Perinatal Mental Health Conference Fairmont Hot Springs, Montana - - PowerPoint PPT Presentation

Perinatal Mental Health Conference

Fairmont Hot Springs, Montana October 2018

Connecting Pathways and Building Bridges

An Integrative Approach for Treating Perinatal Mood and Anxiety Disorders Christine White Deeble, ND

Psycho-Gastro-Neuro-Endo- Immuno

Putting it all together.

My Disclaimers:

• This isn’t about who I work for or what I profit from.

I work for myself and I’m not selling anything or profiting from this other than I have received some payment for my time.

• I believe in the body’s inherent capacity to heal

itself.

• I do not believe that illness, of any kind, manifests

without clues being present. My job, our job as health care providers, is to identify those clues.

• I believe people have a basic right to be offered all

their options, and that our jobs are to facilitate their process in making those choices, and to help them re-evaluate along their journey towards their own

• ptimal health.

Who am I?

• I am a full-time clinician, not a researcher. I am not

regularly on the lecture circuit. Which means I do not have hours to search the archives of medicine for multitudes of studies to cite.

• I do rely on those who have the time to condense

information and my sources will be sources that you can learn from beyond today.

• I don’t mean to be disrespectful to any profession of

type of treatment, but I do expect I will say some things that some of you might be uncomfortable with because it will challenge your paradigm.

Objectives

• Participants will be able to identify and

understand the relevance of several clinical signs and symptoms, through testing and intake, which can guide treatment decisions for women experiencing a PMAD to allow for a more comprehensive care plan.

• Participants will leave with an understanding of

treatment plan options that include a range of integrative medicine options such as diet, lifestyle, nutrients, and herbal medicine.

Homeostasis, Seeking Balance

• Women, by nature, are built to be resilient and

strong, healthy, in harmony while fluctuations occur, and to have balance. We are built to carry and raise

• children. We are complex systems with natural

synchronization.

• Pregnancy and birth are fundamentally understood

to be huge shift in the physiology and biochemistry. These are understood to have significant impact on how the brain functions and our moods. It touches women at the deepest of all levels.

• When balance is lost, the results can be devastating.

Helping correct that balance in a manner that doesn’t respect all the pathways involved will result in an unstable condition that will have a tendency to want to fall out of balance.

Connecting pathways and building bridges

• Bridges must be built with solid footings and

anchored on a firm foundation.

• Pathways are routes we follow to get from one

place to another.

• Let’s build bridges between disciplines and

make obvious the pathways that are responsible for the underlying or root causes of PMAD.

Multi-factoral

• Psycho—life and relationship changes, stress,

trauma

• Neuro—brain chemistry changes
• Endo—rapid hormone fluctuations, steroid and

thyroid…and age and stress levels play a huge role in this element.

• Immuno—inflammatory

The Interconnected Pathways

• “In recent years various neuroendocrine and psycho neuro

immunological involvements in the onset of postpartum depression have been reported. The leading idea behind this is that labor, delivery, and postpartum periods induce multiple inflammatory responses in women, which, in a subset of women could be intensified by genetic predisposition, preexisting inflammatory status, and specific vulnerability leading to depressive symptomatology. Additionally, nutritional status is essential for proper functioning of the hypothalamic- pituitary-adrenal (HPA) axis and adequate immune reactions in the body. During pregnancy due to higher demands for certain nutrients, deficiencies are more likely to occur, leading to dysregulation of immune mechanisms, deprivation of regular cellular mechanisms, and consequently, depressive symptomatology.”

• “Reduced monoamine levels (serotonin, dopamine, and

norepinephrine) in the brain have been proposed as factors contributing to the neurotransmitter insufficiency responsible for the onset of depressive disorders.”

Cont’d

• Changes in the HPA axis are well documented with

depression; elevated cortisol is linked with depression; stress results in HPA axis changes; and stress impacts gut immunity and gut barrier integrity.

• It is well understood and documented that commensal

gut microbes produce serotonin, melatonin, GABA, catecholamines, histamine and acetylcholine. These NTs don’t necessarily cross the BBB to a large degree, the likely impact visceral reactions that impact the CNS. And for example, Lactobacilli alters tryptophan metabolism. The SCFAs in the gut produced by commensal microbes and this is likely one of the communication pathways. Research has shown that Butyrate, a SCFA, can produce impact on the frontal cortex and result in an antidepressant effect.

Paradigm Shift

• We are in an age of medicine where we can no longer chose

to ignore epigenetics, the gut brain axis, the impact of food quality on health, and the relationship of stress and disease

• We are the sum total of our experiences, pregnancy and

postpartum aren’t some sort of reset button which negates who women were before they became pregnant, gave birth,

• r transitioned into motherhood. And when we do consider

pre-pregnancy health, we aren’t just talking about diagnosed mental health issues or frank physical pathology.

• This is the heart of naturopathic or functional medicine.

Understanding whole health, understanding that we can be well based upon conventional standards but ill if we consider a functional perspective.

• We don’t necessarily need new treatments that haven’t

been invented, we need to use what we know already and apply it in the appropriate way to this population. We need to honor the obvious pathways at play.

