Affective Mood Regulation, Interpersonal Connection, and Physiological Health
“Wise mind incorporates both the passion, conviction, and intuition of emotion with the logic and empiricism of rationality. A central tenet of the Zen approach is accepting reality as it is.” (M. Linehan)
I’ve become curious about the similarities of a condition commonly called borderline personality disorder (BPD) and what all people face in situations where stress reaches a certain threshold. The condition often involves chronic negative affect or dysphoria, impulsivity, psychotic or quasi-psychotic episodes, chaotic interpersonal relationships, and presentation of a social veneer that breaks down under stress. Self harm and suicide are also very common among those experiencing BPD. This condition seems increasingly relevant as it highlights ways minds work when experiencing intense stress, social disconnection, or a deep sense of being alone. While reading up and listening about the condition, I was fortunate enough to find a mature and sophisticated podcast published recently and built on approximately 100 hours of research that suggests dramatically improved patient outcomes with newer treatment techniques. Those successfully treated were done so often without the use of any medication.
It seems the condition might more accurately be labelled affect regulation disorder. Successful treatments currently involve dialectical behavioral therapy in the lineage of Dr. Marsha Linehan. Treatments require a significant focus on empathy and connection from the provider. The research mentions traumas connected to BPD at the earliest of ages, which suggests delayed or modified early life developmental tracks. Destructive behaviors associated with the condition can be thought of as ways in which people hack or shortcut the feelings associated with love and connection. Those hacks share consistencies with the full spectrum of destructive human behaviors we all enact from similar emotional sources or impulses.
According to a number of resources there are specific and learnable skills which seem to be part of the path to recovery, and the psychiatric physicians referenced seem to de-emphasize the use of long term psychiatric medications with this condition. The skills list from Marsha Linehan emphasizes 4 categories for symptom management: Emotion Regulation, Interpersonal Effectiveness, Distress Tolerance & Mindfulness Skills and more detailed explanations can be found here. Prior to or coincident with skills training, unhacking the shortcuts should be engaged and encouraged. The sufferer must learn first to identify the states that create a cycle: activated state, lonely state, or even just an awareness of the craving for a rapid path to distraction or euphoria. From those states they learn to return from loneliness into chaotic activation with specific skills and then from chaotic activation to feelings of relaxation and connection with other skills. According to Darcy Trenkle MD, loved ones and physicians best serve a dysregulated person or child, not by doing anything to fix the feelings of loneliness for them but rather by holding space for the person to work out of their dysphoric state through cognitive skill.
The pattern of focusing on a problem to fix rings an interesting note of familiarity with many types of relationships I’ve observed, and some that I’ve been in. For an individual, problem solving is generally very effective for reducing intense emotions and is a critical component of modalities like cognitive behavioral therapy. It is also true that the problem engaged person will not be fully attentive and as such less connected with the more emotional friend or partner. The path or solution I’ve run across seems to be to make the resolution of the disconnection the first or pre-imminent problem to be solved. This article breaking down the “how to” of expressing empathy is an approach for those who find themselves desiring to solve problems in such situations. Outside of addressing the feelings of connection, disconnecting and fixing set up an exacerbation of symptoms which eventually cycle into disruptive conflict or connection seeking elsewhere. It can seem unfortunate or frustrating that certain actions within a desire to render aid may further self destructive or chaotic behaviors of a partner.
From a physiological point of view, I’m drawn to focus on a few points discussed in the podcast review notes: the gender ratio of sufferers is biased towards women by 3:1 according to the publishers of the DSM1. Genetic and epigenetic research seems to implicate estrogen regulation in the expression of BPD, and the neurophysiology of minds with BPD show symptoms of chronic stress associated with fear and anger responses as well as less connectivity to the midcingulate cortex, a region associated with social monitoring and reasoning. The same studies show a return of typical connectivity after completion of dialectical behavioral therapy (DBT) programs.
It seems well established that symptoms are dramatically affected by the phase of the menstrual cycle with significant worsening at about 1 week prior to menses. If all women had the same level and sensitivity to progesterone this might implicate progesterone as causal given its expected peak at that time. Yet, I’m skeptical of that interpretation, given progesterone's role in increasing both gaba (a hormone of relaxation) and allopregnanolone (a neurosteroid associated with positive mood). Progesterone is supportive of healthy thyroid and body temperature levels. I’m inclined to suggest that women and possibly men with BPD are much more likely suffering a progesterone or progesterone receptor deficiency, and relative ratios of estrogen need to be considered much more carefully. Stress, especially chronic, seems to lower progesterone levels and specific research shows that progesterone decreases are further aggravated in personalities more sensitive to social stress and rejection2. This paints a rather clear picture of the restorative role of progesterone3.
