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Friday 14 February 2020

Thirst – Too much or too little (Polydipsia and Hypodipsia) Vasopressin and Angiotensin

Today’s post is about both drinking too much water and drinking too little water.

Polydipsia (drinking too much water) is a known cause of death in autism and schizophrenia.  A big part of the reason we talk about autism being a spectrum, is the pioneering work of an English Psychiatrist called Dr Lorna Wing.  Wing outlived her daughter with severe autism, because her daughter Susie developed Polydipsia around the menopause and this caused the sodium level in her blood to fall to the point where her heart stopped beating and she died.  Even though Mum was a (retired) doctor, the condition was not resolved; but Susie’s death should have been avoidable.  Polydipsia is treatable and people should not be dying from it.

Hypodipsia (drinking too little water) can occur in older people, who are neglected in care homes and for a wide range of other reasons.  People with autism treated by the diuretic Bumetanide are at risk of Hypodipsia and indeed this accounts for some of the side effects some people experience.  The other possible side effects of Bumetanide are caused by low levels of potassium in blood. Hypodipsia is also called Adipsia.

Hypodipsia/Adipsia is treatable and much more easily so than Polydipsia; drink more water. Drugs are not used to treat Hypodipsia/Adipsia, therapy relies on modifying behavior.  Drinks can be made more available and more interesting, some kids love drinking from a water fountain or water dispenser. Use a large glass rather than a small glass.  Many people prefer cold water.

Cold water can increase interest in water, but in people who binge drink, cold water is likely to temper their thirst, through a mechanism explained in the paper below called "Thirst".


The Biology of Thirst

There are multiple pathways involved in thirst and so multiple therapies are needed to treat Polydipsia.  The most likely problem relates to Vasopressin, a hormone produced the hypothalamus, a tiny part in the middle of your brain. Vasopressin release is triggered by a hormone called Angiotensin II.

To understand how complex the biology is there are two excellent papers suggested below.


Our bodies are mostly water, and this water is constantly being lost through evaporative and other means. Thus the evolution of robust mechanisms for finding and consuming water has been critical for the survival of most animals. In this Primer, we discuss how the brain monitors the water content of the body and then transforms that physical information into the motivation to drink.


Angiotensin II, or ANG II, is the key hormone driving thirst because it triggers the release of the hormone Vasopressin.

ANP (Atrial natriuretic peptide) hormone should tell you to stop drinking, because your volume of blood is excessive.  This signal must be too weak in people with Polydipsia.

Polydipsia is also a tell-tale sign of the onset of diabetes. Blood sugar rises, your kidneys cannot process the glucose, so the glucose and fluids are excreted as urine making you dehydrated.  You then drink like a fish; hopefully someone notices, otherwise you lose weight, feel tired and finally end up in hospital.

You see in the chart below that eating should activate certain hormones to make you thirsty.







(A) The most potent hormonal stimulus for thirst is angiotensin II (AngII), which is generated when the rate-limiting enzyme renin is secreted by the kidneys in response to hypovolemia or hypotension. Other hormonal stimuli for thirst are secreted by the stomach and pancreas during eating, as well as by the ovaries during pregnancy. Atrial natriuretic peptide, a potent inhibitor of thirst, is secreted by the heart in response to hypertension.
(B) The physiological stimuli that induce secretion of thirst-related hormones include changes in plasma volume and pressure, as well as eating and pregnancy. Decreases in blood volume and pressure increase levels of the dipsogenic hormone AngII, whereas increases in blood volume increase levels of the thirst-inhibiting hormone ANP.

This paper is interesting for those who like details.



Plasma Osmolality

Plasma osmolality measures the body's electrolyte-water balance

Serious electrolyte disturbances, like dehydration (hypodipsia) and overhydration (polydipsia), may lead to cardiac and neurological complications and result in a medical emergency.

Sodium is the main electrolyte found in extracellular fluid and potassium is the main intracellular electrolyte; both are involved in fluid balance and blood pressure control.

The most serious risk to life is from Hyponatremia, low sodium concentration in the blood.

Hyponatremia is the most common type of electrolyte imbalance. It occurs in about 20% of those admitted to hospital and 10% of people during or after an endurance sporting event.

Hypokalemia is the risk to those with autism taking Bumetanide.  The level of potassium circulating in your blood falls below a safe level and blood pressure may rise and abnormal heart rhythm may be experienced. The person will feel lethargic and may experience constipation.






Vasopressin

The hormone Vasopressin has functions within the brain, mediated by 2 types of receptor (Vasopressin receptor 1A and 1B) which relate to behavior (social bonding, aggressive behavior etc).

There is another type of receptor (Vasopressin receptor 2) which is in your kidneys and relates to diuresis and thirst.

The vasopressin system is well known to be dysfunctional in schizophrenia, so we should expect behavioral effects and effects relating to thirst.   There are even measurable irregularities in vasopressin levels in people with schizophrenia.

