Smoking during pregnancy may increase risk of bipolar disorder in offspring

A study published today in the American Journal of Psychiatry suggests an association between smoking during pregnancy and increased risk for developing bipolar disorder (BD) in adult children. Researchers at the New York State Psychiatric Institute and the Department of Epidemiology at the Mailman School of Public Health at Columbia University, in collaboration with scientists at the Kaiser Permanente Division of Research in Oakland, California, evaluated offspring from a large cohort of pregnant women who participated in the Child Health and Development Study (CHDS) from 1959-1966. The study was based on 79 cases and 654 comparison subjects. Maternal smoking during pregnancy was associated with a twofold increased risk of BD in their offspring.

Smoking during pregnancy is known to contribute to significant problems in utero and following birth, including low birth weight and attentional difficulties. This is the first study to suggest an association between prenatal tobacco exposure and BD, a serious psychiatric illness marked by significant shifts in mood that alternate between periods of depression and mania. Symptoms typically become noticeable in the late teens or early adulthood.

"These findings underscore the value of ongoing public health education on the potentially debilitating, and largely preventable, consequences that smoking may have on children over time," said Alan Brown, MD, MPH, senior author and Professor of Clinical Psychiatry and Epidemiology at the New York State Psychiatric Institute, Columbia University and Mailman School of Public Health.

The authors wrote: “Much of the psychopathology associated with prenatal tobacco exposure clusters around the ‘externalizing’ spectrum, which includes attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), conduct disorder (CD), and substance abuse disorders. Although not diagnostically classified along the externalizing spectrum, BD shares a number of clinical characteristics with these disorders, including inattention, irritability, loss of self-control, and proclivity to drug/alcohol use.” In effect, children who were exposed to tobacco smoke in utero may exhibit some symptoms and behaviors that are found in BD.

A previous study by Dr. Brown and colleagues found that flu virus in pregnant mothers was associated with a fourfold increased risk that their child would develop BD.

(Image: istockphoto)

Nicotine exposure gives baby rats addictive personalities

Results suggest explanation for why people exposed to nicotine in the womb are more likely to become smokers.

Exposure to nicotine in the womb increases the production of brain cells that stimulate appetite, leading to overconsumption of nicotine, alcohol and fatty foods in later life, according to a new study in rats.

Smoking during pregnancy is known to alter fetal brain development and increase the risk of premature birth, low birth weight and miscarriage. Prenatal exposure to nicotine also increases the likelihood of tobacco use and nicotine addiction in later life, but exactly how is unclear.

To understand the mechanisms behind this effect, Sarah Leibowitz, a behavioural neurobiologist at the Rockefeller University in New York, and her colleagues injected pregnant rats with small doses of nicotine — which the researchers say are comparable to the amount a pregnant woman would get from smoking one cigarette a day — and then examined the brains and behaviour of the offspring.   

In a paper published in Journal of Neuroscience, they found that nicotine increased the production of specific types of neurons in the amygdala and hypothalamus. These cells produce orexin, enkephalin and melanin-concentrating hormone, neuropeptides that stimulate appetite and increase food intake.

Rats exposed to nicotine in the womb had more of these cells and produced more of the neuropeptides than those that were not, and this had long-term consequences on their behaviour. As adolescents, they not only self-administered more nicotine, but also ate more fat-rich food and drank more alcohol.

“These peptide systems stimulate food intake,” says Leibowitz, “but we found that they similarly increase the consumption of drugs and stimulate the brain’s reward mechanisms that promote addiction and substance abuse.”

Leibowitz notes that children whose mothers smoked during pregnancy are more likely to smoke themselves during adolescence and adulthood. Her team’s findings suggest a possible mechanism for that.

The use of nicotine patches or e-cigarettes during pregnancy could have a similar effect. “Whether given subcutaneously, as in our study, or via smoking or patches, the same amount of nicotine would still get into the brain to affect neuronal development and function,” Leibowitz says.