Regarding previous slide The predisposing, pregnancy and CUMS factors that contribute to PPD, both directly and via “baby blues” induce TDO and IDO, increasing TRYCATs, including KYNA and QUIN, as well as increasing PiCs and O&NS. Notes: Such increased immuno-inflammation drives down serotonin, melatonin, and á7nAChr, whilst increasing autoimmunity, somatization, and relative amygdalae–cortex activity. Along with decreased omega-3 polyunsaturated fatty acids, this increases PPD. Treatments include psychotherapy and antidepressants. Estrogen can enhance the efficacy of SSRIs, whilst melatonin may provide a safer treatment for both mother and child. Some antidepressants are not recommended if breastfeeding, including those where no relevant data exist. Abbreviations: á7nAChr, alpha 7 nicotinic acetylcholine receptor; CUMS, chronic unpredictable mild stress; E2, estradiol; EDO, indoleamine 2,3-dioxygenase; kyn, kynurenine; KYNA, kynurenic acid; MDD, major depressive disorder; O&NS, oxidative and nitrosative stress; PIC, proinflammatory cytokine; PPD, postpartum depression; QUIN, quinolinic acid; SES, socioeconomic status; SSI, selective serotonin reuptake inhibitor; T3, thyroid hormone; TDO, tryptophan 2,3-dioxygenase; TRYCAT, tryptophan catabolite. Anderson G, Maes M. Postpartum depression: psychoneuroimmunological underpinnings and treatment. Neuropsychiatric Disease and Treatment. 2013;9:277-287. doi:10.2147/NDT.S25320.

Progesterone and Brain Chemistry

• Progesterone is produced in the ovaries, adrenals

and CNS and has many metabolites.

• It can induce anxiety (anxiogenic), it can reduce

anxiety (anxiolytic) and can enhance sleep.

• In the CNS the majority of the effects of

progesterone are by the metabolites Allopregnanolone and Pregnenolone.

• Allopregnanolone is the most neuro-active and is a

major GABA agonist. This results in action on GABA receptors that are important in regulating stress, anxiety, vigilance, alertness and seizures. The result can be calming and supportive of sleep, it can also result in anxiety and depressive moods.

Allopregnenolone, GABA and Serotonin

• When allopregnanolone interacts with the GABA

receptor, it changes it and makes it less reactive to further stimulation and this can then result in decreased GABA-mediated inhibition centrally. This can then translate into anxiety and depression (the theory being if GABA levels are innately to low).

• Additionally, progesterone results in reduced

serotonin action by deceasing platelet uptake of serotonin and thus mood impact or increased anxiety.

• Additionally, progesterone also lowers serotonin

levels by increasing MAO which is the enzyme that breaks down serotonin.

Brexanolone

“Pregnancy causes a dramatic rise in the reproductive hormones estrogen and

• progesterone. It also produces a spike in brain levels of a steroid called

allopregnanolone, which normally activates receptors for GABA—a neurochemical that signals brain cells to stop firing. GABA receptors go dormant during pregnancy to avoid overactivation by allopregnanolone; otherwise a pregnant woman would become virtually anesthetized. Immediately following birth, estrogen, progesterone and allopregnanolone drop back to normal levels, after which GABA receptor levels rebound quickly. But in some new mothers, this rebound takes longer, which may result in postpartum depression. The new drug, developed by Sage Therapeutics, works by elevating

• allopregnanolone. Doing so activates GABA receptors and keeps the neurochemical

at a healthy level. In one of Meltzer-Brody’s studies, a phase II clinical trial of 21 severely depressed postpartum women, 70 percent of those who received the drug went into remission. Most important, the effect occurred immediately after it was administered, and benefits persisted for 30 days. Sage Therapeutics has since conducted two phase III trials with a combined 226 postpartum women, and preliminary reports are promising. The drug, called brexanolone, is now under review by the U.S. Food and Drug Administration.”

Paradigm shift…..

• Do we need a new drug, or do we need a new

way of thinking about PMADs?

• What if we simply begin to use what we know

and cease with a mechanistic approach to health and healing and instead follow the known pathways and utilize the known mechanisms of action.

• Research has shown the administration of oral

pregnenolone increases allopregnanolone levels.

• Assessing and the augmenting progesterone

levels is also a likely mechanism to address allopregnanolone levels.

Another consideration: Genetics vs Epigenetics

• “Genetic vulnerability predisposes subgroups of

women to develop perinatal depression. Yet it is the epigenetics that plays a pivotal role in the development of a majority of illnesses, perinatal depression included. Various external factors influence either triggering or preventing an illness in a predisposed person. Environmental toxins are abundant in our lives and frequently cause oxidative stress, which translates into the inability of the organism to effectively neutralize metabolic products of aerobic oxygenation, leading to different cellular and neuronal damages.”

• Integrative Therapies for Depression, Chpt 28 Integrative Approaches to

Perinatal Depression, Vesna Pirec, MD and Kelly Brogan MD, pg 424

The pathways, the testing and what to do

• HPA Axis Dysfunction and relevance for PMAD
• The Gut-Brain Axis
• The role of hormones and neurotransmittes
• Testing: Conventional, Functional, Interpreting
• Treatment Options
• Resources

Interconnected Pathways: HPA Axis and PMAD

• After 36 weeks of gestational age, estrogen and

progesterone levels drastically increase compared to the pre-pregnancy baseline and so does CRH which regulates the HPA axis. CRH also increases dramatically due to its secretion from the placenta so that its level may increase up to 100 times at 6-8 weeks prior to delivery.

• Thus, cortisol levels increase significantly.
• After birth, Estrogens, Progesterone, CRH and

Cortisol drop rapidly. For some women, this transition is not temporary and predispose them to PMAD.

HPA Axis

• The hypothalamus-pituitary-adrenal (HPA) axis

is the endocrine response to stressors producing adrenocorticotropic hormone (ACTH) from the pituitary gland with measurable changes in levels of plasma cortisol and salivary cortisol as produced in the adrenal cortex. The sympathetic-adrenal-medullary system produces epinephrine and norepinephrine and measurable changes in heart rate are seen.

• These systems work together to generate the

“stress response”.