“It has been found that 69 – 83% of psychiatric polydipsic patients have a diagnosis of schizophrenia, and that 6 –17% of chronic psychiatric patients are polydipsic”

Vasopressin is released within the brain by the action of the hormone Angiotensin II.
Angiotensin II has multiple physiologic effects, including acting in the brain to promote drinking and salt consumption and acting in the periphery to constrict blood vessels and promote water reuptake by the kidneys.

Angiotensin II plays a key role in blood pressure and so there are numerous drugs that reduce Angiotensin II levels.  They are called ACE inhibitors and ARBs.

I did suggest a few years ago that Angiotensin could be an interesting target to treat schizophrenia and some autism.  The reason I was initially interested was the potential immuno-modulatory effect, but Telmisartan in particular has numerous potentially useful effects in autism. 

There are those two old posts:-

Targeting Angiotensin in Schizophrenia and Some Autism


I think it is likely that some sub-types of autism would likely benefit from an ACE inhibitor. As a secondary benefit, it will also reduce any troubling high levels of leptin.

There are other ways to modulate Th1, Th2 and Th17, but if you have elevated Angiotensin Converting Enzyme (ACE), then an ACE inhibitor would appear the logical choice.

How about a clinical trial in adults with Asperger's?


Angiotensin II in the Brain & Therapeutic Considerations


Telmisartan seems to have numerous potentially useful additional effects:


·        Acts as a PPAR gamma agonist, like the glitazone drugs shown effective in autism trials


·        Acts as a PPAR delta agonist, which should activate the impaired PPARδ  PGC-1α signaling pathway, and enhance mitochondrial biogenesis. This should help people with mitochondrial disease and should be evident by increased exercise endurance and, in theory, improved cognitive function.

·        Telmisartan regulates the Bcl-2 cancer gene, implicated in autism


While the effect in autism is complex, Telmisartan is already seen as a potent target for prevention and treatment in human prostate cancer


·        Telmisartan and other ARBs appear to give protection from Alzheimer’s Disease (suggested to be via its effect on PPAR gamma). Perhaps useful for young adults with Down Syndrome, where early onset Alzheimer’s is expected?

·       Telmisartan and other ARBs have a tendency to increase the level of potassium in blood. Up to 10% of people would experience mild hyperkalemia.  For people with autism taking bumetanide, this effect on potassium might actually be helpful. They would need to reduce their potassium supplementation, or might need none at all.


Vasopressin as a behavioral Therapy?

Vasopressin is a target of therapy in both autism and schizophrenia.

The vasopressin system is thought to be dysfunctional in schizophrenia and indeed that life-threatening water intoxication in schizophrenic patients only occurs if it is associated with a concurrent increase in vasopressin secretion.

It is bizarre that the same hormone that controls diuresis also influences social bonding and impulsive and aggressive behavior.  It does explain why in some people all these processes are all disrupted.

It looks like some people need less vasopressin and that can be achieved with an ACE inhibitor. Some people need to tamp down just Vasopressin receptor 1A, encoded by a gene known as the "daring/ruthlessness gene" AVPR1A, which you can with a new drug called Balovaptan.  Some people might want to tamp down just Vasopressin receptor 1B, which may reduce aggressive behaviors.

The research shows that another group of people actually respond to more Vasopressin, this can be achieved with a vasopressin nasal spray.

In the case of our reader Tanya’s son with Polydipsia, I would think an ACE inhibitor may help not only with reducing thirst, but give the Balovaptan effect to his behavior.  My guess is the vasopressin nasal spray from Stanford would have a negative effect on him.

ACE inhibitors are cheap generics with very known safety profiles.  You can achieve the same effect with another class of drugs called angiotensin receptor blockers (ARBs).  It is more a question of which drug produces the least side effects in the specific person. ACE inhibitor and ARBs are use to lower blood pressure.

We will see later that bother ARBs and ACE inhibitors are used in clinical practise to treat Polydipsia.

The recent Vasopressin trials in autism:-

Can manipulating a ‘social’ hormone’s activity treat autism?

Many people with autism have trouble making eye contact, reading the emotions in other faces, and sharing affection. And no drugs are approved to treat such social impairments. Now, results from a small academic clinical trial suggest boosting levels of vasopressin—a hormone active in the brain that’s known to promote bonding in many animals—can improve social deficits in children with autism. But in a confusing twist, a larger, company-sponsored trial that took the reverse approach, tamping down vasopressin’s effects, also found some improvements in adults with autism.
                                                                                                                               
Oxytocin is very similar to Vasopressin, in modifying behavior.



