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Brain Atrophy Responsible for Depression in People Battling Multiple Sclerosis


Senior Member
ScienceDaily (July 4, 2010) Adding to all that ails people managing their multiple sclerosis is depression ― for which MS sufferers have a lifetime risk as high as 50 percent.

Yet despite its prevalence, the cause of this depression is not understood. It's not related to how severe one's MS is, and it can occur at any stage of the disease. That suggests it is not simply a psychological reaction that comes from dealing with the burden of a serious neurologic disorder.

Now, in the first such study in living humans, researchers at UCLA suggest a cause, and it's not psychological, but physical: atrophy of a specific region of the hippocampus, a critical part of the brain involved in mood and memory, among other functions.

Reporting in the early online edition of the journal Biological Psychiatry, senior study author Dr. Nancy Sicotte, a UCLA associate professor of neurology, Stefan Gold, lead author and a postdoctoral fellow in the UCLA Multiple Sclerosis Program, and colleagues used high-resolution magnetic resonance imaging to identify three key sub-regions of the hippocampus that were found to be smaller in people with MS when compared with the brains of healthy individuals.

The researchers also found a relationship between this atrophy and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, a complex set of interactions among three glands. The HPA axis is part of the neuroendocrine system that controls reactions to stress and regulates many physiological processes. It's thought that this dysregulation may play a role in the atrophy of the hippocampus and the development of depression.

"Depression is one of the most common symptoms in patients with multiple sclerosis," Gold said. "It impacts cognitive function, quality of life, work performance and treatment compliance. Worst of all, it's also one of the strongest predictors of suicide."

The researchers examined three sub-regions of the hippocampus region ― CA1, CA3 and the dentate gyrus area of the hippocampal region called CA23DG (CA stands for cornu ammonis). They imaged 29 patients with relapsing remitting multiple sclerosis and compared them with 20 healthy control subjects who did not have MS. They also measured participants' cortisol level three times a day; cortisol is a major stress hormone produced by the HPA axis that affects many tissues in the body, including the brain.

In addition to the difference between MS patients and healthy controls, the researchers found that the multiple sclerosis patients diagnosed with depression showed a smaller CA23DG sub-region of the hippocampus, along with excessive release of cortisol from the HPA axis.

"Interestingly, this idea of a link between excessive activity of the HPA axis and reduced brain volume in the hippocampus hasn't received a lot of attention, despite the fact that the most consistently reproduced findings in psychiatric patients with depression (but without MS) include hyperactivity of the HPA axis and smaller volumes of the hippocampus," Sicotte said.

"So the next step is to compare MS patients with depression to psychiatric patients with depression to see how the disease progresses in each," she said.

Other authors of the study included Kyle C. Kern, Mary-Frances O'Connor, Michael J. Montag, Aileen Kim, Ye S. Yoo and Barbara S. Giesser, all of UCLA.

Funding was provided by the National Multiple Sclerosis Society, the National Institutes of Health, the UCLA Cousins Center for Psychoneuroimmunology, and Claire and William Vaughn.

Thank you for posting this article - even though it is scary to think about in regards to ME-CFS too.


"and this too shall pass"
Vancouver Canada suburbs
Cognition and Hopelessness in Association With Subsyndromal Orthostatic Hypotension


Background. The move from lying to standing is typically associated with a variety of physiological and neurohumoral changes, most especially a slight increase in systolic blood pressure (SBP). Decreased efficacy of the various mechanisms that control orthostatic blood pressure (BP) regulation may result in lightheadedness, dizziness, syncope, and cerebral hypoperfusion. The lack of effective orthostatic BP regulation is a symptom for various problems, including fatigue, depression, anxiety, and reduced attention.
Methods. This study examined men and women (N = 74) who were aged 3075 years and asymptomatic for clinical orthostatic hypotension.
Results. Relatively poor BP regulation in response to orthostasis was associated with decreased verbal memory, decreased concentration, and higher hopelessness scores.
Conclusions. Individuals who exhibited less effective SBP regulation even to a subsyndromal degree in response to an orthostatic challenge may be at increased risk for cognitive and affective problems. The relationship between orthostatic BP regulation is best described as curvilinear


"and this too shall pass"
Vancouver Canada suburbs

Blood Pressure Testing Should Routinely Check for Orthostatic Hypotension Too, Researchers Advise
August 6, 2010

Researchers have found that cognitive processes and mood grow stronger with more effective blood pressure regulation - and, by contrast, can suffer in both children and adults who fail to show an adequate blood pressure increase in response to standing. Next, is there a link to ADHD?

A simple variation to the tried and true method of checking blood pressure can reveal startling information about both older and younger persons, new research suggests.

The standard method of checking blood pressure – taking one measurement while a patient relaxes – can identify hypertension. But health professionals can learn even more by checking pressure while a patient is lying down and again, a couple minutes after they stand up. That’s how to measure for orthostatic hypotension, a form of low blood pressure.

Primarily seen in the elderly, orthostatic hypotension is characterized by a decrease in systolic blood pressure as a patient shifts from lying down to standing. It is associated with dizziness, problems with gait and even diminished cognition. Orthostatic hypotension is also associated with several complications associated with chronic illnesses such as diabetes and Parkinson’s disease.

