Hormonal Moodchanges in women with ADHD - J J Sandra Kooij Psychiater, PsyQ Den Haag Associate professor psychiatrie, VUMc 50e ADHD Netwerk ...
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Hormonal Moodchanges in women with ADHD J J Sandra Kooij Psychiater, PsyQ Den Haag Associate professor psychiatrie, VUMc 50e ADHD Netwerk Meeting 14 mrt 2019
Disclosure belangen spreker
Sandra Kooij
14 maart 2019
(potentiële) belangenverstrengeling Geen
Voor bijeenkomst mogelijk relevante
relaties met bedrijven
Sponsoring of onderzoeksgeld
Honorarium of andere (financiële)
vergoeding
Aandeelhouder Geen
Andere relatie, namelijk …
Women & • Women have twice the risk for depression compared to
men
mood • Women have a fivefold increased risk for seasonal
depression
Goldstein ea 2019; Wirtz-Justice 2018
Mood disorders in ADHD
• In 55% lifetime diagnosis of depression (n=115)
• In 27% seasonal depression
72.9% of females and 52.2% of males
Amons ea 2006
The prevalence of ADHD in
Mood Disorders is:
Prevalence of Adult
ADHD: 15-20% in
bipolar disorder
One in 5 8% in
mood disorder depression
patients
22% in Fayyad ea 2017
dysthymia
NESDA study: N=2053, 3 groups:
HC /Depression /Depression + Anxiety:
ADHD prevalence :
• 0.4% in healthy controls
ADHD • 5.7% in remitted depression
prevalence • 22.1% in current depression (OR=4.5)
increases with
ADHD symptoms were significantly increased among:
severity and • Severe depression (OR=6.8),
chronicity of • Chronic depression (OR=3.8),
Depression • Earlier age of onset of depressive symptoms (OR=1.5),
• Comorbid anxiety disorders (OR=3.4).
Conclusion:
ADHD symptom rates increased across clinical stages of
depression,
up to 22.5% in chronic depression
Bron 2016
Women with ADHD report
Clinical severe premenstrual mood
experience: instability &
increased severity of ADHD:
Premenstrual
mood problems Inattention,
inability to Impulsivity
Irritability and
anger
Depressed
mood
focus outbursts
in women with Symptoms recur
Increased
ADHD sleep
disturbance
Anxiety, panic
attacks
Suicidal
thoughts
next
premenstrual
period
Efficacy of ADHD
medication = DANGER WEEK !!
seems reduced
Besides premenstrual, also postnatal
& perimenopausal mood changes
• From clinical experience, postnatal depression and perimenopausal
depression also seem more severe and more frequent than normal
• But no data so far
• Research question:
Are hormonal mood problems indeed more severe and
more frequent in women with ADHD compared to women
without?
- PMS in 20-30% of women in general
- PMDD in 3-8%
Hylan 1999; Halbreich 2003
1st Pilot study 2016 • Dutch ADHDWoman conference 2016 • N=200 participants Self report questionnaire on mood changes to the level of clinical depression during: • the menstrual cycle : premenstrual dysphoric disorder (PMDD) (=more severe than PMS) • the postnatal period : postpartum depression (PPD) • the perimenopausal period
Neuropsychiatric Interview Plus version
5.0 (M.I.N.I. Plus) for Premenstrual
Dysphoric Disorder (PMDD)
Questionnaire
Edinburgh Postnatal Depression Scale
consisted of (EPDS) for life-time Post Partum
Depression (PPD)
validated
scales, Greene Climacteric Scale (GCS) for
adapted for Perimenopausal Mood Symptoms
selfreport
Munich Chronotype Questionnaire
(MCTQ) for sleep characteristicsADHDWoman 2016
Women with ADHD were asked to vote for their most urgent question to science: Highest votes for hormonal mood changes during the lifecycle
Danger!
• N=200 women
• No clinical diagnoses but ‘indication for PMDD’
• Comparing prevalences of possible PMDD
between women with and without ADHD
Results Results:
• Significantly more ADHD woman had an
indication for PMDD, PPD and perimenopausal
depression compared to controlsReplication • Outpatient Clinic for Adult ADHD at PsyQ, the
study Hague, the Netherlands
• N=209 women with diagnosed ADHD
• Age 18-71 years
Women • Same questionnaires
• Expectation: lower prevalences compared to 1st
diagnosed pilot study in participants ADHDWomen
with ADHD at conference
PsyQSummary
• Confirmation of increased PMDD, PPD and perimenopausal mood symptoms in
ADHD women in a clinical sample
• Three periods of hormonal changes
• Why are these episodes more severe in ADHD?
• How can we treat them better?
Dorani in preparationWhy?
