The Neurobiology of Fear

and Brain pH.

Paula woke up in the middle of the night with an intense sensation of Fear, Distress, and Anguish. Her heart was racing. Her breathing was unaffected. No shortness of breath. Yet sympathetic activation involving fear usually affects BOTH heart rate and breathing. This was very odd, although Paula was already too ill to appreciate it. We know now that Paula was unable to increase her breathing rate and depth without supportive medical help, most likely because of injury to her skeletal respiratory muscle pump system. Her breathing rate, while ill, was stuck [at rest] at 3 breaths per minute, even as she lay there in anguish and scared out of her wits.

[in case you haven’t read our other blogposts, early pioneer biologists, like JS Haldane and others found a wide range of breathing rates [and depths] at rest in healthy adults; from as low as 3 breaths per minute to as high as 28-30 breaths per minute at rest.…in health! There seems to be a lot we still do not understand about pH, PCO2, and O2 regulation in the blood and in the brain.

The risk for unknown respiratory pump failure and hypercapnia to the people at either extremes must be very great, during further respiratory challenges or weakness due to illness].

The amygdala is a chemosensor that detects CO2 and acidosis to elicit fear……

……It is well established that the amygdala integrates sensory input from other brain structures to orchestrate fear behavior; however, the amygdala itself was not previously known to act as a pH sensor. Ziemann et al suspected this possibility after observing that the acid sensing ion channel-1a (ASIC1a) was abundantly expressed in the basolateral amygdala and other fear circuit structures,91,92 and it was found that breathing 10% CO2 lowered pH to levels sufficiently to activate ASIC1a in amygdala neurons. )……...Together these findings suggest that the amygdala itself can act as a chemosensor. These experiments further identify ASIC1a as key molecular mediator of this chemosensitive response.” Neurobiology of panic and pH chemosensation in the brain John A. Wemmie, MD, PhD* Dialogues Clin Neurosci. 2011 Dec; 13(4): 475–483. PMCID: PMC3263394PMID: 22275852

Carbon Dioxide and Acidosis also seem to be implicated in the underlying pathophysiology of schizophrenia and bipolar disorder.

ABSTRACT “Although the brains of patients with schizophrenia and bipolar disorder exhibit decreased brain pH relative to those of healthy controls upon postmortem examination, it remains controversial whether this finding reflects a primary feature of the diseases or is a result of confounding factors such as medication and agonal state. To date, systematic investigation of brain pH has not been undertaken using animal models that can be studied without confounds inherent in human studies. In the present study, we first reevaluated the pH of the postmortem brains of patients with schizophrenia and bipolar disorder by conducting a meta-analysis of existing data sets from 10 studies. We then measured pH, lactate levels, and related metabolite levels in brain homogenates from five neurodevelopmental mouse models of psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorder. All mice were drug naive with the same agonal state, postmortem interval, and age within each strain. Our meta-analysis revealed that brain pH was significantly lower in patients with schizophrenia and bipolar disorder than in control participants, even when a few potential confounding factors (postmortem interval, age, and history of antipsychotic use) were considered. In animal experiments, we observed significantly lower pH and higher lactate levels in the brains of model mice relative to controls, as well as a significant negative correlation between pH and lactate levels. Our findings suggest that lower pH associated with increased lactate levels is not a mere artifact, but rather implicated in the underlying pathophysiology of schizophrenia and bipolar disorder”. Decreased Brain pH as a Shared Endophenotype of Psychiatric Disorders Neuropsychopharmacology. 2018 Feb; 43(3): 459–468. doi: 10.1038/npp.2017.167 Hideo Hagihara,1 Vibeke S Catts,2,3 Yuta Katayama,4 Hirotaka Shoji,1 Tsuyoshi Takagi,5,6 Freesia L Huang,7Akito Nakao,1 Yasuo Mori,8 Kuo-Ping Huang,7 Shunsuke Ishii,6 Isabella A Graef,9 Keiichi I Nakayama,4Cynthia Shannon Weickert,2,3 and  Tsuyoshi Miyakawa1,*

Paula and I think that the explanation is clear. Broken breathing that is unseen, unfelt, and unlooked for [except for the SENSATION [not an emotion] of Anguish or Dyspnea with altered mental and locomotor status is the link between Brain pH abnormalities and bipolar depression [and most likely all stages of manic depressive insanity or as we call it reversible chronic delirium [all motor subtypes].

[ Old ]Theories of panic etiology : Although the mechanisms for panic remain obscure, several [older] theories provide useful foundations for conceptualizing the bases of the attacks: (i) Some theories focus on cognitive distortions and misinterpretations of somatic experiences. For example, sensing one’s heartbeat may be misinterpreted as an impending heart attack, triggering uncontrolled fear (reviewed in ref 4). (ii) [ Ironically ] , …. Other theories focus on ventilation. Klein’s false suffocation alarm theory highlights the similarities between panic attacks and the powerful fear that suffocation evokes; this theory posits that a “suffocation alarm” is falsely triggered, thus inadvertently producing panic.5 Interestingly, patients with a history of respiratory disease have a greater risk of panic disorder than the general population.68 Similarly, panic disorder patients with prominent respiratory symptoms were more likely to have a prior history of respiratory insult.9 Thus, previous experience and adaptive plasticity and/or conditioning might play a role in panic.13 (iii) Growing knowledge of the anatomy underlying fear conditioning led Gorman and others to speculate that a supercharged fear circuit could produce panic in response to a wide variety of arousing stimuli.14,15 This fear circuit is thought to include at least 5 components: (i) Sensory input from viscera via the nucleus of the solitary tract and sensory thalamus, (ii) Processing and conscious control via the prefrontal cortex, cingulate cortex, and insula. (iii) Processing context and fear through the hippocampus and amygdala, (iv) Coordinated output of behavioral, autonomic, and neuroendocrine manifestations from the amygdala via the hypothalamus, periacqueductal gray, locus coeruleus, and parabrachial nucleus.14,16 (v) modulation by monoamines including serotonin and the raphe nuclei.14 Supporting this final component is the well-established benefit of selective serotonin reuptake inhibitors. The Neurobiology of Fear Posted Oct 03, 2019 Psychology Today Aditi Subramaniam, Ph.D.

Oh my goodness; Klein and Gorman were so close! They never imagined that the suffocation alarm was correctly triggered when the patient could not mount a sufficient response to the buildup of acids in the body [a product of cellular metabolism].

With respect to the actions of SSRI’s please look at our blog posts on Serotonin and how it may aid the motor process of breathing.

So ironic!

All this because no one though to tmeasure breathing rate at rest. No one thinks of the early and unfelt [probably due to nerve injury] damage to the skeletal respiratory muscle pump and the structures of the neck and of the torso- limiting the response to rising acids in the blood and/or brain..

It is time we link the mechanical behaviour of the skeletal respiratory muscle pump to severe attacks of bipolar illness. It only takes one minute and a stopwatch watch to test and retest at rest breathing rate and breathing effort- [ active exhaling is one example of the need for additional breathing effort-which is abnormal-exhaling should be passive, taking no energy] .

It is time we investigated the role of too slow breathing in bipolar depression. [only then can we take on the more complicated state of mania -a particular pattern of delirium. [Mania used to mean delirium without fever before psychiatry tried to blur the definition to fit their incorrect and misguided ideas].


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