Other Bipolar Disorders, Anorexia Nervosa and Bulimia, Opiate and Stimulant Addictions

Here is an enlightened article showing how cognitive training (which increases BDNF, synapticity, nerve function and nerve cell integrity)  potentially allows better decision making by activating cognitive and salience networks via working memory and cognitive training.

This results in better choices, less denial and greater levels of BDNF (that has been shown to rise in 26 weeks of opiate addiction recovery to levels below normal controls).  Perhaps cognitive brain training will increase BDNF levels above normal and provide more resilience!  Perhaps other BDNF increasing lifestyle interventions would further improve central executive function, promote brain plasticity and result in above average serum BDNF levels establishing resilience against relapse and global improvement in performance status of mental, emotional and physical resilience in general.

A debate on working memory and cognitive control: can we learn about the treatment of substance use disorders from the neural correlates of anorexia nervosa? | BMC Psychiatry | Full Text

http://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-016-0714-z

Joseph Thomas (Tony) Liverman, Jr. MD 

Prevent and Reduce The Disease of Addiction; Increase BDNF, Treat Comorbidities

Conjecture: What perpetuates addictions is the following:

Addictions are begun by excitement, novelty and escape seeking.  The under 21 year old population is especially vulnerable because of developmental stage.  Those treated for pain and disability are vulnerable due to lifestyle changes that reduce BDNF.  Those who  experiment are vulnerable because opiates, and stimulants reduce BDNF.  So vulnerability to addictions are increased or decreased by BDNF levels.

Opiate Use and Depressant lifestyle change- reduces BDNF, leading to dysphoric mood and greater need to achieve escape velocity either up or down.

BDNF increases improve mood, memory and metabolism and reduces the need for escape velocity either up or down.

The desire to resume drugs for euphoria and escape remains inversely proportional to BDNF levels.

Some persons have "addictive personality" in proportion to their risks for dysphoric moods.  I.e. Bipolar patients.  See abstract below.

http://www.sciencedirect.com/science/article/pii/S0165032706001327

The evidence supports a lifestyle that increasing BDNF results in a better mood, better memory and better metabolism.  Less pain and less dysphoric mood reduces but does not eliminate relapse.  I am convinced, by the overwhelming evidence, that, the disease, addiction could be partially prevented or reduced by increasing BDNF before drug use and after treatment.

The options include:

Lifestyle alone.

Lifestyle plus supplements.

Lifestyle, supplements and nonnarcotic medications.

Lifestyle, supplements, nonnarcotic medications and opiate agonists.

Addiction would be treated like asthma.  Control the stage of disease and reduce therapy to the lowest cost lowest risk medication as determined by control.

In abstract below, Brain-derived neurotrophic factor serum levels are lowest after withdrawal rising but lower than normal controls after 26 weeks of abstinence.  The rise indicates successful treatment! and increasing resilience?  My conjecture states that lifestyle changes, supplements and nonnarcotic medications that raise BDNF levels above normal would increase resilience against addictions generally.

http://www.sciencedirect.com/science/article/pii/S0010440X15301139

Brain-derived neurotrophic factor serum levels in heroin-dependent patients after 26 weeks of withdrawal

Joseph Thomas (Tony) Liverman, Jr. MD

Implications of Klotho gene variant for BDNF Improving Memory, Mood and Metabolism

Implications of Klotho gene polymorphism for BDNF Improving Memory, Mood and Metabolism

Follow the bullets of the article linked below.  It depicts a bio marker of improved mood. BDNF which is only one of its three facets!

Bottom line-  differences in rate of learning, baseline mood and baseline physical performance can be greatly increased or optimized by increasing BDNF.  BDNF can be nick named 3M because it increases Memory, Mood and Metabolism.

Persons having only a single variant copy of the klotho longevity gene have increased memory associated with reduced mental loss with aging because of Glu2B amplification of nerve plasticity, an effect of BDNF.  Ergo it takes less BDNF to promote neurogenesis and network creation for learning and remembering in individuals and groups that have one copy of the variant Klotho gene and one common Klotho gene.

What are the implications of this finding?

It therefore follows that the rate of learning is strongest for individuals with one copy of variant gene or 23% of the population, average for 2 copies of the common Klotho gene and negative for two copies of the variant gene or 23% of the population.  This is a normal distribution of gene inheritance for a recessive gene that adds when one copy is present and subtracts when two copies are present.  As in Goldilocks 1 common and 1 variant gene copy is just right.  See GT, TT, GG at Klotho Rs9536314 on Wikipedia.  This is analogous to sickle cell inheritance with two variant copies having sickle cell disease, two normal copies having increased mortality to malaria and one copy of each being protective for malaria.