Cycle often exclusion
Little research on criterion due to
No studies in women
hormonal influences on changing hormonal
with ADHD
the brain in women levels, more research in
males• Low dopamine levels in certain brain regions in ADHD
• Estrogen & progesteron modulate neurotransmitters like
serotonin and dopamine
• Sex hormones have been implicated in neurite outgrowth,
synaptogenesis, dendritic branching, myelination, and
other important mechanisms of neural plasticity
• Sex hormones interact with BDNF, oxidative stress and
How? inflammation pathways
• Ovarian hormones also directly effect the brain regarding
cognition, memory, learning and emotion
• Estrogen influences blood flow and metabolic rate of
glucose, and this changes during the cycle
• Hormonal changes may influence reward-related
motivation, impulsivity, and temporal decision-making
Haimov-Kochman 2014; Volkow 2009; Barth 2015; Diekhof 2015; Soares & Zitek
2008; Fanselov & Dong 2010; Hines 2010; Reiman 1996; Sacher 2014; Frey 2014;
Song 2019Estrogen and Progesteron x Dopamine
Estrogen:
• increases dopamine synthesis and decreases its degradation, reuptake, and
recapture
• upregulates dopaminergic receptors
• effect of estrogen esp. in the PFC, a region with high amounts of estrogen
• It impacts working memory function by affecting dopamine levels.
• effects on limbic regions (such as the nucleus accumbens), estrogen influences
emotional and motivational behaviors
Progesteron:
• effect of progesterone on dopaminergic systems depends primarily on the
previous priming by estrogen
Giannini 2018Hypothesis in ADHD women
• Low prefrontal dopamine in ADHD x low estrogen in the luteal phase
reinforce each other:
• 2x low levels of dopamine (enhancement): you’re stuck
• Explaining increased mood instability and increased ADHD severity …
Jacobs & d’Esposito 2011; Song 2019• Study in 32 normal women,
18-22 years of age, regular
cycle
• Roberts 2018
Reproductive • Relationships between
estrogen, (E) progesteron
Steroids and (P), testosteron (T) and daily
ADHD symptoms
ADHD • Higher impulsivity and
inattention with decreased
Symptoms E and increased P/T
Across the • Higher inattention in luteal
phase of cycle
Menstrual
Cycle • NB Stimulant response may
also differ across the cycleEffect of estradiol on cognition has been inconsistent,
probably due to differences in baseline dopamine levels in
individuals
Estrogen • Study on the relationship between estrogen and dopamine
shapes related performance on working memory during the cycle
• 79 normal women
dopamine- • Comt gene (Val/Met)
dependent • 2x in cycle:
• fMRI while working memory and emotional task
cognitive • Estradiol
processes Result: Estrogen acts as ‘dopamine-agonist’, depending on
Comt genotype
Jacobs & ‘d Esposito 2011So far these treatments have been
shown effective for PMDD in general:
• Contraceptives, continuously (without
stopweek) (esp. for somatic Sx)
• Anti-depressants (SSRIs) (for mood Sx)
Treatment
Not proven effective yet: Light therapy
options in PMDD
Probably in ADHD women also:
• Increased dosage of ADHD meds in week
before period (but no data!)
Ryu 2015• SSRI’s
Treatment of • Estradiol (sublingual, transdermal)
PPD
Gregoire 1996; Ahokas 2001• Low adrenal androgen and • Barrett-Connor 1999;
Treatment dehydroepiandrosterone Santoro 2005; Schmidt
options in (DHEA) in menopausal
depression; Tx with DHEA 2005
climacteric effective
• With estradiol suppletion
depression less depression • Cohen 2006; Soares 2006
• SSRIs / SNRI
• Combined SSRI + estradiol • Soares & Zitek 2008Next step:
MoodCycles study in ADHD women
MoodCycles:
Measuring mood and ADHD symptoms during the
cycle, as well as cognitive performance, genes,
hormone levels, sleep, emotional lability, in ADHD
women compared to controls.
Twice in one cycle:
• fMRI performance during cognitive and emotional
task
• Qb test
• Hormone levels
• Genes
• Questionnaires on mood, sleep, & ADHDHowever, the Moodcycles study was denied funding
• Non-profit organisation founded by
Sandra Kooij in 2014
• To facilitate ADHD research based on
patients priorities, using
questionnaires and online votes
• Funding by patients, researchers and
their networks who benefit from the
results
• Empowerment of people with ADHD
• 4 studies partly funded
• Prioritised by women with ADHD:
MoodCycles studyWebinar ADHD Women’s Palooza, Feb 16
End of ADHDFund in 2018
Patient organisations
worldwide did not
Little or no donations succeed to campaign
for their preferred
researchNevertheless: the MoodCycles study will start Because ADHD women need it Because we got support from PsyQ & ADHD Netwerk! Study sample has been reduced and some measures are left out • Medical Ethical approval ongoing • Start in May-June 2019
DISCUSSION
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