Lawrence Perlmuter, PhD, a psychologist at Chicago’s Rosalind Franklin University of Medicine and Science, has found that both adults and children who show an inadequate increase in blood pressure in response to standing also perform more poorly on neuropsychological tests and may be at higher risk for depression.

“If a person fails to adequately adjust to the switch from supine to standing, one can expect to find some adverse effects that may be behavioral, cognitive and affective,” says Dr. Perlmuter.
“When we stand, gravity pulls down on the blood flow. A complex set of processes, including a response by the nervous system, must occur almost immediately to prevent the blood from flowing downward, instead of upward toward the brain.”

Hospitalizations related to clinical orthostatic hypotension numbered slightly more than 80,000 in the United States in 2004 and these rates increased with age, according to the American Journal of Medicine.

About 20% of participants in research conducted by Rosalind Franklin University show measurable subsyndromal effects, or very mild symptoms not considered severe enough for clinical diagnosis.

Dr. Perlmuter first studied orthostatic hypotension in 1982 among diabetic patients at Massachusetts General Hospital in association with the Harvard University School of Dental Medicine. He later explored the relationship between orthostatic blood pressure and Alzheimer’s patients under a grant from the Illinois Department of Public Health. The condition’s broader implications soon captured his interest.

• “Blood pressure changes in response to standing are so multifaceted and can be a clinical problem in older people,” Dr. Perlmuter said.

• “But the latest research shows that children and adolescents are not immune to these very mild blood pressure changes, affecting their thinking and behaviors as well as depression and anxiety.”

Dr. Perlmuter found that poor orthostatic blood pressure regulation is a factor in poor academic performance, decreased concentration and lowered motivation. “And it’s a psychosocial educational issue,” he said. “Even though the magnitude is subclinical in orthostasis, its effect on depression and other behaviors are nevertheless measurable.”

But poor systolic blood pressure regulation can have important behavioral implications, particularly for children.

“When a person stands from a lying position, several processes are in need of correction,” Dr. Perlmuter said. “For example, if the brain chemical dopamine is not released in a sufficient amount this indicates that measurable cognitive problems as well as elevations in depression may be evident.

In a study published in 2008 in the International Journal of Psychology, Dr. Perlmuter examined systolic blood pressure regulation in children ages 7 to 11 in relation to teacher evaluations of those students’ grades and classroom effort. Forty-five students at a Waukegan elementary school took part in the study, which found a correlation between weak systolic blood pressure response to orthostatic challenge and reduced academic effort. The teachers were blind to these findings.

Researchers found that cognitive processes grew stronger as blood pressure regulation proved more effective.

“When we’re studying blood pressure change, this simple procedure provides a marker of what’s going on underneath,” Dr. Perlmuter said. “If the blood pressure increase isn’t adequate, that’s a reflection of some underlying problem that can affect a child’s learning and personality, possibility resulting in inappropriately acting out.”

In another study published in the same journal in 2009, Dr. Perlmuter and fellow researchers looked at 3- to 5-year-olds from a local Head Start program. They examined the relationship between the preschoolers’ orthostatic blood pressure regulation and their performance on a screening test used to uncover developmental delays.

Children who exhibited an appropriate increase in systolic blood pressure upon standing scored best in terms of composite motor skills, an index of cognitive function.

Checking for orthostatic hypotension in early childhood could help identify children at risk for depression and learning difficulties. Such children could then be offered an early academic intervention.

Maternal anxiety, low birth weight, and suboptimal BP regulation linked.

Rosalind Franklin University researchers are also examining the relationship between maternal anxiety and blood pressure regulation. Anxiety in mothers not only correlated with anxiety scores in their children, but also predicted poor blood pressure regulation in their children. Dr. Perlmuter’s research has also found that low birth weight can predict orthostatic hypotension in children.

However, his latest study revisits the other end of life’s spectrum. The report, “Cognition and Hopelessness in Association with Subsyndromal Orthostatic Hypotension,” published in the August issue of the Journal of Gerontology, examined men and women ages 30 to 75.

• Poor blood pressure regulation in response to standing was associated with decreased verbal memory, decreased concentration and higher hopelessness scores.

• The study concludes that “routine assessment and identification of orthostatic hypotension may provide an opportunity to reduce the risk for cognitive and affective decline through positive lifestyle changes and physical exercise.”

Next, Research to Determine if There’s a Link with ADHD

With regard to future implications, Dr. Perlmuter hopes his research succeeds in “identifying one of the antecedents” to Attention Deficit Hyperactivity Disorder (ADHD) as well to aggressive and impulsive behaviors. This research is getting underway with Head Start children in September.

“A question is whether we view this topic as a clinical phenomenon,” Dr. Perlmuter said. “It nevertheless has broad health and psychosocial implications. Finally, it should be recognized that since subclinical orthostatic hypotension is a phenomenon crossing physiological, cognitive and emotional boundaries with people, we weren’t expecting these relationships – thus researchers have not until now looked for them.”

Source: Rosalind Franklin University of Medicine and Science (Chicago) news release, Aug 3, 2010