Weekly Neuroscience Update

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Neuroscientists at the University of Bristol are a step closer to understanding how the connections in our brain which control our episodic memory work in sync to make some memories stronger than others. The findings, published in Nature Neuroscience, reveal a previously unsuspected division of memory function in the pathways between two areas of the brain, and suggest that certain subnetworks within the brain work separately, to enhance the distinctiveness of memories.

A new study pinpoints the brain area responsible for forming direct links between environmental stimuli and enhanced focus.

Every few seconds, our eyelids automatically shutter and our eyeballs roll back in their sockets. So why doesn’t blinking plunge us into intermittent darkness and light? New research led by the University of California, Berkeley, shows that the brain works extra hard to stabilize our vision despite our fluttering eyes.

Our personality traits are linked to differences in the thickness and volume of various parts of our brains, an international study has suggested.

Researchers have found significant differences in the brains of teens with bipolar disorder that attempt to take their lives over those with the disorder who have never attempted suicide.

Women with lower estrogen levels may be more susceptible to developing PTSD according to new research.

A new study raises the question of whether a genetic mutation associated with neurodegeneration in one environment could act in a positive way in a different setting.

Researchers report early indicators of depression and anxiety may be evident in the brain from birth.

A cutting edge, non-invasive brain stimulation technique could improve cognitive control for people with conditions such as schizophrenia and autism.

A new computerized ‘mirror game’ has been shown to give more accurate diagnosis of schizophrenia than clinical interviews.

A new study reports on how a single instance of extreme stress can lead to long term neurological changes and trauma.

Social difficulties in people with autism are exacerbated by how other people perceive them at first meeting, researchers say.

Finally this week, researchers have revealed regions of the brain implicated in delusional misidentification syndromes.

What’s going on with Charlie Sheen?

Is Charlie Sheen suffering from bipolar disorder?

As actor Charlie Sheen’s bizarre media blitz continues, viewers are left to ponder if Sheen’s interviews are some kind of brilliant performance art or evidence of an epic meltdown, or some combination of the two. Or is his current behaviour evidence of a more worrying mental illness.

Some psychologists have stated that Charlie Sheen appears to have bipolar disorder. Dr. Drew Pinsky has said that Charlie Sheen appears to be having a “manic episode.”

Another psychologist says that Charlie Sheen is showing classic symptoms of bipolar disorder. “The symptom I see is the pressured speech.” he says. “[Sheen is] really pushing to get those words out; he’s really on a roll. He’s getting everything coming out pretty fast, almost faster than his brain can think and that’s very common with people who have bipolar disorder.” 1

What is bipolar disorder?

Over 300,000 people in Ireland suffer from depression, however a less common form of depression is manic depression also known as bipolar disorder which affects about 20,000 Irish people. Bipolar disorder is a mood disorder characterised by extreme lows with feelings of hopelessness and sadness followed by elated manic highs where in your mind anything becomes possible. 

Vicious cycles

These extremes of mood often follow each other in regular cycles that may be days, months or even years apart although on average there are twice as many episodes of depression then for mania. Like any other mental illness bipolar disorder is related to genetic background and personality type but can also be triggered by stressful events. However in a lot of cases bipolar disorder can arise ‘out of the blue’ when people’s lives’ are going quite well. 

Similarities to classic depression

The depressive symptoms experienced by people with bipolar disorder are similar to those people who experience classic depression.  One minute you are working away in your garden and the next you can be overtaken by profound feelings of despair – a sense of being totally worthless – that can take you down into the depths of depression. In this situation the mood is very low and daily life can become so overwhelming that it can be difficult to endure. As the feelings deepen – thoughts of suicide and a preoccupation with suicide often emerges. 

Manic depression

The German psychiatrist Emil Krapelin coined the term ‘manic depression’ after examining many patients with this condition back in the 1800’s. Even then Krapelin believed that this condition was caused by a specific abnormality in the brain. 

Where in the brain does depression occur?

Depression is associated with a disturbance in the prefrontal lobe of the brain – found just behind the eyes. This region of the brain is involved in judging things to be good or bad. It is also involved in social behaviour and interpreting social situations so it is not surprising that the low mood, reduced motivation and social withdrawal are key symptoms of depression. For this reason, people who are depressed often feel rejected or cut off from the world and blame themselves for wars in distant lands – even though they may have never visited that country. 

The role of amines in depression

Neuroscientists still don’t know for certain why people develop bipolar disorder but they do know that it is related to imbalances in brain chemicals called neurotransmitters which are involved in communication. However, research over the past 40 years has the confirmed that depression is associated with low levels of family of chemicals called amines. Amines are neurotransmitters that help nerve cells to stay in touch with each other. A lack of these amines particularly dopamine and serotonin which are carried by nerve pathways into the frontal lobe leads to a kind of starvation of nerve cells in the frontal lobe – giving rise to the symptoms of depression. 

Reserpine and depression

The link between low amine levels and depression was made when reserpine a drug to lower blood pressure also lowered brain amine levels and caused very profound depression. Also, addictive drugs such as cocaine, amphetamine and alcohol which inappropriately increase amine levels in the brain can trigger depression upon withdrawal. So the message is simple – in order to avoid depression you need healthy levels of these amines in our brain and you need healthy mental health habits to keep them there. 

