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In research using patient medical records, investigators from Johns Hopkins and Sheppard Pratt Health System report that people with serious mental disorders who were hospitalized for mania were more likely to be on antibiotics to treat active infections than a group of people without a mental disorder.

Although the researchers caution that their study does not suggest cause and effect, they note that it does suggest that an infection, use of antibiotics or other factors that change the body’s natural collection of gut and other bacteria may individually or collectively contribute to behavioral changes in some people with mental disorders.

Their findings, published in Bipolar Disorders, add to evidence that the body’s immune system, the so-called gut brain axis, and the particular bacterial microbiome each person has play an integral part in the ebb and flow of psychiatric symptoms and psychiatric disorders, including bipolar disorder and schizophrenia.

“More research is needed, but ours suggests that if we can prevent infections and minimize antibiotic treatment in people with mental illness, then we might be able to prevent the occurrence of manic episodes,” says Robert Yolken, M.D., the Theodore and Vada Stanley Distinguished Professor of Neurovirology in Pediatrics at the Johns Hopkins University School of Medicine. “This means we should focus on good-quality health care and infection prevention methods for this susceptible population and pay extra attention to such things as flu shots, safe sex practices and urinary tract infections in female patients.”

Yolken says his team’s study grew out of an interest in long-observed connections among infections, the microbiome and symptoms of mental illness. For example, numerous studies have shown that experimental alterations in the microbiome of animals can alter their behavior.

Because antibiotics kill bacteria and can disrupt the makeup of the microbiome, Yolken and his research colleagues looked at records of antibiotic use in patients treated at the Sheppard Pratt – a psychiatric hospital in Baltimore – either as an inpatient or day hospital patient. Just over 64 percent of the patients were female, and all were 18 to 65. Two hundred and thirty-four people were hospitalized for mania, 101 for bipolar disorder, 70 for major depression and 197 for schizophrenia. Patients taking antibiotics were receiving a wide range of medications, including tetracycline, penicillin, sulfonamide, cephalosporin, fluoroquinolone and macrolides for skin, respiratory, urinary tract and mouth infections.

For comparison, they surveyed 555 healthy controls ruled not to have a mental disorder, including 347 women and 208 men between the ages of 20 and 60, about their current antibiotic use.

The researchers examined antibiotic usage as an indirect way to measure for the presence of infection. Antibiotic usages were assessed through medical records with the patients and through an interview with participants in the comparison group.

Of those hospitalized for mania, episodes of heightened energy and overactivity often associated with bipolar disorder – 18 participants, or 7.7 percent, were taking antibiotics, compared to only 1.3 percent of the controls. This represents a more than fivefold increase in the odds of being in the mania group if taking antibiotics. On the other hand, just over 3 percent of people hospitalized for schizophrenia, 4 percent of people hospitalized for bipolar depression and 2.9 percent of people hospitalized for major depression were taking antibiotics.

The researchers investigated whether the site of infection, such as mouth, skin or respiratory system, correlated with hospitalization, and they found that location of the infection didn’t seem to matter, although 15 women had urinary tract infections, which didn’t occur in any men.

Yolken says there are several ways that infection and antibiotic use could directly or indirectly impact psychiatric symptoms. Among the possibilities are that systemic inflammation caused by the infection itself may lead to psychiatric symptoms or, alternatively, that antibiotics disrupt the gut’s microbiome by killing off “good bacteria,” which may also affect the mind by increasing inflammation if more “bad bacteria” are present.

Yolken says that the research team is currently looking for how these connections might actually work. One study is investigating, for example, whether suppressing inflammation in the gut with probiotics in people with mental illness will reduce the recurrence of manic episodes.

The study was funded by grants from the Stanley Medical Research Institute and the National Institute of Mental Health (grant number PA 50 MH942680).

Article: Individuals hospitalized with acute mania have increased exposure to antimicrobial medications, Robert Yolken, Maria Adamos, Emily Katsafanas, Sunil Khushalani, Andrea Origoni, Christina Savage, Lucy Schweinfurth, Cassie Stallings, Kevin Sweeney and Faith Dickerson, Bipolar Disorders, doi: 10.1111/bdi.12416, published online 17 July 2016.

