Could previous researchers have been wrong about the role of amyloid in Alzheimer's disease?

Amyloid proteins in the brain have long been implicated as the culprit behind Alzheimer's disease. Amyloid are insoluble protein aggregates that arise from inappropriately folded proteins and polypeptides. These form tangles or plaques. They have been associated in the pathology of more than 20 serious neurodegenerative disorders, including Alzheimer's disease. They’re thought to disrupt the seamless workings of the neurons responsible for memory and movement.
Recent studies in the US and in Australia, have however found that amyloid may not be as destructive as previously thought.

Two recent US studies have found that amyloid proteins may in fact play a protective rather than a destructive role in the brain. The studies run by Professor Lawrence Steinman of Stanford University found that treating mice with multiple sclerosis (MS) with amyloid proteins reduced brain inflammation and reversed MS-related paralysis.

A second study extended the finding to show that small portions of several notorious amyloid-forming proteins (including tau and prion proteins) can also alleviate symptoms in mice with the condition — despite the fact that the fragments can and do form the long tendrils, or fibrils, previously thought harmful to nerve health. This supported previous research showing that Alzeimer's disease is much worse in animals born without the genes that produce amyloid.

He reported, "we were so fixated on the idea that amyloid is bad for the brain that if one goes back and looks at the old literature and the new literature, one finds there's a lot of publications where people have ignored these kinds of experiments in humans where, for instance, lower levels of amyloid are associated with earlier dementia".

In another recent Australian study run by Dr Bryce Vissel of the Garvan Institute of Medical Research, researchers have found that the amyloid plaques that are characteristic of Alzheimer's disease appear much later in the disease than previously thought, and after the development of cognitive symptoms. This indicates that neurodegenerative processes such as memory loss and executive dysfunction occur independently of amyloid plaques.

Instead it is proposed that inflammation in the brain is the leading cause of brain damage and neurodegeneration in Alzheimer's disease. Lawrence suggested that amyloid proteins may soak up harmful molecules that are responsible for inflammation.

The studies suggest that anti-amyloid therapies may not be the best way to manage the disease, and that therapies focusing on reducing inflammation may be more beneficial.

The importance of wearing helmets

Australia is one of the few countries in the world with mandatory helmet laws for motorcyclists and bicycle riders. They were introduced in 1991 in New South Wales and have been the subject of controversy since. A recent study provides evidence supporting the importance of wearing helmets in reducing the risk and severity of head injury, particularly for bicycle riders.

Dr Michael Dinh from the University of Sydney and colleagues studied 348 adult patients admitted to hospitals following bicycle and motorcycle accidents in Sydney for one year between 2008-2009.

They found that cyclists who didn't wear helmets were almost 6 times more likely to suffer a head injury than those wearing helmets, and more than 5 times more likely to suffer a severe head injury. The benefits for motorcyclists were not as marked but still significant, with those without helmets 2 times more likely to suffer a head injury and 3.5 more likely to suffer a severe head injury compared to those without helmets.

Head injuries are rated on a scale from mild to extremely severe, based on a ranges of factors including level of consciousness following the incident and length of coma.

These outcomes also have implications for hospital care. The study found that patients who suffered severe head injuries from not wearing a helmet cost hospitals 3 times as much in treatment. For those who suffered a severe head injury, median hospital costs for non-helmeted patients were $72,000 while for those with helmets the figure was $24,000.

Older riders were more likely to wear helmets than younger riders. The average age of helmet wearing cyclists was 41, compared to 35 for non-helmet wearers, and for motorcyclists the average ages were 31 for those wearing helmets and 25 for those who did not.

The study was published in the Medical Journal of Australia. It supports previous research on the subject. In 2011 Dr Jake Oliver and colleagues from the University of New South Wales and the Sax Institute studied the number of head injuries before and after the mandatory helmet laws came into effect. They found that head injuries fell by up to 29%.

There are clear benefits from helmet wearing that clearly outweigh concerns about mandatory helmet laws reducing the number of cyclists. Studies such as those by Dr Dinh and Dr Oliver have also prompted debate about the usefulness of mandatory helmet laws in the US. More information can be found here.

