14 January 2009

Maps highlight malfunctions in the mind

By
Cosmos Magazine
Advances in brain scanning are allowing psychiatrists to move from cautiously diagnosing symptoms to actually seeing the underlying malfunctions of the mind.
Mindmap

Electronic mapping of brain signals can assist in diagnosing mental conditions. Credit: Photolibrary

LAUREN BACK ALWAYS KNEW something was wrong with her mind, she just didn’t know what it was. “I always tried so hard at school but just wasn’t able to do it,” she says. “When I struggle, my mind is always where I don’t want it to be. I can’t help it if I don’t like the light, or if I’m not the right temperature. I can’t help it if I just had an argument on the phone before studying … But I knew that couldn’t be normal.”

With a family melting pot of disorders – her father has bipolar disorder and attention deficit hyperactivity disorder (ADHD), and her mother suffers from chronic fatigue syndrome, alcoholism and depression – Back inherited a susceptibility to psychiatric conditions.

At 16, the American teenager was diagnosed and treated for depression and anxiety, but her slow reading skills, poor time management, lack of concentration and procrastination continued. When the stresses of Back’s first year at the University of Colorado at Boulder tipped the journalism student into a breakdown, she knew there was more to her problems. “I just wasn’t surviving,” she says.

Determined to find out what was going on in her head, Back, now 23, sought help at a clinic in Boulder, Colorado. “I brought in a list of things that I knew just weren’t right,” she says. “It was a page long.”

The clinic used a powerful new technique which helps diagnose and treat mental disorders by peering into patients’ brains and analysing waves of electrical activity. Called quantitative EEG (short for electroencephalogram), or QEEG, the process detects biological markers for psychiatric disorders by measuring distinct patterns in a person’s brain waves.

Back’s QEEG results boiled down to charts, numbers and a two-dimensional map of her brain highlighting areas of weakness. Her brain waves revealed classic markers of ADHD.

Brain waves are electrical signals generated when neurons fire, and like instruments in an orchestra, different neurons have different frequencies at which they discharge.

Advances in computing in recent decades have allowed scientists to apply increasingly powerful mathematics to help glean more from an EEG than they can see unaided. These computations – the QEEG – show patterns such as the strength of brain waves at a particular frequency, the relationship between the waves, or how much the waves are in sync. The data are represented by scores and charts and mapped onto two-dimensional pictures of the brain. And slowly, researchers have found specific brainwave patterns that correlate to dozens of conditions, from ADHD and schizophrenia, to depression and dementia.

“The profile of a schizophrenic patient looks very different from a depressed patient. They each indicate abnormalities, but there are distinctive patterns,” says neuropsychiatrist Leslie Prichep, associate director of the Brain Research Laboratories at New York University, based at New York’s famed Bellevue Hospital. She has spent more than 30 years researching QEEG.

The use of such technology in psychiatry signifies the current shift in the field from a symptoms-based approach to diagnosing and treating mental disorders, to a more evidence-based approach that looks at the underlying causes of malfunctions in the mind.
As part of this shift, psychiatrists are beginning to readdress how disorders are classified and what ‘normal’ really means.

“It’s a wonderfully exciting time,” says Kerry Coburn, professor of psychiatry and behavioural sciences at Mercer University School of Medicine in Macon, Georgia. “ We’re moving from general psychiatry to an era of neuropsychiatry where psychiatric disorders, or at least the major ones, are considered to be disorders of the brain.”

ACCURATE DIAGNOSIS SEEMS simple enough: assess symptoms, compare with what’s known, and slap a label on it. But that’s often been far from what happens. In medicine, doctors know a great deal about the normal and abnormal functioning of the heart, bones and muscles. But so little is really known about the brain that we often don’t have a handle on how it functions normally, let alone what causes functioning to go awry. The same symptoms might signify a myriad of different disorders, and without knowing the cause doctors can only use their best judgement to treat the patient.