Adrenal Dysfunction/ Adrenal Fatigue

• HPA axis dysfunction, or adrenal

dysfunction/adrenal fatigue is an alteration of the stress response resulting in a dysregulation

• f stress hormones – mainly an alteration in the

quantity and/or diurnal pattern of adrenal hormone secretion (cortisol and DHEA).

• Those experiencing HPA axis dysregulation

commonly complain of fatigue but may also experience sleep disruptions, weight changes, salt and/or sugar cravings, heightened allergies, anxiousness, nervousness, blood pressure alterations and numerous other symptoms

Gut-Brain Axis

• “Through several factors like microbial balance, gut barrier

integrity, immune stimulation, and altered systemic inflammatory load, the health of the gut is increasingly being seen as vital to mental health.” Integrative Therapies for Depression, Chapter

3, The Gut-Brain Axis, The Role of the Gut in Brain Health,. Greenblatt and Brogan.2016

• Population-based studies have shown that individuals

consuming a “traditional” diet consisting of vegetables, fruits, and lean, non-processed meats have a decreased likelihood of

• anxiety. Conversely, individuals consuming a “Western diet,”

high in processed meats, pizza, chocolates, sweets, soft drinks, margarine, French fries, beer, coffee, cake and ice cream, have been shown to have a significantly increased likelihood of anxiety.

• There appears to be a higher prevalence of SAD [Social Anxiety

Disorder] in individuals who have celiac disease or a sensitivity to gluten. Greater rates of anxiety are also seen in people suffering from irritable bowel syndrome (IBS), a condition that has also been linked to food allergies/sensitivities. Therefore, ruling out the possibility of food allergies and intolerances is a reasonable step to take when investigating underlying causes of SAD.” NDNR March 11, 2015

Serotonin and the gut

• “In the CNS, serotonin is involved primarily in

regulating emotions and stress, sleep, and

• appetite. In the GI tract, serotonin modulates

intestinal secretions, GI motility, and other critical functions. Changes to the gut microbiome have been shown to profoundly influence neurotransmission of serotonin in both the PNS and CNS. Probiotics could potentially improve CNS symptoms by promoting the production of free tryptophan, which then serves to increase the availability of serotonin.” THE MICROBIOTA-GUT-BRAIN AXIS: THE BIOLOGICAL & CLINICAL BASIS

FOR USING PROBIOTICS IN MENTAL HEALTH DISORDERS March 2, 2018 Jeremy Appleton, ND

Serotonin, tryptophan metabolism and the brain-gut-microbiome axis S.M. O’Mahonya,b,1,

• G. Clarkea,c,∗,1, Y.E. Borrea, T.G. Dinana,c, J.F. Cryana,b

Abstract Gut microbiota-brain axis is the two-way information communication network between intestinal microbiota and brain, whose composition includes gut microbes and their metabolite, intestinal tract, enteric nervous system and the sympathetic and parasympathetic branch of the autonomic nervous system, neural immune system, neuroendocrine system and central nervous system. Gut microbiota-brain axis has become one of the hotspots in the field of neuroscience. A growing body

• f evidences have revealed that gut microbes not only play an important role in maintaining normal

healthy homeostasis, but also can affect the individual’s mental health through inflammation, immune system, stress reaction and HPA axis. Dietary changes gut microbes associated with the risk of suffering from mood disorders. Probiotics supplementation not only plays an important role in the treatment of mental disease and regulating gut microbes, but also is a valuable therapy pathway for developing the new treatment methods to treat the brain disorder.

Hongxing Wang and Yuping Wang. “Gut Microbiota-Brain Axis and Mental Health”. EC Psychology and Psychiatry 1.2 (2016): 55-60.

Gut Microbiota-Brain Axis Gut microbiota-brain axis refers to two-way information flow network between gut microbiotia and brain, with its components including gut microbiota and their metabolic products, enteric nervous system, sympathetic and parasympathetic branch within autonomic nervous system, neural immune system, neuroendocrine system and central nervous system. Through this network, the brain affects gut movement, sensory and secretion function. On the contrary, viscera information from the gut also affects brain function. For example, incoming and

• utgoing branches of vagus nerve allow information to transfer in and out of gut. Activation of the

vagus nerve has anti-inflammatory effect. Positive effects of many gut microbiota and probiotics

• n brain function are dependent on the activity of vagus nerve. But other independent

mechanism also plays a role.

Hongxing Wang and Yuping Wang. “Gut Microbiota-Brain Axis and Mental Health”. EC Psychology and Psychiatry 1.2 (2016): 55-60.

Gut, inflammation and immune system Development of gut immune system depends on gut microbiota. Segmented filamentous bacterium in gut can restore the full functions of gut B and T lymphocytes. Bacteria communicate with the host through a variety of ways, and the receptor-TLRs of host cell plays a key role in this communication between bacteria and host. These receptors are the first step to produce cytokine reaction and is also widely distributed on neurons. So, intestinal epithelial cells can transport microbial composition or metabolites into inner environment, and the nervous system also interacts with these bacterial and viral components. The balance of gut microbiota may change the regulation of inflammatory response and this mechanism may also get involved in the regulation of emotion and behavior.

Hongxing Wang and Yuping Wang. “Gut Microbiota-Brain Axis and Mental Health”. EC Psychology and Psychiatry 1.2 (2016): 55-60.