Whereas OT plays a key role both in prosocial behavior and in the central nervous control of stress and anxiety, AVP has primarily  been implicated in male-typical social behaviors, including aggression and pair-bond formation, and in stress-responsiveness.  Although most of the studies conducted thus far on human social behavior have focused on OT, few studies on AVP suggest behavioral effects similar to those found in animal research.  Coccaro and colleagues [33] examined the relationship between cerebrospinal fluid (CSF) AVP and indices of aggression in personality-disordered subjects. The authors found a positive correlation between levels of CSF AVP and life histories of general aggression and aggression against other persons, suggesting an enhancing effect of central AVP in individuals with impulsive aggressive  behavior. Two recent studies examined the effect of intranasal AVP administration on human facial responses related to social  communication. In a first study, Thompson and colleagues [144] examined the effects of 20 IU intranasal AVP on cognitive, autonomic, and somatic responses to emotionally expressive facial stimuli in healthy male students using a placebo-controlled, double-blind design. Whereas AVP did not affect attention toward, or autonomic arousal in response to, emotional facial expressions with different valence (neutral, happy, and angry), the authors did observe selective enhancements of the corrugator supercilii electromyogram (EMG) responses evoked by emotionally neutral facial expressions. Interestingly, subjects of the AVP group yielded magnitudes in response to neutral facial expressions that were similar to the magnitudes of placebo subjects in response to angry facial expressions [144]. In view to the crucial role of this muscle group for species specific agonistic social communication [86], these results suggest that AVP may influence aggression by biasing individuals to respond to emotionally ambiguous social stimuli as if they were threatening or aggressive.

Vasopressin receptor 1A  (encoded by the AVPR1A gene)

The genetic variants of the AVPR1A gene might be related to narcissism and gentle behavior. NatureNews has referred to AVPR1A as the "daring gene". The term "ruthlessness gene" has also been coined by Nature.com

Balovaptan  is a selective small molecule antagonist of the vasopressin receptor 1A, which is under development by Roche for the treatment of autism.  On 29 January 2018, Roche announced that the US Food and Drug Administration (FDA) had granted Breakthrough Therapy Designation for balovaptan in individuals with autism. The FDA granted this based on the results of the adult phase II clinical trial called VANILLA (Vasopressin ANtagonist to Improve sociaL communication in Autism) study.

So, Roche hope that blocking the rector encoded by the “ruthlessness gene” will improve social behavior.  This is reducing the effect of Vasopressin selectively, so not affecting diuresis.

I think you would expect the people who respond well to Balovaptan to also respond well to an ACE inhibitor or ARB, and vice versa.

In my son, an ARB made him want to sing, so I expect Balovaptan would likely have a similar effect.

In my son, increasing oxytocin in the blood, via increasing oxytocin produced in the gut, using the bacteria Lreuteri DSM 17938 did make him more emotional.

Neither of the above two effects were that significant to bother with.


Vasopressin V1b receptor 

 

“Inactivation of the Avpr1b gene in mice (knockout) produces mice with greatly reduced aggression and a reduced ability to recognize recently investigated mice.[13] Defensive behaviour and predatory behaviours appear normal in these knockout mice,[14] but there is evidence that social motivation or awareness is reduced.[15] The AVPR1B antagonist, SSR149415, has been shown to have anti-aggressive actions in hamsters[16] and anti-depressant- and anxiety (anxiolytic)-like behaviors in rats.[17] A single nucleotide polymorphism (SNP) has been associated with susceptibility to depression in humans.[6]

                              

Vasopressin, social cognition and schizophrenia

Introduction: vasopressin, also known as arginine-vasopressin (AVP) or antidiuretic hormone, is mainly synthesized on hypothalamus. It acts on three receptors, of which the centrally expressed V1A and V1B are known to mediate a variety of mental and behavioural effects. In recent years, research on social attachment and cognition in both animal models and humans has also revealed the involvement of vasopressin. Social dysfunction is a key feature of schizophrenia, and in the late 1970’s there were reports associating endogenous vasopressin and psychotic disorders. Indeed, studying the brains of untreated individuals with schizophrenia revealed heightened vasopressin levels, findings which were replicated in plasma levels; the latter were found to normalize after antipsychotic treatment. Methods: searches were undertaken in PubMed and other databases using keywords such as ‘vasopressin’, ‘social cognition’, ‘schizophrenia’ and ‘psychosis’. Results: recent data in human studies suggest that peripheral vasopressin relates to severity of acute psychosis in women with acutely-ill untreated first-episode psychosis, and that the administration of AVP may alter the valence of social stimuli in a sex-dependent manner. In fact, polymorphisms in genes in the AVP pathway have been associated with schizophrenia. The role of the V1A and V1B receptors in the neural regulation of social behaviour has also been studied with several genetic animal models of schizophrenia that reproduce certain aspects of the human disease phenotype. These findings add further evidence that the central vasopressin system may have therapeutics effects on positive and negative symptoms of schizophrenia, probably due to interactions with the glutamatergic and dopaminergic systems. Conclusions: vasopressin plays a significant role in the regulation of social recognition, social communication, and aggression, in integration with the “social behaviour” neural network. Vasopressin regulation is altered in schizophrenia and it has been hypothesized that this might relate to some clinical symptoms and cognition dysfunction. However, other putative factors (e.g., polydipsia, antipsychotics) could account for the results, and the published literature does not yet support a cohesive perspective regarding vasopressin and schizophrenia. Future studies should consider variations in AVP and its receptor genes as potential moderators of the relationship between hormone levels, clinical symptoms, and social cognition.