Using neuroimaging to differentiate between Bipolar Disorder and Borderline Personality Disorder

Bipolar Disorder (BD) and Borderline Personality Disorder (BPD) are often confused and misdiagnosed. Both disorders involve dysregulation of emotional responses as key diagnostic criteria. BD is a mental illness involving a set of significant 'mood swings'. The most common form of Bipolar involves 'highs' (or mania) and 'lows' (depression). BPD is a type of personality disorder, or a set of long-standing traits and behaviours associated with significant distress or disability. A key feature of BPD is affective liability, meaning that people with BPD have difficulty stabilising their moods and therefore can demonstrate erratic mood swings. They are also prone to depression. More information about both disorders can be found on the website of the Black Dog Institute.

As it is personality based BDP tends to be a long-term disorder, whereas BD can come and go and with the right treatment can be cured or well managed. Appropriate treatment and management requires proper diagnosis. Unfortunately until now there have been no biological markers for psychiatric disorders.

However, some promising new research has found that there may be a way to differentiate between BD and BPD at a biological level. Professor Gin Malhi from the Sydney University has found biological differences in the brains between people with the two conditions. Professor Malhi and colleagues scanned the brains of people with BD (who were not depressed at the time of the study), BPD and controls with no mental illness while they undertook a task that focuses on emotional responses and is cognitively taxing (the emotional Stroop task). They found a significant difference in the response of the emotional circuits in the brain of the two patient groups and between the patients and controls during the task.

Individuals with BP drew more on the dorsomedial prefrontal cortex of the brain, whilst people with BPD showed heightened activity in the amygdala, a lower level part of the brain which coordinates emotional responses and processes negative emotions such as fear. Professor Malhi reported that people with BPD were not able to regulate this "key node in the lower part of the brain that co-ordinates emotional understanding". In contrast, people with BP were able to function quite normally when well, and just needed to expend more effort in the brain than controls.

While the results are very promising, Prfessor Malhi stresses the need for replication of the study.

He concluded: "for the first time in the past two decades we have the technology to see the brain functioning [but] these insights and understanding have to be translated into clinical practice."

Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-V)

The DSM is the 'bible' for mental health practitioners around the world. It is used to diagnose disorders affecting mood, personality, identity, development and cognition. It has recently undergone a major revision from the previous edition, the DSM-IV (released in 1994), and is set to be released in May 2013.

There have been many significant changes from the previous edition. Keep reading to find out about some of the most important changes.

New or amended diagnoses
Autism Spectrum Disorder (ASD)
This is one of the most important changes, given the prevalence and severity of ASD in the community. ASD is characterised by communication deficits, difficulties interpreting nonverbal communication, social difficulties, issues coping with change to routines, and intense focus or obsessions with inappropriate items. Some symptoms must be shown from early childhood. The symptoms fall on a continuum, with some individuals showing mild symptoms and others having much more severe symptoms. ASD is a single umbrella disorder which incorporates four separate disorders from the DSM-IV: autistic disorder, Asperger’s disorder, childhood disintegrative disorder and pervasive developmental disorder not otherwise specified.Researchers from the DSM-V workgroup found that these separate diagnoses were not consistently applied across different clinics and treatment centres, and that a single disorder improves diagnosis of ASD.

Disruptive Mood Dysregulation Disorder
This is characterised by severe outbursts or tantrums and prolonged irritable mood in children. It was included to capture children who display these characteristics and are misdiagnosed with Bipolar Disorder and/or Attention Deficit Hyperactivity Disorder.

Hoarding Disorder
Public interest in hoarding, the compulsive collection of possessions that may or may not have monetary value, is demonstrated by the popularity of reality television shows and docu-dramas dealing with this issue. Hoarding will now be listed as a separate condition from obssessive compulsive disorder in recognition of its unique symptoms and effects.

Structure
The complex multiaxial system with five 'levels' or axes of disorders will be removed. The DSM-V will instead present a simplified list of 20 chapters by grouping related disorders.