The results highlight the toxic effects of nicotine exposure on brain development, says George Koob, a neurobiologist at the Scripps Research Institute in La Jolla, California. He also adds that the study casts new light on the role of these neuropeptides in reward and motivation.

In earlier work, Leibowitz and her colleagues showed that rats exposed to fat and alcohol in the womb likewise overconsume these substances as adolescents. “Our studies make it very clear that neuronal development in utero is highly sensitive to these substances,” she says, “with each promoting their overconsumption and addictive-like behaviour in the offspring.” 

She and her collaborators are now comparing the effects of nicotine, fat and alcohol to learn more about how this promotion occurs. They are also exploring ways to reverse the effects of prenatal exposure to these substances, thus preventing their overconsumption in later life, which could lead to addiction and obesity.

Researchers find caffeine during pregnancy negatively impacts mice brains

A team of European researchers has found that mice who consume caffeine while pregnant give birth to pups with negative changes to their brains. In their paper published in the journal Science Translational Medicine, the team reports on their findings after examining the brains of mice pups whose mothers were given caffeine during pregnancy.

Medical researchers have shown that drugs such as cocaine, heroin or even marijuana can have a negative impact on fetal development—in contrast most believe that moderate amounts of caffeine consumption during pregnancy is “safe” meaning it has little or no adverse impact on fetal development. This new study doesn’t change that view, but it does suggest that perhaps more research needs to be done.

In their study, the researchers administered the equivalent of 4 or 5 cups of coffee a day to pregnant mice—afterwards they studied the brains of the pups that were born. In so doing, they found that GABA neurons didn’t migrate during brain development to their proper location in the Hippocampus at the same rate as untreated mice. GABA neurons are responsible for controlling the flow of information in the brain. Subsequent tests found the treated pups to be more susceptible to seizures.

The team also found that if they allowed the treated pups to grow to adulthood, they tended to demonstrate problems with memory—instead of playing with new objects placed in their cages, for example, they were satisfied with playing with objects they already knew—a trait that is uncommon for mice. Autopsies of adult brains also showed fewer neurons in the Hippocampus.

The researchers point out that their results in mice are not necessarily applicable to humans and to reinforce that point another team of researchers also published a Focus piece in the same journal pointing out that there are significant differences in the developmental process of humans and mice fetuses and thus the study with mice has no real bearing on whether caffeine may or may not cause developmental problems with human babies.

Still, the results do indicate that perhaps more research should be done to find out if caffeine does indeed have an unknown negative impact on human fetal development.

Drinking alcohol during pregnancy affects learning and memory function in offspring?

Maternal alcohol consumption during pregnancy has detrimental effects on fetal central nervous system development. Maternal alcohol consumption prior to and during pregnancy significantly affects cognitive functions in offspring, which may be related to changes in cyclin-dependent kinase 5 because it is associated with modulation of synaptic plasticity and impaired learning and memory. Prof. Ruiling Zhang and team from Xinxiang Medical University explored the correlation between cyclin-dependent kinase 5 expression in the hippocampus and neurological impairments following prenatal ethanol exposure, and found that prenatal ethanol exposure could affect cyclin-dependent kinase 5 and its activator p35 in the hippocampus of offspring rats. These findings, which reported in the Neural Regeneration Research (Vol. 8, No. 18, 2013), propose new insights into the mechanisms underlying the role of ethanol exposure in central nervous system injuries, and provide a new strategy for treating the consequences of prenatal ethanol exposure.

Mom’s Placenta Reflects Her Exposure to Stress

The mammalian placenta is more than just a filter through which nutrition and oxygen are passed from a mother to her unborn child. According to a new study by a research group from the University of Pennsylvania School of Veterinary Medicine, if a mother is exposed to stress during pregnancy, her placenta translates that experience to her fetus by altering levels of a protein that affects the developing brains of male and female offspring differently.