Psychogenic Polydipsia (PPD) and Hyponatremia in the research

The first thing to note is that the same condition gets called different things.  The fanciest sounding term is Psychogenic polydipsia (PPD), the simplest is Excessive water drinking behavior.  Take your pick, but Google them all.  The best research is the schizophrenia research, as is often the case.


The aim of this study was to determine the incidence of polydipsia in 49 autistic children, and also the influence of psychotropic drugs and residential factors on water drinking behavior, as compared with in 89 mentally retarded children, in schools for mentally handicapped children in Fukui prefecture. Questionnaires were used to detect polydipsia and to assess the severity of the water drinking behavior in the autistic children and mentally retarded children. The incidence of polydipsia in the autistic children tended to be higher (P = 0.074) than that in the retarded children. The severity of water drinking behavior was significantly higher in autism (P = 0.022) than in mental retardation. The majority of the autistic children with polydipsia had been taking no psychotropic drugs. The incidence of polydipsia showed no significant difference between two residential situations, i.e. 'not at home' and 'at home'. The present study suggests that polydipsia or excessive water drinking behavior occurs more often in autism than in mental retardation, possibly due to some intrinsic factor in autism itself.

The present study indicates that polydipsia tends to occur somewhat more often in autism than in mental retardation, and is significantly more severe in autism. Bremner et al. studied 877 mentally handicapped inpatients. In their study, the prevalence of polydipsia in autism was 27.2% (six of 22 cases), compared with 16.3% in the present study. Furthermore, they described a case of autism with fatal water intoxication, who was taking fluvoxamine and chlorpromazine, but did not discuss the role of the drugs as a cause of polydipsia. Autism has been stated to be associated with a hypothalamic-pituitary dysfunction indicated by a blunted-plasma growth-hormone response following the oral administration of l-dopa, an abnormal plasma growth hormone response to insulin-induced hypoglycemia, and a premature or delayed response of growth hormone to clonidine and l-dopa. The blunted growth hormone response exhibited by at least 30% of autistic children to a provocative challenge with l-dopa suggests an alternation of hypothalamic dopamine receptor sensitivity (subsensitivity) in autistic children. The premature response of growth hormone to clonidine and delayed response to l-dopa suggest possible abnormalities of both dopaminergic and noradrenergic neurotransmission in subjects with autism. Furthermore, Hiratani et al. described a case of autism with water intoxication and the episodic release of antidiuretic hormone. The thirst center is said to be located in the hypothalamus. Therefore, a possible factor causing polydipsia in autism may be a hypothalamic–pituitary dysfunction. In 1988, the male case described by Hiratani et al. , who was 19-years old at that time, exhibited a remarkable daily body weight change that was probably due to excessive water drinking. After mild water restriction and intermittent forced water restriction according to the setting of a body weight limit, the daily change became smaller in 1994. We have often observed that autistic children sometimes fiddle with water, or only drink from a single faucet, presumably one manifestation of the restricted interest characteristic of autism. Therefore, preservative tendencies may contribute to compulsive water drinking. In conclusion, in view of the present results, it is possible that the principal cause of polydipsia is some intrinsic factor in autism itself (e.g. a hypothalamic–pituitary dysfunction, restricted interest and activity)


Note in this paper,   Vasopressin  = ADH (antidiuretic hormone)

Psychogenic polydipsia (PPD), a clinical disorder characterized by polyuria and polydipsia, is a common occurrence in inpatients with psychiatric disorders. The underlying pathophysiology of this syndrome is unclear, and multiple factors have been implicated, including a hypothalamic defect and adverse medication effects. Hyponatremia in PPD can progress to water intoxication and is characterized by symptoms of confusion, lethargy, and psychosis, and seizures or death. Evaluation of psychiatric patients with polydipsia warrants a comprehensive evaluation for other medical causes of polydipsia, polyuria, hyponatremia, and the syndrome of inappropriate secretion of antidiuretic hormone. The management strategy in psychiatric patients should include fluid restriction and behavioral and pharmacologic modalities.

In addition to high water intake, risk of hyponatremia is further compounded by impaired water excretion. Impairment in excretion can be due to coexisting ADH increases secondary to stress, nausea, or a syndrome of inappropriate secretion of ADH (SIADH)


Most psychiatric patients with hyponatremia will fit into the final category and will have low plasma osmolality. They will have normovolemia and will lack clinical indicators of altered volume status. PPD and SIADH fit into this category. Most cases of PPD severe enough to cause hyponatremia have a very high volume of intake. These cases have very low levels of ADH and have urine osmolality that is very low (< 100). SIADH by definition has high ADH levels and high urine osmolality (> 500). SIADH, as opposed to the other conditions listed (except salt wasting), has high urine sodium (> 20). High urine sodium occurs in SIADH due to low activation of the RAA system.