Gut, stress reaction and HPA axis Depressive disorder involves inflammation and HPA. Gut microbiota affect the hypothalamus function via pro-inflammatory factors and anti-inflammatory factors. Among them, pro-inflammatory factors stimulate release of corticotrophin releasing hormone (CRH) which is the main polypeptide regulator

• f HPA axis. HPA stimulates the adrenal glands to release adreno-cortico-tropic-hormone (ACTH), and

ACTH is necessary component to the normal stress. However, over-expression of CRH promotes stress over-reaction. The system disorder is associated with depression and anxiety. The germ-free mice study indicates that the symbiotic microbiota plays a key role of healthy and balanced immune system. Damage of gut microbiota stimulates HPA activities to release stress hormones, and exogenous stress source direct stimulates HPA. At the same time, HPA also has devastating effects on gut

• microbiome. Stress leads to changes of intestinal motility and secretion function, which have negative

effect on regeneration ability of intestinal mucosa and gut microbiota. Stress reaction releases neuro- transmitters and pro-inflammatory factors, and these neuro-transmitters and pro-inflammatory factors affect intestinal physiology.

Hongxing Wang and Yuping Wang. “Gut Microbiota-Brain Axis and Mental Health”. EC Psychology and Psychiatry 1.2 (2016): 55- 60.

We are what we eat: what to consider about diet and exercise

• Nutrition and exercise matter;
• A history with using exercise to manage mental

health and stress is key to understand;

• Less than ideal diets high in carbohydrates,

processed foods, or if women are not eating regularly due to parenting an infant will impact health and mental health.

• A lack of actual nutrients and elevated stress

hormones means nutrient depletion. B vitamins, magnesium and quality protein are key to brain chemistry.

Stress, exercise and probiotics

• Studies are showing that bacterial/microbiome

imbalances are related to higher levels of perceived psychological stress as measured by standardized testing and that the introduction

• f probiotics resulted in decreased levels of

urinary cortisol levels.

• Increased levels of activity and exercise have

shown positive impact on the microbiome.

• We all need movement and exercise. But also

consider the new mother who is used to be very active and is now become sedentary as she cares for an impact. There is a real physiologic impact.

Steroid Hormones

Estrogen, Progesterone, DHEA, Testosterone

Estrogens

• Estrone (E1)-5-10% of total estrogen, greater than

10x weaker than E2

• Estradiol (E2)—The most abundant estrogen and

women’s brain estrogen receptors are specific to this form.

• Estriol (E3)—produced in large quantities in

pregnancy.

• There is vast evidence to prove women’s moods are

strongly linked to shifts in E levels.

• Multiple studies have shown rapid improvement in

PMAD with E2 treatment.

• Nearly every neural pathway is impacted by

estrogen.

Progesterone

• Produced by the ovaries, adrenal glands, and the

CNS.

• It exerts neuropsychological and neuroprotective

effects.

• It can increase anxiety and induce sleep.
• It can be low in women with a history of

miscarriages and that deficiency can translate into postpartum resulting in impacts on the HPA Axis and menstrual cycles.

• It is implicated in PMS and PMDD.
• In short, progesterone can be part of the solution

and part of the problem.

DHEA and Testosterone

• DHEA is the most abundant steroid hormone in

the body.

• In later stage HPA Axis dysfunction, DHEA levels

will drop along with the cortisol. It is an indicator of the degree of dysfunction.

• It is a precursor to testosterone and the

estrogens.

• It has been shown in studies to positively

impact depression in men and women.

• Testosterone-May or may not play a role in

PMAD but can have an impact on quality of life; imbalance with Estrogens can lead to acne.

Neurotransmitters

• Serotonin, GABA, Dopamine, Norepinephrine,

Epinephrine (Adrenaline), Glutamate, Glycine, Histamine and PEA

Serotonin

• SEROTONIN is a key neurotransmitter that is

involved in the regulation of sleep, appetite and

• aggression. Serotonin imbalance is a common

contributor to mood problems, and pharmacologic agents that alter serotonin levels are among the most commonly used class of drugs prescribed for anxiety and depression.

• High stress, insufficient nutrients, fluctuating

hormones and the use of stimulant medications or caffeine can all contribute to the depletion of serotonin over time. When serotonin is out of range, depression, anxiety, worry, obsessive thoughts and behaviors, carbohydrate cravings, PMS, difficulty with pain control, and sleep cycle disturbances can result

GABA

• GABA is the major inhibitory neurotransmitter

found in the CNS and is important for balancing excitatory action of other neurotransmitters. High levels can result in a ‘calming’ action that may contribute to sluggish energy, feelings of sedation, and foggy thinking. Low GABA levels are associated with dysregulation of the adrenal stress response. Without the inhibiting function

• f GABA, people can become anxious and/or

reactive and those symptoms can extend from poor impulse control to seizure disorders. Alcohol as well as benzodiazepine drugs act on GABA receptors and imitate the effects of GABA.

Dopamine

• DOPAMINE is largely responsible for regulating the pleasure

reward pathway, memory and motor control. Its creates both inhibitory and excitatory action depending on the dopaminergic receptor it binds to. Memory issues are common with both elevations and depressions in dopamine levels. Caffeine and

• ther stimulants, such as medications for ADD/ADHD, often

improve focus by increasing dopamine release, although continual stimulation of this release can deplete dopamine over time.

• Common symptoms associated with low dopamine levels

include loss of motor control, cravings, compulsions, loss of satisfaction and addictive behaviors including: drug and alcohol use, smoking cigarettes, gambling, and overeating. These actions often result from an unconscious attempt to self- medicate, looking for the satisfaction that is not occurring naturally in the body.

• Elevated dopamine levels may contribute to hyperactivity or

anxiety and have been observed in patients with schizophrenia. High dopamine may also be related to autism, mood swings, psychosis and attention disorders. L-DOPA is a precursor to dopamine, and is used therapeutically for low dopamine conditions such as Parkinson’s disease. These medications can cause elevations in dopamine.

