Bipolar Genes Linked to Autism

Many psychiatric diseases share genetic roots. A new study, run by researchers at three different laboratories, suggests that rare genetic variations linked to bipolar disorder are also linked to schizophrenia and especially autism.

The study, by researchers at Johns Hopkins School of Medicine, Cold Spring Harbor Laboratory, and the University of Iowa Carver College of Medicine, is among the first to demonstrate the overlap between bipolar disorder and autism.

Despite bipolar disorder’s demonstrated inheritability, pinpointing genes relating to the disease has been exorbitantly difficult. But advances made in medical science recently have allowed scientists to start to figure out which genetic variations affect patients with bipolar disorder.

The researchers behind the study linking autism with bipolar disorder combined a case-control approach with “family-based exome sequencing” to try to discover which genetic variations contribute to bipolar. Case-control approaches look at genetic variants in people who have the disorder compared to people who don’t to figure out which genes increased susceptibility to the disease. The key to this approach is large pools of data.

Family-based exome sequencing is more difficult to perform. Scientists compare all the expressed genes in a genome (known as the exome). The researchers first examine the DNA that encodes proteins (known as exons), and then put that DNA into sequence using computers. This allows technicians to see variants that “travel with” the disease, especially in cases where the disorder is passed from parent to child.

This two-pronged approach identified 84 rare variants in 82 genes that traveled with bipolar disorder. The research team then examined these

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84 variants in three case-control datasets of 3,541 individuals with bipolar disorder and 4,774 control patients to figure out which variants predicted the disorder.

 

Nineteen genes were over-represented in bipolar disorder patients compared to the controls. However, while the data on these genes wasn’t enough to specifically pinpoint the genetic culprits of bipolar disorder, several of the genes were linked to autism and schizophrenia, with autism being especially prominent.

The findings suggest that schizophrenia, bipolar disorder, and autism have similar roots, and are simply different manifestations of similar diseases. The researchers from the study hope that by linking these diseases and finding which genes are responsible, new treatments will be discovered for all of them.

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Bipolar Disorder Increases Risk of Early Death From Natural Causes

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Wow, what a headline! After reviewing 17 studies involving more than 331,000 patients, University of Washington (UW) researchers have linked bipolar disorder to a risk of early death from natural causes, such as medical illness. The risk of premature death is from 35 to 200 percent more than people without bipolar disorder, and is the same between men and women. The most common conditions leading to death were heart disease, diabetes, and stroke.

 

Before this study, the higher rate of death linked to bipolar disorder was attributed to suicides and accidents. While patients who suffer from mental illnesses do have a higher chance of accidents and suicides, the new evidence points to medical illnesses as the primary cause of premature deaths.

According to the UW report published in the journal Psychiatric Services, there are many reasons behind the poor health among bipolar disorder sufferers. Reasons such as unhealthy diet, added stress, lack of exercise, substance abuse, and biases among health professionals towards people with mental illnesses.

In addition to those reasons, bipolar disorder can also stress the immune system and the hypothalamic-pituitary axis, a system which handles many processes in the body. Mental illnesses also trigger the flight-or-fight response to stress.

Even more troubling, psychiatric medications that help treat bipolar disorders tend to cause weight gain, leading to obesity and other complications.

But there are attempts to try to reduce the risk of death in people with mental illnesses, such as providing guidelines to mental health professionals to monitor their patients’ physical health. Psychiatrists are also encouraged to teach their patients about how to quit smoking, how to exercise, and about healthy diets.

This study is a step forward in preventing premature deaths, despite its gloomy nature.

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New Research Pinpoints Bipolar Disorder Gene

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A new study published in the Molecular Psychiatry journal reports that researchers have found a mutation in a gene that causes bipolar disorder in as many as ten percent of cases. This is fantastic news! Finally, the causes of bipolar disorder are starting to be pinpointed.

The gene, G protein receptorkinase 3 (GRK3), regulates neurotransmitters such as dopamine. The mutation happens in a section of the gene called the promoter, which turns GRK3 on and off. Scientists at the University of California, San Diego (UCSD) School of Medicine hypothesize that what causes bipolar disorder is that the mutation makes the gene hypersensitive to dopamine.

