Infections, antibiotic use linked to manic episodes in people with serious mental illness

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).

 

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Study identifies symptoms of suicide risk for people with depression

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.

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Psychosis: Causes, Symptoms, and Treatments

Broadly speaking, psychosis means a loss of contact with reality; it is a symptom of mental illness rather than a medical condition in its own right.

Generally, there are two types of psychiatric disorder that produce psychotic symptoms: schizophrenia and mood disorders, such as bipolar disorder.

This page offers a full description of psychosis, what causes it, and how it is treated.

Fast facts on psychosis

Here are some key points about psychosis. More detail and supporting information is in the main article.

  • Psychosis is not a disease in its own right; it is a symptom
  • A common psychotic delusion is the belief that the patient is an important figure
  • Earlier diagnosis of psychosis improves long-term outcomes

What is psychosis?

[Sad man by window]
Psychosis is a symptom rather than a disease.

Psychosis is an umbrella term and means that an individual experiences things that no one else experiences and has beliefs with no basis in reality.

Psychosis is classically associated with schizophrenia spectrum disorders, and, while there are other symptoms, one of the defining criteria for schizophrenia is the presence of psychosis.

Other disorders also have psychotic symptoms, including:

  • Schizophrenia
  • Schizoaffective disorder and other subtypes of schizophrenia
  • Acute and transient psychotic disorders
  • Bipolar disorder (previously known as manic depression)
  • Major depressive disorder with psychotic features
  • Postpartum (also called postnatal) psychosis – a severe form of postnatal depression
  • Substance-induced psychosis (including alcohol, certain illegal drugs, and some prescription drugs, including steroids and stimulants)

These are the primary causes of psychotic symptoms, but psychosis can also be secondary to other disorders and diseases, including:

Causes of psychosis

The exact causes of psychosis are not well understood but might involve:

  • Genetics – research shows that schizophrenia and bipolar disorder may share a common genetic cause.
  • Brain changes – alterations in brain structure and changes in certain chemicals are found in people who have psychosis. Brain scans have revealed reduced gray matter in the brains of some individuals who have had a history of psychosis, which may explain effects on thought processing.
  • Hormones/Sleep – postpartum psychosis occurs very soon after giving birth (normally within 2 weeks). The exact causes are not known, but some researchers believe it might be due to changes in hormone levels and disrupted sleep patterns.

Symptoms of psychosis

Psychotic symptoms can be separated out and given specific descriptions. The classic signs of psychosis are:

  • Hallucinations – hearing, seeing, or feeling things that do not exist
  • Delusions – false beliefs, especially based on fear or suspicion of things that are not real

Psychotic symptoms in disorders such as schizophrenia may also include:

  • Disorganized thought, speech, or behavior
  • Disordered thinking – jumping between unrelated topics, making strange connections between thoughts
  • Catatonia – unresponsiveness

Depending on the cause, psychosis can come on quickly or slowly. The same is the case in schizophrenia, although symptoms are more likely to have a slow onset and begin with milder psychosis, which in some cases does not convert to the full disorder.

The slow onset of schizophrenia (also called the prodromal phase) is often not recognized by the patient or their family and friends. The milder, initial symptoms of psychosis might include:

  • Feelings of suspicion
  • Distorted perceptions
  • Depression and suicidal feelings
  • Obsessive thinking
  • Sleep problems

Hallucinations can affect any of the senses (sight, sound, smell, taste, and touch) in the person with psychosis, but in about two-thirds of patients with schizophrenia, hallucinations are auditory – hearing things and believing them to be real when they do not exist.

The following auditory hallucinations are common in schizophrenia:

  • Hearing several voices talking, often negatively, about the patient
  • A voice giving a commentary on what the patient is doing, or
  • Repeating what the patient is thinking

Bizarre delusions are experienced during psychosis

[Man hallucinating]
Paranoia is a common part of psychotic delusions.

Examples of psychotic delusions include the paranoid type – more likely to be associated with schizophrenia – and delusions of grandeur.

Paranoid delusions: these may cause the person with psychosis to be unduly suspicious of individuals or organizations, believing them to be plotting to cause them harm.

Delusions of grandeur: clearly false but strongly held belief in having a special power or authority – for instance, they may believe that they are a world leader.

Diagnosis of psychosis

In this section, we will discuss the available tests and methods for diagnosing psychosis.

Early diagnosis

Early diagnosis of psychosis improves long-term outcomes. This is not always achieved, however. The milder forms of psychosis that can lead to schizophrenia are left untreated for an average of 2 years, and even full psychosis can take a number of years before it receives the attention of medical professionals.

