Brain Imaging: Lyme, ME, depression

This summary includes information on Single Photon Emission Computerized Tomography (SPECT) scans & MRI’s. Here are examples of normal spects,

normal SPECT

And a guide (from a primary CFS SPECT study) to brain regions in the SPECTS

note: it is standard for the SPECT to reverse left and right; this is labelled on the sheet

Swartz et al found hypofusion in areas 5, 2 & 6.
Mena & Villaneueva-Meyer found hypofusion in temporal lobes 1 & 2
Ichise et al found decreased radionuclide uptake mainly in 1,2/4,5, but also in 8, 3 & 6.

These are reversible and correlate with changes in clinical severity.


SPECT: In Lyme Disease, the most common finding is of heterogeneous hypoperfusion diffusely throughout the brain, similar to in Lupus, chronic cocaine abuse or other vasculitic inflammatory disorders. This pattern is different to primary depression or Alzheimer’s disease. Approximately 70% of patients with chronic Lyme disease will have multiple areas of hypoperfusion, but it cannot be used for diagnosis, as blood flow is rated relative to the cerebellum or deep grey matter which is presumed to be normal.

The above images are from hypobaric treatment where SPECT can be used as a marker of improvement.

From ‘looking at lyme‘:

SPECT scan of the brain before (A) and after (B) antibiotic brain specttreatment.

These transaxial images are from a 51-year-old man diagnosed with Lyme disease with a recent change in memory. Representative pretreatment images show hypoperfusion within the mid posterior and mid temporoparietal cortex bilaterally. Representative posttreatment images (14 months later) reveal improved perfusion to the posterior temporoparietal cortex bilaterally, correlating with improved symptoms. Perfusion within the remaining cerebral cortex, basal ganglia, thalamus, and cerebellum was normal.

MRI:  Looks similar to MS: Up to 40% of adults with Lyme disease may have small white matter hyperintensities suggestive of inflammation or areas of demyelination., but it should be noted that the number of hyperintensities increase with age – even among patients who do not have Lyme disease.

Youtube has many video tutorials on interpreting brain mri.


SPECT: Hyde considered an abnormal SPECT as well as an abnormal EEG or PET scan and/or neuropsychological abnormalities required for ME diagnosis, in particular decreased perfusion of blood in the left middle cerebral artery and the branches of the parietal lobes, present very early in the illness. He strongly emphasised vascular issues (moreso than PEM), and ‘difficulty concentrating and finding words, etc, problems sleeping, poor muscle functioning, trouble standing without exaggerated heart rates and dizziness, little ability to exert themselves, cold fingers, loose joints and gut problems’.

Screenshot (47)

EG “Intrinsic Functional Hypoconnectivity in Core Neurolocognitive Networks Suggests Central Nervous System Pathology in Patients with Myalgic Encephalomyelitis”, PMID: 26869373 or “Functional Neural Network Connectivity in Myalgic Encephalomyelitis

The ICC for ME notes SPECT abnormalities, however it specifies *with contrast*. Contrast can be reactive and cause side effects. Repeated SPECT scans done at the same medical center to allow for a fair comparison across images can track progress of treatment or disease progression.

ICC case study : Extensive areas of hypoperfusion are characteristic of ME… marked hypoperfusion in the lateral aspects of the temporal lobe, extending to the frontal and parietal lobes… extensive hypoperfusion in the limbic system involving anterior, medial and posterior cingulates. There is left temporal medial hypoperfusion that denotes hypofunction in the projection of the hippocampus. Both posterior cingulate and hippocampal hypofunction denote cognitive impairment. Finally, there is hypoperfusion in the occipital lobe.

Taken from Ireland ME which has good overview brain abnormality summary and study quotes.

brain areas

Medial temporal lobes (area 1) hypofusion seen in concussion, head injuries, hippocampus, memory impairment



Both hypo and hyperfusion is found in fibromyalgia.

Red: HYPOfusion, green: HYPERfusion

The images show the anatomical localization of peak significant differences between brain SPECT of patients with fibromyalgia and healthy subjects. Patients with fibromyalgia exhibited posterior hyperperfusion (red), including of the somatosensory cortex, and hypoperfusion (green) of frontal, cingulate, temporal, and cerebellar cortices. Images courtesy of the Journal of Nuclear Medicine


Severity was “positively correlated with bilateral parietal perfusion, including postcentral cortex. These clusters of correlation were included in the areas of significant hyperperfusion. [Severity] was also negatively correlated with perfusion of a left anterior temporal cluster, included in the areas of significant hypoperfusions. No other clinical correlation was observed with regional cerebral blood flow.”

Compared with healthy controls, patients with fibromyalgia exhibited posterior hyperperfusion, including of the somatosensory cortex, and hypoperfusion of the frontal, cingulate, temporal, and cerebellar cortices in particular, the temporal hypoperfusion including the polar and mediobasal cortices.

Positive correlations (both on left) represent hyperfusion, negative (right) represents hypofusion- ie low blood flow.


Brain perfusion abnormalities in patients with fibromyalgia “are independent of the patient’s anxiety and depression status and correlate with the clinical severity of the disease, expressed by the disability and evaluated by the FIQ total score.”

shows increased activity in the thalamus and basal ganglia (study)

below- here is an example of normal basal ganglia flow, the basal ganglia is in the centre
(note the rest may be abnormal as this woman had tremors.
note- basal ganglia abnormalities may also occur with lupus).


This same region is relevant for ADD: people with Anxious ADD show the hallmark ADD signature of low prefrontal cortex activity (image on the right) combined with overactivity in the basal ganglia (image on the left)—a region of the brain that allows for smooth integration of emotions, thoughts, and physical movement.



One review found differences between cfs & depression spects, with significantly more defects in the occipital lobe in depression; fischler found major depression showed significantly lower left superofrontal regional perfusion, in line with previous reports

while note: its normal to see more activity in the right than the left temporal lobe, with slightly larger left than right volume; this assymetry may be more pronounced in depression

depression            depression brain scan

depression         e7e6d170266384b583dfb80ba97875d9





severe anxiety neurosis revealed hyperactive prefrontal cortices and basal ganglia in technetium-99m-hexamethylpropyleneamineoxime brain perfusion single photon emission computed tomography images. (a) Transverse view, (b) sagittal view, (c) right lateral view of three-dimensional Talairach cortical perfusion report, (d) extracted basal ganglia and thalamus by “Neurogam” processing, (e) color scale for (c and d):


See: Brain perfusion single photon emission computed tomography in major psychiatric disorders: From basics to clinical practice


On CFS vs Depression, and CFS neurology scans in general:

spect textbook neurology.png

NOTES: my results ‘ischemia

‘A mild-moderate symetrical reduction uptake in the posterior tempero-parietal cerebral cortex is seen. There is a sparing of the posterior cingulate and the visual association cortex. Normal perfusion within the basal ganglia and the cerabellum… Bilateral mild to moderate posterior tempero-parietal cortical hypoperfusion’.