Traditionally in psychiatry, doctors use the patient’s history and check symptoms against the American Psychiatric Association’s reference book, called the Diagnostic and Statistical Manual of Mental Disorders, currently in its fourth edition and commonly known as the DSM-IV. Used in much of the world including the U.S. and Australia, the guide contains checklists of symptoms for all disorders recognised at the time of publication. If a person displays enough of the recognised symptoms over a certain period of time, and those symptoms hinder the person’s daily activities, then they’re diagnosed with that disorder.

To use the DSM-IV to diagnose people, psychiatrists must first agree on the symptoms used to classify a disorder. Typically, if a group of symptoms manifest consistently and distinctly enough in patients, psychiatrists will label it as a disorder and give it a name. Just as an entomologist ponders whether to classify a new species of butterfly based on its colours, wingspan, patterns, or antenna length, psychiatrists must decide how to classify a disorder and what symptoms to include.

Disorders are determined by an expert committee, which spends years reviewing the latest research. Disorders are not a priori and may be renamed, recategorised, or discarded, as conventional wisdom and social norms change. For example, homosexuality was classified as a disorder in the DSM until 1973. And ADHD may be one of the most studied and best understood of conditions, but the definition and name of “attention deficit hyperactivity disorder” has changed with virtually every edition of the DSM. The current guide recognises three different categories of ADHD.

Diagnosis has also posed a challenge because each patient presents a unique history and differing intensity and variety of symptoms. “The DSM is discriminant, but it really depends on the psychiatrist looking at the patient and trying to decide if the patient is complaining of depression symptoms enough to be depressed, or complaining of unusual experiences enough to be called delusional. It involves a lot of difficult judgments,” Coburn says.

“Symptom criteria were meant to – and were a somewhat successful attempt to – make psychiatry more scientific,” says Jerome Wakefield, who studies the sociology of diagnosis at New York University. “This helped a lot to make diagnosis more precise, but it didn’t solve as much as it might seem.”

Clinicians using symptoms-based guidelines may misinterpret symptoms or find their intensity difficult to classify, Wakefield says. Worse still, the symptom checklist may act as an impersonal substitute for in-depth doctor–patient communication. “When using symptom criteria, you take out what psychiatrists used to contribute: understanding of the person’s life and whether the symptoms are normal given the context,” he says.

In 2007, Wakefield published a study in the journal Archives of General Psychiatry, which revealed that many clinicians failed to take into account the context of people’s feelings of sadness when diagnosing depression. About one quarter of patients who were naturally sad about life events, like divorce or job loss, were pegged with clinical depression because the checklist doesn’t specifically list such factors as exclusion criteria.

Wakefield puts it down to overworked physicians, who often lack the time required to fully explore the patient’s history, taking symptoms out of context. He says the current symptoms-based system of diagnosis is far from perfect, but for now, it’s a good enough stop-gap until more knowledge and better technology come along.

“When symptom diagnoses were created it was already envisioned that research would eventually tell us more about the underlying biological causes of these disorders, and the criteria would change to use biological measures,” he says. “I think we’re going to find out the biological or psychological dysfunctions that underlie disorders and we will have ways of recognising them, just as in physical medicine we used to just have various ‘fevers’ and different ‘symptom complexes’.”

Technology such as QEEG may provide a better way of making more definite distinctions between normal and abnormal functioning of the mind. “If you want to use a tool for describing abnormality, the definition of ‘normal’ becomes critical,” Prichep says.

The term ‘normal’ takes on different meanings in different scientific contexts. In experiments, researchers use control subjects, or normals, who are statistically close to the middle of the bell curve; in medicine, normal tends to mean healthy; in psychiatry, it denotes a person who doesn’t have behaviours that stop them from carrying out day-to-day activities. Using QEEG, the definition of normal stems from what brainwaves look like: Prichep and colleagues found evidence that brainwave patterns signifying psychiatric disorders are so distinct that they stand out more than differences in characteristics like gender, exercise routines, eating habits, handedness and IQ.

In the 1980s, Prichep and her colleagues at the Brain Research Laboratories began compiling a database of QEEGs from people aged six to ninety with normal brains. Along the way, they added QEEGs from people with disorders ranging from ADHD and dementia, to obsessive-compulsive disorder, schizophrenia, and depression. The database contains more than 20,000 QEEGs and has been tested against data across 15 countries, showing that brain waves change in a recognisable pattern as we age, regardless of gender or race.