Long delays mean missed opportunities for early intervention to reduce the severity of episodes of bipolar disorder.

Crucial opportunities to manage bipolar disorder early are being lost because individuals are waiting an average of almost six years after the onset of the condition before diagnosis and treatment.

That is the key finding of a joint UNSW Australia and Italian study published in the Canadian Journal of Psychiatry.

The meta-analysis of 9,415 patients from 27 studies, the largest of its kind, was led by clinical psychiatrist and Conjoint Professor Matthew Large from UNSW’s School of Psychiatry and his colleague, Dr Giovanni de Girolamo, from the St John of God Research Centre, Italy.

Many patients experience distressing and disruptive symptoms for many years until receiving proper treatment for bipolar disorder, which was previously known as manic depressive illness.

According to the lead researcher, Professor Large, a psychiatrist at Prince of Wales Hospital, the delay is often longer for young people because moodiness is sometimes mistaken by parents and doctors as the ups and downs of the teenage years rather than the emergence of bipolar disorder, which can be effectively treated with mood stabilising medication.

“This is a lost opportunity because the severity and frequency of episodes can be reduced with medication and other interventions,” Professor Large said.

“While some patients, particularly those who present with psychosis, probably do receive timely treatment, the diagnosis of the early phase of bipolar disorder can be difficult”.

“This is because mental health clinicians are sometimes unable to distinguish the depressed phase of bipolar disorder from other types of depression.”

“The diagnosis of bipolar disorder can also be missed because it relies on a detailed life history and corroborative information from carers and family, information that takes time and care to gather”.

“Clinicians should look more closely at a patient’s history of mood symptoms, looking for distinct changes in mood, and other risk factors, for example, a family history and mood swings caused by external events such as treatment withantidepressants, overseas travel and taking drugs,” Professor Large said.

The researchers are calling for a consistent approach to the recording of the onset of symptoms of bipolar disorder, further studies on the early symptoms and predictors of bipolar disorder and the reasons for treatment delay.

The study was conducted in collaboration with researchers from St Vincent’s Hospital, Sydney and Italy’s St John of God Clinical Research Centre and University of Bari.

Brain scans have revealed how a genetic mutation linked to major psychiatric disorders affects the structure, function and chemistry of the brain.

The study offers further clues about how the mutation increases the risk of schizophrenia, bipolar disorder anddepression.

Experts say the findings could help in the quest for new treatments.

Researchers led by the University of Edinburgh scanned the brains of people that have a specific genetic mutation that causes part of one chromosome to swap places with another.

The mutation results in disruption of a gene called DISC1, which is associated with schizophrenia, bipolar disorder and recurrent major depression.

The team found that people with the genetic mutation had changes in the structure of their brain. These changes were linked with the severity of their symptoms of mental ill health.

They also showed that carriers of the mutation had lower levels of a chemical called glutamate in certain areas of their brain. Reduced glutamate levels have been strongly linked with schizophrenia in previous studies.

Researchers say their findings confirm that the DISC1 mutation is associated with a significantly increased risk of psychiatric illness.

They hope that continuing to study people with the mutation will reveal new insights to the biological mechanisms that underpin these conditions.

The DISC1 mutation was first identified in a Scottish family that showed unusually high rates of major psychiatric disorders. Scientists have been studying generations of the family for 40 years but this is the first time they have scanned their brains.

The study is published in the Nature partner journal Schizophrenia and was funded by the Translational Medicine Research Collaboration – a consortium of Scottish universities and NHS Health Boards, Scottish Enterprise and Pfizer.

Professor Stephen Lawrie, Head of the Division of Psychiatry at the University of Edinburgh, said: “This study confirms and extends the genetics of DISC1, and shows how that and similar genetic effects can increase the risk of major mental illnesses.”

Article: Balanced translocation linked to psychiatric disorder, glutamate, and cortical structure/function, Pippa A Thomson, Barbara Duff, Douglas H R Blackwood, Liana Romaniuk, Andrew Watson, Heather C Whalley, Xiang Li, Maria R Dauvermann, T William J Moorhead, Catherine Bois, Niamh M Ryan, Holly Redpath, Lynsey Hall, Stewart W Morris, Edwin J R van Beek, Neil Roberts, David J Porteous, David St. Clair, Brandon Whitcher, John Dunlop, Nicholas J Brandon, Zoë A Hughes, Jeremy Hall, Andrew McIntosh & Stephen M Lawrie, Schizophrenia, doi:10.1038/npjschz.2016.24, published online 10 August 2016.