These findings suggest one way in which maternal-stress exposure may be linked to neurodevelopmental diseases such as autism and schizophrenia, which affect males more frequently or more severely than females.

“Most everything experienced by a woman during a pregnancy has to interact with the placenta in order to transmit to the fetus,” said Tracy L. Bale, senior author on the paper and an associate professor in the Department of Animal Biology at Penn Vet. “Now we have a marker that appears to signal to the fetus that its mother has experienced stress.”

Bale also holds an appointment in the Department of Psychiatry in Penn’s Perelman School of Medicine. Her coauthors include lead author and postdoctoral researcher Christopher L. Howerton, graduate student Christopher Morgan and former technician David B. Fischer, all of Penn Vet.

Published in the Proceedings of the National Academy of Sciences, the study builds on previous work by Bale and her colleagues which found that female mice exposed to stress during pregnancy gave birth to males who had heightened reactions to stress. Further research showed that the effect extended to the second generation: The sons of those male mice also had abnormal stress reactions.

Meanwhile, human studies conducted by other researchers have shown that males born to women who experience stress in the first trimester of pregnancy are at an increased risk of developing schizophrenia.

The Penn team hoped to find a biomarker that could account for these changes and risk factors. To be an effective signal of maternal stress, the researchers reasoned, a biomarker would need to show differences in expression between male and female offspring and would need to be different between stressed and unstressed mothers. They also wanted to find a marker that behaved similarly in humans.

Malign environmental combination favours schizophrenia

The interplay between an infection during pregnancy and stress in puberty plays a key role in the development of schizophrenia, as behaviourists from ETH Zurich demonstrate in a mouse model. However, there is no need to panic.

Around one per cent of the population suffers from schizophrenia, a serious mental disorder that usually does not develop until adulthood and is incurable. Psychiatrists and neuroscientists have long suspected that adverse enviromental factors may play an important role in the development of schizophrenia. Prenatal infections such as toxoplasmosis or influenza, psychological, stress or family history have all come into question as risk factors. Nevertheless, until now researchers were unable to identify the interplay of the individual factors linked to this serious mental disease.

However, a research group headed by Urs Meyer, a senior scientist at the Laboratory of Physiology & Behaviour at ETH Zurich, has now made a breakthrough: for the first time, they were able to find clear evidence that the combination of two environmental factors contributes significantly to the development of schizophrenia-relevant brain changes and at which stages in a person’s life they need to come into play for the disorder to break out. The researchers developed a special mouse model, with which they were able to simulate the processes in humans virtually in fast forward. The study has just been published in the journal Science.

Prenatal inflammation linked to autism risk

Maternal inflammation during early pregnancy may be related to an increased risk of autism in children, according to new findings supported by the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health.Researchers found this in children of mothers with elevated C-reactive protein (CRP), a well-established marker of systemic inflammation.

The risk of autism among children in the study was increased by 43 percent among mothers with CRP levels in the top 20th percentile, and by 80 percent for maternal CRP in the top 10th percentile. The findings appear in the journal Molecular Psychiatry and add to mounting evidence that an overactive immune response can alter the development of the central nervous system in the fetus.

“Elevated CRP is a signal that the body is undergoing a response to inflammation from, for example, a viral or bacterial infection,” said lead scientist on the study, Alan Brown, M.D., professor of clinical psychiatry and epidemiology at Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, and Mailman School of Public Health. “The higher the level of CRP in the mother, the greater the risk of autism in the child.”

Light Exposure During Pregnancy Key to Normal Eye Development

New research in Nature concludes the eye – which depends on light to see – also needs light to develop normally during pregnancy.

Scientists say the unexpected finding offers a new basic understanding of fetal eye development and ocular diseases caused by vascular disorders – in particular one called retinopathy of prematurity that can blind premature infants. The research, led by scientists at Cincinnati Children’s Hospital Medical Center and the University of California, San Francisco (UCSF), appears online Jan. 16 ahead of print publication.