A significant opportunity also exists with supplemental intranasal oxytocin. According to an article in 2019 a single daily dose of intranasal oxytocin at 24 IUs changed borderline patients' affiliative behaviors to those in line with population norms:
“findings provide the first evidence for a beneficial effect of oxytocin on deficits in affective empathy and approach motivation of BPD. Our results indicate a beneficial effect of a single dose of oxytocin on affective empathy and approach motivation in women with BPD adapting their level of social functioning to that of healthy controls.4”
Other recent studies seem to corroborate the use of oxytocin. Oxytocin is also known to increase core temperature up to a healthy baseline. This is consistent with increasing peripheral metabolism while reducing hunger:
“the peripheral beneficial effects oxytocin exerts on key metabolic organs, including suppression of visceral adipose tissue inflammation, skeletal muscle regeneration, and bone tissue mineralization...weight loss induced by chronic oxytocin treatment is related not only to its anorexigenic effects, but also to the resulting increase in energy expenditure and lipolysis.5”
Numerous recent studies seem to show the critical role of oxytocin in energy homeostasis and its potential use for treating disorders such as obesity. Within the lense of evolutionary biology and psychology, affiliative bonds for social mammals are important for an organism’s body budgeting. A social mammal with sufficiently tight kin bonds will be able to share actual heat, caloric resources, protection, and litter care. This will reduce the need to store as many resources internally as fat and reduce the need to raise blood sugar. As an aside to be discussed later in this series, surviving the cold and potential famine of winter is evolutionary purpose of diabetes6. If oxytocin is one of the main signals of the quality of one’s social relationships, it stands to reason that it would do much to modulate one’s physiology in accordance with those bonds.
Beyond the two ‘big guns’ of oxytocin and progesterone, I would add a few more to my list of potentially helpful substances. Pregnenolone is a neurosteroid associated with neurite growth and brain health and is a precursor to most steroids and neurosteroids. It would be critical to replace it if taking progesterone, but it alone might do all that is required by converting sufficiently into progesterone. Lithium orotate7 at a low dose of between 5 and 25mgs in the evening has a noticeable and immediate effect on mood. It is associated with stabilization and neuronal health and longevity which makes it hard not to recommend for anyone, but especially those suffering with anything mood or brain related.
“In animals, lithium upregulates neurotrophins, including brain-derived neurotrophic factor (BDNF), nerve growth factor, neurotrophin-3 (NT3), as well as receptors to these growth factors in the brain. Lithium also stimulates proliferation of stem cells, including bone marrow and neural stem cells in the subventricular zone, striatum, and forebrain. The stimulation of endogenous neural stem cells may explain why lithium increases brain cell density and volume in patients with bipolar disorders. Lithium also increases brain concentrations of the neuronal markers n-acetyl-aspartate and myoinositol. Lithium also remarkably protects neurons against glutamate, seizures, and apoptosis due to a wide variety of neurotoxins.8”
Adding to my list, magnesium threonate is also an important mineral with a helpful amino acid bonded to it. Magnesium is essential to cellular relaxation. For sleep, a combination of (Apigenin 100mg, L-Theanine 400mg, and Magnesium Threonate 144mg - of elemental magnesium) is recommended as an addition or substitute for melatonin by respectable neuroscientist: Dr. Andrew Huberman. This is something I’m currently using. Apigenin is an estrogen antagonist and a progesterone receptor agonist as well as an immune inflammation modulator. Going further, creatine monohydrate at 5 grams a day should also be strongly considered given creatine’s significant role in mental and neurological health:
“Subsequent studies have demonstrated that cognitive processing, that is either experimentally imparied (following sleep deprivation) or naturally impaired(due to aging), can be improved with creatine supplementation.9”
Personally, I attribute some of my own improved cognitive performance from supplementing with creatine. I expect it might reduce impulsivity and symptoms of attention switching consistent with having more energy in the relevant neurons of attentional control.
This is probably a long enough list for a first approach to aiding neurological repair as well as mitigating symptoms of borderline or affect dysregulation. If I was trying to aid a loved one suffering from BPD I would aim for both the behavioral approach coupled with the physiological. It might seem expensive, but avoiding the emotional and actual financial costs related to the activities we’ve called “connection hacks”, the investment is very likely to pay dividends.
I’ve left out any discussion of diet, which is very important, but also likely very difficult or impossible to change without being in a situation with shared goals in that specific domain and a noticeably increased impulse control from the loved one.
