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Mood Disorders



In a previous article I have outlined a neurodegenerative process which might account for the sleep disturbances seen in Narcolepsy. One of the intriguing aspects of this process is that it encompass a preclinical phase,  a period of time when cell damage has not yet reached a threshold level and the expected diagnostic symptoms are not yet apparent.  I believe this period also presents symptomatically, but those manifestations are currently recognized as psychiatric disorders.


The affective spectrum disorders are a group of illnesses include mental and behavioral disorders.

  • They occur comorbidly-  if you have one, you are likely to have at least one other.

  • They aggregate in families-   if you have one, your family members are likely to also have one.


There is no exact list of ailments which are considered "affective", but in general  anxiety, depression, pain, eating, sleep and mood disorders are included.

This range of symptoms closely parallels the spectrum of functions of the orexin system. 

  • Hypothalamic orexin neurons have influences over a variety of brain functions, including affective behavior, autonomic control, pain perception, cognition, and sensorimotor integration.

  • The distribution of orexin-reactive neurons and processes indicates that the orexins may participate in a host of functions. For example, the lateral hypothalamus and perifornical area are reported to relate to cardiovascular responses to emotional situations or defensive behavior.




A cognitive disorder characterized by a pervasive low mood, loss of interest in a person's usual activities and diminished ability to experience pleasure.  Symptoms associated with depression include changes such as loss of appetite and/or weight loss (or conversely overeating and weight gain); insomnia, early morning awakening, or oversleeping; decreased energy, fatigue, and persistent physical symptoms such as headaches, digestive problems, and chronic pain.


Depression is at the genetic center of the affective spectrum disorders.

Affective spectrum disorder aggregates strongly in families, and major depression displays a significant familial coaggregation with other forms of ASD.


If depression is a preliminary symptom of  zombipathy, it should be prevalent in those disorders:

 Orexin itself has been correlated with depression.    

  • Cerebrospinal levels of orexin-A were significantly lower in patients suicidal patients with major depression.

  • Low orexin levels are related to symptoms of inertia and reduced motor activity in suicidal patients.  The lower the orexin levels, the higher were ratings of overall illness, as determined by a psychiatric specialist.

Rimonabant blocks the effects of orexin A.

  • The obesity drug Rimonabant (Accomplia) causes depressive reactions in one in 10 patients and even in those who have no obvious risk factors apart from obesity itself, warned the drugs regulator.   Over 40% of the 1,971 adverse reactions reported with rimonabant were for psychiatric reactions, with almost a half occurring within the first 2 weeks of treatment.


Lowered levels of dopamine and serotonin are also associated with depression:

Since orexin stimulates the production of these neurotransmitters, orexin deficiency also lowers their levels.

  • Orexin induces dopamine in the ventral tegmental area of the brain.   This area is associated with desire, initiative, and reward.

  • Orexin-A produces a dose-dependent increase of serotonin in the dorsal raphe nucleus.


Another interesting corelation is with the hippocampus:

  • A significant correlation between hippocampal volume and total lifetime duration of depression has been shown.  The depressed patients had smaller hippocampi.

  • One study suggest that orexin induces an antidepressive-like effect, at least in part, via the enhancement of cell proliferation in the hippocampus.

Post-partum depression-

Narcolepsy often presents around pregnancy.   It's possible that post partum depression is triggered by the same physiological state (possibly strep infection), however the patient has a less vigorous immune response so the symptoms are less severe.  In addition, pregnancy increases insulin production.



Seasonal affective disorder is probably caused by a combination of factors.   Low light understimulates the orexin cells.   Low light also reduces vitamin D levels.  Low vitamin D levels increase antibody production.





The anxiety disorders, individually and as a group, exhibit remarkably high rates of comorbidity with each other and with major depression.


Orexin is likely involved in generation of anxiety-like behavior.

  • Orexin acts via the amygdala to augment arousal and evoke the physical and behavioral responses associated with fear, stress or emotion.

  • Other  results point to the orexin cells in the lateral hypothalamus as the source of the cells responsible for the responses associated with emotion or defense reactions.


Panic Disorder


Narcolepsy is highly associated with panic disorder.   It's called Cataplexy.



  • Generalized anxiety disorder, panic disorder  and post-traumatic stress disorder often co-occur.  There is no evidence that shared environment contributes to the development of posttraumatic stress disorder symptoms.

  • Sleep disorders including nightmares, insomnia, sleep apnea and periodic limb movements are highly prevalent in PTSD.

  • Three veterans with probable or possible war-related PTSD were found to have substantially lower locus coeruleus  neuronal counts compared to four comparison subjects.

  • The brain region receiving the densest innervation from orexin cells is the locus coeruleus.



I need to explain a certain contradiction.  The co-occurance of depression and anxiety.   Simultaneous hypo- and hyper- activity...

Oddly enough they are both the product of lowered orexin levels.  


I think it is best illustrated as a food example:  After a meal you have low orexin levels and are sluggish and vulnerable.   To compensate, the locus coeruleus disinhibits the vagus nerve and causes an increased startle response in case of emergency.  


On a long term basis, this is experienced as depression and anxiety.