Norepinephrine

• NOREPINEPHRINE, also called noradrenaline, is an

excitatory neurotransmitter produced in the CNS, as well as a stress hormone produced in the adrenal

• medulla. Norepinephrine is involved in a wide

variety of actions including attention, focus, regulating heart rate, affecting blood flow, and suppressing inflammation. Involved in arousal, it prepares the body for action by relaying messages in the sympathetic nervous system as part of the autonomic nervous system’s fight-or-flight response. High levels of norepinephrine are often linked to anxiety, stress, elevated blood pressure, and hyperactivity, whereas low levels are associated with lack of energy, focus, and motivation.

Epinephrine

• EPINEPHRINE, often better known as adrenaline, is

synthesized from norepinephrine in both the CNS and the adrenal medulla. Much like norepinephrine, this excitatory neurotransmitter helps regulate muscle contraction, heart rate, glycogen breakdown, blood pressure and more, and is heavily involved in a stress response. Elevated levels of epinephrine are

• ften associated with hyperactivity, ADHD, anxiety,

sleep issues, and low adrenal function. Over time, chronic stress and stimulation can deplete epinephrine stores leading to difficulty concentrating, fatigue, depression, insufficient cortisol production, chronic stress, poor recovery from illness, dizziness and more.

Glutamate and Glycine

• GLUTAMATE is an excitatory neurotransmitter and is considered to

be the most abundant neurotransmitter in the nervous system. Glutamate is involved in most aspects of normal brain function including cognition, memory and learning, although high levels of glutamate can cause excitotoxicity, a process where nerve cells are damaged by excessive stimulation. Elevated glutamate levels are commonly associated with panic attacks, anxiety, difficulty concentrating, OCD and depression, whereas low glutamate levels may result in agitation, memory loss, sleeplessness, low energy levels and depression.

• GLYCINE is inhibitory and plays dual roles as both a

neurotransmitter and an amino acid that serves as a building block

• f proteins. Glycine improves sleep quality, calms aggression, and

serves as an anti-inflammatory agent. Glycine has been shown to boost mental performance and memory. Elevated glycine levels may be associated with compromised cognitive processing. Low levels of glycine may contribute to poor sleep, poor cognitive function, and issues with memory.

Histamine and PEA

• HISTAMINE is an excitatory neurotransmitter involved in the

sleep/wake cycle and inflammatory response. Histamine plays a dual role in the body as both a neurotransmitter and immunomodulator increasing metabolism, promoting wakefulness, attention, circadian rhythms, learning, and memory. Elevated levels may be associated with allergy-like symptoms, gastro-intestinal concerns, and inflammation. Elevated histamine can contribute to

• insomnia. Low histamine may affect digestion and appetite control,

learning, memory, and mood, and may result in drowsiness.

• PEA (PHENETHYLAMINE) promotes energy, elevates mood,

regulates attention and aggression, and serves as a biomarker for

• ADHD. Elevated PEA may contribute to anxiety, with very high levels

having amphetamine-like effects. Elevated PEA levels may be associated with higher cortisol levels. Low PEA may be associated with ADHD, depression, Parkinson’s disease and bipolar disorder.

Testing Options

• Conventional vs Functional
• Blood, Urine and Saliva
• Interpretation and Perinatal Considerations

Conventional vs Functional

• Conventional testing generally refers to serum testing vs functional

which can also include saliva or urine.

• Functional testing refers to testing that seeks to show what might

be called sub-clinical levels or which utilizes methodology not considered conventional or standard of care.

• Functional also refers to the ranges used to interpret lab results.
• Functional testing includes urine hormone and neurotransmitter

testing, for example, and salivary hormones. It also includes digestive health stool testing which measures a far more comprehensive set of markers than conventional stool testing.

• With the perinatal population, you will need to interpret lab values

in the context of the ssx she is presenting with, pre-pregnancy values if they exist, pregnancy values if within a few weeks to a few months of birth, and in the context of her menstrual cycle if cycles have resumed. If she is taking hormonal contraception or psychoactive medications, those too much be taken into account.

Testing

• Look for extreme values within the normal

ranges, use third trimester ranges for comparison, compare with pre-pregnancy levels if possible. Listen to her symptoms, take a good history and then use that to guide your interpretation.

• Medicine is a practice, there is art to treating

the whole person.

Blood, Saliva and Urine

• This choice may be dictated by time or financial
• resources. Insurance sometimes covers these

tests.

• Blood, urine and saliva each provide unique

information.

• Establish a relationship with a lab company or

another practitioner who can help you with interpreting labs. Functional lab companies have staff dedicated to helping clinicians with interpretation.

• If you are going to consider doing testing other

than conventional serum testing, you will need to have test kits on hand.

Blood (Serum) Testing

• Use for the basics, and thyroid, consider other

testing methods for other hormones.

• It provides a snap shot which will not show daily

fluctuations and with some hormones that is critical

• Generally shows only total hormones, not free
• r unbound.
• Should at least run a SHBG to assess this binding

protein to understand free vs total hormones.

• And, if it is all you can do, then get the levels,

but you have to interpret in the context of her symptoms.

Blood Testing- the basics

• CMP, lipids, CBC with auto diff—look for what

is in the high or low end of the ranges.

• Ferritin, Iron, and TIBC –impacts energy levels,

thyroid and dopamine production.

• HCRP-high sensitivity C reactive protein—

inflammatory marker.

• Thyroid-TSH, Free T3 and T4, Reverse T3, Anti-

thyroid anti-bodies, Anti-peroxidase antibody

• Consider Celiac testing, pregnancy is a known

stressor that can trigger the onset of active celiac disease

Copper, consider in multiparas women and PPP

• Copper levels rise with pregnancy and should drop rapidly

postpartum; previous pregnancies can result in rising levels in women who don’t clear it well. Excess copper in the brain alters the balance of dopamine and norepinephrine which both regulate mood. Copper toxicity with elevated estrogen (such as with HRT or oral contraceptives) can further complicate the picture. Ideally, run serum copper and ceruloplasmin to get a free copper level.