“This fundamentally changes our understanding of how the retina develops,” says study co-author Richard Lang, PhD, a researcher in the Division of Pediatric Ophthalmology at Cincinnati Children’s Hospital Medical Center. “We have identified a light-response pathway that controls the number of retinal neurons. This has downstream effects on developing vasculature in the eye and is important because several major eye diseases are vascular diseases.”

Lang is a principal investigator on the ongoing research along with project collaborator, David Copenhagen, PhD, a scientist in the departments of Ophthalmology and Physiology at UCSF. The scientists say their current study, conducted in mouse models, includes several unexpected findings.

"Several stages of mouse eye development occur after birth," says Copenhagen. "Because of this, we had always assumed that if light played a role in the development of the eye, it would also happen only after birth."

But researchers in the current study found that activation of the newly described light-response pathway must happen during pregnancy to activate the carefully choreographed program that produces a healthy eye. Specifically, they say it is important for a sufficient number of photons to enter the mother’s body by late gestation, or about 16 days into a mouse pregnancy.

Researchers were also surprised to learn that photons of light activate a protein called melanopsin directly in the fetus – not the mother – to help initiate normal development of blood vessels and retinal neurons in the eye.

One purpose of the light-response pathway is to suppress the number of blood vessels that form in the retina. These vessels are critical to retinal neurons, which require large amounts of oxygen to form and to function. When retinopathy of prematurity occurs in infants, retinal vessels grow almost unchecked. This continued expansion puts intense pressure on the developing eye and in extreme cases causes severe damage and blindness.

The research team led by Lang and Copenhagen conducted several experiments in laboratory mouse models that allowed them to identify the light-response pathway’s specific components and function.

Mice were reared in the dark and in a normal day-night cycle beginning at late gestation to observe the comparative effects on vascular development of the eye. The researchers verified the function of the light response pathway by mutating an opsin gene in mice called Opn4 that produces melanopsin, in essence preventing activation of the photo pigment.

Both mice reared under dark conditions from late gestation, and those with mutated Opn4, exhibited nearly identical promiscuous expansion of hyaloid vessels and abnormal retinal vascular growth. The unchecked vascular growth was driven by the protein vascular endothelial growth factor (Vegfa). When the light response pathway is properly engaged, it modulates Vegfa to help prevent promiscuous vascular growth, according to researchers.

The melanopsin protein is present in both mice and humans during pregnancy. Lang said the research team is continuing to study how the light-response pathway might influence the susceptibility of pre-term infants to retinopathy of prematurity and also be related to other diseases of the eye.

Scientists Discover Children’s Cells Living in Mothers’ Brains

The link between a mother and child is profound, and new research suggests a physical connection even deeper than anyone thought. The profound psychological and physical bonds shared by the mother and her child begin during gestation when the mother is everything for the developing fetus, supplying warmth and sustenance, while her heartbeat provides a soothing constant rhythm.

The physical connection between mother and fetus is provided by the placenta, an organ, built of cells from both the mother and fetus, which serves as a conduit for the exchange of nutrients, gasses, and wastes. Cells may migrate through the placenta between the mother and the fetus, taking up residence in many organs of the body including the lung, thyroid muscle, liver, heart, kidney and skin. These may have a broad range of impacts, from tissue repair and cancer prevention to sparking immune disorders.

It is remarkable that it is so common for cells from one individual to integrate into the tissues of another distinct person. We are accustomed to thinking of ourselves as singular autonomous individuals, and these foreign cells seem to belie that notion, and suggest that most people carry remnants of other individuals. As remarkable as this may be, stunning results from a new study show that cells from other individuals are also found in the brain. In this study, male cells were found in the brains of women and had been living there, in some cases, for several decades. What impact they may have had is now only a guess, but this study revealed that these cells were less common in the brains of women who had Alzheimer’s disease, suggesting they may be related to the health of the brain.

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