To increase the chances of early detection, guidance for healthcare systems drawn up by psychiatrists recommend that the “possibility of a psychotic disorder should be carefully considered” in a young person who is:

  • Becoming more socially withdrawn
  • Performing worse for a sustained period at school or work, or
  • Becoming more distressed or agitated yet unable to explain why

There is no biological test for psychosis itself, and if laboratory tests are done, it is to rule out other medical problems that might provide an alternative explanation.

Questions for patient and family

Psychosis is primarily diagnosed by clinical examination and history – the doctor examines the patient and asks about their symptoms, experiences, thoughts, and daily activities, and they will also ask if there is a family history of psychiatric illness.

Other medical conditions are ruled out first of all, especially delirium (sudden onset of a confused state), but epilepsy and a number of other medical explanations are possible.

Doctors will also check for any history of intoxication with drugs, both legal and illegal, and toxins, usually asking for a urine sample to check this.

Once psychosis is narrowed down to a psychiatric cause, there are clearly defined criteria that must be met before a diagnosis is confirmed. Psychiatrists generally rely on the American Psychiatric Association (APA)’s publication known as the DSM (Diagnostic and Statistical Manual of Mental Disorders) to make psychiatric diagnoses.

Brain scans

Brain scans may be done in the early stages of medical attention so that other conditions – often treatable and reversible – can be ruled out.

EEG (electroencephalography) testing records the brain’s electrical activity and may help to rule out delirium, head injury, or epilepsy as possible causes of psychotic symptoms.

Treatments for psychosis

In this section, we discuss the treatments for psychosis and some methods of prevention.

Antipsychotic drugs

Treatment with a class of drugs known as antipsychotics is the most common therapy for people with a psychotic illness.

Antipsychotics are effective at reducing psychosis symptoms in psychiatric disorders such as schizophrenia, but they do not themselves treat or cure underlying psychotic illnesses.

So-called second-generation antipsychotics are most commonly used by doctors to treat psychosis. While their use is widespread in the United States, this is controversial. The World Health Organization (WHO) does not recommend them, except clozapine (branded Clozaril and FazaClo in the U.S.), which may be used, under special supervision, if there has been no response to other antipsychotic medicines.

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Cannabis use affects processing of emotions

 

Cannabis appears to have a significant impact on the recognition and processing of human emotions like happiness, sadness and anger, according to research published in the journal PLOS One.

Scientists are only just starting to understand how cannabis affects the brain.

Cannabis consumption is known to cause immediate, residual and long-term changes in brain activity that can affect appetite and food intake, sleep patterns, executive function and emotional behavior.

Conflicting evidence has suggested that it can intensify both positive and negative mood states.

Lucy Troup, assistant professor of psychology at Colorado State University, and her graduate students wanted to look at how, if at all, cannabis use impacts a person’s ability to process emotions.

For nearly 2 years, the team has been conducting experiments using an electroencephalogram (EEG) to measure the brain activities of about 70 volunteers.

All the participants identified themselves as chronic, moderate or non-users of cannabis. They were all confirmed to be legal users of marijuana under Colorado Amendment 64, either medical marijuana users aged 18 years and above, or as recreational users aged 21 years or older.

An EEG can record a wide variety of generalized brain activity. In this study, the researchers used it to measure the “P3 event-related potential” of the participants.

P3 refers to the electrical activity in the brain that is triggered by noticing something visually. P3 activity is known to be related to attention in emotional processing.

Marijuana use may reduce ability to empathize

While connected to an EEG, participants responded to faces wearing four separate expressions: neutral, happy, fearful and angry. The team collected P3 data that captured the reactions in certain parts of the brain when subjects focused on the face.

Cannabis users responded more intensely to faces showing negative expression, particularly angry ones, compared with controls. Conversely, their response to positive expressions, represented by happy faces, was smaller than that of the controls.

Little difference was observed between the reactions of cannabis users and non-users when asked to pay attention to and “explicitly” identify the emotion.

However, cannabis users scored lower in a task that asked them to focus on the sex of the face and then to identify the emotion. This suggests a reduced ability to “implicitly” identify emotions and to empathize on a deeper emotional level.

The researchers conclude that cannabis affects the brain’s ability to process emotion, but that the brain may be able to counter the effects, depending on whether the emotions are explicitly or implicitly detected.

Troup comments:

“We’re not taking a pro or anti stance, but we just want to know, what does it do? It’s really about making sense of it.”