Investigation

A comprehensive work-up needs to include a thorough history, physical examination, and routine laboratory tests. Low-cost and high-yield tests for determining diagnosis include the plasma and urine osmolality and plasma and urine sodium. Other tests that may be of benefit include a complete metabolic panel, urinalysis, urea, chest x-ray, and CT head.

Whereas history, serum sodium, and osmolality produce some diagnostic certainty, a water restriction test is the gold standard for diagnosis. A valid test achieves plasma osmolarity greater than 295 mOsm/kg, producing a maximal renal response of ADH in normal individuals. Plasma ADH can be drawn before and after water restriction and then sent if other results are equivocal. With the diagnosis of PPD alone, urine is very dilute prior to water restriction (< 100 mOsm/kg), and plasma ADH is low. The picture can be clouded if there is a corresponding central defect of SIADH and PPD. Then ADH will be elevated (due to SIADH), and the urine will not be maximally dilute. If the defect is renal hypersensitivity to ADH and PPD, the urine still will not be maximally dilute. However, in this setting, ADH could be low or normal (but its increased effect on the kidney would produce an SIADH-like picture). With both comorbid conditions, the added problem of increased renal retention of water will produce hyponatremia more often than the increased intake of PPD alone. In DI, as with PPD, urine would be dilute prior to a water restriction test. ADH levels would depend on whether the defect is central DI (low ADH secretion) or renal DI (low renal response to ADH). Hence, prior to a water restriction test, central DI and PPD can appear similar (low ADH and dilute urine). Although PPD can have low sodium, whereas DI can have high sodium, both can coexist, as exemplified in a case study. After water restriction, PPD alone shows very concentrated urine (> 600 mOsm/L) and high ADH. On the other hand, DI shows urine concentration that rises little even after fluid restriction (< 600 mOsm/L). (Urine concentration can rise somewhat if DI is only a partial defect.) As with PPD, ADH will be elevated in renal DI, but ADH will be low in the case of central DI. Exogenous ADH can be administered immediately following a nondiagnostic water restriction test. In PPD, no increase in urinary concentration occurs after exogenous ADH is administered. Yet in central DI, in which this hormone is lacking, a dramatic increase in urinary concentration will occur. Some impairment in concentrating ability often is present in chronic PPD due to medullary gradient washout and down-regulation of ADH release. These factors can cloud the picture even more. Chronic PPD patients can have maximal urine concentrations closer to 600 mOsm/L instead of the normal range, greater than 800 mOsm/L. (Note: Raising osmolarity with hypertonic saline is best completed by nephrology [0.5 mL/kg for up to 2 hours] if needed due to poor compliance. Raising plasma osmolarity should be avoided in patients strongly suspected of having nephrogenic DI, as it could induce hypernatremia [eg, long-term lithium use]. Drugs listed under “Contributing factors” could interfere with an accurate test.)

Treatment for hyponatremia

See the full paper


Treatment for PPD

Behavioral treatments

Therapeutic fluid restriction is an inexpensive form of treatment; given the higher rates of noncompliance, it may take several days for an effect to be seen in patients with mental illness. Patient weights often are used to determine water intake diurnally. Differences in weight in PPD patients (2.2%) can be much greater than in controls (0.6%) [33]. Reinforcement schedules using tokens to get rewards, as well as removal of these tokens for nonadherence have been used with some success. Most behavioral intervention studies are in inpatients, as they often require close monitoring and substantial time commitment from staff. In extreme cases of nonadherence, patients may require a locked unit away from all water sources. Another novel behavioral outpatient treatment that may suit higher-functioning patients addresses several areas of behavioral change. Therapists used cognitive techniques to address thoughts leading to drinking behavior and then implemented a behavioral program to restrict water intake. They implemented a stimulus control device that included positive reinforcement and coping skills. They followed the patient with weekly visits for 12 weeks and addressed delusions and fears related to drinking excessively. The patient used a record book for time, fluid amount, and situation for each beverage consumed. The patient was given a 500-mL water jug as a stimulus control device and instructed to fill it only six times daily to achieve a goal of less than 3 L for water restriction. The patient used coping skills (substituting ice cubes for drinks, taking small sips, distracting activities). Positive feedback from the therapist and improvement of urinary frequency reinforced fluid restriction.