The ICC for ME says: ↓ reduced blood flow in temporal lobes may contribute to memory and cognitive impairment & fatigue

Hyde mentions abnormalities in the parietal lobe and the left middle cerebral artery: The middle cerebral artery is the largest branch of the artery that supplies a portion of the frontal lobe and the lateral surface of the temporal and parietal lobes, including the primary motor and sensory areas of the face, throat, hand and arm, and in the dominant hemisphere, the areas for speech. Low blood flow in the temporal and parietal lobes likely results from not enough blood coming through the cerebral artery.
There was no hyperperfusion, as seen in PTSD or fibromyalgia, or hypofusion in the superofrontal lobes, as seen in depression. Brain stem was not reported on; this is used to differentiate depression & ME. FND/conversion disorder expects abnormal functional but normal structural imaging, as I have, but is a debatable clinical entity.
This does not rule out lyme which shows a similar pattern, abnormalities in perfusion to various areas of the brain, most notably the frontal, temporal, and parietal lobes- those these may be asymmetrical?
I have orthostatic intolerance, which can be linked to low blood volume. I was well hydrated, and as I was laying down, this may be of negliable significance, especially as only some regions of the brain were affected

The ICC also states: Greater source activity and more parts of the brain are utilized in cognitive processing, which supports patients’ perception of greater effort… These observed pathological changes are consistent with neurological disorders but not psychiatric conditions…


The parietal lobes involves sensation and perception and integrates sensory input, primarily with the visual system. Neurons in the parietal lobes receive touch, visual and other sensory information from a part of the brain called the thalamus. The thalamus relays nerve signals and sensory information between the peripheral nervous system and the cerebral cortex. The temporal lobes are involved in high-level auditory processing such as selective listening, language recognition of words, and Mathematical Computation! Problems include the inability to recall the correct names of everyday items, difficulty in making exact movements, inability to perform complex tasks in the proper order

The temporal lobes play an important role in organizing sensory input, auditory perception, language and speech production, language comprehension, as well as memory association and formation. Structures of the limbic system, including the olfactory cortex, amygdala, and the hippocampus are located within the temporal lobes. Damage to this area of the brain can result in problems with memory, understanding language, and maintaining emotional control. This is also important for facial recognition and regulating fight or flight!

The frontal lobes are involved in reasoning and personality expression is fine! The posterior cingulate is between the frontal and parietal lobes and is considered part of the default mode network, a group of brain structures that are more active when an individual is not involved in a task that requires externally-focused attention, also implicated in moral judgments


fig-29-05brain diagram amygdala 416


Hypoperfusion Neuro-SPECT ↓ regional blood flow (rCBF), ↓ absolute cortical blood flow ↓ hypoperfusion in brainstem distinguishes ME from depression ↓ further reduction in cerebral blood flow after exercise; Greater involvement of the brain correlates with greater severity


Review: Stan Tatkin Attachment Podcast

Following up on the previous blog detailing attachment, here is a summary of the podcast interview by Stan Tatkin. (listen here, or see

Stan Tatkin returns and serves up another awesome dose of relationship advice through the lens of adult attachment. From how relationships impact your health, to helping your triggered or upset partner, to dealing with an avoidant partner.

Allostatic load is the price we pay for adaptation, neurobiological wear and tear
cardiovascular, neuroimmune, inflammation

Chronic health issues have a correlation with insecure attachment
good stress occurs when there is a solution/end to a problem
interpersonal stress is both acute and chronic, and takes toll on brain, body, and nervous system. A good marriage extends life, in a terrible marriage, we die sooner.
EG: not trusting- feeling betrayed- feeling abused- feeling neglected- feeling misunderstood- not getting anything done- fighting with no repair- take a toll
interpersonal stress the most common and likely to age, poor health, feeling crap
insecurity and unsafety.

We take things personally when our nervous system memories result in us being flooded. the important thing in a connection is that both people have a common/mutual interest of shortening the distress, to get to relief
move through distress as quickly and efficiently as possible
this requires the person who has the urge to defend or explain, asking tell me what i did, i wasn’t aware, you’re right in order to relieve the person who is aroused or threatened and waiting to see if you’re friendly or unfriendly

Secure attachment requires accepting the other as is… taking full responsibility for one’s own faults. It makes no sense to choose but not accept/to want to change and find fault.

a secure environment/milieu allows both to be free to be themselves, accepted as they are;
yet there is a requirement to take responsibility for the things i do that get in the way of secure attachment, such as island behaviour, wave behaviour, plain rude behaviour

Secure functioning isn’t ‘love’- its safety and security, with agreement and loyalty.

Avoidants can be considered as an ISLAND
to get them on board; avoidants need to be in touch with their original longing-
to give and receive coregulation, validate and reassure others, and ask for their own needs

Attachment leaves the avoidant/island encumbered by an overwhelming amount of interpersonal stress. The feel relief when they leave, and auto regulate, skipping over missing the other person. Object constancy is missing and out of sight out of mind-
alone they feel relief. Untethered. HOWEVER their eating changes, sleep changes, addictive behaviours- the island is not okay, not independent.
it’s important to assume and to speak to the dependency, loss, as the ‘island’ is actually very needy with unmet infant dependency needs
they may be annoyed that you’d suggest they’d have a problem. Yet after separation, there can be acting out, reunion causes behaviour, cancelling, coming late.
the avoidant/island is ensconced in memory of relationship trauma, of being exploited, interrupted, not allowed to be separate but not allowed to depend, misunderstood, expected to perform for others but not for them, etc. don’t poke the bear.
For the island, to be held and talked to be intrusive, they feel caught, trapped, demanded upon. Catch and release, loosen sooner than expected to deamplify the behaviour. Proving won’t hurt them as they anticipate- talk to them like they will love and miss you, and slowly increasing the window of tolerance, like titration

For anxious WAVES it can be hard to have confidence- as they fear they are too much, a pain in the butt, fear rejection, withdraw, afraid they will be alone, can’t do this by myself

Both have FEAR: the island scanning for being taken advantage of: wave scanning for withdrawal and punishment

It’s important for the wave to see the island is actually more inept, developmentally delayed, less well defended; socially and emotionally inept, tense, unable to relax or let go… The wave is actually more able to hold things together

eye contact to regulate, after or during conflict, to get the other adult to soften
(book gabler matay pure orientation)
babies who were intruded upon by an invasive parent
joint attention on a third object. Amplify pleasure, baby looks at her. Comment. Then connect. Amplify through third thing as a bridge. parallel play can help, but too much creates a loneliness that is quite profound, being in the room and not relating to me is different to being not in the room, withdrawn, isolating, disturbing. Worse than not being here.