The NET effect of Klotho 2 gene variant status GG or 2 common gene status TT is poorer intellectual function and faster decline IN THE ABSENCE of HIGH or NORMAL BDNF.  To wit some depressed persons have greater memory and intellectual loss with low BDNF states or depression than others.

However, all persons would have greater Intellectual development and performance with higher levels of BDNF. Greater amplification of controlled synaptic activity and brain network development with higher levels of BDNF.  This is entirely analogous to cholesterol patterns in the population with the Mediterranean diet versus the American diet.  Ergo some persons are affected more or less by diet but all benefit from the Mediterranean diet.  Some persons are affected more or less by BDNF level but all persons benefit from higher or optimum levels of BDNF.

A lifestyle that promotes BDNF promotes the following:

Intellectual brain network development and speed.

Normal or improved mood

Improved mental, emotional and physical performance through time.

Resilience against addictions, opiates, gambling etc.

That lifestyle includes the following:

Weekly intermittent fasting to trigger expression of survival longevity genes including BDNF.

Slow paced diaphragmatic breathing for two minutes twice daily to reduce TNF alpha and brain cortisol levels thereby raising BDNF levels.

High intensity interval Tabata training or exhaustive lactate producing aerobic steady state exercise to maximally increase BDNF.

BrainHQ.com brain training to increase BDNF.

Raise BDNF with lifestyle, and when pathological mood disorders are present, medications to improve the entire person both memory, mood and metabolism.

This is clearly a shift the mean strategy for individuals and groups and has profound potential for education, healthcare, law enforcement and economics.

http://www.sciencedirect.com/science/article/pii/S002839081530157X

Respiratory Muscle and Function Decline Of Aging Reversible?

Aging, Pneumonia, Exercise Shortness of Breath and BDNF

This article is relevant to aging, pneumonia, exercise dyspnea and BDNF.

The lifestyle changes that increase BDNF preserves diaphragm innervation and type 2 fibers required for explosive movements such as clearing the airway of secretions or aspiration. One can measure inspiratory and expiratory force, timing of cough to irritants (a proxy for aspiration). Exertional dyspnea correlates with peak inspiratory and expiratory force, inspiratory force/vital capacity ratio and 6 minute walk in COPD patients. (Shortness of breath with exercise improves with measures of strength of lung muscles to breathe in and breathe out, lung inspiratory strength to lung volume or size ratio, and the distance walked in 6 minutes in lung disease patients.)

BDNF likely improves presbyesophagous, epiglottis dysfunction and pharyngoesophageal dysphagia in the aging sarcopenic patient. I.e. Neuromuscular function and integrity. BDNF reverses aging of swallowing in patients losing muscle due to inflamaging. 

The heart and respiratory muscles are crucial to human power production.  Their poor performance is associated with increased IL-6 an inflammatory marker.  In effect poor muscle function of the heart and lungs produces waste or exhausts like a car with a poorly functioning power plant.

Could interventions that increase BDNF increase 6 minute walk times? Reverse loss of respiratory muscle loss and function loss?

Weekly Intermittent fasting?

Resistance breathing training?

Slow paced breathing 2 minutes twice daily?

Antidepressant medications?

4 minute HIIE?

Is the diaphragm/lung or heart/circulatory system the stronger limiting factor for functional performance?  Doesn't BDNF improve both and all?

http://www.sciencedirect.com/science/article/pii/S1569904815300550

Melatonin strengthens bone, Synergy with Vitamins D and K2

Why does Melatonin increase bone strength, cartilage and collagen quality?

Consistent with my recent post about collagen cross linking and osteoporosis is this article showing antioxidants reduce non-enzymatic weak collagen cross linking in connective tissue including bone.

Collagen cross links are trivalent strong or bivalent weaker forms from enzymatic activity;  respectfully (the product of cellular activity requiring ATP) and non-enzymatic from AGP advanced glycosylated products (diabetes and aging) and Reactive Oxygen Species (aging).

Here Melatonin reduces the products that increase weak cross linkages thereby strengthening bone both in the cell and extra cellular matrix.  The quality of bone with strong cross linkages is independent of calcification or mineral content!  Ideally, one with/or at risk of osteoporosis will have both.  I also note that Melatonin is unique in its ability to reduce the rate of neurodegenerative brain changes by reducing activation of the inflamasome or innate cellular immune "autoimmunity."

Also note that Alpha Lipoic acid an antioxidant has also made bone stronger likely through the same mechanism of melatonin.

http://www.omicsgroup.org/journals/an-early-development-budget-impact-model-for-the-use-of-melatonin-in-the-treatment-and-prevention-of-osteoporosi-2167-065X-1000132.pdf

Vitamin D3 K2 Synergy Reduces Aging in Collagen-Cross Lnking?

How does Vitamin K2 improve cartilage, bone and reduce fractures?  