Drug treatments

Atypical antipsychotic agents have been shown in case reports to have some success in alleviating symptoms of PPD. Clozapine has had effects in the literature in management of PPD but remains unproven in large trials. Low-dose risperidone and olanzapine improved polydipsia in a case report. Their effect potentially stemmed from dopamine receptor regeneration after chronic, typical neuroleptic administration. Kruse et al.  theorized that this reduction in dopamine supersensitivity decreased thirst stimulation. Beta blockers such as propranolol have been found to be effective. Another method of treatment for patients with chronic hyponatremia is demeclocycline, 600 to 1200 mg/d, which directly inhibits ADH action at the level of the distal renal tubules and reduces urine concentration. Demeclocycline is expensive and is associated with nephrotoxicity [15], and it has not been found to be efficacious in double-blind, placebo-controlled trials. Lithium, which works as a direct competitive antagonist of ADH action by inducing nephrogenic DI, is rarely used because its own adverse effects are potentially nephrotoxic and thyrotoxic. A double-blind, placebo-controlled pharmacologic study (crossover design) looked at the use of clonidine, an B-adrenergic blocking agent, and enalapril, an ACE inhibitor, in 14 chronically psychotic, institutionalized patients who suffered from PPD. These medications were administered separately and individually at a dose of clonidine, 0.2 mg orally twice daily, and enalapril, 10 mg orally twice daily. The study found improvement in fluid consumption (determined by calculated urine output and urine osmolality) in approximately 60% of the test subjects who were on either drug, although no behavioral improvement was demonstrated. The study concluded that medications known to affect body water balance might decrease excess fluid intake in some patients with histories of water abuse. ACE inhibitors in other trials as PPD treatment have produced equivocal results. Irbesartan, an angiotensin receptor blocker, was found to be an effective adjunct in the treatment of PPD in a case report of a schizophrenic patient due to a proposed effect of blocking the thirstinducing effect of angiotensin. Recently, newer agents called “aquaretics” that antagonize ADH receptors were developed. These agents have been found to increase free water clearance without directly affecting the handling of tubular sodium. Conivaptan is an aquaretic that recently has been approved by the US Food and Drug Administration for the treatment of euvolemic hyponatremia in hospitalized patients.


Conclusion

I have rather gone into the details in today’s post, because for some people with autism, and more with schizophrenia, it will literally be a matter of life or death.

People do not usually die the first time they binge drink water.

The first medical emergency should set alarm bells ringing, because drinking water to excess is known to be habit forming.  One day your luck may run out.

In today’s post there were a whole range of therapies (ACE Inhibitor, ARB, Propranolol, Clozapine etc) and a list of medical investigations that can be carried out. 



As Agnieszka pointed out to Tanya in the comments recently, a treatable tumor of the Pituitary gland was the cause of death for a well-known Greek girl with autism; the symptom she presented with was Polydipsia. Had the patient had a CT scan of the head, as suggested in the above paper by Dundas, Harris and Narasimhanm, she might be alive today. A tumor there is likely going to affect function of the hypothalamus, where Vasopressin is produced.

I do wonder whether, somewhat paradoxically, treating a person with Polydispsia, with a diuretic might not be a very clever solution.

If you take Bumetanide (or a non-sulfonamide diuretic, for those, like Tanya’s son, with an allergy), you actually get to drink a lot of water, without a problem with low sodium levels (hyponatremia); you just need to eat bananas to maintain potassium levels.  You also might be so preoccupied about dashing urgently for the toilet, you lose all interest in binge drinking water.











Thursday 6 February 2020

Monty in Mardin – on the Silk Road with Autism



Mardin is a city in Southeastern Turkey on the overland Silk Road (in red)


Today’s post does not have any science.

Just after the new year Monty went to southeast Turkey to visit Mardin, an old city that was on the Silk Road linking Asia to Europe and then to see more of Istanbul.

Travel can be difficult for people with autism, even fully verbal people with above average IQ.  Some people with Asperger’s refuse to fly because they fear the plane is going to crash.  Exaggerations and distortions of normal perception are actually examples of psychotic behavior, in the extreme these are the "positive" symptoms of schizophrenia.  This loss of touch with reality does feature to varying degrees in some Aspies.

Monty started to fly while still a baby and, in spite of a few glitches along the way, has become quite a seasoned traveller for a 16 year old.  

The latest trip was a little off the beaten track for western tourists, in fact we did not see any other western tourists, just a few people visiting from Istanbul.

Mardin is an old town built up the side of a small mountain giving panoramic views across Mesopotamia.  All the old merchant’s houses have large terraces facing the same direction, so they could see incoming traffic from the Silk Road.



Mardin


            A merchant’s house in Mardin



The Front Door of the Deyrilzafaran Monastery




Midyat, a three-thousand-year-old city



Passing for Normal

The Holy Grail for treating someone born with severe autism is just passing for normal.

Passing for normal may not be politically correct, but it is practically correct in actual daily life.

Two recent events stand out in my mind. Walking around the narrow streets of Mardin we entered one of the most impressive old houses.  In the courtyard was a security office; it was clearly was some kind of official building. On the large upper terrace, with the stunning view over Mesopotamia, was a well-dressed man and we started a conversation in English.  He beckoned us to come up past the security guard and see the old house.  It is now used as a school for tourism and hotel/catering.  He offered us Turkish tea and was telling us all about the history of the building and the city.