She explains that the aim of the emotion-processing paradigm was to see if the reactions in people who use cannabis would be different from those who do not.

In further studies, Troup is looking into the effects of cannabis on mood disorders like depression and anxiety, and one of her team members is investigating the effect of cannabis on learning.

Medical News Today recently reported that cannabis use could put young people more at risk of schizophrenia.

 

 

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Schizophrenia, bipolar tied to yeast infection

A current or previous infection with Candida albicans appears to be more common in some people with mental illness than people without the condition. This is according to a study that found this to be the case in a group of men with schizophrenia or bipolar disorder and a group of women with these disorders who had memory problems.

The study, led by Johns Hopkins University School of Medicine in Baltimore, MD, is published in the journal npj Schizophrenia.

The Johns Hopkins researchers are part of a group that is investigating whether pathogens – such as fungi, bacteria, or viruses – trigger or contribute to certain mental illnesses.

They caution that their findings do not show that Candida yeast infections cause mental illness or memory impairment, or vice versa, merely that they appear to be strongly related.

A more detailed investigation of lifestyle, immune system factors, and gut-brain connections could shed more light on the underlying cause-and-effect mechanisms, they note.

However, Emily Severance, first author and assistant professor of pediatrics, says, nevertheless, “clinicians should make it a point to look out for these infections in their patients with mental illness.”

She notes that most Candida infections are treatable in the early stages. They can also be avoided by reducing sugar intake and other changes to diet, improving hygiene, and avoiding unnecessary antibiotics.

C. albicans – a yeast-like fungus – is found in small amounts in the healthy gut of humans and animals, but it can get out of balance and cause infection. In infants and those with weakened immune systems, it can lead to rashes in the throat or mouth (thrush) and it can cause sexually transmittable genital yeast infections in men and women.

The infection can become severe if it enters the bloodstream. In most people, however, healthy levels of bacteria and a strong immune system can stop the fungus getting out of balance.

Different patterns of mental illness linked to Candida in men, women
For their study, the team tested blood samples from 808 people aged 18-65 for antibody evidence of a previous or current infection with Candida. The group included 261 individuals with schizophrenia, 270 people with bipolar disorder, and 277 without a history of mental disorder (the controls).

The researchers also included data from another group of 139 people with first-episode schizophrenia, 78 of whom had not yet been treated with medication.

After taking into account factors that could skew the results – such as age, race, medication, and socioeconomic status – the researchers looked for links between mental illness and yeast infection.

Overall, there was no link between presence of mental illness and current or previous yeast infection. It was when the team drilled down to look at men and women separately that the patterns emerged.

For example, in the men, they found 26 percent of those with schizophrenia had a current or previous Candida infection, compared with only 14 percent of the male controls.

However, among women, while a greater proportion had a current or previous yeast infection, the difference between those with schizophrenia and the controls was much smaller (31.3 percent versus 29.4 percent, respectively).

Men with bipolar disorder showed a similar higher rate of Candida infection, compared with controls (26.4 percent versus 14 percent).

However, when they looked more closely, the researchers found that the link between bipolar disorder and yeast infection in the men was most likely due to homelessness. No such explanation could be found in the men with schizophrenia, however.

Candida infection linked to worse memory for women with mental illness
The participants also took part in tests of mental ability, such as short-term memory, delayed memory, attention, language skills, and visual-spatial skills.

The mental skills tests showed no measurable differences in control men and women with and without a current or previous Candida infection. However, women with schizophrenia or bipolar disorder with current or previous Candida infection had lower scores on the memory tests, compared with women without infection.

The researchers note that while they could not show a direct link between Candida yeast infection and brain processes, the results show something linked to infection appears to affect memory performance in women with schizophrenia and bipolar disorder and warrants further investigation.

They point out that one drawback of their study design is the fact they could not tell which part of the body was affected by yeast infection, and whether or not participants had a current or past infection. Also, it was not possible to account for every lifestyle variable that might affect the results.

“Because Candida is a natural component of the human body microbiome, yeast overgrowth or infection in the digestive tract, for example, may disrupt the gut-brain axis. This disruption in conjunction with an abnormally functioning immune system could collectively disturb those brain processes that are important for memory.”

Prof. Emily Severance

Prof. Severance says she and her colleagues now plan to look at the gut-brain connection in mice to find out whether there is a cause-and-effect mechanism between Candida and memory deficits.

Learn how a breakthrough discovery about a gene sheds light on the biological origins of schizophrenia.

Written by Catharine Paddock PhD

 

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