The study took place over a year, and screened DNA samples from more than 400 families with bipolar disorder. The researchers found six mutations in the promoter region of GRK3. Most notable was that the P-5 mutation happened three times more frequently in people who suffer from bipolar disorder than those who don’t.

Research has long pointed to several genes being the causes of bipolar disorder. But this is the first time a single gene has been determined as a cause. Bipolar disorder is characterized by extreme highs and lows. Few therapies work to treat the mental illness, and those that do work aren’t effective for all people who suffer from it. The scientists involved in this study hope that specific therapies that target genes on a molecular level will be developed.

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Bipolar Patients More Than Twice As Likely to Have Suffered Childhood Adversity

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A new study published in the British Journal of Psychiatry looking at more than thirty years into bipolar disorder research found that people with the disorder are 2.63 times more likely to have suffered adversity as children than the general population.

Adversity is defined here as emotional, sexual, or physical abuse, or the loss of a parent before the age of nineteen. While the loss of a parent did not raise the risk of a bipolar diagnosis significantly, people who were emotionally abused were more than four times as likely to have a subsequent diagnosis of bipolar disorder.

The study, run by researchers at the University of Manchester, gathered data from millions of patient interviews in nineteen studies between 1980 and 2014. The authors of the study believed that bipolar disorder had a similar link to childhood adversity like schizophrenia, and does not just stem from bio-genetics.

The hope that the researchers have is that specialized therapy plans can be put into place for people who have suffered childhood abuse, and that future diagnoses can take into account personal histories.

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Scientists Predict Who Will Respond to Lithium

Lithium is a salt which treats both mania and depression in a lucky thirty percent of people with bipolar disorder. But prior to the discovery of a new method to predict who will respond to lithium, people were playing roulette.

Now scientists at the Salk Institute can predict, with 92 percent accuracy, who will be a lithium responder. All they need is five cells and a test. They discovered that the neurons of people with bipolar disorder are more excitable when exposed to stimuli and fire more rapid electrical impulses than individuals without the disorder. This means that people with bipolar are more easily stimulated.

In an old study, the scientists found that soaking skin cells from bipolar patients in a lithium solution calmed the hyperexcitability–but only for some of them. The next study proved even more fruitful. The researchers soaked lymphocytes (immune cells) rom known lithium responders in lithium solutions, and found the same results–the hyperexcitabilty was calmed. But even though both responders and non-responders had the same excitability, the electrophysiological properties were different.

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The Salk team looked for electrical firing patterns in neuronal lines, measuring the threshold for evoking a reaction, and other qualities. Overall, the patterns in responders were completely different than in non-responders.

The scientists were able to replicate the results again and again, which means that this test is proven to work. Now a blood draw is all that’s needed to test whether a patient with bipolar disorder will respond to lithium.

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Bipolar Disorder in Children

Bipolar disorder affects people of all ages, including children as young as six. The disorder has periods of elevated mood, called mania, as well as periods of depression.

Common symptoms in children are:

  • Mood swings ranging from depression to irritability to elation, sometimes up to several times a day
  • Racing thoughts (while manic)
  • Hyperactive or aggressive behavior
  • Casual sex or spending sprees that are out of character
  • Decreased need for sleep
  • Inflated ego
  • Suicidal ideation in older children
  • Separation anxiety
  • Carbohydrate cravings
  • Difficulty waking in the mornings
  • Oversensitivity to emotional situations
  • Bed-wetting (especially in boys)
  • Obsession with gore or other socially inappropriate topics
  • Night terrors

 

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Symptoms in children look slightly different than those of adults. Children can be more irritable than adults during a manic phase, with less elevated mood, and are more likely to experience psychotic features, such as auditory hallucinations. As for depression, children are more likely to complain about physical pain. Between episodes, kids return to their normal mood. Something of note is that they cycle between these episodes several times a day, as opposed to weeks or months.

Some experts believe the disorder is rare and thus over-diagnosed; others believe the opposite, so there’s little agreement. It’s also difficult to diagnose the disorder in children, because symptoms can overlap with other diagnoses like conduct disorders or Attention Hyperactivity Deficit Disorder (ADHD)–which can occur in conjunction with bipolar disorder, making an accurate diagnosis even more tricky.

So, if you suspect your child has bipolar disorder, please speak with a mental health professional specializing in disorders in children. Ask your pediatrician for recommendations.