Web Resources (Understanding BPD):
Explaining Borderline Personality Disorder
(PDF) Dialectical-behavioral therapy for borderline personality disorder
Hormone series Part 2: Cortisol and Progesterone Levels & Symptoms
Therapy References:
What Works in the Treatment of Borderline Personality Disorder
The role of the midcingulate cortex in monitoring others' decisions
Dialectical behavior therapy as treatment for borderline personality disorder
Amygdala Functional Connectivity in Young Women with Borderline Personality Disorder
Dialectical-behavioral_therapy_for_borderline_personality_disorder
What Works in the Treatment of Borderline Personality Disorder
(PDF) Dialectical-behavioral therapy for borderline personality disorder
Pharma options:
Progesterone References:
Low progesterone and cortisol steal
Chaste tree (Vitex agnus-castus)--pharmacology and clinical indications
“Post-hoc analysis examining person-centered progesterone showed negative correlations with most symptoms, according to the authors.”
Oxytocin References:
The effects of oxytocin on social cognition in borderline personality disorder
Effects of intranasal oxytocin administration on empathy and approach motivation in women
[Oxytocin and postpartum depression]
The effects of oxytocin on eating behaviour and metabolism in humans
with borderline personality disorder: a randomized controlled trial
The effects of oxytocin on eating behaviour and metabolism in humans
Oxytocin Involvement in Body Composition Unveils the True Identity of Oxytocin
Oxytocin: A Potential Therapeutic for Obesity
Creatine References:
Creatine for the Treatment of Depression
Beyond muscles: The untapped potential of creatine
Use of creatine in the elderly and evidence for effects on cognitive function in young and old
Creatine supplementation in the aging population: effects on skeletal muscle, bone and brain
Low dose lithium:
The New News about Lithium: An Underutilized Treatment in the United States
Low-Dose Lithium Supplements for Mental Health
Purchase Links:
Progesterone:
https://farmaciasdelnino.mx/eng/item/1319/geslutin-progesterona-200mg-15-perlas
(much more expensive than my current MD prescription which is ~$1.00 per 200mg)
https://www.longnaturalhealth.com
(search for Dr-Peats-Progest-E-Complex-34-ml)
http://www.idealabsdc.com/lab/ “Progestene”
Oxytocin:
Buy Oxytocin Nasal Spray(I use this)
Allopregnanolone:
This is ultimately what is driving a lot of the mood benefits of progesterone. I was surprised to find it. I’ll be trying it soon. I would use it in conjunction with Progesterone but potentially lower the Progesterone dose. I’ll be curious to see how it feels.
http://www.idealabsdc.com/lab/ “AlloP”
Lithium:
This seems to be contentious with a strong counter argument that males with similar behaviors will not likely end up seeking treatment or being cared for, but rather will likely end up encountering the criminal justice system, or in rare cases being high functioning enough that their behavior is left socially unaddressed.
This linked paper was most interesting in terms of understanding the differential effects of those with high social stress sensitivities.
Taking exogenous progesterone suppresses GnRH and LH which cause peripheral tissues such as gonads to initiate production of the steroid cascade. I see this as a potentially beneficial effect given LH’s role in most conditions associated with aging; however, other hormones such a pregnenolone and DHEA will likely also need replacement concurrent to progesterone use.
Domes, G., Ower, N., von Dawans, B. et al.Effects of intranasal oxytocin administration on empathy and approach motivation in women with borderline personality disorder: a randomized controlled trial. Transl Psychiatry 9, 328 (2019). https://doi.org/10.1038/s41398-019-0658-4
Kerem L, Lawson EA. The Effects of Oxytocin on Appetite Regulation, Food Intake and Metabolism in Humans. Int J Mol Sci. 2021 Jul 20;22(14):7737. doi: 10.3390/ijms22147737. PMID: 34299356; PMCID: PMC8306733.
Survival of The Sickest (Moalem 2007) Chapters 2 & 3
Low dose lithium orotate should not be confused with perscribable lithium carbonate. Lithium carbonate is most often prescribed at ranges of 500 mgs to over 1000 mgs for bipolar disorder. Those doses are known to cause kidney problems for some of their prescribed population after years to decades of use.
Young W. Review of lithium effects on brain and blood. Cell Transplant. 2009;18(9):951-75. doi: 10.3727/096368909X471251. Epub 2009 May 13. PMID: 19523343.
Rawson ES, Venezia AC. Use of creatine in the elderly and evidence for effects on cognitive function in young and old. Amino Acids. 2011 May;40(5):1349-62. doi: 10.1007/s00726-011-0855-9. Epub 2011 Mar 11. PMID: 21394604.