Rejected diagnoses
A number of proposed diagnoses were subsequently rejected and will not be included as separate disorders in the DSM-V. These include: Anxiety Depressive-Syndrome, Attenuated Psychosis, Hypersexual Disorder, Parental Alienation Syndrome and Sensory Processing Disorder.

Certain specifics of the DSM-V will not be made public until its release. However, more details about what has been publicly released can be found at the DSM-V development website.

While various websites publish diagnostic criteria from the DSM-IV (and likely the DSM-V once its released), a trained, experienced psychologist, neuropsychologist or psychiatrist is the best person to help you clarify or confirm a diagnosis of a psychological disorder. If you would like more information about our neuropsychological services, please contact us.

Right brain/left brain

If further proof was needed that the human brain is a fascinating organ, because of the way our brains are organised, there is a slight but discernible difference between the left and right sides of our faces.

Our brains are composed of approximately 100 billion neurons (nerve cells), with 50 billion neurons in each half. However, only approximately 250 million neurons join the two halves, meaning that our left and right brains are mostly unconnected and work separately. One result of this is our faces are unsymmetrical.

Many actors and other famous people (such as David Caruso, pictured) are known for having a 'good side' - preferring to be photographed on one side of their face than the other. Research shows support for the assertion that the different sides of our faces are different and one side is actually considered to be more attractive than the other.

Professors Kelsey Blackburn and James Schirillo from the University of Wake Forest asked undergraduate university psychology students to rate the attractiveness of 20 volunteers who had been photographed on both their left and right sides, about 37 degrees from the centre on each side. Some photographs were untouched, while other photos has been Photoshopped so that they were mirror-reversed so the left side looked like the right and vice versa.

As well as asking them about their preferences, the researchers examined the students' pupils. The size of one's pupil is related to the intensity of our emotional response to stimuli. In general, the students preferred the left face of the both men and women — regardless of whether they were shown the untouched left face, or a left face which had been mirror-reversed to look like a right face. This was regardless of the gender of the person in the photo, and the gender of the person doing the judging. And the pupils of the volunteers opened larger when they rated the faces more attractive.

The echoism app, developed by artist Julian Wolkenstein shows a combined image of two photos of either the left or right side of people's faces, with most of these photos posted on line being very different from the people's actual image. This indicates that 'symmetrical' faces don't look quite right. Judge for yourself whether you think the right or left images are more attractive.

The psychopathic brain

A very interesting article by Dr Karl Kruszelnicki revealed that psychopathology, characterised by features such as egocentricity, a lack of empathy, remorse and poor impulse control, may be associated with the orbito-frontal cortex in the human brain. The orbito-frontal cortex (OFC) is located in the pre-frontal area of the frontal lobes behind the eyes, as indicated by the green shading on the image to the right.

The OFC controls those behaviours which are known to be impaired in psychopaths, including impulse control, planning and calculating risk. It also has a role in processing odours, and research has shown that psychopaths have a poor sense of smell.

Shamay-Tsoory, Harari, Aharon-Peretz, and Levkovitz (2010) proposed that psychopathy is associated with impairments in theory of mind (TOM) which is also associated with the OFC. TOM is the ability to understand what another person may be thinking and feeling, and to be able to appreciate their perspective. Shamay-Tsoory et al. showed that people with lesions in the OFC performed poorly on complex TOM tasks, particularly those drawing on affective TOM, which involves interpreting emotions. People with psychopathic tendencies had similar difficulties on complex TOM tasks as those individuals with lesions in the OFC.

The authors suggested that psychopaths may not appreciate the emotions, fears and sorrow of other people, which allows them to behave callously without feelings of remorse.

The OFC also has extensive projections to a part of the brain called the amygdala. The amygdala is involved in processing fearful and sad facial expressions and emotions and has a role in instrumental learning. Several neuroimaging studies have shown that people with psychopathic tendencies have reduced amygdala volume (Kiehl et al., 2001; Tiihonen et al., 2000).

References

Kiehl, K.A., Smith, A.M., Hare, R.D., et al. (2001). Limbic abnormalities in affective processing by criminal psychopaths as revealed by functional magnetic resonance imaging. Biological Psychiatry, 50, 677-684.