• Total serum copper normal range = 10-22 umol/L (63.7-140

ug/dL)

• Total serum copper high-normal = 17.5 – 20.0 umol/L (110 –

125 ug/dL)

• Total serum copper high = >20 umol/L (125 ug/dL)
• Percentage free copper above 20% is classified as elevated.

Saliva Testing

• Has been shown to indicate higher than

physiological levels of hormones in people using transdermal hormones.

• Saliva testing cannot show metabolites, which

can be very helpful in understanding complex cases.

• Any oral supplementation will skew results and

cross-reactivity occurs.

• In the context of postpartum women, it is best

for circadian patters for free cortisol. Often paired with DHEA which can also be useful.

• Also helpful for cycle mapping.

Urine Testing

• When to consider and not to consider.
• Hormones
• 24 hr urine
• DUTCH-Dried Urine Testing for

Comprehensive Testing

• Neurotransmitters
• Urine testing is easy and provides good

insight into overall levels

Urine Testing: 24-hr collection and DUTCH

• 24-hr urine is a reliable method of assessing active

hormones and their metabolites (and metabolites have physiologic activity).

• Show total daily production, anabolic to catabolic

activity, all sex and adrenal hormones, and some labs will also do a Free T3 and Free T4 which can be used with serum testing to further evaluate complex cases.

• Are done at home which makes them convenient

and can capture a ideally less stressful or more representative day in a woman’s life.

• Gives greater information to assess low adrenal

function status as an element of or reason for depressive symptom picture.

Hormone Testing: Cortisol, DHEA, Estrone, Estradiol, Progesterone

• Salivary
• 4-point cortisol (serum AM cortisol is NOT helpful

except in severe cases)

• Estrogens, Progesterone, however best for cycle

mapping

• Urine
• Steroid hormones (if available, can be more useful

than blood levels due to metabolites and levels of free hormone, vs bound)

• Melatonin (measured during the night)
• Neurotransmitters (Serotonin, GABA, Epinephrine,

Norepinephrine, Dopamine); no need to stop any psychoactive medications for this testing; supplements may interfere, follow lab recommendations.

Neurotransmitter Levels

• Urine testing provides indirect information

regarding levels through analytes in urine.

• Some are produced in the brain and cross the

BBB, and some are produced in the periphery. The kidneys filter them into the urine. Some measurements represent what is in the CNS and for others it represents what is made in the periphery.

• Overall it represents the systemic

neurotransmitter tone and allows guidance for treatment decisions.

Treatment Options

• Food-Diet—Let food be your medicine and medicine be your food.
• Lifestyle-movement and mindfulness
• Getting outside
• Walking
• Change of scenery
• Mind-body practices
• Talking, connecting, acknowledging—take away the guilt. Yes they

are tired, its OK to say it, they aren’t whining and the aren’t weak.

• HRT
• Not really “replacement”. Is about augmenting current levels,

it is about physiologic dosing and bioidentical composition.

• Rx—short term, long term, complementary with other approaches
• Supplements

Nutrients

• D3—Vitamin D Council
• https://www.vitamindcouncil.org/i-tested-

my-vitamin-d-level-what-do-my-results- mean/

• Folate vs folic acid
• Magnesium—chelates are more absorbable.

Some combined with B6, B12, methylfolate, and malic acid to improve absorption.

• B’s—B complex, verify folate, not folic acid.
• PUFAs—fish oil, omega 3-6-9 blends
• Protein, Protein, Protein—meat, plant, powders

Vitamin D Deficiency

• People with darker skin. People who spend a lot of time

indoors during the day. For example, if you’re housebound, work nights or are in hospital for a long time.

• People who cover their skin all of the time. For example, if

you wear sunscreen or if your skin is covered with clothes.

• People that live in the North of the United States or Canada.
• Older people have thinner skin than younger people and this

may mean that they can’t produce as much vitamin D.

• Infants that are breastfed and aren’t given a vitamin D
• supplement. If you’re feeding your baby on breast milk

alone, and you don’t give your baby a vitamin D supplement

• r take a supplement yourself, your baby is more likely to be

deficient in vitamin D.

• Pregnant women.
• People who are very overweight (obese)

Food

• Vegetables, Fruit and Protein-
• Meat or protein powders
• Organic if possible—EWG.org
• Fats
• Water and electrolytes
• Limit grains, especially refined
• Caution with dairy
• Limit the refined sugar
• Limit the coffee or soda/caffeine
• Limit nuts and legumes, they can just become

to dominant

Food, Mood, and the value of non-GMO and

• rganic food

Glyphosate has been linked to the depletion of the serotonin precursor,

• tryptophan. It has also been shown to

negatively impact the gut micro biome (gut bugs) which then impacts the absorption of nutrients and thus negatively impacts the formation of elements necessary and critical for maintaining mood stability, such as

• neurotransmitters. This harm to cell-to-

cell communication is referred to as endocrine-disruption.

Samsel, A and Seneff S. 2013. Glyphosate’s suppression of cytochrome P450 enzymes and amino acid biosynthesis by the gut microbiome: Pathways to modern

• diseases. Entropy. 15(4):1416-1463.

Food, Mood, Deficiencies and “sugar”

• Sugar isn’t just sugar.
• HFCS (high-fructose corn syrup, natural corn syrup,

isolated fructose, maize syrup, glucose/fructose syrup and tapioca syrup) is a damaging sugar by the nature of how it impacts your gut enzymes, is made from crops treated with glyphosate, and is processed in the liver and turned into fat.

