By Michael A. Keys, MD

Dr. Keys is a geriatric psychiatrist, Adjunct Associate Clinical Professor of Psychiatry at the University of Cincinnati College of Medicine, and Director of The Senior Health Program at the Lindner Center of HOPE, Mason, Ohio.

It may be taboo to suggest that women and men age differently in terms of relative risk of developing significant mental health issues.   But you might be surprised to learn that female gender is one of the most significant risk factors in developing the essential diagnoses of geriatric psychiatry, namely depression, Alzheimer’s disease (AD), and late-onset schizophrenia. In fact, women make up the majority of patients seen by geriatric mental health providers.  As such an important aspect of women’s health, the question is why are women more vulnerable to these late life issues?

Common answers are that women live longer and are more likely to seek treatment.   In terms of depression and anxiety disorders, the World Health Organization postulates that women are more likely to experience sexual abuse, gender based violence, socioeconomic disadvantage, low income and income inequality, subordinate social status and rank, and responsibility for the care of others.

But when we look at large population studies and control for factors such as longevity, the findings are still striking.  For example, depression, the most common and important mental health cause for disability, is nearly twice as common and more persistent in women.

While it is easy to understand socioeconomic factors contributing to depression, these issues are more difficult to understand as contributory to an illness like Alzheimer’s disease.  It is generally recognized that Alzheimer’s disease is more common in women particularly with advancing age.  Researchers from Boston University School of Medicine have estimated that one in six women are at risk for developing Alzheimer’s disease (AD) in their lifetime, while the risk for men is one in ten.  But the reasons for this relative increase in risk are not well understood.

Then there is the curious increase in late-onset schizophrenia and what it might teach us about brain aging and gender differences.  Schizophrenia is a severe mental disorder commonly presenting with psychotic symptoms such auditory hallucinations, paranoia or bizarre delusions, disorganized thoughts and often significant social and occupational impairment.   Onset of the illness is most commonly seen in late adolescence and early adult life.  Men predominate in the onset of illness in early adulthood and are less likely to develop the illness after middle age.  But there is a variant of the illness with onset in a patient’s forties or fifties, and here there is a striking predominance of women.  The predominance of women continues with increasing age of onset beyond the age of 65.   The gender difference is estimated to be at least 2 to 1 with some studies suggesting a much higher incidence.  Often these women have been married, raised families, had jobs and careers.  Essentially, they have adjusted well in life.  Their symptoms are often paranoid in quality and generally respond well to treatment.

The difference in age of onset has been speculated to be related to the role of estrogen and testosterone on the brain.  The higher incidence of young men developing the illness may in part be triggered by the relative increased levels of androgens, particularly testosterone in young adult life with the waning of new cases in men later in life explained by relative decrease in androgens.

Onset of illness in women at about the time of menopause has implicated the role of estrogen — and more specifically the role of diminished estrogen — as contributing to the later onset of this illness in women.   It is thought that estrogen is protective in terms of brain aging.  It is known that estrogen is a natural blocker and modifier of the effects of dopamine, a neurotransmitter thought central to the symptoms of schizophrenia.  Perhaps the decreased levels of estrogen leave some women vulnerable to the development of this illness.  But it leaves us with many questions.  Certainly most women do not develop schizophrenia after menopause.  Why would some women develop the illness in their 60’s decades after menopause?  While there have been case reports of benefits of estrogen augmentation,  this strategy needs further research.  Do women who develop late-onset schizophrenia have increased risk for developing cognitive disorders such as Alzheimer’s disease?  We don’t know the answer, but there is some compelling research to suggest they might.  There has been much interest in possible shared brain changes in both Alzheimer’s Disease and late-onset schizophrenia.

Perhaps late-onset schizophrenia, which is a rare disorder, allows us to better understand the aging brain and differences in terms of how women and men age differently.  Hopefully in the future it will help us contribute to more effective interventions and prevention in women’s mental health, giving way to successful aging.

Written by Michael A. Keys, MD

Contributed by and printed with permission from the Lindner Center of Hope

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