Shamay-Tsoory, S. G., Harari, H., Aharon-Peretz, J., & Levkovitz, Y. (2010). The role of the orbitofrontal cortex in affective theory of mind in criminal offenders with psychopathic tendencies. Cortex, 46, 668-677.

Tiihonen, J., Hodgins, S., Vaurio, O., et al. (2000). Amygdaloid volume loss in psychopathy. Society for Neuroscience Abstracts, 2017.

The neuropsychology of humour

Humour is very important to humans, and therefore to psychology. According to Brownell and Gardner (1998):

Humour plays a powerful and unique role in human life,
with wide-ranging effects on many aspects of functioning.
Humour is a basic ingredient of binding in society; it provides
an effective means of communicating a wide range of ideas,
feelings and opinions.

Lacking, or losing (such as through brain injury) a sense of humour can very be damaging to one's social interactions and self-esteem. Having difficulty appreciating and understanding humour is a key feature of many psychological and neuropsychological conditions, including Autistic Spectrum Disorders, psychotic conditions, certain acquired brain injuries and some forms of dementia.

For these reasons there has been extensive neuropsychological research on humour. This research has shown that damage to the right hemipshere, particularly the frontal lobe most disrupted the ability to appreciate humour. Interestingly, this was also correlated with other cognitive processes, such as visual search, ability to focus attention and to hold relevant information in mind and mentally manipulate it (working memory). This makes sense, as appreciating a joke involves: being able to listen and focus on the joke, holding relevant information in mind and relating it back to the punchline, and/or scanning cartoons or other visual material. Humour is a complex business!Disorders of humour such as foolishness and a tendency toward making inappropriate jokes have also been reported in patients with damage to the frontal lobes.

It is thought that the right frontal lobe may be unique in integrating cognitive and affective information, to allow us to appreciate jokes and other emotive material.

Neuroimaging studies have revealed that the physical expression of laughter involves the amygdala (emotion centre), thalamic, hypothalamic and subthamalic regions (sensory relay areas) and the brainstem, as well as the premotor/frontal area through to the motor cortex (to aid the motor movements involved when laughing). These studies have confirmed that the perception of humour involves the right frontal cortex, as well as the prefrontal cortex (higher level executive area and personality), temporal regions (memory centres) and possibly the cerebellum.

Because they are associated with different parts of the brain, disorders of laughter can occur independently of disorders of humour. Difficulties with expressing laughter are most commonly associated with a type of stroke known as pseudobulbar palsy, when laughter can be intermixed with crying. 'Laughing' seizures are associated with a tumour in the hypothalamus. These individuals may have an intact sense of humour but may have difficulty expressing laughter approriately.

Finally, just to show that neuropsychologists have a sense of humour, the following (mildly edited) joke is taken from the Humour in Neuropsychology webpage:

DINNER ARRANGEMENTS

A group of 40-year-old buddies discuss and discuss where they should meet for dinner. Finally it is agreed upon that they should meet at the Gausthof zum Lowen restaurant because the waitresses there have low cut blouses.

10 years later, at 50 years of age, the group meets again and once again they discuss and discuss where they should meet. Finally it is agreed that they should meet at the Gausthof zum Lowen because the food there is very good and the wine selection is good also.

10 years later at 60 years of age, the group meets again and once again they discuss and discuss where they should meet. Finally it is agreed they should meet at the Gausthof zum Lowen because they can eat there in peace and quiet and the restaurant is smoke free.

10 years later, at 70 years of age, the group meets again and once again they discuss and discuss where they should meet. Finally it is agreed that they should meet at the Gausthof zum Lowen because the restaurant is wheel chair accessible and they even have an elevator.

10 years later, at 80 years of age, the group meets again and once again they discuss and discuss where they should meet. Finally it is agreed that they should meet at the Gausthof zum Lowen because that would be a great idea because they have never been there before.

References
Brownwell, H.H., & Gardner, H. (1988). Neuropsychological insights into humour. In J. Durant, & J. Miller (Eds.), Laughing matters: a serious look at humour (pp.17-34). New York, Wiley.