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New Northwestern Medicine® research offers one of the first in-depth studies of how physiological changes during pregnancy reduce the effects of a commonly used drug to treat bipolar disorder, making women more vulnerable to recurring episodes. The new findings will help psychiatrists and physicians prevent bipolar manic and depressive symptoms during pregnancy, which are risky for the health of the mother and her unborn child.

When a woman with bipolar disorder becomes pregnant, she and her physician often don’t realize her medication needs adjusting to prevent the symptoms from coming back – a higher risk during pregnancy. There also is little information and research to guide dosing for psychiatric medications during pregnancy.

Approximately 4.4 million women in the U.S. have bipolar disorder with women of childbearing age having the highest prevalence.

The new study shows the blood concentration of the commonly used drug lamotrigine decreases in pregnant women. About half of the women in the study had worsening depressive symptoms as their lamotrigine blood levels dropped. The drug levels fall because women have increased metabolism during pregnancy.

“Now physicians change the dose of the drug in response to women’s symptoms worsening,” said lead investigator Crystal Clark, M.D., an assistant professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine and a psychiatrist at Northwestern Memorial Hospital. “We need to optimize their medication dosing so they stay well.”

The study results will help physicians understand how to increase their patients’ doses during pregnancy and then reduce them postpartum to avoid toxicity, Clark said. Guidelines for prescribing the drug for pregnant women with the disorder also are included.

The study was published in the American Journal of Psychiatry.

Depressive episodes — as opposed to manic — are most likely to recur in pregnant women with bipolar disorder.

“The safety of the fetus is at risk,” Clark said. “Pregnant women that are depressed are less likely to take care of themselves which often leads to poor nutrition, lack of compliance with prenatal care and isolation from family and friends. It has also been linked to premature births and babies with low birth weights among other poor birth outcomes.”

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Although older adults with serious mental illness didn’t have more recorded physical illness and had fewer outpatient visits to primary care physicians, they made more medical emergency department visits and had considerably longer medical hospitalizations than older adults without mental illness according to a study conducted by researchers from the Regenstrief Institute and the Indiana University Center for Aging Research.

“Our comparison of health care utilization between seriously mentally ill patients and age-matched primary-care patients provides critical data for the physicians, health care systems and policy makers who will be caring for the growing number of older adults, many of whom have mental illness,” said Regenstrief Institute investigator Hugh C. Hendrie, M.B., Ch.B., D.Sc., Indiana University Center for Aging Research center scientist and professor of psychiatry at the IU School of Medicine. Dr. Hendrie, who is a geriatric psychiatrist and health services researcher, is the first author of the study.

The study, “Comorbidity Profile and Healthcare Utilization in Elderly Patients With Serious Mental Illnesses,” is published in the December issue of The American Journal of Geriatric Psychiatry.

A 2012 report from the Institute of Medicine estimated that as many of one in five older adults have one or more mental health conditions or problems stemming from substance misuse or abuse. The IOM report authors included Regenstrief Institute investigator Christopher Callahan, M.D., Cornelius and Yvonne Pettinga Professor of Medicine at the IU School of Medicine who is also a co-author of the new study. Dr. Callahan is founding director of the IU Center for Aging Research.

The American Journal of Geriatric Psychiatry study notes, “The increased likelihood of falls together with the significantly greater number of emergency department visits and length of hospitalization also suggest that those with severe mental illness represent a vulnerable elderly population that deserve more intensive studies, leading hopefully to a better integrated model of medical and psychiatric care including consideration of psychosocial factors.”

Individuals with severe mental illness in the study were patients of Eskenazi Health Midtown Community Mental Health. The patients had severe chronic depression (48 percent), schizophrenia (39 percent) and bipolar disorder (14 percent). Others in the study were patients from Wishard-Eskenazi primary care sites.

“This study highlights a major challenge faced by older adults with severe mental illnesses and the increased burden it places on our health care system,” said Julie L. Szempruch, RN, CNS, associate vice president of Eskenazi Health Midtown Community Mental Health.

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A new study published in the British Medical Journal finds a small but significant increase in psychosis risk for people who suffer the loss of a family member in childhood.

Although we know that adult health can be influenced by the genes we inherit from our parents, as well as the environment and lifestyle we experience as children, some evidence has suggested that psychological stress from the mother can also affect the development of a fetus.