Lead with relief
use eye contact and touch to reach out
to help calm them down and sooth them
to know you’re safe and that you’re on their team

SECURITY FREES UP RESOURCES otherwise used for chronic anxiety, planning to run, cling, etc. development moves when there are resources. Massive insecurity or trauma interrupts it. Relationship constantly threatening and may not exist tomorrow- tremendous resource drain. Acceptance of each other allows space, resistance ties up resources

WIRED FOR DATING: we subconsciously choosing emotionally unavailable partners. We pick familiars. Recognition, until we metabolise the experiences- organise them- learn to handle them inside oneself- challenges until we learn how, mastered them

The important question:
DOES THIS PERSON WANT TO PLAY: two person systems, on the same page, fully engaged, wants to be here, messed up is ok.
Requires collaboration, cooperation, justice, mutual agreement, fairness, sensitivity, aiming for me and for them, mutual, fair, agreed upon

If not invested. Doesn’t see, doesn’t care to see what they’re doing, doesn’t matter to them what their partner thinks, doesn’t matter whether this is a secure functioning relationship, then said goodbye.



50-75% of CFS meet ME/CFS criteria, and less again meet the ICC definition of ME. This discrepency results in the variance in prevalence estimates (0.2-6.4%)

Beyond this, a number of studies have attempted to break the heteogenous group of ‘CFS’ down into sub-components. This has been done via genes, microbiome, or by secondary symptoms.

According to Jason & Zinn (2015), secondary symptoms of ME might include symptoms within immune, neuro-endocrine, autonomic, and pain domains. ‘Despite the reported lower prevalence of these domains, these secondary symptoms are nonetheless found with enough frequency in the literature to utilize them for patient subtyping, such as, ME-immune, ME-autonomic, ME-neuroendocrine, ME-pain, or ME-combination’.

‘Glucocorticoid sensitivity was greater among ME/CFS patients overall compared to healthy controls and between ME/CFS GC-Hypersensitive (red circle) compared to ME/CFS GC-Typical (blue circle; p’s ≤0.05)’… ‘Mild hypocortisolism and enhanced negative feedback to glucocorticoids were observed in several studies of GC responses in ME/CFS [3, 49]. The presence of both the GC-Typical and GC-Hypersensitive subgroups within our ME/CFS cohort thus aligns with the observed heterogeneity of HPA-related differences in these previous reports.’

Exercise & gene expression: two subgroups of patients with CFS can be identified by gene expression changes following exercise. The larger subgroup showed increases in mRNA for sensory and adrenergic receptors and a cytokine. The smaller subgroup contained most of the patients with CFS with orthostatic intolerance, showed no postexercise increases in any gene and was defined by decreases in mRNA for α-2A.  Postexercise increases for four genes meet published criteria as an objective biomarker for CFS and could be useful in guiding treatment selection for different subgroups.

Immunity weirdness

I’m investigating strange immune reactions, such as coldsore/ulcer outbreaks from SB probiotics, and a failure to seroconvert antibodies. Here’s some info about immunity  (Phoenix Rising):

T cells are T lymphocytes, a type of white blood cell found in the blood and in the lymph system, that mature in the thymus gland. T cells are part of the adaptive immune system. T helper cells (Th) help other cells in the immune system to respond appropriately to threats. 

T cells start out as naive T cells, and then they get converted to the types that are needed depending on the requirements of the body. There are two types of helper T cells, Th1 and Th2. Th1 cells act by activating macrophages so that they can attack bacteria that are inside the macrophages. So Th1 cells are formed when the best approach for defending the body is to activate the macrophages. This is called “cell-mediated” immunity. The weapons of the Th1 system include cytotoxic T cells and Natural Killer (NK) cells (low in ME/CFS). On the other hand, for bacteria that are extracellular, i.e. not inside macrophages, the better approach is to make antibodies that will attach to the bacteria. Its weapons include eosinophiles (Eos), polymononuclear cells (PMN), and antibody secreting cells (Ab). This is called “humoral” or “antibody mediated” immunity. 

Antibodies are made by B lymphocytes, which turn into plasma cells. In order to help them to act, Th2 lymphocytes are needed. 

In the presence of a virus, cancer, yeast, or intracellular bacteria (like mycoplasma or chlamydia pneumonia), a cytokine called Interleukin 12 activates Th1. In the presence of normal bacteria, parasites, toxins, and allergens, Interleukin 10 (IL-10) triggers the production of Th2.

In stress and ME/CFS, Th2 dominates (although Th1 may dominate in the gut, with th3). When they are Th2 activated, they no longer have the defense mechanisms to protect or keep dormant things caught in the past. They cannot suppress or control them anymore, and the EBV, chlamydia pneumonia, mycoplasma, rickettsia, CMV, etc. reactivate. There is also not a good defense against viruses or fungi, including yeasts. These infections that are found in ME/CFS because the immune system is not able to effectively defend against them, because of the shift to Th2.
The cause of this shift is not agreed upon. Allergies may be a sign of a very early or inherent th2 domination. There may be a role of stress, high cortisol suppressing inflammation, low glutathione causing low b12 and HPA disruption with low ATCH & low cortisol, or viruses may disturb neurotransmitter receptors. Viruses, especially herpes viruses like EBV, CMV and HHV6, make cytokine proteins that mimic IL-10 and cause a Th2 shift. Zinc deficiency may be associated with lowered Th1 activity.

Vit D is a TH2 promotor. MS is a TH1 dominant condition.