Stay tuned for next week’s post: What to do if Your Child has Bipolar Disorder.

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How to Apply for Disability Benefits for Mental Disorders

Sometimes people just need a little help. If you can prove that you have a disability that prevents you from working, you may qualify for Social Security Disability Insurance (SSDI) or Social Security Income (SSI).

Types of Benefits

SSDI is a benefit which offers monthly payments that requires you to have had a steady work history over the past decade. You must have a disability and submit an application to the Social Security Administration (SSA). You must also currently be able to earn no more than $1,170 per month, and your condition must prevent you from working for a year–either the past year, or the foreseeable future. SSDI needs you to have earned 40 “work credits,” where you earn and pay taxes on a minimum of $1,260 per month. You can gather up to four work credits per year. Twenty of them must be earned in the decade before the disability was diagnosed. Younger claimants may qualify based on their parents’ work history.

SSI, on the other hand, is a needs-based program. To qualify, you may not own more than $2,000 in assets excluding your home and one vehicle worth $4,500 or less. If you’re married, you may own up to $3,000 in assets. Your income must be below a certain threshold depending on where you live.

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Which Disabilities Are Accepted

The SSA publishes a “Blue Book” which describes the criteria required for disabilities to be accepted for benefits. Bipolar disorder and other mood disorders are part of this Blue Book, as well as schizophrenia, anxiety disorders, and intellectual disabilities, like autism. Unfortunately, illnesses like bipolar disorder or depression need a great deal of evidence to demonstrate that your condition impairs your ability to work, even after treatment.

Application Process

The process to apply for these benefits for a mental disorder is not that much different from applying for a physical disability. Your best bet in submitting an application is to visit your local SSA office. There, you can talk to a representative who will help you fill out the forms. If you’re not comfortable with talking to the representatives in person, you can call them. They will fill out the forms for you and send a medical release form for you to sign, along with a postage-paid envelope. They will also let you know what documents you need to send them in order to prove your disability, like medical records from up to a year before your disability diagnosis.

Medical Records

The SSA is obligated to help you find and submit all of your medical records, though if you submit them yourself, your case will be delayed less. List all of your treatment team and where they work on your application form, from counselors to psychiatrists. The SSA will have you sign an Authorization to Disclose Information (SSA-827) to obtain the required records from your providers. Your medical records should contain the results of any tests–like IQ tests in the case of intellectual disabilities–as well as treatment notes. Your doctor can also fill out an optional mental residual functional capacity (RFC) assessment form, which is the best thing you can do for your case, as it demonstrates your doctor’s opinion on whether or not you can function.

It is very important to provide evidence towards your disability, like diagnoses, treatment plans, prognoses, every medication tried, and how you responded to medication. In the best case scenario, your treatment notes will include details on how your disability impedes your ability to work.

ADLs

The representative will also have you fill out a survey about your “activities of daily living,” or ADL. The Function Report form (SSA-3373) makes you describe how your disorder impairs your daily life, including during social engagements, housework, shopping, transportation, and how you spend money. If you have trouble working with coworkers or following instructions, then you need to talk about that in your ADL.

Managing Expectations

Try not to get your hopes up that your initial claim will be approved. Over 60% of claims are denied at first, and over 80% of appeals are denied. That’s not to say you shouldn’t appeal! You definitely should. You may consider hiring a Social Security Disability lawyer to help you fill out your forms and represent you in your hearing with an Administrative Law Judge.

You can be disqualified from receiving benefits by not following your doctor’s treatment plan. It’s very important to take your medication and attend your talk therapy appointments during your application process.

Applying for disability benefits can be a daunting procedure, but it can be done. It takes effort and patience and communication with your treatment team. Make sure that you jump in feet first.

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Antibiotics Linked to Manic Episodes

Have you ever taken an antibiotic and felt more manic? There might be a reason for that.

 

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Researchers have found a link–not cause and effect, mind, just a link–between antibiotics and manic episodes in people with mental disorders. Robert Yolken and a research team at John Hopkins University reviewed medical records of patients treated for mania, major depression, bipolar disorder, and schizophrenia at the Sheppard Pratt, a psychiatric hospital in Baltimore. The scientists also surveyed over five hundred controls–people without mental disorders–about their antibiotic use.