Major depression and bipolar disorder put teenagers at greater risk for heart disease and should be considered as independent risk factors for the condition. This is according to a scientific statement from the American Heart Association, published in the journal Circulation.

Previous research has associated mood disorders in adults with greater risk for heart problems. In February 2014, for example,Medical News Today reported on a study claiming depression is acausal risk for coronary heart disease among adults.

What is more, studies have indicated that adults with major depression and bipolar disorder are more likely to suffer heart disease at an earlier age.

Lead author of the scientific statement Dr. Benjamin I. Goldstein – a child-adolescent psychiatrist at Sunnybrook Health Sciences Centre and the University of Toronto in Canada – and colleagues systematically assessed published research investigating the risk of heart disease among adolescents with mood disorders.

The team found that teenagers with major depression or bipolar disorder were more likely to have a number of risk factors for heart disease – including hypertension, high cholesterol, obesity, type 2 diabetes and atherosclerosis – compared with teenagers without these mood disorders.

The increased cardiovascular risk factors identified among adolescents with bipolar or major depression were not fully explained by other factors, such as lack of exercise, smoking or drug abuse, according to the statement authors.

While medication for mood disorders is associated with weight gain, hypertension, high cholesterol and increased blood sugar levels, the team notes that the majority of the teenagers included in the studies were not receiving such medication.

Dr. Goldstein and colleagues are unable to explain the biological causes behind their findings, but they point to previous studies that have associated adolescent mood disorders with increased inflammation and other forms of cell damage.

Early action needed to lower heart disease risk in teens with mood disorders

According to the National Institute of Mental Health, in 2012, around 2.2 million American teenagers aged 12-17 had a major depressive episode in the past year, while a 2012 study estimated that around 2.5% of adolescents aged 13-18 in the US have met the criteria for bipolar disorder in their lifetime.

Based on their findings, Dr. Goldstein and colleagues conclude that major depression and bipolar disorder should be classified as moderate risk factors for heart disease in teenagers. He says:

“Mood disorders are often lifelong conditions, and managing cardiovascular risk early and assertively is tremendously important if we are to be successful in ensuring that the next generation of youth has better cardiovascular outcomes.

These disorders indicate an increased risk of heart disease that requires increased vigilance and action at the earliest possible stage.”

Dr. Goldstein hopes that the scientific statement will prompt adolescents with depression or bipolar, their families and health care providers to take early action to reduce heart disease risk.

In June, MNT reported on a study that found individuals who suffer from panic disorder may be at greater risk of heart attack and heart disease later in life.

A new study finds behavior patterns such as risky behavior, psychomotor agitation and impulsivity occur before 50% of suicide attempts.

The findings were recently presented at the 28th European College of Neuropsychopharmacology (ECNP) Congress in Amsterdam, the Netherlands.

The study researchers analyzed 2,811 individuals with depressionwho were a part of the Bridge-II-MIX study – an international study of depression and suicide. All participants were assessed by a psychiatrist using the Diagnostic and Statistical Manual of Mental Disorders (DSM) – the standard classification of mental disorders used by mental health professionals in the US.

Many parameters were studied, including previous suicide attempts, family history, current and previous treatments and the patient’s clinical presentations. Psychiatric symptoms, sociodemographic and clinical risk factors for bipolar disorder were also collected. Of the participants, 628 had already attempted suicide.

“The strength of this study is that it’s not a clinical trial, with ideal patients – it’s a big study, from the real world,” says study author Dr. Dina Popovic, a psychiatrist at Barcelona Hospital Clinic and the Clinical Research Institute of Biomedical Research in Spain.

Suicide is the 10th leading cause of death for Americans, according to the American Foundation for Suicide Prevention.

Among American men, the suicide rate is about four times higher than among women. The suicide rate for Americans is also higher in white men (14.2 deaths per 100,000) than Native Americans (11.7 deaths per 100,000).