Astragalus may shif the immune response back toward Th1, as does Lactobacillus paracasei. Heat killed saccromyces cereviseae induces a th1 response Study. Mouth ulcers are causes by th1 Study. Herpes simplex is a ‘delayed type hypersensitivity’ reaction based on th1 as well, Quoting: “HSV lesions demostrate a prevailing Th1 pattern in which the induction of MCH-II on epidermal cells and the activation of CD8+ T cells through IL-12 and IFN-y are particularly important in the control of recurring infections”.

More to come, regarding testing: 
t1/t2- t lymphocytes- helper/suppressor ratio
Secretory IgA
Low IgG


Cortisol is the body’s buffer against stress. With increased stress it can rise. With acute stress it is elevated, with prolonged stress it can become low (as in adrenal fatigue). Cortisol can be tested by 24hr urine, 9am blood draw (can be artificially elevated) or repeated salivary tests from home throughout the day- as markers of the ‘diurnal’ (daily) pattern of cortisol rising and falling.

Free cortisol measured in saliva has been shown to have the same diurnal rhythm as serum cortisol, one that typically declines rapidly throughout the waking day. A recent study showed that over 15% of a sample of community individuals who were monitored over two days did not show the typical diurnal rhythm. Link

A flattened diurnal cortisol curve as well as a diminished dexamethasone suppression are both considered to be consequences of frequently repeated or chronic challenges of the HPA axis by factors such as environmental stress Link

…diurnal cortisol variation was significantly reduced in exhausted individuals. The difference in cortisol variation was mainly due to lowered morning cortisol in the exhausted group. Differences in cortisol levels at each sampling time or in mean diurnal output of cortisol were not statistically significant. The results would support the notion that exhaustion is associated with HPA axis hypoactivity as assessed by salivary cortisol. Link

A flattening of the diurnal cortisol rhythm indicated by a smaller drop in cortisol from morning to afternoon or evening compared to a control group) can be due to higher evening cortisol. In this instance it is not so much flattened morning cortisol but a flattening due to high evening cortisol which predicts trait anxiety and adolescents scoring high on depression.

The reason CFS patients have lowered cortisol output is not clear; one possibility is that it is a primary factor in the development of the illness, although it has also been hypothesized that lowered cortisol itself is of multifactorial aetiology in CFS and occurs, in part, secondary to aspects of CFS, such as inactivity, sleep disturbance or stress (Cleare, 2004). A recent study suggests that impaired cortisol responses in CFS are restricted to those with a history of childhood abuse, which is itself sixfold higher in CFS than in controls (Heim et al. 2009).-hypocortisol & CBT

urinary free cortisol
CFS alone 24-h UFC 92.8¡59.0
CFS and co-morbid depression on either 24-h UFC 82.1(50.4) nmol/day
levels were defined as ‘low UFC’ group, using 59 nmol/day,
the salivary cortisol output
CFS alone AUC values 73.2(23.0) nmol/ l h
CFS and co-morbid depression 67.3(20.7) nmol/ l h
the salivary cortisol day curve, from 0800 to 2000 hours by calculating the area under the curve (AUC)

Childhood physical abuse predicted flattened diurnal cortisol rhythms as well as greater cortisol responses to awakening. Sexual abuse was a second predictor of increased awakening cortisol responses. Patients with a history of trauma had markedly low levels of cortisol at the time of first awakening, partly explaining the results. These findings suggest that severe traumatic experiences in childhood may be a factor of adult neuroendocrine dysregulation among fibromyalgia sufferers. Link

Repetitive maternal separation led to increased cortisol reactivity to the separation protocol in female infants and alterations in mother-infant interaction. It also resulted in a flattened diurnal rhythm of cortisol secretion and increased acoustic startle reactivity at later ages. Link

Cotisol & DHEA (dehydroepiandrosterone) could theoretically, be used to differentiate between fatigue caused by depression and chronic fatigue syndrome or adrenal fatigue.

Evening cortisol hypersecretion and morning DHEA hyposecretion were significantly, and independently, associated with major depression. High evening cortisol (> 0·594 ng/ml) and low morning DHEA (< 0·200 ng/ml) identified subgroups of depressives with different types of adrenal hormone dysregulation. Link

Depression is associated with hypercotisolaemia and reduced central 5-HT neurotransmission and suggest that CFS may be associated with hypocortisolaemia and increased 5-HT function. The opposing responses in CFS and depression may be related to reversed patterns of behavioural dysfunction seen in these conditions. These findings attest to biological distinctions between these disorders. Link

It could also be used to differentiate from burnout.

Female burnout patients had higher cortisol levels than did the females with low burnout at awakening and at +15, +30, and +60 min after awakening. They also had a greater area under the curve (AUC) for salivary cortisol than did the female participants with low burnout.

Attenuated= weakened, reduced

Female CFS patients exhibited significantly attenuated morning cortisol profiles compared with well women. In contrast, cortisol profiles were similar in men with CFS and male controls.
A sex difference in hypocortisolism may contribute to increased risk of CFS in women.Link

In line with this, ‘Neurasthenia (literally meaning “nervous exhaustion”) is a diagnosis included in the International classification of diseases (ICD-10) to describe a syndrome of mental and physical fatigue of at least three months’ duration. The term has a long tradition of use in psychiatric classification,48 but the extent of its overlap with CFS, and with common psychological disorders such as anxiety and depression, remains to be determined.49 Although patients are rarely labelled as having neurasthenia in Australia, the UK or the US, the diagnostic term is widely used in Europe and elsewhere. Neurasthenia has a prevalence of 5.4% (range, 2%-10%) in primary care settings worldwide.50‘ (RACGP 2002).

On Cortisol & PTSD

Reduced 09.00 h salivary cortisol has been reported in chronic fatigue syndrome compared to controls (Strickland et al, 1998 ), in some studies of post-traumatic stress disorder and after traumatic events. In PTSD this is low but not abnormal, see great discussion by Yukuda ‘between 20 to 90 micrograms per 24 hours of urine—the means we would get in PTSD were in the 40s’. Babies of mothers with PTSD have lowered cortisol—’mothers who are stressed during pregnancy can program the stress response of their offspring’.

See related links on trauma and adrenal fatigue and depression vs ME/CFS.

Differentiating ME/CFS from depression (and fibromyalgia)

POTS is often misdiagnosed as anxiety, and exhaustion misdiagnosed as depression.