• Fats, trans fats, hydrogenated oils—”Natural” fats

are generally healthier.

• As study done in 2000 showed that pregnant

women in the US tend to consume inadequate levels of essential nutrients such as calcium, magnesium, iron, zinc, vitamin D, and folate.

Food and Diet Strategies

• Rice Cooker or One Pot
• Frozen vegetables and fruit
• Prepare ahead, like hard boiled eggs
• Soup, miso, canned—it needs to be easy.
• Bone broth—store bought, in powders
• Greens powders
• There needs to be choice and it needs to be

easy, whatever these mean for individual women.

Probiotic supplementation and safety

• https://ndnr.com/pain-medicine/probiotics-and-gastrointestinal-

health/

• Other resources
• Do your research, make specific recommendations.

Melatonin

• Melatonin is a normal component of human milk which is

synthesized from the amino acid tryptophan.

• A study with lactating women showed laughter raised

melatonin levels.

• Mothers are recommended to nurse in the dark at night so

preserve melatonin levels and help preserve sleep rhythms in infants.

• “In studies in which exogenous oral melatonin was given to

women, the resulting serum melatonin was variable, but peak serum concentrations ranged from 1.1 to 2.6 mcg/L for each 1 mg administered. This would result in an average increase in breastmilk melatonin concentration from 0.4 to 1 mcg/L for each 1 mg administered to the mother… resulting concentrations would be higher than the typical physiologic peak milk concentrations of 0.02 mcg/L, it would present a considerably lower dose to the infant than the 10 mg/kg dosages of melatonin that have been safely administered to neonates in clinical studies.”

• Delivery matters, oral doses are approx. 15% bioavailable.

Sublingual delivery allows for greater bioavailability. Ideal dosing, sublingual 1-3 mg at bedtime.

Homocysteine and Serotonin: Association with Postpartum Depression

• Postpartum depression (PPD) is a disorder of multifactorial origin with significant consequences on both

maternal and child health. One of the biological factors implicated is perturbed methionine–homocysteine

• metabolism. Since this metabolic pathway plays a significant role in myelination of nerve fibers, the growth

and development of the child would also be adversely affected. We carried out this study in 103 women (58 with PPD and 45 without PPD) who delivered their child in our institute from December 2010 to November

• 2011. The study group was evaluated for PPD using Edinburgh postnatal depression scale with a cut-off score
• f 10. Assessment of fetal well being was done by APGAR score assessed immediately after birth. Serum folic

acid, vitamin B12, homocysteine and serotonin was done by ELISA. We found significantly elevated levels of homocysteine in women with PPD as compared to those without PPD, both at 24–48 h as well as six weeks after delivery, although no associations were found with folate and vitamin B12 levels. Also, there was a significant negative correlation between serum homocysteine and serotonin levels in the postpartum depression group with a significant negative correlation between homocysteine and serotonin. Our study showed a significantly lower APGAR score in the infants born to mothers with PPD. Our study also shows that homocysteinemia is associated with PPD whether at the first week or sixth week, while low serum serotonin may play a role in depression during the first week, but may not have a role in depression status at the sixth week. Also, PPD in the mother is related to a low APGAR score in infants born to these mothers emphasizing the significance of both mental as well as nutritional status of the mother.

• (http://dx.doi.org/10.1016/j.ajp.2013.05.007) Asian Journal of Psychiatry

Fish Oil

• Anti-inflammatory which addresses IL-1 and H-

CRP

• No GI irritation as Rx and OTC medications can

cause.

• Loose stools and belching common side effects.
• These side effects can be ameliorated by taking

frozen or with a digestive enzyme or apple cider vinegar.

• 1200-2400 mg EPA/DHA typical and safe

starting dose.

J Affect Disord. 2018 May 16;238:47-61. doi: 10.1016/j.jad.2018.05.018. [Epub ahead of print]

Omega-3 polyunsaturated fatty acid supplementation in prevention and treatment of maternal depression: Putative mechanism and recommendation.

Omega-3 fatty acid deficiency, due to inadequate intake, fast depletion during pregnancy and lactation, is one of the risk factors of PPD. Associations between neuroinflammation (elevated pro-inflammatory cytokines) and aberrant neurotransmission (low serotonergic transmission activity) and risk of PPD have also been reported by numerous studies. Supplementation with eicosapentaenoic acid (EPA)-rich oil can effectively reduce depression during pregnancy and PPD after childbirth. Long term treatment with docosahexaenoic acid (DHA)-rich oil can be effective in reducing the risk of PPD in healthy women, but not in lactating

• women. Supplementation of DHA-rich oil to women begun at pregnancy and

continued after childbirth exerts no beneficial effect on depression.

Amino Acid Support for Neurotransmitters

• L-tryptophan
• 5 HTP
• L-tyrosine
• GABA and phenibut
• L-theanine

Magnesium and other minerals

• Magnesium, types for better absorption
• Companion nutrients
• Electrolytes and electrolyte supplementation
• Calcium
• Selenium

Herbal Medicine

• Adaptogens
• Anti Inflammatory
• Nervine
• Phytohormonal

Adaptogens

• Herbs used to strengthen the bodies immune

response and help the body cope with physical and mental stress.

• They are used as tonics and their MOA is unlike

pharmaceuticals in that they do not target specific organs or systems.

• They impact the HPA axis.

Rhodiola rosea

• Effects upon the Central Nervous System:
• The systematic study of the pharmacological effects of R.

rosea, begun in 1965, found that small and medium doses had a simulating effect and in contrast, larger doses were found to have more sedative effects.