The locus coeruleus is also a major location of pain modulation. Orexin cell axons also extend from the brain into the spinal cord and are involved in pain perception.  



  • Migraine prevalence was increased twofold to fourfold in the narcoleptic patients.

  • Sleep disturbances are linked to tension headache.

  • Sleep disorders associated with headache include obstructive sleep apnea, periodic limb movement disorder, insomnia, and hypersomnia.

  • Data supports a substantial sleep/migraine relationship, and implicate sleep disturbance in specific headache patterns and severity.

  • Migraines are also associated with depression and suicidal ideation.

  • The occurrence of headache, dysthymia and signs of peripheral neuropathy was significantly higher in patients with celiac disease than in control subjects.

Antimigraine drugs block neurogenic vasodilation. A current study shows that orexin A is also inhibits neurogenic vasodilation in trigeminal neurons.

The orexin sytem is a key regulator in the modulation of trigeminovascular processing.



I am becoming convinced this is a microbial issue.  The trigeminal nerve seems to be the most desirable real estate available for herpes viruses.  They can easily be found in human specimens.  It is also connected to the nose and mouth, common sites of strep infection.  What I think actually happens is orexin system disregulation causes blood glucose and insulin fluctuations which activate the infections causing the pain.   




Premenstrual Disorders


Characteristic symptoms may include physical symptoms as headache, fatigue, constipation, abdominal cramping and weight gain.  Emotional and behavioral changes may include anxiety, depression, irritability, panic attacks and altered libido.


  • Premenstrual distress syndrome was associated with higher depression, anger, and cognitive problems at both luteal and menses phases.

  • Women with menstrual-related problems to report frequent anxiety and depression, insomnia, excessive sleepiness, and pain over the past 12 months. Cigarette smoking, drinking heavily, and being overweight or obese were also more frequently reported among women with menstrual-related problems than those without.


Orexin is directly involved with reproductive processes.

  • Orexin cells innervate the ovaries.  And the absence of orexin negatively impacts follicles.

  • Orexin stimulates the secretion of luteinizing hormone.

  • Luteinizing hormone triggers ovulation, the release of the ovum from the follicle.

  • The follicle then becomes a corpus leteum and produces progesterone.

  • Women with PMS have altered progesterone at the luteal phase.



I believe this process also accounts for PCOS.   The rapidly fluctuating orexin levels of gluten sensitive individuals may produce multiple immature follicles during a cycle.   Later, when orexin levels diminish further, single cysts appear.





Orexin is the "feeding" neurotransmitter.  It was named orexin because it is orexigenic- it stimulates you to eat.  




The primary symptoms of irritable bowel syndrome are abdominal pain or discomfort in association with frequent diarrhea or constipation. 

  • Individuals who reported symptoms of IBS were 40% more likely to suffer from depression and 60% more likely to suffer from migraine.

  • Celiac disease in particular is often misdiagnosed as IBS.


Orexin is also directly involved in gastrointestinal function.

Important Note:   There are a couple different things at play here.    The zombie disorders (IgG antibodies) cause impairment of intestinal movement and therefore constipation.    If you also have celiac disease (IgA antibodies) you will have the diarrheal symptoms.


Eating Disorders


Orexin stimulates you to eat.   It's only logical that orexin problems would cause eating disorders.

  • The majority of patients with narcolepsy experience a number of symptoms of eating disorders, with an irresistible craving for food and binge eating as the most prominent.

  • Eating disorders are linked to anxiety, alcohol/substance abuse, and strongly linked to depression.

  • Eating disorder patients with a first-degree family history of alcoholism demonstrate increased psychopathology in eating behavior, substance use, and personality vulnerability.

  • Multiple studies find high rates of suicide in patients with anorexia nervosa.

  • Psychiatric disorders are common in adults who have had anorexia.


Blood sugar control in any form is an effective way of raising orexin levels.

This would alleviate the pain, anxiety and depression these patients report.  As dysfunctional as it seems, it's diet therapy.


NOTE:   I am not recommending drastic dieting.   Eliminating gluten and monitoring carbohydrate intake is the proper regimen for alleviating the mood problems.


Smoking/ Addictions 

I am convinced that substance"abuse" is actually self-medication of the symptoms of chronic neurological impairment caused by orexin deficiency. 


Other Sleep Disorders




Any therapy involving lowering orexin levels should be avoided!!

Mood dysregulation is the expected outcome, not an unpredictable side effect.



New Research:

Is this peptide a key to happiness?
Scientists at UCLA have measured the release of a specific peptide, a neurotransmitter called hypocretin, that greatly increased when subjects were happy but decreased when they were sad.
"These results suggest a previously unappreciated emotional specificity in the activation of arousal and sleep in humans," Siegel said. "The findings suggest that abnormalities in the pattern of activation of these systems may contribute to a number of psychiatric disorders." Siegel noted that hypocretin antagonists are now being developed by several drug companies for use as sleeping pills. The current work suggests that these drugs will alter mood as well as sleep tendency.






 Big Fat Disclaimer:  The research on this website has not been peer reviewed in any way.   The conclusions presented are strictly the opinion of the author.  It is being self-published as a public service in consideration for sufferers and as a stimulus to the medical research community.  Information presented on this page may be freely distributed or copied. 


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