Use of the fukada & oxford definitions of ‘CFS’ has resulted in patients with depression being included in samples of patients with pathophysiological abnormalities. For a while this convuluted research results and resulted in contradictory findings (likewise with research into ‘generalised fatigue’ being passed as ME/CFS research). The ME ICC & ME/CFS CCC definitions, however, rely on reportable physical symptoms beyond just fatigue.

‘Some patients with major depressive disorder also have chronic fatigue, sleep disturbances, and poor concentration; therefore, it is possible that some patients with a primary affective disorder could be misdiagnosed as having SEID. However, ME symptoms including night sweats, sore throats, and swollen lymph nodes are not commonly found in depression.’ –Jason, 2015

Variables that successfully differentiated patients

Jason 2006 found the best differentiators were post-exertional malaise, unrefreshing sleep, and impaired memory-concentration, as well as shortness of breath severity (potentially indicating neurally mediated hypotension). Symptom severity of these, as well as how often the patient experienced fatigue (CFS more often) or presence of less self-reproach, classified 100% patients correctly.


The above is taken from Stein, 2015.

POTS as a diagnostic marker: Studies on rates of prevalence of POTS in ME/CFS vary, in part due to differing case criteria which may have included depressed patients presenting as CFs (EG Jason et al 2009 found that 38% of those with a diagnosis of a major depressive disorder were misclassified as having CFS using the CDC empirical case definition of Reeves et al).  SEID and other criteria which use OI as a diagnostic marker. This study found a prevalence of only 5.7%, but found 7% of fatigue clinic patient ‘controls’ to have POTS; study design flawed as did not test for OI/dysautonomia, which can include bradycardia, use of a CFS criteria where 25% didn’t have PEM, of which POTS is a symptom, 100 patients were excluded due to inconsistent blood pressure readings, and elevations within the first 2 mins were ignored).

Other sources list Symptoms that differentiate from depression as:(REF)

unrefreshing sleep
Words switching
Memory issues
Recurrent sore throats

2001 study: the depressed group was distinguished by low self-esteem, the propensity to make cognitive distortions across all situations, and to attribute their illness to psychological factors. CFS patients were characterized by low ratings of their current health status, a strong illness identity, external attributions for their illness, and distortions in thinking that were specific to somatic experiences. They were also more likely than depressed patients to cope with their illness by limiting stress and activity levels.


Low basal temperature is found in fibromyalgia, and no disturbance is found in circadian rhythms in CFS. Lower HRV associated with poor sleep was found in CFS compared to controls. One study found slightly higher hsCRP levels in fibro but normal IL-8 , IL-6, and ESR in FMS, though obesity. At contribute.

Studies have found IL-1, TNF-b and neopterin may differentiate between ‘chronic fatigue’, ME & CFS. Others found substance p, BDNF and IL-8 differentiate between CFS & fibro, with levels of these low in CFS.

Serum IgM antibodies to three anchorage molecules and NO-phenylalanine were significantly higher in ME/CFS than in depression. Both depression and CFS are associated with oxidative and nitrosative stress (O&NS) which damages the antibody system, including autoimmune responses directed against acetylcholine, hence the overlap; oxidative stress causes autoimmunity in ME/CFS and causes symptoms, hence ‘neuroimmune’;In depression, there is a cholinergic predominance.

Aberrations in the 2′–5′ oligoadenylate (2–5 A) synthetase/RNase L (OAS/RNase L) system are specific to ME/CFS, whereas induction of the TRYCAT (tryptophan catabolite) pathway by activating indoleamine 2–3-dioxygenase, and activation of neuroprogressive pathways are specific to depression (above link).

John Richardson (Book, 2001) emphasised the role of enteroviruses and their effects on body systems and organs; reports recorded blood flow in the brain with extensive hypofusion in the brain stem and cortex that are markedly different from endogenous depression.

Neuroendocrine studies have identified abnormalities in several hypothalamic endocrine releasing hormone axes, abnormalities that often are the opposite of what is seen in major depression (medical primer).

One study found ‘despite overtly similar cognitive and symptom profiles, depression and CFS patients can be differentiated with psychophysiological measures’, specifically lower electrodermal skin conductance, and higher skin temperature in CFS than controls or depressives (study on females only).

‘ME/CFS patients who were not medicated were reliably differentiated from healthy controls and those with depression using EEG spectral coherence (Duffy et al., 2011).’

The 2012 guide by IAMECFS suggests ‘Specific tests may show low morning cortisol, elevated antinuclear antibody (ANA), and/or immunoglobulin abnormalities. In addition, vitamin D levels are often low’.

‘Research in major depression, which is characterized by hypercortisolism in contrast to the hypocortisolism of CFS, where those with the highest degree of HPA axis overactivity have the lowest response rates to CBT’ (Thase et al. 1996); specifically, those with a flattened diurnal curve, though the direction of causation is unknown (eg inactivity and sleep) and the correlation was small (-0.23, cortisol & cbt). A later study found mean evening cortisol significantly lower in the chronic fatigue syndrome patients compared to controls with depression in a 1998 study which summarised: ‘Chronic fatigue syndrome patients display cortisol hyposecretion in saliva as well as plasma compared to patients with depression and healthy controls’.

The assumption of hypercortisolism in depression (1994, 9am bloods) has since been challenged with normal levels of cortisol found in a 2002 study finding reduced morning salivary and serum cortisol (though this may be high compared to their non-depressed state)—though in depression, chronic stress is associated with increased cortisol secretion, and the study mainly used mildly depressed patients. Abnormal results have been obscured with the cortisol awakening response, with increased response being associated with depression, though this is also seen in healthy individuals and in response to daily stress. See cortisol & adrenal fatigue for more indepth discussion.

The finding of hypocortisol in ME/CFS seem reasonably robust, however some studies have claimed normal HPA function by 24hr and 9am cortisol-but not salivary cortisol. In adolescents  salivary morning awakening cortisol normalises with recovery.

It has been estimated that 20-70% of the patients with FM meet the criteria for CFS. Conversely, 35-70% of those with CFS also have FM. Some of the differences attributed to CFS may actually been found in fibromyalgia, which is considered by some to be discrete from CFS and by others to be on a continuum- for example, it may begin as predominantly fibromyalgia with pain and progress to dominant fatigue and immune disturbances (alike the differences between acute and chronic immune abnormalities).