• Overall, in small and medium doses, R. rosea stimulated

norepinephrine (NE), dopamine (DA), serotonin (5-HT), and nicotinic cholinergic effects in the central nervous system (CNS). It also enhanced the effects of these neurotransmitters on the brain by increasing the permeability of the blood brain barrier to precursors of DA and 5-HT.

• Rhodiola rosea: A Phytomedicinal Overview Richard P. Brown, Patricia L. Gerbarg,

Zakir Ramazanov HerbalGram. 2002; 56:40-52 American Botanical Council

Anti- Inflammatories

• Turmeric/Curcuma
• Others not fully discussed today but for which

there is extensive support:

• White Willow/Salix Alba
• Green Tea/Camella Sinensis
• Boswellia/Frankenscence
• Rosemary
• Resveretrol
• Ginger/Zingiber

Turmeric/Curcumin

Herbal Nervines

• Eschscholzia/California poppy
• Matricaria/chamomile
• Cratageus/hawthorne
• Lavenduala/lavender
• Melissa off./Lemon Balm
• Leonarus cardiac/motherwort
• Avena Sativa/oat straw
• Passiflora/passionflower
• Scutellaria/skullcap
• Hypericum/st johns wort
• Valeriana/valerian

Lavender

Topical Lavender Cream Alleviates Anxiety, Stress, and Depression in Pregnant Women

• The authors conclude that lavender cream…for 8 weeks

significantly improved anxiety, stress, and depression in pregnant women. They recommend further studies to assess the effect of lavender on pregnant women with psychological disorders and women with postpartum

• depression. It is important to note that this study applies

to the topical use of lavender essential oil.

• Effati-Daryani F, Mohammad-Alizadeh-Charandabi S, Mirghafourvand M, Taghizadeh M, Mohammadi A. Effect of

lavender cream with or without foot-bath on anxiety, stress and depression in pregnancy: a randomized placebo- controlled trial. J Caring Sci. 2015;4(1):63-73.

Lavender

Melissa Off./ Lemon balm

• Nervine and anti-inflammatory
• A number of clinical studies have shown various positive
• utcomes when M. officinalis is used in combination with
• ther herbs. These include the following: promoting sleep

(with valerian);

• treating restlessness in children (with valerian);
• stimulating alpha1 electrical brain activity (with lavender,

hops, and oat);

• treating infantile colic (with German chamomile) and fennel;
• reducing oxidative stress (with cinnamon) and laboratory-

induced stress (with valerian);

• treating dyspepsia;
• treating abdominal pain and bloating in patients with

irritable bowel syndrome (with spearmint and coriander).

Phytohormonal

• Flax Seeds
• Sesame Seeds
• Soy

Phyto- hormonal

• Phyto-estrogens: The term phytoestrogen is used loosely

in the herbal community. There is no current agreed upon definition for this term. Basically the term is used for any plant that: 1) Has one or more constituents with similar chemical or anatomical structure to estrogen. 2) Is changed into a similar compound in vivo. 3) Clinically produces effects that the clinician would expect from giving exogenous estrogens.

• Phyto-progesterones: Some herbs contain diosgenin,

sarsasapogenin or other related compounds that can be manipulated chemically in laboratories to create progesterone as well as estrone, testoster- 8 and adrenocortical hormones. Some people have thought these herbs have had a progesterone type action in the

• body. It appears the body can not turn these constituents

into progesterone.

Herbal Neurotransmitter Influence

• St John’s Wort/Hypericum
• Saffron

St John’s Wort/ Hypericum

• St. John's wort (Hypericum perforatum) has

been used to treat depression, as well as digestive disorders, wound healing, fevers, and snakebites, for centuries. In 1984, German physicians had SJW approved by Commission E as a prescription medicine for mild-to moderate

• depression. Almost 10% of women experience

depression during pregnancy and women with a history of depression are at risk for worsening

• f mood during pregnancy.
• American Botanical Council

Saffron Comparable to Fluoxetine in the Treatment of Postpartum Depression

• At study end, 18.8% of the saffron group and 21.9% of the fluoxetine group were

remitters; there was no significant difference between the two groups. A total of 40.6% of the saffron group and 50% of the fluoxetine group were responders; there was no significant difference between the groups. All patients had at least a partial response, and there was no significant difference between the two groups in HDRS score reduction from baseline. Patients in the fluoxetine group had a greater frequency of headache, dry mouth, daytime drowsiness, constipation, and sweating, but there was no significant difference between groups in the incidence of these adverse effects

• Kashani L, Eslatmanesh S, Saedi N, et al. Comparison of saffron versus fluoxetine in treatment of mild to moderate postpartum depression: a double-blind,

randomized clinical trial. Pharmacopsychiatry. 2017;50(2):64-68.

Acupuncture

• Effectiveness of acupuncture in postpartum

depression: a systematic review and meta- analysis.

• Li S1,2, Zhong W3, Peng W4, Jiang G1. Acupunct Med. 2018 Jun
• 15. pii: acupmed-2017-011530. doi: 10.1136/acupmed-2017-

011530.

Supplement Choice

• Quality matters and it costs manufactures to insure it.
• Know your companies.
• Ask questions.
• Build relationships.
• If your plan doesn’t work, it might be dose or quality dependent.

Resources

• Integrative Therapies for Depression: Refining Models for

Assessment, Treatment, and Prevention. James Greenblatt, MD and Kelly Brogan, MD

• Women’s International Pharmacy
• Functional Medicine Practitioners and Naturopathic Physicians
• Probiotics: https://ndnr.com/mindbody/the-microbiota-gut-brain-axis-the-biological-clinical-basis-for-

using-probiotics-in-mental-health-disorders/

• EWG Clean 15 and Dirty Dozen
• Women’s Herbs, Dr. Sharol Tilgner, http://www.herbaltransitions.com/Newsletters