At first, he thought Monty was a local boy acting as our guide, then later on he turned to Monty and said “what are you going to study later at University?”.  Instead of me having to explain that Monty has autism and so probably will not be going to University, Monty just answered “science”.   Bravo Monty.

The other recent event was the school’s poetry night, when they combine music recitals with poetry readings.  Monty went up on stage for his piano recital, bowed at the end and, as the school principal pointed out to me later, what you saw was just another quiet teenager with some musical talent, not the token one with a disability.  She has known him for 13 years and did not expect him to cope in high school, even with his assistant. Bravo again, Monty.

Unlike how autism is now portrayed in media, people with autism often do look very different and act very differently to other people.  The looking different part could be used to identify the underlying biological cause, but usually is not.  The acting different part is often the result of behaviors learned from their autistic peers and then reinforced by them.  This is a big disadvantage of special schools and group homes, “odd” behaviors get copied until everyone has them.

In a somewhat bizarre twist of nature, sometimes the unusual facial features show up instead on the sibling of the child with autism.  This was recently highlighted again in the research.


Back to Istanbul

Istanbul is one of the world’s great cities, with an amazing location on the Bosporus which connects the Black Sea to the Mediterranean.  It is full of interesting things to see and is great value.  The overland Silk Road ended in Constantinople, now called Istanbul; goods then moved west by sea to Venice.

Istanbul is a good place for people, like Monty, who like to eat fish and also all kinds of cakes and desserts.  Monty even acquired a taste for drinking Turkish tea in small glasses. There are some good, very child-friendly, museums, with parent-friendly admission prices.




Seagulls with the Dolmabahçe Palace on the European side of the Bosphorus in the background




The Rumeli Fortress in Europe and the third Bosphorus Bridge, leading to Asia



Life before the PolyPill

The summer before Monty started his autism Polypill in 2012, we went to Portugal. I still clearly remember having to pin him down in his seat with my arms and legs, as he went berserk in the plane. We had rented a car, but we could not leave Monty in the back with his older brother, because he would attack him.  That was travel with a 9-year-old with medically untreated severe autism.


Expect the unexpected

As our reader Tanya, recently commented, life with autism is always full of surprises, to be overcome.  It is perhaps an adventure you would rather not be on, like a trip with Bear Grylls.  

We still encounter some travel issues, but they are now trivial.  Monty’s ears do not pop when the plane lands and then they hurt and this affects behavior.  The first solution was his idea, jump deep down into a swimming pool.  Ears pop and the problem is solved.

Recently this developed into not swallowing after the plane has landed.  Mouth fills up with saliva, so you cannot talk and also your face bulges and the automatic face recognition at passport control does not work.

I did earlier have Monty’s ears checked and the ENT doctor found nothing, but suggested using the Dymista allergy nose spray containing Azelastine and the steroid Fluticasone. We already have this and it does not help ears pop.

The solution I came up with is to bring a sports-type water bottle on the plane, the type you have to suck to get the water.  During the last 10 minutes of the flight, suck the water, swallow, then squeeze your nose tightly and try to swallow several times.  It works, one problem solved and now we await the next one.

Autism flare-ups, sudden onset vocal or motor tics have all come, been figured out and then been overcome.


Autism and vacations in the literature

Researchers even publish papers about holidays/vacations taken by people with autism.  In short, autism families rarely have holidays and when they do it can be quite stressful for everyone.

The key to happy holidays is medically treating severe autism. 



This work aims at identifying the types of holiday experienced by families of children with autism spectrum disorder (ASD). 35 families of ASD children and 25 control families of children with Down’s Syndrome (DS) living in Scotland took part in a small scale semi-qualitative study to explore their experiences on holiday. In both groups, a significant proportion of the families had not taken any holiday away from home more than once in the last 3 years and there was limited use of children holiday centers. Families of ASD children who had been on holiday expressed overall less positive impressions of their experiences and showed limited use of public places such as restaurants, cafes, cinemas and hotels normally accessed by typical families whilst on vacation. Five areas were identified as influencing the quality of their experiences: 1-child’s disability, particularly with regard to behavior, 2-lack of suitable holiday structures, 3-financial limitation of the family, 4-lack of empathy from surrounding communities towards the disabled child and his or her family, 5- general state of exhaustion of the parents. The paper further describes two pilot holiday community experiences organised with 10 families with ASD children in an attempt to address some of the issues hereby identified. A retrospective analysis of these experiences and surveys suggests that amongst all five identified barriers, the issue of the child’s behavior is the most significant difficulty encountered by these families. Supporting families in understanding and improving their child’s’ behavior is needed to enable families to maximise their experience on holiday. Increasing the understanding of the condition, improving access to leisure activities and some financial aid would equally be beneficial

  

There is an evolving tourism literature around psychological wellbeing, social exclusion and disability. This paper advances tourism knowledge into the terrain of psychological health and developmental complexities, and psychological distress. It draws on a phenomenological position to understand the lived experiences of mothers of children with developmental difficulties, in this case diagnosed with autism spectrum disorder (ASD). It discusses the emotional and everyday challenges of caring for a child diagnosed with ASD on holiday, discusses the perceived benefits holidays offer and outlines care-giving strategies adopted by mothers to manage their children’s tourism experiences. The paper discusses the uniqueness of the context of autism and problematizes popular discourses, which predominantly frame tourism as pleasurable settings of escape, stimulation, novelty and relaxation.