IOM ch 4: Memory impairment does appear to distinguish ME/CFS from such psychiatric disorders as depression and anxiety. Studies on cognitive impairment found no relationship with depression, even though ME/CFS patients have high rates of depression (Busichio et al., 2004; DeLuca et al., 1995; Short et al., 2002), Up to two-thirds of adults with CFS have either prior or concurrent major depression (2002 racgp)/ one half of all patients with CFS have experienced at least one episode of major depression. (Craig & Kakumanu 2002). Others found lower levels- Cella et al. studied the prevalence of comorbid psychiatric diagnoses in 640 patients with CFS. Of those patients, 14% had an anxiety disorder, 14% also had a depressive disorder, and 18% had both depression and anxiety disorders. In studies that divided ME/CFS patients according to whether they had a comorbid psychiatric condition, those without such a comorbidity showed more severe memory impairment (DeLuca et al., 2004b; Tiersky et al., 2003).

‘It is well known that estimates may be inflated as a result of confounding, i.e. the inclusion of symptoms of the medical condition as criteria for the diagnosis of psychiatric disorders (56, 57, 58, 59). The symptoms most often used for this purpose include fatigue, insomnia, loss of appetite, psychomotor retardation and difficulties with concentration (60, 61, 62, 63, 64, 65). Not surprisingly, omitting one or more of these from the list of criteria can have a significant effect on the estimates of psychopathology. For example, in their study on chronic fatigue, Katon et al eliminated fatigue as a criterium of depression and found that this alone reduced the prevalence rate from 15.3% to 10.2% (66). The inclusion of disability-related items in self-rating scales can cause similar problems. For instance, Yeomans and Conway (53) reported that 33% of their patients with ME scored 11 or more on the depression subscale of the Hospital Anxiety and Depression questionnaire (HAD). However, when they excluded the item ‘I feel as if I am slowed down’, no one exceeded the cut-off point for caseness.’-The psychologisation of illness

Studies have found depression to be brain inflammation, which may be part of why it is so common in ME/CFS. It has also been noted as a symptom of PEM. Other studies (ref req) have noted antiviral use in cfs patients alleviated depression. although anti-depressants are often prescribed (with side effects) there is generally minimal efficacy. see this patient survey, for example

One study found two subsets of CFS patients- those with normal serotonin, and those with high serotonin. this may explain the lack of efficacy of antidepressants. (side note, the symptoms of high serotonin, presumably similar to serotonin syndrome, are

The IOM suggestion of the SEID ‘systemic exertion intolerance disorder’ criteria was rejected in part due to a criteria which didn’t differentiate between major depression disorder and SEID:

“The presence of other illnesses should not preclude patients from receiving a diagnosis of ME/CFS (SEID) except in the unlikely event that all symptoms can be accounted for by these other illnesses.” –Jason, 2015

One criticism of the canadian consensus criteria was that the higher number of symptoms (7, compared to 4 for fukuda/reeves/oxford) would lead to it classifying patients with higher levels of somatisation, and therefore lead to higher levels of psychiatric patients being captured. Jason 2004 found this is not the case: ‘The Canadian criteria, in contrast to the Fukuda et al. criteria, selected cases with less psychiatric comorbidity, more physical functioning impairment, more fatigue and weakness, and more neuropsychiatric and neurological symptoms’

Serotonergic system: Smith et al. found three markers in the serotonin receptor to be associated with an enhanced activity of the receptor in CFS patients. This abnormality was associated with a reduction in general health, vitality, and social function which suggests that CFS patients might experience difficulties in managing stress reactions.


is the inability to experience pleasure from activities usually found enjoyable, e.g. exercise, hobbies, music, sexual activities or social interactions.

A brief comment on CFS stigmatised as depression

This review pre-2001 uses a poor definition of cfs ‘fatigue’, then concludes ‘only depression seemed to be associated with unemployment in patients with CFS…. Patients with CFS in these studies thus seem to have a higher lifetime incidence of psychiatric diagnoses than controls. However, no relationship of psychiatric diagnoses to disability can be established in these studies.’. Studies could only use cognitive measures as a marker, before CPET developed to show measurable disability. The study states ‘No other measurable impairment seemed to be consistently associated with disability or work outcomes. Only cognitive behavior therapy, rehabilitation, and exercise therapy interventions were associated with restoring the ability to work.’

Studies like this were done in an attempt to disprove CFS and alleviate the massive financial burden. While this study discusses  its own limitations at length, it is a good example of how CFS became so stigmatised.

If you want to see an example of doctors dismissing CFS as depression, see this letter to the editor from a GP in 2002. Warning, irritating

For further reading see this phoenix rising thread on cfs vs depression

Gas lighting & the Wall of Nope 

Today I read a great article which captures my experience of the past year or so quite well.

The ‘Wall of Nope’ describes the experience of a previously conscientious and motivated person not wanting to continue making an effort for anything non-essential. A deep inner refusal for effort, an exhausted inner bank account. And for me, the wall of nope currently extends to trying experimental treatments, too.

Yes I want to do yoga, to work hard and be successful and have amazing sex and birth my own baby at home and buy a property and grow medicinal herbs and manage a small tribe of humans. Yes I want to hike the Himalayas and scuba dive.

No I do not to see an exercise therapist who has at best a vague understanding of my condition, have them trial and error me, see if it helps temporarily or gamble with becoming tube fed & unable to speak. No I do not want to see the doctor who successfully diagnosed your fibroids. I don’t want to try LDN or cannabis oil. (No offence—it’s the Wall of NOPE). I don’t want to rush into a handful of supplements, monitor symptoms & variables only to find out it has side effects or isn’t right for me, or have it mask my condition, push the imbalances deeper, elicit new symptoms or allow me to overdo it. I don’t want false hope, and I don’t want band-aid solution cocktail of pharmaceutical meds. I don’t want to be a guinea pig, and I don’t want to gamble on poor odds without proper support. I’ve had enough experimentation, and I don’t want to deal with the consequences of ignorance.

I was belatedly diagnosed with ME/CFS & POTS within the past year. In the years before that, I started my own company so I could work for home and sleep in. Not because I like it, but because my body could not do mornings. Mornings, or the requirements of a regular work schedule, made me sob on the inside and crash, emotionally and physically. Working for myself meant working for a week and sleeping for a week to recover. In the years before that, despite being an ‘exceptionally gifted’ and excelling as a child, I limped through university, struggled to stay awake in class, had no energy for extracurricular volunteering, and was the only starving student my naturopath had ever known to spend half their weekly income on massage and supplements. That wasn’t because it was fun or I was treating myself or really valued health. It was because I could not physically cope.