But previous studies examining a link between a mother’s psychological stress and her offspring’s mental health have not been very conclusive.

This new study wanted to test this link further by seeing if children born to mothers who went through severe bereavement before, during or after pregnancy would be more likely to show symptoms of psychosis in adulthood.

The study was a large systematic review analyzing the medical records of 946,994 people born between 1973 and 1985 in Sweden.

The researchers identified mothers who had experienced the death of their parents, offspring or father of their children in a period between 6 months before conceiving and up to 13 years after giving birth. They also took into account the cause of death when bereavements had occurred in these families.

Overall, 321,249 (33%) of the children in the study experienced a family death before the age of 13.

‘No link’ between grieving during pregnancy and offspring mental health

The researchers found that 1,323 (0.4%) of these children later developed a delusional or “non-affective” psychosis (such as schizophrenia), while 556 (0.17%) of these children went on to develop an emotional disorder or “affective” psychosis (such as bipolar disorder).

By looking at when the bereavements occurred, the study concluded that mothers who suffered a bereavement before or during their pregnancy were not more likely than usual to have children who would develop psychosis.

So, it could not be proved that the psychological stress of a grieving mother can affect the future mental health of her fetus.

Dr. Kathryn Abel, lead author of the study, told Medical News Today that, despite previous studies suggesting the contrary, she was not surprised by their results:

“Previous findings relating to risk of schizophrenia or other illnesses have not been very strong and often were only seen in particular groups, such as those without a history of psychosis already in the family, or only in men.”

But the researchers did measure a small increased risk of people developing psychosis who had experienced the death of a family member in their childhood.

The study found that this risk increased in people who had lost a loved one from suicide (rather than from natural causes), and the risk also increased the earlier in childhood that this death occurred.

How reliable are the results?

woman with bipolar disorder
Of the bereaved children, 0.17% went on to develop an “affective” psychosis, such as bipolar disorder.

Although the study could identify when and how bereavements had occurred in these families, it is difficult to measure the level of psychological stress experienced by the families in the study.

Some families may have grieved for a long time, and some may have grieved comparatively little – for example, if the death was of an elderly relative who had been ill for some time – in which case, their passing may have provided some relief for the family. So some aspects of the study’s results may be subjective.

There are also a lot of other contributing childhood factors that can contribute to whether a person is more at risk of psychosis. These include socioeconomic status, neglect, abuse and bullying. These factors could also have had an effect on the results that was difficult to measure.

Also, the study only examined how experiencing a family death in childhood affects people born in Sweden. The researchers believe that further research needs to be done in non-Western and ethnically diverse populations to give us an overall picture of how grief might affect psychological development.

Dr. Abel told Medical News Today that it is possible “in non-Western populations, some societies might provide more support to bereaved families, or manage death and bereavement across society so it is less stressful and has less broad consequences on childhood.”

But Dr. Abel also mentioned that, in some societies, the opposite could be true, and “differences between risk of psychosis in those exposed and unexposed [to bereavement in childhood] could be greater.”

The researchers hope that having a better understanding of the childhood factors influencing risk of adult psychosis will ensure that “appropriately timed and appropriately resourced interventions can be developed to protect vulnerable families and children.”

Written by David McNamee

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How does an animal recognize another of the same species? Researchers from the Columbia University Medical Center in New York say they have uncovered the brain region responsible for this process – known as social memory.

The research team says their findings could assist in the understanding and treatment of disorders associated with altered social behaviors, including autism, schizophrenia and bipolar disorder.

The hippocampus is an area of the brain that is known to be associated with memory.

According to the researchers, recent studies have shown there are subregions in the hippocampus that have different responsibilities.

They note that the dentate gyrus subregion allows us to distinguish between different environments, the CA3 subregion enables us to recall memories from partial cues, and the CA1 subregion plays an important role in all areas of memory.

But there is another subregion in the hippocampus between CA3 and CA1, called CA2. Until now, scientists have been unclear on what role this subregion plays in memory.

Inactivated CA2 region led to a lack of social memory

To find out, the researchers were able to selectively block CA2 neurons in the adult offspring of a transgenic mouse.

mouse
Researchers found that mice with an inactivated CA2 region in the brain lacked social memory.

These mice were then subject to a series of behavioral experiments. When it came to social memory, the researchers found that the mice were displaying interesting behavior.