Conjecture: Vitamin K2 and Vitamin D synergy reduces Collagen Cross-Links through 2 mechanisms;  

1. increased energy production during connective tissue use, and 

2. improved structure, architecture and calcification  during bone formation.

Vitamin K2 can substitute for coenzyme Q10 in the electron transport system in mitochondrial energy production.  Vitamin K2 is also the essential cofactor for matrix gla protein which removes calcium deposits from soft tissue to sequester calcium in bone and other vitamin k dependent proteins that produce healthy cartilage and well formed matrix for bone trabecular formation.

In this article below, age related collagen cross linkages affect bone quality independent of bone density.  

Vitamin K2 potentially reduces collagen cross linkages by providing more ATP energy, more antioxidant activity during the bone formation interval AND also makes well formed bone forming matrix and delays calcification until well formed even in the presence of hypomagnesemia which is notorious for premature calcification and poor quality bone. One may remember that magnesium is required for each Mg-ATP energy molecule.  Without energy from Mg-ATP to ACTIVELY form bone INACTIVE calcification occurs even of soft tissue or poorly formed bone matrix. 

The Bone constantly remodels and is effectively replaced every 7 years.

If during this seven year cycle of bone turn over and replacement vitamin k2 and vitamin D3 levels (which promotes vitamin k2 dependent proteins production) are normal or sufficient, one could form better quality bone and higher bone density thereby reducing fragility and fracture risk.  

It might also allow regeneration of better quality bone cartilage interface and better cartilage during that interval.

How does these functions of K2 relate to my DrLiverman.blogspot.com about BDNF increasing improving metabolic health of body brain function reciprocity?  In case I lost you, performing body and brain functions at their limits of low energy supply or high energy demand is the stimulus to increase BDNF (brain derived neurotrophic factor) allowing the individual to optimum energy production via somatic fat burning and cerebral glucose and beta hydroxybutyrate burning.  

Energy can be further amplified in every cell and all cells by higher BDNF levels from a metabolic healthy lifestyle of intermittent fasting, slow paced breathing, lactate producing high intensity interval exercise, resistance training or Prolonged steady state endurance exercise, BrainHQ sub cortical brain speed training that increases BDNF, increases synapticity or nerve connections allowing sensory imputs to parallel process and perceive and encode faster into the CPU or hippocampus while simultaneously increasing synapticity or nerve network capacity and storage down from the cortex processing neurons focused by attentional states.  

A maintained faster brain body is the end result of metabolic Heath.  In effect metabolic health speeds up the network of sensory imputs to the CPU of the brain and memory and meaning storage imputs gated by ATTENTION from the CPU.  Attentional states are convergent or divergent or some combination of both at all times.  Highly educated brain networks appear, to me, to expand convergent networks into more divergent metaphorical, virtual and multiple meanings for each convergent symbol.  E.g.  In the hippocampal processing interval that the slow learner processes three real symbols, ball flag and tree, the medium fast learner can also process a golf ball on a green with a flag in the hole and a green side tree, and the fast learner can also process a virtual tree with flags replacing leaves and balls replacing seeds falling from the tree!  For expansion on this discussion of the brain as an organ for improvement and the model of top down bottom up see my Livermanlearnngtolearn.blogspot.com and start at the beginning with increasing bandwidth.

http://link.springer.com/chapter/10.1007/978-4-431-55778-4_3

Collagen Cross-Links as a Determinant of Bone Quality

Aging, Disconnection Syndrome and Brain Network Weakening for Lack of BDNF

Here is the concept of disconnection syndrome related to aging and directly proportional to peripheral BDNF.  I recently blogged that decreased BDNF first resulted in loss of connections or synapticity first, neuron function second and neuron integrity last.

Peripheral levels of BDNF directly correlate to network or synaptic connectivity .

Raise peripheral BDNF levels and preserve motor function by preserving nerve connections or brain synapticity or network health first, neuron health second and neuron integrity last.

This study uses fMRI to show the direct correlation of BDNF and Connectivity.

Babies walk slowly and with poor balance.

Elders walk slowly and with declining balance.

Both are respectfully due to immature networks with high BDNF and mature networks with low BDNF.

Babies gain and elders lose network connectivity in relation to BDNF and synapticity or  brain network connection strength.

Would elders reduce falls and increase their timed walking distance with cognitive brain speed training?  This has been confirmed as superior to leg strengthening and gait training, the usual recommended treatment to prevent falls.

What if the goal was redirected to maximize BDNF?  

BDNF is a bio marker that directly correlates to "connectivity" and function should follow the peripheral level of BDNF  and the restoration of brain body learning as in post stroke motor rehabilitation.

http://www.sciencedirect.com/science/article/pii/S0197458015005552

Serum BDNF correlates with connectivity in the (pre)motor hub in the aging human brain—a resting-state fMRI pilot study