Before I had a diagnosis, normality was a superhuman effort. Shopping, cooking, cleaning, work. I could have relationships or maintain my health, not both. I could work or I could do yoga, not both.

I was managing with limited spoons that only lessened as time went on, and trying to meet an expectation of normality that seemed impossible. As my work succeeded, expectations increased, and the deeper I sank into a feeling of ‘why is this so hard? why is it getting harder?’—with periodic checks to the doctor and him assuring me that my blood pressure is fine, and don’t worry about the blackout headpain when I stand up. Or the increasing inability to walk up stairs (probably just low iron). Or the troubling difficulty raising my arms to hang out the washing (?!).

This past week someone ignorant accused me of not wanting to recover, because I wouldn’t go to hospital. What is the hospital going to do? (‘No known curative or effective treatment’.)

My medical experience (until recently) has been one of denial and dismissal, gaslighting and at times outright abuse- and not surprisingly, the request of making effort on variable odds hits the Wall of Nope… for the sake of my will to live and my sanity.

I don’t want to exert superhuman effort for a half life. I don’t want bandaid solutions and short term freedom. I want a full and vibrant life, I want clarity in diagnosis and efficacy in treatment. I’m willing to stop deadstill, to keep my heart rate low, wait for the right specialists, request tests, read research, and pray… until I know how to get that.

To donate to ME/CFS research, click here (microbe discovery/lipkin research) or here (solve CFS).

Metabolomics studies

New study out on ME/CFS today, using the Canadian consensus criteria which is dependant on PEM, and using recruits for the rituximab studies.

Basically energy production is disturbed, as shown from low serum amino acids, and cultured muscle cells put under energy strain with ME blood. Proteins are being used for energy instead of carbs or fat- this is very inefficient and creates low amino acid levels and a lot of lactate, which results in pain and inability to continue.

Something (unknown) interferes with the immune system- this results in metabolic dysfunction- the body adapts. The body increases consumption of amino acids (not dependant on PDH, see below category II & III). The asterisks in the diagram indicate amino acids that were significantly reduced in serum of ME/CFS patients, primarily women.

PD kinase, an enzyme which inhibits PDH, and SIRT4 are likely responsible. The researchers found increased gene expressions (sRNA) of PDK that inhibits PDH:  basically some gene thing that stops energy cycle enzymes working properly, correlates with me/cfs severity, duration and activity. That was the same in men and women. BUT all the messed up proteins were mainly in women: ‘this indicates that the disease-causing mechanism triggers different compensatory effects in women and men’, possibly due to higher muscle mass in men.

They’re saying it’s defective oxidative metabolism involving the PDK-PDH-lactate axis, with partly sex-specific compensatory (secondary) effects related to adaptations in energy metabolism, where ketogenic amino acids to fuel the TCA cycle.

Note the Nauviex study earlier in the year found similar from urinary metabolites- males and females differed and there were widespread decreases in sphingolipids, glycosphingolipids, and phospholipids.

The present study also grew muscle tissue in the lab, put me/cfs blood (vs controls) on it, and then induced aerobic and anaerobic metabolism. It showed low lactate at rest and excess in response to exertion.’Based on these observations, ME/CFS patient serum appears to carry substance(s) that induce a cellular response to support mitochondrial energy production.’

Regarding causation: ‘Autoantibodies may potentially interfere with receptors as well as involved in cell signaling. A recent study showed that serum levels of autoantibodies to several autonomic receptors were higher in ME/CFS patients than in healthy controls. Similar autoantibodies were detected in postural orthostatic tachycardia syndrome and in complex regional pain syndrome, conditions with some resemblances to ME/CFS, affecting fertile women after a triggering event.

dec 22 2016:

Workwell Foundation

The Workwell foundation research team developed the CPET 24hr repeat test protocol to demonstrate post-exertional symptoms. Cardio pulmunary exercise stress testing is used in many conditions, including cardiac failure. Normal controls do an exercise test which causes muscle soreness but recover within 1-2 days (study- vanness journal of women’s health 2010), whereas ME/CFS patients have an amplification of symptoms and worse results the following day. CPETs show heteogenity in ME/CFS- that is, CFS is a mixed group of subtypes with high and low functioning, length and magnitude.

Workwell  recommend management of energy expenditure, especially pacing by heart rate monitoring followed by recumbent exercise remaining close to resting Heart Rate, with the understanding that patients with ME do not condition aerobically the same as healthy controls. This aims to reduce post-exertional symptoms which occur as a result of immune response to exertion.

In ME/CFS patients, the anaerobic threshold can be as low as 55% of maximum heart rate, so this number can serve the upper limit for activities. ( Estimated as 226 – your age = ______ x 0.55 = anaerobic threshold). A CPET will tell you exactly. Usually 100-116bpm.


Mark Vaness is one of the Workwell researchers. His talk (below) is an overview  (which I’ve summarised here)-Balancing the need for rest and recovery with the need to do physical activity to maintain physical function.


Metabolically, there may be an inability for the muscles to use oxygen.

Energy systems are aerobic (long-term, used to maintain posture, to walk, low level exercise, uses oxygen, creates c02) anaerobic/glycolitic (short-term, creates lactic acid). In ME/CFS, impairment is seen with ability to exchange air, the heart rate to rise and deliver blood, blood pressure and redistribution of blood flow to brain and muscles- all the systems which need to respond to exercise. As a result, aerobic capacity is diminished. This is worse again when post-exertional.

The lack of improvement in aerobic functioning with exercise suggests it is not due to deconditioning but due to a damaged aerobic system. Aerobic creates 30-36 ATP per glucose, whereas the anerobic system  creates only 2 ATP, making it inefficient.  The anaerobic system is designed for short term use only, but with pacing activities to under 2 mins, can be used as the dominant system. This involves avoiding prolonged walking or standing.


The heart has its own intrinsic activity, through the adrenal  gland, the vagus nerve withdraws, sympathetic innervation increases, this allows heart rate to rise with exercise.

There is chronotopic incompetence- a failure of the heart rate to rise adequately in response to exercise, recognised in cardiovascular disease where it causes exercise intolerance. (This is inline with abnormally high sympathetic activity at rest, and low during exercise). This worsens again with stress, such as post-exertional exacerbation.


