Researching darting mice could help study ADHD, autism, and bipolar disorder

A study of mice with darting behavior could help research ADHD, autism, and bipolar disorder in humans.

A darting mouse may hold an important clue in the development of Attention Deficit Hyperactivity Disorder (ADHD), autism and bipolar disorder, according to a study by a Vanderbilt University-led research team recently published in the Proceedings of the National Academy of Sciences.

The transgenic mouse, into which was inserted a rare human genetic variation in the dopamine transporter (DAT), could lead to improvements in the diagnosis and treatment of these all-too-common brain disorders, said Randy Blakely, Ph.D., the report's senior author.

The mutation, which has been found in people with ADHD, autism and bipolar disorder, affects the function of DAT, a protein that regulates the brain's supply of the neurotransmitter by removing excess dopamine from the synapse, or the space between nerve cells.

The DAT mutation causes the transporter to become "leaky" and spew out dopamine like "a vacuum cleaner in reverse," said Blakely, Allan D. Bass Professor of Pharmacology.

While mice with leaky DAT proteins have too much dopamine hanging around their synapses, surprisingly they aren't particularly hyperactive, possibly because DAT can still remove some of the dopamine.

But the mice exhibit an unusual "darting behavior." While their wild-type littermates are docile and quite unresponsive when researchers pick them up, those with the mutation "take off."

"Early on," Blakely said, "we could tell which ones carried the mutation by observing this response." Heightened anxiety does not appear to be the cause.

Blakely and his colleagues wonder whether this behavior is a form of "impulsivity." Rather than acting on their memories of being picked up a lot, the mice are opting for an inappropriate escape strategy.

Normal mice also stand up a lot to explore their cage. This "rearing" behavior is exacerbated by stimulant drugs. But not in these mice.

"We wonder whether this may be a sign that their behavior is driven less by searching for clues to appropriate behavior versus acting on innate impulses," Blakely said.

Other, better tests of impulsivity that evaluate premature decision-making can be applied in rodents and humans. "These tests are next on our docket," he said.

The actions of amphetamine and methylphenidate (Ritalin) are also affected by the mutation. In normal animals and people without ADHD, the stimulants flood the synapse with dopamine, eliciting hyperactivity.

But when given to the mutant animals, the drug demonstrates a "blunted" effect on both dopamine release and on locomotor activation compared to normal animals.

Blakely wonders whether stimulants like Adderall and Ritalin quell hyperactive and impulsive behaviors in some children with ADHD by reducing inappropriate dopamine leak. "These mice may give us much better clues as to how these drugs are acting," he said.

To that end, Blakely recently received a five-year, $2-million grant from the National Institutes of Health (NIH grant number MH109054) to pursue explorations of these mice.

"Dopamine has classically been implicated in reward and the ability to detect novelty and to respond to pleasure and to engage in effective social interactions," he continued. The darting mice thus might shed light on a much broader spectrum of behaviors.

"We've got a lot to do," he said, "a lot of needy people (to help)."

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Autism in adults leads to many health problems

This article discusses how autism in adults can result in many other health problems.

Autism apparently isn't a stand-alone disorder, with new research revealing that adults with autism often face a host of mental and physical illnesses.

Kaiser Permanente researchers found that nearly all medical conditions are significantly more common in adults with autism spectrum disorders than those without, ranging from depression to gastrointestinal problems to obesity. Notably, however, adults with autism are much less likely to smoke or use alcohol than other adults, and cancer rates are similar.

"Some of these conditions we've seen in children with autism, so we expected higher rates of anxiety and depression, and some of the medical disorders, such as gastrointestinal disturbances, in adults," said study author Lisa Croen, director of the Kaiser Permanente Autism Research Program in Oakland, Calif.

"That's been reported for a long time in children, so we're not surprised to see those continue to be elevated," she added. "But we were surprised by the magnitude of what we found."