Dr. Popovic says they found that “depressive mixed states” often preceded suicide attempts and that mixed depressive features were associated with hallmarks of bipolarity. She explains:

“A ‘depressive mixed state’ is where a patient is depressed, but also has symptoms of ‘excitation,’ or mania. We found this significantly more in patients who had previously attempted suicide, than those who had not. In fact, 40% of all the depressed patients who attempted suicide had a ‘mixed episode’ rather than just depression.”

Patients who suffer from ‘mixed depression’ are at a much higher risk of suicide

A comparison was made between those who had and those who had not attempted suicide but who were depressed.

Risk of attempting suicide is at least 50% higher, the scientists found, if a depressed patient presents any of the following symptoms:

• Risky behavior (for example, reckless driving, promiscuous behavior)
• Psychomotor agitation (pacing around a room, wringing one’s hands, pulling off clothing and putting it back on and other similar actions)
• Impulsivity (acting on a whim, displaying behavior characterized by little or no forethought, reflection or consideration of the consequences).

There is an important message here, the study says, for all health care professionals who see patients suffering from depression and who may not pay enough attention to these symptoms. Early identification of symptoms and timely treatment of mixed depressive states could represent a major step in suicide prevention.

Dr. Popovic adds:

“In our opinion, assessing these symptoms in every depressed patient we see is extremely important, and has immense therapeutical implications. Most of these symptoms will not be spontaneously referred by the patient, the clinician needs to inquire directly, and many clinicians may not be aware of the importance of looking at these symptoms before deciding to treat depressed patients.”

In a previous report from Medical News Today, a draft recommendation issued by the US Preventive Services Task Force suggested that doctors should screen all adults for depression.

Diagnosing bipolar disorder is a difficult task. No chemical markers are yet known, and prescribing the wrong treatment can be detrimental. A new study makes headway into this complex arena.

Bipolar Disorder previously referred to as “manic depression” involves extreme changes in activity levels within sufferers.

Different from life’s normal ups and downs, those with bipolar disorder experience the most manic highs and the most dismal lows.

Bouts of sleeplessness, racing thoughts and delusions of grandiosity give way to boundless swathes of the bleakest misery.

The effects on everyday life can be devastating; relationships, jobs and friendships can be shattered. Bipolar can be treated, but it is essential that diagnosis of the condition is accurate.

There is a nebulous array of symptoms, many of which overlap with other conditions, such as unipolar depression, schizophrenia and other personality disorders.

To muddy the waters further, there are a number of different bipolar conditions to consider.

Types of bipolar disorder

According to the Diagnostic and Statistical Manual of Mental Disorders (DSM), there are four recognized clinical subsections within bipolar disorder:

• Bipolar I disorder: manic episodes that last at least 1 week. The attacks may be so severe that the individual needs immediate hospitalization. Depressive episodes are also present, often 2 weeks in duration
• Bipolar II disorder: depressive episodes and hypomanic (less serious than manic) episodes. No full manic episodes
• Bipolar Disorder Not Otherwise Specified (BP-NOS): bipolar symptoms are presented but do not fit the criteria for types I or II
• Cyclothymic Disorder (Cyclothymia): episodes of hypomania and mild depression for at least 2 years but not meeting the diagnostic requirements of the bipolar types above.

Current diagnosis of bipolar disorder is purely interview based; sometimes a brain scan and blood test are involved, but these are only to rule out other potential conditions. There are no blood-based or scan anomalies that can assist in the diagnosis.

People with bipolar disorder are often substance abusers. The reasons for this link are unclear, but a certain amount of self-medication is thought to be involved. This can add its own mental health issues and potentially increase the severity of depressive symptoms, making diagnosis more difficult.

Because of the disruptive effect of bipolar on an individual’s life, it is essential that the correct diagnosis is made as swiftly as possible.

A protein marker for bipolar disorder?

Recent research carried out by the Mayo Clinic attempts to identify a marker in the blood for bipolar. To this end, they investigated 272 different proteins within 288 patients’ blood samples.

The group of participants was split between bipolar I disorder (46), bipolar II disorder (49), unipolar depression (52) and 141 individuals without mood disorders, to act as controls.

The researchers believe this biochemical study to be:

“One of the first studies to assess the feasibility of high throughput multiplexed immunoassay technology (272 proteins) trying to distinguish different types of mood disorders.”