There is a diminished cardiovascular operating window- which becomes narrower with PENE. Heart rate monitoring allows for doing more within this narrow range.

There is also diminshed systolic blood pressure response resulting in poor blood flow and supply of nutrients to muscles. Dysautonomia- some patients heart rate will bottom out/drop during exertion.

Salt does not just improve blood volume- improves autonomic function by activating the forebrain areas- this is inline with ‘adrenal cocktail’ salt improvements.

Regarding hypoglycemia symptoms experienced by patients- related to autonomic nervous system activity and chronotropic incompetence-hepatic glucose production maintains glucose supply during activity-if impaired to heart, logically will be impaired to liver as well. Always ingest carbs before activity.

Medication for POTS is protective of the heart but may exacerbate the underlying pathology with physical capability.

Suggested aetiologies: viruses impair the mitochondria, theres fewer, they dont fuse. OR something is impaired in the mitochondria for how it deals with oxidative stress, sequestering of hydrogen ions is messed up OR oxygen delivery- heart doesnt deliver well, oxygen carrying capacity of the blood is damaged.

Pulmonary system- air flow problems

Breathing isn’t working properly with diminished ventilatory response to activity- same as in chronotopic incompetence. Evidence of carbon dioxide retention in blood and lungs (CO2 combines with water to form the potent carbonic acid, a big problem), poor oxygenation, and respiratory fatigue. Chemosensitive areas trigger the brain stem to breathe more- these must be blunted to allow less breathing. Very low amounts of expired air even at baseline. Belly breathing (parasympathetic) is very energy efficient- chest breathing is much harder.

Analeptic therapy (restorative) is recommended more so than aerobic exercise. With the aim of maintenance without decline, like a turtle, to improve quality of life. Functional movement that’s restorative. The body needs to be able to recover from the damage of exercise, and in ME/CFS patients, recovery is impaired to a greater or lesser recovery. Even just maintenance without further damage is a worthy goal. Aquatic therapy can help with venous return, with buoyancy. For bedridden patients, the emphasis is on maintaining joints and low level stretching and stretching.

The Workwell foundation also recommend belly breathing, pursed lip breathing (in for 2 out for 4, as the positive backpressure favours alveolar expansion, releases trapped air, used at altitude), ‘energy conservation therapy’ (sitting rather than standing, especially in the shower, use terry cloth robes, taking rest breaks, activity planning- saying no, accepting help, prioritising), working with good times of day (usually early afternoon, not mornings), salts, compression stockings. Doing the same task but much slower with rests inbetween avoids post-exertional malaise.

Full talks:
Part 1-
Part 2-

Attachment Part 2: Forming secure relationships

Following on from the previous blog avoidance and attachment styles;

Love and commitment make high achievers out of good partners, as they face reality as partners and survive in harsh environment. This requires patience, and someone you can trust and believe in. (Linked to better health outcomes!)


  • raise an issue softly and respectfully, friendship
  • let him influence me, ideas feelings and perspectives real and valid
  • be responsive to requests, don’t say no to needs outright, negotiate compromise
  • show respect for win-win. Positive intentions create understanding – make and receive repair attempts
  • self-soothe. Time outs and reflections. Realign with positive goals, calm down
  • pin point real issue. Underlying needs dreams and goals- as well as fears. Don’t get side-tracked
  • asking what the real issue is, be curious
  • compromise. Mindset for both dreams and interests for creative win wins
    FEARs- not afraid just mad, self, used, hurt Etc
  • conflict in personality and life interests- accept differences
  • make requests instead of demands. Respectful discussion. Otherwise intensify power struggle- interrupt cycle
  • recognised cocreated cycle, do something different

1. Build love maps.
2. Share fondness and admiration, Appreciation and respect
3. Turn towards. State needs, respond to bids
4. Positive perspective- success of repair attempts
5. Manage conflict. Natural. Functional positive aspects. Handle perpetual problems and solvable problems different
6. Positive atmosphere
7. Create shared meaning, myths and metaphors
8. Trust. Maximise partners best interest, have their back
9. Commitment. Your relationship is a life long journey for better or for worse. Cherishing, comparing favourably, not trashing and nurturing resentment

Sympathetic honesty
Tactful tough love
The truth about what you need and feel
Speak tactfully and kindly
Realistic shared worldview
(Otherwise disappointment and distrust)

More kindness- will be more kind
Need- turn toward your partner even if tired, busy or distracted
Treat them like the most important person in the world to you
Open and positive communication, combined with empathy

Responsiveness is being there when needed, calm, responsive and cheerful BUT not hovering


Beware the hostile forms of communication – breakdown
1. Criticism, blaming, attack character
2. Contempt, lack of respect for their dignity, seeing them as unworthy, name calling, swearing, hostile humour, mockery, eye rolling
3. Defensive. Denies statements, avoids responsibility, deflects complaints back onto the other person, creates adversarial.
4. Stonewalling from emotional overload. Won’t give verbal or non verbal feedback. Get up and leave the room. Containment strategy to avoid escalation of conflict. MEN

A fight anatomy: Style with avoidant husband
Harsh start up from partner – negative tone
Avoidant Defends, withdraws
Fight escalates and partners become FLOODED- Rapid heart rate, sweating, urge to leave or attack. Self-preservation kicks in
Anxious Become aggressive, avoidant tries to escape

Habitual harsh startups result in stonewalling, dismissing, withdrawal



Therapeutic handbook of attachment, theory research and clinical application

Insecure attachment in love: how can make you feel jealous and needy


Other notes.

All relationships have reoccurring issues- both successful and unsuccessful. Despite persistent unresolved issues persistently for decades. Unsuccessfuls insisted on resolving fucking everything- void of disagreement, void of relationship too.

Regarding sexuality, Suppression = infidelity. These individuals will project into partner, becoming blindingly jealous, demanding attention, trying to control. Suppressed energy = Waking up disgruntled and frustrated and not knowing why.

Regarding roles- some women are Super woman expected to do it all. They are Intelligent, motivated, in control, cheerful, powerful. They choose Men who mesh with life plan and ideals- men who are cooperative, agreeable, supportive, take their lead in areas women finds important. This may be problematic for them long term.

Regarding evolution- traditionally parents were involved, and distributed more resources to women with poor partners. Daughters exploited by accepting less helpful mates and Daughters became less choosy. This breaks down now? Parents no longer helping.