Medication for depression

Over the past 25 years neuroscientists been working hard to develop drugs that can safely raise amine levels in the brain – the so-called antidepressant drugs – and better, more effective antidepressants come on the market every decade. 

The manic phase of bipolar disorder

In contrast to the depressive phase, the manic phase of bipolar disorder is the ‘polar’ opposite of depression. Feelings of boundless energy and that anything is possible are often felt. Many people are often creative in this phase.  The German composer Robert Schuman experienced bipolar disorder throughout his life. He completed four works in 1829 when in a depressed phase and twenty-five works a year later when in a manic phase. 

The secret of our success…

If bipolar disorder were due to a bad gene then why has it not been weeded out over the generations? One answer is that despite the truly awful cost to the life of the individual the gene for bipolar depression continues to exist because it confers an advantage on our species such as the creative insights leading to discoveries, inventions and exceptional performances in science, the arts, drama, music, sport and business – contributing to the great advances in our civilization – from which we all benefit. Ironically then, bipolar disorder may be the secret of our success as a species.  

…comes at a very high cost

Very tragically the rate of suicide in bipolar disorder is very high. The cycle of depression and mania lead the German composer Robert Schuman to an attempted suicide in 1854. Almost a quarter (22%) of people with this condition will commit suicide.  This is higher than that observed in schizophrenia. 

Recognizing the manic phase

In severe mania an individual will behave in an uncharacteristic way. They will become very talkative, loud, verbal, very expressive, extremely confident even uncharacteristically confident. Some people will start-up companies in this phase. They will go out and direct traffic, invest unwisely. They don’t see things as being limited by their circumstances or by their personal capacities. In the manic phase literally anything is possible! 

The manic phase can come on quickly or gradually. The person may not be fully aware what is happening to them. They may find themselves drinking more, wanting to be with people, going to pubs and nightclubs and dancing all night despite the fact that they may be too old for it. There is a tremendous pressure to ‘do things’ such as going out to dig the garden at 4am in the morning – for the stay-at-home types. 

The brain, stress and bipolar disorder

Whenever you encounter a stressful situation the pituitary gland in your brain sends a signal to your adrenal glands (just above your kidneys) to release cortisol which in turn gets your body ready for action. However blood cortisol levels are much higher than normal in depression and bipolar disorder causing a general state of high alert including early morning wakening which contributes to mental exhaustion.

Neuroscientists believe that the manic phase is an over activity of the dopamine and serotonin pathways in the frontal lobe.  In this way a dysfunction in the serotonin pathway in the brain has a ‘knock-on’ affect in the regulation the pituitary gland which in turn inappropriately over-activates the adrenals to release too much cortisol. However neuroscientists still don’t know for certain why people develop bipolar disorder.

Lithium and treatment of bipolar disorder

Mania is very resistant to treatment – benzodiazepines, major tranquilizers and antidepressants don’t work adequately. Fortunately there is lithium – an element found as a salt in soil and rocks and thus very cheap to make. Because it is element lithium cannot be patented (owned) by the drug industry. It was for this reason that lithium was largely ignored for years by the pharmaceutical industry. However, even in ancient times lithium was known to be a mild sedative. The mood stabilising effect of lithium was rediscovered by accident by an Australian psychiatrist John Cade in 1949 when working with guinea pigs. After ingesting lithium himself to ensure its safety in humans, Cade published an article “Lithium salts in the treatment of psychotic excitement” – which is still the number one most cited article in the Medical Journal of Australia. Lithium was eventually accepted as a treatment for mania in the 1970s.

Lithium – a truly life saving drug

Initially investigated as a treatment for gout, lithium has the effect of calming nerve cells. While lithium is the conventional treatment for the manic phase of bipolar disorder and reaches the brain within hours it can take up to six weeks to show an effect. Lithium is also very toxic particularly to the thyroid and kidneys. The required dosage 400–600 mg (15–20 mg per kg of body weight) is slightly less than the toxic level, requiring blood levels of lithium to be monitored closely during treatment. Within four to five days of stopping lithium a person can begin to get high again. Despite its limitations lithium is truly is a life saving drug – the only one to have an anti-suicide effect – allowing people to manage their moods and get on with their lives.  

The cup that cheers

Hundreds of soft drinks once included lithium salts or lithia water (naturally occurring mineral waters with higher lithium amounts). An early version of Coca Cola available in pharmacies’ soda fountains was called Lithia Coke and was a mixture of Coca Cola syrup and lithia water. The soft drink 7 Up, originally named “Bib-Label Lithiated Lemon-Lime Soda”, contained lithium citrate until it was reformulated in 1950. Lithia light beer was brewed at the West Bend Lithia Company in Wisconsin.

In 2009, Japanese researchers at Oita University reported that low levels of naturally-occurring lithium in drinking water supplies reduced suicide rates. A previous report had found similar data in the American state of Texas. In response, psychiatrist Peter Kramer raised the hypothetical possibility of adding lithium to drinking water.

A possible future treatment?

Research shows that manic depression seems to run in families so genetics also plays a role. Nobel Prize winner Paul Greengard of Rockefeller University, New York believes that a low-level of expression in a gene called P11 – which regulates serotonin levels in the brain – may underlie bipolar disorder. Gene therapy whereby healthy P11 genes are injected into the brain may be a future treatment.    

1 Source: kfor.com