The team found 73 of the measured proteins differed between the four study groups, and six were found to significantly differ between bipolar I disorder and the control group.

Although the trial is on a relatively small scale, it gives a starting point for the next round of investigations.

Previous research and hope for the future

Although there is no cure for bipolar disorder, many people do respond well to treatment. Sadly, symptoms generally persist, even once treatment has begun.

The sooner medication begins and the closer an individual works with health care professionals, the better the outcome. A quicker and more accurate diagnosis could positively influence the lives of sufferers.

Previous research, looking at proteins in cerebrospinal fluid, threw out some interesting results. They found altered concentrations of neurofilament light chain proteins (a marker for nerve damage) in participants with bipolar disorder.

Other studies have found elevated levels of C-reactive protein (a protein of the immune system involved in inflammation) in people with bipolar disorder.

Researchers elsewhere have searched for links between bipolar and increased levels of brain-derived neurotrophic factors (factors involved in nerve growth).

Science has certainly carved inroads toward a deeper understanding of bipolar chemistry, and this current study is the next level. Dr. Mark Frye, lead author of the study and head of psychiatry and psychology at Mayo Clinic, says:

“The potential of having a biological test to help accurately diagnose bipolar disorder would make a huge difference to medical practice. It would then help clinicians to choose the most appropriate treatment for hard-to-diagnose individuals.”

A reliable and consistent biomarker for bipolar disorder may still be some distance away, but now more than ever, it seems plausible. Perhaps even imminent.

Medical News Today recently covered research showing that bipolar may increase the risk of heart disease in teens.

A recent study published in the Proceedings of the National Academy of Sciences finds links between sleeping patterns, circadian rhythms, bipolar disorder and specific phenotypes.

Bipolar Disorder previously referred to as manic depression, is characterized by periods of hyperactivity followed by bouts of depression.

The manic phase can include feelings of creativity, racing thoughts and delusions of grandeur. The lows might involve lethargy and feelings of worthlessness.

According to the National Institute of Mental Health, around 2.6% of the adult population of America has experienced bipolar disorder in the last 12 months.

Despite the large number of individuals with the condition, the exact causes of bipolar, as with many other mental disorders, are not known. Genetics, however, do seem to be of importance; bipolar disorder is known to run in families.

Sleep and bipolar disorder

Sleep and circadian rhythms are also known to play a part in bipolar disorder. Manic phases generally see the individual sleeping less; conversely, during depressive periods, sleep is often more prevalent.

Some researchers have concluded that sleep might be a factor in bipolar relapses, or perhaps an early warning sign of bipolar events on the horizon.

The current research, carried out by Dr. Joseph Takahashi at the University of Texas Southwestern Medical Center and the University of California-Los Angeles, takes a deeper look at the familial component of bipolar disorder and its specific effects on sleep patterns.

Twin studies have already shown that there is a genetic component to some sleep parameters. For instance, the quantity of rapid eye movement (REM) and delta sleep that an individual has during a night’s sleep is more similar in people who are more genetically alike.

Dr. Takahashi’s study looks to bring the genetics of sleep research and the circadian facets of bipolar disorder into the same frame.

The investigation focused on 558 members of 26 families from Central Valley, Costa Rica, and Antioquia, Colombia. This group consisted of 136 individuals with bipolar disorder and 422 of their relatives without the disorder.

Each participant wore an accelerometer on their wrist for 14 days. The data from these devices allowed the research team to define their sleep-wake cycles and the amount of general activity each participant undertook.

Dr. Takahashi says:

“We were able to identify 13 sleep and activity measures, most of which are inherited, that correlated with whether an individual had bipolar disorder. In addition, we were able to trace some of these traits to a specific chromosome.”

The study showed that, in general, individuals with bipolar disorder were less active while they were awake, they went to sleep later and slept for longer than non-bipolar individuals.