Conclusion The mothers in this study navigated the emotional dimensions of their family holidays through a range of strategies. Firstly, they chose destinations and accommodation, which provided detailed information on all aspects of the holiday to prepare their child in advance. Secondly, they selected quiet destinations and accommodation and thirdly, they packed familiar possessions that are important to the child’s daily routine and ensured that the accommodation could provide for their child’s needs (e.g. Wi-Fi and television). Some mothers also carried an identification card or official document from health or psychology services for their child to deal with public censure if the child’s behaviour became too extreme or to confirm his entitlement to preferential attention, such as in theme park queues. Such strategies could be employed by other parents and, if we can appreciate the coping approaches of parents of children with a disability, these may ‘‘provide valuable insight for other families and parents” (Dodd et al., 2009, p.266). Tourism researchers have much to do to provide such insight and to adequately connect disability, psychological health, distress and the family. This paper has contributed to the unfolding work on this area and, in focusing on developmental difficulties and psychological distress, has widened the scope of an evolving tourism literature exploring wellbeing and psychological health. The area of psychological distress in general, and specifically in tourism, requires much more investigation since studies on disability too often assume that the ‘‘obstacles, barriers and constraints which face disabled people are identical across all people with a disability” (Blichfeldt & Nicolaisen, 2011, p.83). Our research has highlighted the unique context of autism and the challenges faced by mothers of children diagnosed with ASD, illuminating their complex care-giving responsibilities and the impact these have on family holiday experiences, including those of siblings. Whilst all the mothers we spoke with identified benefits to holiday-taking, they balance these against the disruption to routines and exposure to sensory-stimulating environments (Bellini, 2004), which make holidays a challenging experience for both them and their child or children. In addition, expectations to conform to certain behaviours and public reactions to their child’s behaviour can exacerbate the difficulties of holidaying and make them an isolating experience. In this, families with children diagnosed with ASD share common ground with other groups who experience stressful travel encounters in an unaccommodating world (Small & Harris, 2012). Embodiment, attitude, behaviours and stigma are common across disability groups and tourism’s gaze of discipline and surveillance, which causes such stress to many people with disabilities (Eichhorn et al., 2013) and to parents of young children in general, bears further scrutiny. This leads us to perhaps the most thought-provoking contribution of our study. It illustrates the ways in which tourism experiences are journeys of mixed emotions: far from the binary of pleasure and apprehension, they are indeed multifaceted, complex, interlinked and intersubjective (Williams & Aaker, 2002). We need to know more in this area. We also require further explorations of the multiple, complex and nuanced meanings of ‘the holiday’; especially ones that investigate what constitutes a holiday for individuals and families who fall outside of our world’s increasingly unforgiving expectations and norms. Conceptualisations of the holiday have focused on its benefits and on its opportunities for positive transformation and renewal (e.g. Reisinger, 2013). Holidays also entail considerable ‘work’, anxiety and emotional labour (Dieffendorff et al., 2005), especially for care-givers, and particularly as here, for mothers of children diagnosed with ASD. At each stage of the holiday and planning process, the women invested significant time, energy and emotional labour to facilitate trips for their families, in which they themselves experienced both stress and escapism. Indeed, different holiday practices (e.g. air transport, visiting resorts) evoke a series of different emotions and emotional labour depending on the life-world of our participants. With the consequences of emotional labour often resulting in psychological distress (Strazdins & Broom, 2004), we suggest more attention should be given to this area in future tourism research, alongside a more comprehensive account of gender and the lived experience of care-givers in the tourism context.



Conclusion

The target for people with autism should be to live independently.  You may not achieve this, but the closer you get, the better life will be.

Traveling is a good way to learn some of the important life skills you are going to need later.

You can strive to make accommodations for the disability of autism with special autism-friendly periods in shops, theatre, cinemas, etc. There can even be disabled parking privileges for parents, although most people with autism can walk just fine.

The other extreme is tough love, where you always push for being “normal” and fitting in, over acceptance of being different and then just excluding yourself.

What works best for you is determined by how severely disabled the person really is.  Only 15-20% of modern autism is severely disabling; those people really need a lot of help, and indeed personalized medicine.  The majority of those with autism in 2020 are starting from a point (level 1 and 2 in DSM5), not so far away from normal.

Away from the bubble of social media, the real world has changed little.  Strangers on the street did not get more tolerant; kids at school did not stop bullying the odd one out; best to be as "normal" as you can.

Whether you chose travel, sport, music or something else, better to broaden horizons and ambitions with actions, rather than tweet about all the problems.