To figure out whether a patient’s brain waves are abnormal, clinicians using QEEG need to compare their patients’ brain waves with those of normal people. Without knowing the normal brain wave patterns for an average 22-year-old, Lauren Back’s psychiatrist wouldn’t know whether hers were typical of someone with ADHD, or someone younger who naturally has less brain wave activity.

QEEG also helps doctors distinguish one disorder from another, and to clarify sub-categories within the same disorder. Researchers have found that people with the same symptoms, and diagnosed with the standard symptoms based criteria, can often manifest different QEEG patterns. This revelation may explain why people diagnosed with the same disorder respond differently to medication.

In a study conducted in the late 1990s, for example, Prichep discovered two unique QEEG patterns among patients diagnosed with obsessive-compulsive disorder. Patients with one variant of the QEEG pattern improved after taking the standard drugs, called selective serotonin reuptake inhibitors, or SSRIs (such as Zoloft), while patients in the second group didn’t respond to the same medication. Since then, using the QEEGs, the scientists have been able to predict, with more than 90 per cent accuracy, which obsessive-compulsive patients would be helped by taking SSRIs.

While still a nascent area of research, the use of QEEG to predict medication response has shown promising results in studies of ADHD, depression, mood disorders and autism. “Once you can characterise the underlying pathophysiology using quantitative EEG, you can optimise treatment in a much more meaningful, realistic and successful way,” Prichep says.

TREATING PATIENTS’ SYMPTOMS is quite hit-or-miss, and often involves lengthy periods of trial and error. A study funded by the U.S. National Institutes of Mental Health, and published in 2006 in the American Journal of Psychiatry, found that of the two thirds of patients who responded to medication, half had to switch medications at least once before they benefited. Not encouraging news for people like Back, who spend significant amounts of time and money finding a way to alleviate their suffering. “I’ve been on six different medications in the last six years and [have] been extremely frustrated that I haven’t found one that works for me,” she says.

At the moment, however, trial and error is the best method available, because the breadth of causes of psychiatric dysfunction is largely unknown. “We can all be depressed in many different ways impacting on many different underlying pathways,” Prichep says.

As to what causes brain waves to short circuit, factors such as genetics, head injuries and drugs may be responsible. Whatever the cause, though, technology such as QEEG clearly shows that psychiatric disorders have a biological basis. This information in itself may help destigmatise those people afflicted and help them understand their own differences. “I think the only thing that keeps me grounded is reminding myself that it’s chemical and physical and I can’t control it,” Back says.

Clinicians and researchers agree on QEEG’s value as a research tool for gaining greater understanding of psychiatric disorders. But many remain sceptical of its use in a real world doctor-patient setting. “It’s kind of sexy to think about all this technology coming in and saving us from the problems of symptoms-based criteria, but I don’t know that we’re there yet,” Wakefield says. Some clinicians are concerned that the extra information is surrounded by enough uncertainty that it won’t tell them much more than they could discern from the patient’s history and symptoms.

Proponents of QEEG stress that it is not a blanket test for particular disorders, and won’t ever replace the clinician; a doctor still needs to evaluate the patient’s symptoms and history before making a complete diagnosis. But while admitting QEEG is no panacea for psychiatric illness, they believe it will become a standard part of psychiatric consultations in the near future. “I think that it will have a major impact,” Coburn says, It’s not revolutionary, but very much evolutionary.”

As for Back, while the ADHD stimulant medication, Adderall, she’s taking, along with medication for her depression and anxiety, has helped, the drugs haven’t cured all her maladies. “I’m not going to lie; being on medication helps,” she says. “But just the diagnosis and some meds doesn’t always make it better. There’s a lot to be figured out before I’m successfully treated.”

Carolyn Barry is a science journalist in Sydney and the editor of G-Online.
NEWSLETTER

Sign up to our free newsletter and have "This Week in Cosmos" delivered to your inbox every Monday.

>> More information
Latest
issue
CONNECT
Like us on Facebook
Follow @COSMOSmagazine
Add COSMOS to your Google+ circles