else fails, reverting to the most primitive structural system. 5. The phylogenetic stage of the autonomic nervous system determines affective states and the range of social behavior.

24. In the ANS, the parasympathetic system is the oldest, reflecting the survival needs of a primitive passive feeders. The sympathetic nervous system is a later development, adding mobility, mobilization and a wider range of possible survival responses. Porges has shown clear evidence of a third, more modern branch of the ANS, with a survival value specific to more sophisticated animals especially primates. “Social Nervous System ” is the proposed term for this third branch of the ANS.

25. Drawing on the “Theory of Dissolution” (J.H. Jackson, ca.1910 ), Porges also shows that under stress, the human system tries its newest, most sophisticated and efficient equipment first. If that doesn’t work, older strategies are attempted, and if they don’t work, the oldest resources are employed. Therefore under stress, the human first uses its social/relational tactics, then fight/flight, then immobility, as survival strategies

26. The theory proposes that physiological state limits the range of behavior and psychological experience The theory proposes that the different branches are related to unique, adaptive behavioral strategies and articulates three phylogenetic stages of the development of the mammalian autonomic nervous system -

27. HEIRARCHIAL RESPONSE STRATEGY 1. The ventral vagal complex VVC : a mammalian signaling system for motion, emotion, and communication. 2 . The sympathetic nervous system SNS : an adaptive mobilization system supporting fight or flight behaviors. 3 . The dorsal vagal complex DVC : a vestigial immobilization system . The polyvagal theory proposes a hierarchical response strategy to environmental challenges, with the most recent modifications (1) employed first and the most primitive (3) last. However, the response strategy is not all-or-none, and may include transitional blends between the boundaries of the three hierarchical stages.

28. IMPORTANCE OF ANS IN PSYCHIATRY

29. Dysregulation of the autonomic nervous system (ANS) is a common characteristic of a variety of psychiatric disorders, including depression , schizophrenia, and panic disorder (Friedman and Thayer , 1998a; Karavidas et al., 2007; Valkonen-Korhonen et al., 2003 ) Heart rate variability (HRV) represents a sensitive measure of autonomic system function (Low and Pfeifer, 1997) and can be utilized as a tool to assess the effect of psychopathology and disease on the balance between sympathetic and parasympathetic input to the heart.

30. Mood disorders are strongly associated with changes in cardiovascular function (Johnson and Grippo , 2006) and alterations in HRV. Cardiac patients with more severe depression exhibit less HRV compared to those with less severe depression ( Krittayaphong et al., 1997) and successful treatment of depression tends to be accompanied by an increase in HRV ( Balogh et al., 1993; Chambers and Allen, 2002 ) Vagal nerve stimulation (VNS) has been reported to successfully improve affect in treatment-resistant depression (George et al., 2005), suggesting a strong link between sympathovagal dysregulation and symptoms of depression

31. Anxiety disorders have long been associated with autonomic abnormalities , including low HRV, decreased cardiac vagal tone,and elevated sympathetic heart rate control (Friedman and Thayer,1998b) A growing number of reports have also observed HRV dysfunction in schizophrenia (SCZ) (Bar et al., 2005; Boettger et al., 2006; Valkonen - Korhonen et al., 2003). There is a decrease in parasympathetic activity independent of medication effects in schizophrenia. Manic BD patients demonstrated a significant reduction in HRV, parasympathetic activity, compared to control subjects, while SCZ patients demonstrated a similar, but non- significant , trend towards lower HRV. Reduction in parasympathetic tone was significantly correlated with higher YMRS scores and the unusual thought content subscale on the BPRS (Brook et al, 2009).

32. HPA axis in psychiatry The HPA axis is involved in the neurobiology of  mood disorders  and functional illnesses, including  anxiety disorder ,  bipolar disorder ,  insomnia ,  posttraumatic stress disorder , borderline personality disorder ,  ADHD ,  major depressive disorder ,  burnout ,  chronic fatigue syndrome ,  fibromyalgia ,  irritable bowel syndrome , and  alcoholism . Antidepressants , which are routinely prescribed for many of these illnesses, serve to regulate HPA axis function ( Pariante , 2003)

33. Prolonged maternal stress during gestation is associated with mild impairment of intellectual activity and language development in their children, and with behaviour disorders such as  attention deficits ,  schizophrenia ,  anxiety  and  depression ; S elf-reported maternal stress is associated with a higher irritability, emotional and attentional problems A 2010 literature review article regarding neurophysiological findings in Borderline PD noted several studies supporting at least the potential of abnormal HPA axis sensitivity and function.  

34. Preliminary studies found that individuals diagnosed with Borderline PD tend to have : an exaggerated response to HPA activation ; 2) increased basal cortisol levels; and 3) reduced feedback system, which impairs the brains ability to know when to “shut off” the cascade of events leading to cortisol secretion, when compared with psychiatric controls ( Wingenfeld , Spitzer, Rullkotter ,  & Lowe, 2010)

35. Most people with PTSD also show a low secretion of  cortisol  and high secretion of   catecholamines  in  urine ,  with a  norepinephrine / cortisol ratio consequently higher than comparable non-diagnosed individuals .   This is in contrast to the normative  fight-or-flight response , in which both  catecholamine  and cortisol levels are elevated after exposure to a stressor . Brain  catecholamine  levels are high ,  and  corticotropin -releasing factor  (CRF) concentrations are high .   Together , these findings suggest abnormality in the  hypothalamic-pituitary-adrenal (HPA) axis

36. SKIN CONDUCTANCE TESTING Skin conductance , also known as  galvanic skin response  (GSR),  electrodermal response  (EDR), psychogalvanic reflex  (PGR),  skin conductance response  (SCR), or  skin conductance level  (SCL), is a method of measuring the  electrical conductance  of the  skin , which varies depending on the amount of sweat-induced moisture on the skin. Sweat is controlled by the  sympathetic nervous system , so skin conductance is used as an indication of psychological or physiological  arousal . If the sympathetic branch of the autonomic nervous system is highly aroused, then sweat gland activity also increases, which in turn increases skin conductance

37. SCR is used widely in psychological research due to its low cost and high utility. Many  biofeedback  therapy devices utilize skin conductance to measure and display an individual's stress response with the goal of helping the user to control anxiety. Skin conductance measurement is also becoming more popular in  hypnotherapy  and  psychotherapy  practices where it can be used as a method of detecting depth of hypnotic trance prior to the commencement of  suggestion therapy .

38. DEPRESSION Depressed patients are twice as likely as nondepressed patients to have a major cardiac event within 12 months of the diagnosis of coronary artery disease (Carney et al, 1988) and they are significantly more likely to die in the years following the diagnosis (Barefoot et al, 1996)

39. ANXIETY DISORDER

40. The ANS of some patients with anxiety disorder, especially those with panic disorder, exhibits increased sympathetic tone, adapt slowly to repeated stimuli and respond excessively to moderate stimuli. Affected patients may have poorly regulated NA system with occasional bursts of activity. Patients with anxiety disoders , have elevated CSF or urinary levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), a NA metabolite In patients with panic disorder, blunted ACTH responses to CRF has been reported in some studies

41. SCHIZOPHRENIA Balance in the autonomic nervous system is altered in schizophrenic patients with a hyperexcitability in both the sympathetic and the parasympathetic division (Nielsen et al, 1988) Heart-rate response to standing was used as a measure of sympathetic function. Heart-rate response to inspiration was greater in non-medicated schizophrenics compared to normal subjects.

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