 

What they found is shocking. In the manic patients, 7.7 percent were taking antibiotics, compared to 1.3 percent of the controls. This is a more than a fivefold increase in the odds of being in the mania group. However, only 4 percent of the people hospitalized for bipolar depression and 3 percent of the people hospitalized for schizophrenia were taking antibiotics.

Yolken’s team examined whether the place of infection, such as the mouth, skin, or respiratory system correlated with hospitalization, and determined that the site of the infection didn’t seem to matter.

There are several ways that antibiotic use could impact psychiatric symptoms. The infection itself could lead to inflammation. Or the antibiotic could kill off good bacteria, which could also lead to inflammation.

The research team is conducting more studies to see how this link works. For example, one study is examining whether suppressing inflammation in the gut will reduce the recurrence of manic episodes.

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Bipolar Disorder is Toxic–Literally

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Apparently the blood of people with bipolar disorder is toxic to their brains. Let me explain.

Bipolar disorder, also known as manic-depressive illness, is a brain disorder characterized by changes in mood and energy levels, affecting a sufferer’s ability to function. People affected by the disorder endure periods of both mania–with elevated mood, irritability, and rapid thoughts–and depression.

Lately, researchers have begun classifying patients as early or late-stage. Early-stage patients have dealt with fewer mood episodes; late-stage patients have dealt with more frequent and more severe episodes.

A recent study compared neurons exposed to blood serum from bipolar patients to neurons exposed to blood serum from healthy controls. Researchers Fabio Klamt and Flávio Kapczinski found that the first neurons suffered a significant loss in the density of neurites, which estimate the number of brain connections. However, neurons exposed to serum from early-stage bipolar disorder patients showed no difference in neurite density compared to the healthy controls’. The scientists also found that, except for those neurons exposed to serum from patients at very late stages of the disease, the number of neurons weren’t that different between samples.

Previous studies have shown that people with bipolar disorder have lower neurotrophins–proteins that promote brain growth. Also lowered is the early-growth response 3 (EGR3), a protein which helps the brain cope with stressors such as environmental changes and overstimulation. In addition, another study showed that bipolar patients have abnormally low levels of chemokines–proteins that signal other cells, so reactions to stimuli are slower.

So, what does that all mean? In short: researchers have found definitive proof that the blood of people with bipolar disorder is toxic to their brains. The more mood episodes a person has, the fewer brain connections he or she will create, and the slower their brains will grow. People in later stages of the disease also produce more cells which impair the brain’s ability to deal with environmental changes, inflammation, and stress.

Further studies will concentrate on creating drugs which can offset the toxicity of the bipolar patients’ blood.

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Antibodies That Cause Encephalitis Linked to Psychosis

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Psychosis, a break from reality, is a common feature of bipolar disorder. People can suffer delusions, hallucinations, depression, anxiety, and incoherent speech. The breaks are especially dangerous for postpartum women, who may harm their infants. The causes of psychosis are varied, ranging from mental illnesses such as schizophrenia or bipolar disorder, to sleep deprivation, substance abuse, or prescription drugs.

But new research has linked psychosis to antibodies that cause encephalitis, a life-threatening disease which inflames the brain. There is hope that removing these antibodies will treat psychosis just as much as doing so treats encephalitis. Some of the antibodies act against a nerve cell protein called NMDAR, or the NMDA receptor.

Belinda R. Lennox, a psychiatry professor at the University of Oxford in the United Kingdom, led a team of researchers who conducted a study on 228 people with first-episode psychosis. The scientists drew blood from the patients within the first six weeks of treatment. They also collected blood from a group of healthy people and used that as the control group for the study.

Seven–three percent–of the patients with first-episode psychosis presented with NMDAR antibodies. None of the controls did. A previous study from 2015 found that children experiencing their first episode of psychosis also had antibodies relating to the NMDAR.

The good news is that, Lennox and her team, using an experimental immunotherapy that targets the antibodies, successfully treated patients with psychosis, and helped them recover function after their episodes.

Three percent may not be much, but it’s three percent more of people who may be able to be treated with immunosuppressant therapies. This is a significant minority, one that shows promise. Lennox and her team plan to conduct a randomized, controlled trial of immune treatment in people with psychosis in 2017.

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