A few days ago, I was glad to read the following study which supports the hypothesis I plan to present at the upcoming Days of Molecular Medicine Conference in Sweden.

In a study published this month in the Journal of Clinical Psychiatry, researchers at the University of Salt Lake City in Utah, reported that although boys with attention-deficit hyperactivity disorder (ADHD) appear to be more impulsive and troubled than their female counterparts, in adulthood the condition seems to have more impact in women than in men.[1]

“We found that adult women with ADHD frequently have high levels of emotional symptoms as well as the cognitive problems found in ADHD,” Dr. Frederick W. Reimherr, head of the study, told Reuters Health.

Reimherr and colleagues analyzed data collected from two clinical trials of the medication Strattera, known generically as atomoxetine, in adults with ADHD. In all, the researchers collected information on ADHD symptoms and treatment response in 515 individuals, about a third of whom were women.

More women (75 percent) had combined-type ADHD than did men (62 percent). Women also had higher scores on measures of anxiety and depression and had more sleep problems. Poor temper control, mood volatility, and emotional over-reactivity were more common in women (37 percent) than in men (29 percent). In contrast to results of studies involving children, “women were more impaired than men on ADHD scales in our study,” the investigators conclude.

The study supports my hypothesis, namely because the researchers found that in childhood – a time before puberty and hormonal development – boys actually appeared to be more troubled by the symptoms of ADHD then their female counterparts.

But after puberty, as both women and men reached adulthood, this situation completely reversed. Later in life it was women, rather than men, who started to suffer from more severe symptoms of ADHD. This strongly suggests that differences in hormonal expression between the sexes could explain why adult women tend become more susceptible to the Th1 pathogens that cause numerous forms of cognitive dysfunction. As described in my presentation, the nuclear receptors – such as the androgen, progesterone, and estrogen receptors – fluctuate during the female menstrual cycle and during pregnancy. This is in contrast to males, in which the activity of the receptors remains fairly constant.

Since the nuclear receptors transcribe antimicrobial peptides (AMPs) that are able to kill the Th1 pathogens, the fact that their expression fluctuates in women may allow for periods when the Th1 pathogens can more easily infect a variety of tissues including those of the brain. Furthermore, since the Vitamin D Receptor is expressed in the cycling endometrium, women have more VDRs then men. Thus, they are disproportionately affected by the negative effects of VDR blockage, blockage that again leads to a decrease in AMP production and a more hospitable environment for pathogens.

I would love to see a research team (or many research teams!) track rates of Th1 disease in childhood, middle age, and then during the years after women go through menopause. My guess is that the rate of certain Th1 diseases that affect more women then men during early adulthood might even out after women become postmenopausal – a time when menstruation and pregnancy no longer cause fluctuations in nuclear receptor expression.

REFERENCES

  1. Robison, Reid J et al. 2008.
    “Gender differences in 2 clinical trials of adults with attention-deficit/hyperactivity disorder: a retrospective data analysis.” The Journal of clinical psychiatry 69(2):213-21. []