Circadian differences in bipolar disorder

Below is a list of the specific sleep and circadian phenotypes that were found to significantly vary between those with bipolar disorder and those without:

• Mean awake duration: average length of time spent awake per day
• Amplitude: a measure of the strength of an individual’s circadian rhythm
• Hill acrophase: time of day at which activity peaked
• Interdaily stability: the degree of variation in levels of activity each day
• Interdaily variability: a measure of the fragmentation of circadian rhythm
• Median activity: average amount of activity per day
• Relative amplitude: the difference between the least and the most intense periods of activity across 24 hours
• Mean length of sleep bouts during the sleep period: average amount of time spent in each bout of sleep during the night
• Mean number of sleep bouts during awake period: average length of naps during the day
• Time of sleep offset: time of awakening in the morning
• Mean total minutes scored awake: average time spent awake per day
• WASO: total minutes spent awake after the onset of sleep.

The study is the first to link specific phenotypes to the etiology of bipolar disorder. The hope is that these findings will help unravel the mechanisms of the disease and potentially provide novel targets for future pharmaceutical interventions.

Everyone has days when they feel low, but when these symptoms persist and impact on someone’s life, then antidepressants are used to relieve the symptoms. They are used for:

• Moderate to severe depressive illness (Not mild depression)
• Severe anxiety and panic attacks
• Obsessive compulsive disorders
• Chronic pain
• Eating disorders
• Post-traumatic stress disorder

Types of antidepressants

There are four types that may be prescribed:

You can find more information about these in our main leaflet.

How does it feel to take antidepressants?

Overall: After three months of treatment, 5-6 out of 10 people with depression will feel much improved.

Side effects of antidepressants?

Most people only get mild side-effects which wear off over a couple of weeks, but you should be aware of them.

SSRIs and SNRIs: for the first couple of weeks, they can make you feel sick and anxious. This can cause indigestion, but this improves if you eat. They can also cause diarrhoea, constipation and tiredness. They can interfere with your sexual function.

Venlafaxine is an SNRI and it can increase your blood pressure, so this should be monitored regularly.

Are antidepressants addictive?

Antidepressants are not addictive like tranquillisers, alcohol or nicotine. You don’t need to keep increasing the dose for them to work and you don’t find yourself craving them.

But, one third of people who stop SSRIs and SNRIs can get withdrawal symptoms. These include stomach upsets, flu-like symptoms, anxiety, dizziness, vivid dreams at night or sensations in the body that feel like electric shocks. These withdrawal effects are usually mild, but for some people they can be quite a problem.

It is best to reduce the dose gradually rather than stop it suddenly.

What about driving or operating machinery?

Some antidepressants (especially the tricyclics) make you sleepy and slow down your reactions.  Remember, depression itself will interfere with your concentration and make it more likely that you will have an accident. If in doubt, check with your doctor.

Do people experience feelings of suicide?

Evidence suggests that young people who take SSRIs have increased suicidal thoughts (but not actual suicidal acts). Therefore, in the UK, SSRIs are not licensed for people under 18, although specialists may use Fluoxetine in some cases.

There is no clear evidence that adults have an increased risk of self-harm and suicidal thoughts if they take antidepressants. It is known that younger adults are more likely to commit suicide than older adults, so a young adult needs close monitoring if they take an antidepressant.

How long will I have to take them for?

Antidepressants don’t necessarily treat the cause of the depression or take it away completely. If you stop the medication too soon, the symptoms of depression are more likely to come back. It is  best to take antidepressants for at least six months after you start to recover. During this time, it is worth thinking about what might have triggered off your depression and ways to prevent it happening again. If you have had two or more attacks of depression, then you should take an antidepressant for at least two years.

What if the depression comes back?

Some people have repeated depressions and need to take antidepressants for several years to control them. Sometimes other drugs, such as lithium, may be used. Psychotherapy can help alongside to the tablets.

What other treatments for depression are available?

• Talking treatments are best for mild depression. Over a year, many talking treatments are as affective as antidepressants in moderate depression. However, antidepressants and psychotherapy (talking treatment) are often used together. Some talking treatments are now available in book form or as Internet modules.
• St John’s Wort:  Herbal remedies.
• Light boxes for seasonal affective disorder.

For more in-depth information see our main leaflet: Antidepressants

This leaflet reflects the most up-to-date evidence at the time of writing.

Produced by the RCPsych Public Education Editorial Board.

Series Editor: Dr Philip Timms

Reviewed by Dr Sophie Swinhoe