The study is scheduled to be presented Thursday at the International Meeting for Autism Research in Atlanta. Research presented at scientific conferences typically has not been peer-reviewed or published and results are considered preliminary.

Diagnosed in about 1 in 68 American children, autism spectrum disorder is the fastest-growing serious developmental disability in the United States, according to the advocacy and research organization Autism Speaks.

The disorder can be mild or severe, but symptoms typically include social and communication difficulties and repetitive behaviors.

Croen and her colleagues examined medical records from 2008 to 2012, and compared the prevalence of psychiatric, behavioral and medical diagnoses among 2,100 adults with an autism spectrum disorder to 21,000 adults without the disorder.

Adults diagnosed with an autism spectrum disorder had markedly higher rates of mental health problems than the other adults:

• Depression (38 percent versus 17 percent)
• Anxiety (39 percent versus 18 percent)
• Bipolar disorder (30 percent versus 9 percent)
• Suicide attempts (1.6 percent versus 0.3 percent)

People with autism spectrum disorders were also more likely than adults without the disorder to have physical ailments, such as:

• Diabetes (6 percent versus 4 percent)
• Gastrointestinal disorders (47 percent versus 38 percent)
• Epilepsy (12 percent versus 1 percent)
• Sleep disorders (19 percent versus 10 percent)
• High cholesterol (26 percent versus 18 percent)
• High blood pressure (27 percent versus 19 percent)
• Obesity (27 percent versus 16 percent)

"What the data show is really an extension of what we've learned already of children and adolescents with autism," said Dr. Paul Wang, senior vice president and head of medical research for Autism Speaks, who wasn't involved in the study. "It's not just a brain disorder -- it's really a disorder that affects the whole body. And this shows that these problems don't go away."

Croen said that many possible reasons exist for the wide gap in mental and physical ailments suffered by adults with autism, including a potential genetic basis. But the "core impairments" of those with autism -- such as communication problems and heightened sensitivity to touch -- can also make it difficult for them to be properly examined by clinicians, she said.

"People with autism often have very selective eating and their nutrition suffers," Croen added. "Their social impairments can lead to isolation, which leads to a lack of exercise. So some lifestyle factors can create more unhealthy lifestyles."

Social isolation may also explain why adults with autism are less likely to drink alcohol or smoke, noted Croen, also a senior research scientist at Kaiser Permanente Northern California Division of Research.

"Smoking and drinking are more social behaviors, especially in young people," she said. "Or, that's how it gets started. These young people with autism are out of the mainstream."

Croen and Wang agreed that autism researchers should extend their focus beyond the brain to multiple bodily systems as well as examine the transition from pediatric to adult health care.

"I hope these findings raise awareness among the medical community and others that adults with autism have a really high burden of medical and psychiatric conditions, much more than people think," Croen said. "There's a real need for doctors to be educated about autism and the characteristics of these adults so they can provide adequate and effective care."

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Link between migraines and bipolar disorder

A study shows that there may be a link between migraine headaches and bipolar disorder.

Doctors who work with patients with bipolar disorder should keep in mind that those people are also at high risk for migraine headaches, a Pennsylvania State University researcher says.

A new study led by Erika Saunders, executive vice-chair of psychiatry at the Penn State Milton S. Hershey Medical Center, found that people with bipolar disorder were far likelier than the general population to get migraines and that those who got the awful headaches were at risk for worse psychosocial functioning, more severe depression, and earlier onset of bipolar symptoms.

"All of those are markers for more severity of bipolar disorder," Saunders said.

Bipolar disorder, which affects 2.6 percent of the U.S. population, is characterized by extreme mood shifts. Symptoms can include hallucinations and delusions.

Six percent of Saunders' healthy control group had migraines, compared with 31 percent of the 412 bipolar patients. In both groups, migraines were more common in women than in men.

Men with bipolar disease who got migraines tended to have bipolar II, a variant with more severe depression and less severe mania or "high" periods.

Migraine was more common in patients who had suffered emotional or sexual abuse or emotional neglect.