“Normally, mice are naturally curious about a mouse they’ve never met; they spend more time investigating an unfamiliar mouse than a familiar one,” explains first author Dr. Frederick L. Hitti.

“In our experiment, however, mice with an inactivated CA2 region showed no preference for a novel mouse versus a previously encountered mouse, indicating a lack of social memory.”

On conducting two other experiments in the CA2-deficient mice, which tested how they recognized new objects through vision and smell, the researchers found the mice acted normally. This indicates that the CA2 subregion may be solely responsible for social memory.

CA2 potential new target for treatment of social disorders

The investigators say these findings may have important implications for behavioral disorders, such as autism, schizophrenia and bipolar disorder, since these conditions are associated with impaired social memory.

They say previous studies have shown that people with schizophrenia and bipolar disorder have less active CA2 neurons, compared with healthy individuals.

Furthermore, research has shown that people with autism have impaired signaling of vasopressin – a hormone that is thought to play a role in social behavior.

Prof. Steven A. Siegelbaum, senior author of the study, says:

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Columbia University Medical Center (CUMC) researchers have determined that a small region of the hippocampus known as CA2 is essential for social memory, the ability of an animal to recognize another of the same species. A better grasp of the function of CA2 could prove useful in understanding and treating disorders characterized by altered social behaviors, such as autism, schizophrenia, and bipolar disorder. The findings, made in mice, were published today in the online edition of Nature.

Scientists have long understood that the hippocampus – a pair of seahorse-shaped structures in the brain’s temporal lobes – plays a critical role in our ability to remember the who, what, where, and when of our daily lives. Recent studies have shown that different subregions of the hippocampus have different functions. For instance, the dentate gyrus is critical for distinguishing between similar environments, while CA3 enables us to recall a memory from partial cues (e.g., Proust’s famous madeleine). The CA1 region is critical for all forms of memory.

“However, the role of CA2, a relatively small region of the hippocampus sandwiched between CA3 and CA1, has remained largely unknown,” said senior author Steven A. Siegelbaum, PhD, professor of neuroscience and pharmacology, chair of the Department of Neuroscience, a member of the Mortimer B. Zuckerman Mind Brain Behavior Institute and Kavli Institute for Brain Science, and a Howard Hughes Medical Institute Investigator. A few studies have suggested that CA2 might be involved in social memory, as this region has a high level of expression of a receptor for vasopressin, a hormone linked to sexual motivation, bonding, and other social behaviors.

To learn more about this part of the hippocampus, the researchers created a transgenic mouse in which CA2 neurons could be selectively inhibited in adult animals. Once the neurons were inhibited, the mice were given a series of behavioral tests. “The mice looked quite normal until we looked at social memory,” said first author Frederick L. Hitti, an MD-PhD student in Dr. Siegelbaum’s laboratory, who developed the transgenic mouse. “Normally, mice are naturally curious about a mouse they’ve never met; they spend more time investigating an unfamiliar mouse than a familiar one. In our experiment, however, mice with an inactivated CA2 region showed no preference for a novel mouse versus a previously encountered mouse, indicating a lack of social memory.”

In two separate novel-object recognition tests, the CA2-deficient mice showed a normal preference for an object they had not previously encountered, showing that the mice did not have a global lack of interest in novelty. In another experiment, the researchers tested whether the animals’ inability to form social memories might have to do with deficits in olfaction (sense of smell), which is crucial for normal social interaction. However, the mice showed no loss in ability to discriminate social or non-social odors.

In humans, the importance of the hippocampus for social memory was famously illustrated by the case of Henry Molaison, who had much of his hippocampus removed by surgeons in 1953 in an attempt to cure severe epilepsy. Molaison (often referred to as HM in the scientific literature) was subsequently unable to form new memories of people. Scientists have observed that lesions limited to the hippocampus also impair social memory in both rodents and humans.

“Because several neuropsychiatric disorders are associated with altered social behaviors, our findings raise the possibility that CA2 dysfunction may contribute to these behavioral changes,” said Dr. Siegelbaum. This possibility is supported by findings of a decreased number of CA2 inhibitory neurons in individuals with schizophrenia and bipolar disorder and altered vasopressin signaling in autism. Thus, CA2 may provide a new target for therapeutic approaches to the treatment of social disorders.

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