Neurovisceral phenotypes in the expression of psychiatric symptoms

Neurovisceral phenotypes in the expression of psychiatric symptoms | Autonomic Neuroscience | Review ARTICLE |February 2015 

This review supports what I’ve long suspected: it’s not just my body that’s hypermobile, but my emotions as well. Physical instability is neurologically related to mental instability.

This review explores the proposal that vulnerability to psychological symptoms, particularly anxiety, originates in constitutional differences in the control of bodily state, exemplified by a set of conditions that include Joint Hypermobility, Postural Tachycardia Syndrome and Vasovagal Syncope.

Research is revealing how brain-body mechanisms underlie individual differences in psychophysiological reactivity that can be important for predicting, stratifying and treating individuals with anxiety disorders and related conditions. 

One common constitutional difference is Joint Hypermobility, in which there is an increased range of joint movement as a result of a variant of collagen. Joint hypermobility is over-represented in people with anxiety, mood and neurodevelopmental disorders. It is also linked to stress-sensitive medical conditions such as irritable bowel syndrome, chronic fatigue syndrome and fibromyalgia

Structural differences in “emotional” brain regions are reported in hypermobile individuals, and many people with joint hypermobility manifest autonomic abnormalities, typically Postural Tachycardia Syndrome.

Enhanced heart rate reactivity during postural change and as recently recognized factors causing vasodilatation (as noted post-prandially, post-exertion and with heat) is characteristic of Postural Tachycardia Syndrome, and there is a phenomenological overlap with anxiety disorders, which may be partially accounted for by exaggerated neural reactivity within ventromedial prefrontal cortex

People who experience Vasovagal Syncope, a heritable tendency to fainting induced by emotional challenges (and needle/blood phobia), are also more vulnerable to anxiety disorders.

Neuroimaging implicates brainstem differences in vulnerability to faints, yet the structural integrity of the caudate nucleus appears important for the control of fainting frequency in relation to parasympathetic tone and anxiety.

Together there is clinical and neuroanatomical evidence to show that common constitutional differences affecting autonomic responsivity are linked to psychiatric symptoms, notably anxiety.


Influential theories argue that bodily states of arousal are a key component to emotions, and are the basis to emotional feeling states. Emotional processes are intrinsically coupled to autonomic bodily responses through shared neural substrates

Exaggerated patterns of autonomic responsivity can enhance the expression of panic or anxiety symptoms. Some of the vulnerability to psychological symptoms, particularly anxiety, originates in constitutional differences in the control of bodily states of arousal.

By characterizing the interplay between brain and body in detail, clinically relevant insights can be gained into the mechanisms that underpin both adaptive and maladaptive psychological and physical states.

We argue that there are specific yet common constitutional variants (i.e., phenotypes) in physiological reactivity (i.e., related to the autonomic nervous system) that have major influences on emotional state and by extension on vulnerability to psychiatric disorder.

Below we discuss the relevance of three of these “neurovisceral phenotypes” (Joint Hypermobility, Postural Tachycardia Syndrome and Vasovagal Syncope) to psychiatric symptoms.

Joint Hypermobility

Joint hypermobility affects up to 20% of the general population (Mulvey et al., 2013) yet is often poorly recognized (Grahame, 2008). It is characterized by a variation in the type and distribution pattern of collagen.

Over recent years there has been growing recognition of extra-articular features of Joint Hypermobility: these affect almost every system of the body (unsurprisingly as collagen is not confined to joints). Conditions associated with joint hypermobility go beyond rheumatology to include Chronic Fatigue Syndrome (Nijs et al., 2006), Fibromyalgia (Ofluoglu et al., 2006), and Irritable Bowel Syndrome (Zarate et al., 2010).

Association with psychiatric disorder

Psychiatric phenomena are increasingly recognized as another important extra-articular manifestation of joint hypermobility.

This means that I have pain not because I’m crazy, but that I’m crazy from my pain.

A recent meta-analysis of 3597 subjects demonstrates consistently that in both healthy and clinical population’s hypermobile people experience significantly more intense fears, agoraphobia, panic, anxiety, and depressive disorders (Smith et al., 2014).