The study, done with researchers from the University of Michigan, was published in the Journal of Clinical Psychiatry.

Saunders suspects that many psychiatrists do not know their patients also have migraines. The doctors may be distracted by the many other medical problems such patients tend to have. Patients may consider headaches a problem for a primary care doctor, not a psychiatrist.

She now wants to explore the possibility of a shared biological link between bipolar disorder and migraine. Valproic acid, an antiseizure medicine, is used to treat mania and prevent migraines. Abnormal inflammatory mechanisms have been found in both, and both are episodic conditions. "There is something going on in the brain that's happening only at certain times for some reason," she said.

Saunders plans to study a dietary program she hopes will affect the inflammatory response, improve mood stability, and reduce migraines. She said it would involve changing the intake of fatty acids, but wouldn't talk about the details.

Some patients, she said, have more stable moods when their migraines are well-controlled.

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Smoking during pregnancy may result in bipolar disorder in child

This study claims that a mother who smokes while pregnant has two times the risk of her child developing bipolar disorder compared to a mother who does not smoke while pregnant.

A study published today in theAmerican 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.

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Link between sleep apnea and mental illness

This article discusses the interesting link that exists between sleep apnea and mental illnesses such as depression and bipolar disorder.

With bipolar disorder cropping up from celebrities to politicians, you may be wondering what truly affects these individuals. Yes, a mental illness is typically a misfire of chemical and electrical  waves within the brain. Nevertheless, is there another, underlying cause? One cause can point to a varying disorder called sleep anpea, a condition that can create a mental abnormality. Does the lack of oxygen to the brain due to lack of sleep cause a mental illness?

If you snore, the two greater factors of blame are pointed to either, obstructive sleep apnea or obesity. The lack of oxygen to the brain can cause one to be tired during the day, inciting drastic mood swings. In most cases, individuals suffer from depression and inconsistent sleep schedules, resulting in lying awake at night. Sleep is imperative to the overall general health of an individual. Finding the serenity of slumber should be natural, without one becoming dependent on sleep aids.

If you are prescribed a muscle relaxant, your lack of sleep can actually become worse; especially, sufferers of obstructive sleep apnea. It’s not advised to have certain muscle relaxants including medications, such as: Valium, Ativan and Klonopin. These prescriptions can cause the surrounding airway muscles to collapse- causing sleep depravity, resulting in mood changes and chemical imbalances.

Medication for many, is imperative to live a functionally, normal life, but many contemplate what can be done to lesson the side-effects they feel? The first suggestion is moderate exercise and changing your diet. For some, it is not that simple and many should look into acquiring a prescribed CPAP. This machine produces the air that individuals need when the body is having complications during sleeping. This machine has been used on individuals who have undergone a sleep study and suffer from conditions that require its use. Speak to your doctor who will determine the machine type, they will also determine the air pressure that you need to stay consistently asleep. Once sleep is obtained normally, the mental balance can once again become stabilized.

Sleep deprivation is a condition millions of Americans suffer from. Psych Central advises individuals can suffer from memory loss, a disorientation of rationalization, resulting in severe mood swings. When your body is tired, it becomes dehydrated and this combination can be a deadly mix to your mental stability. Some individuals with a deeper severity of sleep loss had reported hallucinations and slurred speech. Dr. Yasinski of Yasinski Psychiatry states,

“Without adequate oxygen to your brain, the ability of psychiatric medications, exercise and healthy living to improve depression or bipolar disorder is decreased and thus many patients present as ‘treatment resistant’ when in reality they are resistant only due to a co-morbid sleep apnea disorder that has gone unrecognized.”

A sleep study is highly recommended for individuals who suffer from sleep disruption and mental disorders like bipolar. This painless test can gauge the level of severity from children to adults. If sleep apnea is the cause of the mental illness, treatment can be recommended and prescribed by a doctor, leading to stability of sleep, mind and life.

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