Additionally significantly higher rates of joint hypermobility can be observed among patients with Bipolar Disorder and Neurodevelopmental disorders, such as Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder (Eccles et al., 2014a,b).

brain and body are intrinsically and dynamically coupled; perceptions, emotions and cognitions respond to, and change, the state of the body

In disorders that typically involve impaired collagen (present in blood vessels) such as joint hypermobility and postural tachycardia syndrome it is likely that reduced venous return during standing due to venous pooling or denervation causing low plasma volume may be responsible for a an increased sympathetic state –as the body attempts to compensate for these abnormalities—resulting in orthostatic intolerance and associated symptoms (Bohora, 2010; Benarroch, 2012; Mathias et al., 2012).

Thus, we postulate that a major factor is the dysregulation of the autonomic nervous system, which particularly drives the expression of anxiety, a pervasive symptom across almost all psychological disorders.

Evidence of autonomic dysfunction in Joint Hypermobility

Symptoms related to the autonomic nervous system, such as syncope and presyncope, orthostatic intolerance, palpitations, chest discomfort, fatigue, and heat intolerance, are significantly more common among hypermobile patients.

Patients with Joint Hypermobility Syndrome have a greater mean drop in systolic blood pressure during hyperventilation, and a greater increase in systolic blood pressure after a cold pressor test, than controls. They also have evidence of heighted vasoconstriction mediated by alpha-adrenergic and beta-adrenergic hyper-responsiveness

Symptoms suggestive of autonomic dysfunction are also more common in patient with Joint hypermobility Syndrome. These include including presyncope, palpitations and gastrointestinal disturbances (Hakim and Grahame, 2004). Measures of heart rate reactivity and reactions to the Valsalva maneuver, during autonomic functional testing also indicate autonomic dysregulation in Joint Hypermobility Syndrome patients compared to controls, including (De Wandele et al., 2014).

Overall, hypermobile patients had higher mean autonomic dysfunction and orthostatic intolerance than non-hypermobile patients.

Evidence of brain-body interactions from neuroimaging

Structural differences in key emotion processing brain regions, notably affecting the amygdala bilaterally, are observed in these otherwise healthy individuals. The hypermobile group as a whole also display decreased anterior cingulate and left parietal cortical volume while the degree of hypermobility correlates negatively with both superior temporal and inferior parietal volume (Eccles et al., 2012).


These data suggest that specific brain regions mediate the interaction between psychological processes and the physiological state of the body, in a manner ultimately crucial to the generation of anxiety and related symptoms in the joint hypermobility phenotype.

The amygdala is a key region supporting motivational and behaviors and emotional memory; it is implicated in threat processing, generation of bodily arousal reactions and the expression of mood symptoms.

there is evidence to suggest that the autonomic nervous system is dysregulated in hypermobile individuals. Theoretically, anxiety is linked to the unpredictable states of bodily arousal, engaging regions such as amygdala and insula (Paulus and Stein, 2006).

Observed differences in dorsal right anterior cingulate cortex were also observed. This region is implicated in autonomic reactivity, and engaged in the cognitive control of pain and negative feeling states (Critchley, 2009; Tracey and Bushnell, 2009).

Hypermobility was also linked to reduced right superior temporal volume. Right superior temporal cortex supports the sensory processing of social emotional information and structural abnormalities of this region are observed in autism (Boddaert et al., 2004), where neurodevelopmental emotional deficits are frequently accompanied by heightened anxiety

Patients with joint hypermobility show heightened interoceptive sensibility compared to those without (Eccles et al., 2012) and interoceptive sensitivity has been show to mediate the relationship between state anxiety and hypermobility and it could be hypothesized combining functional neuroimaging with autonomic monitoring will show that inefficient neural co-ordination of efferent autonomic drive with imprecise interoceptive representations may be amplified in hypermobile individuals.  

The article continues with the same kind of writeup for two other autonomic disorders: Postural Tachycardia Syndrome and Vasovagal Syncope.

Another article in this journal “Frontiers of Neuroscience” also explores the link between neurological and neuropsychiatric disorders:

Potential interactions between the autonomic nervous system and higher level functions in neurological and neuropsychiatric conditions

In this review, we will discuss potential relationships between ANS and higher level dysfunctions in a selection of neurological and neuropsychiatric disorders.


2 thoughts on “Neurovisceral phenotypes in the expression of psychiatric symptoms

  1. Pingback: Joint Hypermobility Associated with Anxiety | EDS and Chronic Pain News & Info

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