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6 | advancing Knowledge
Brain waves
Brain imaging is revealing distinctive brain activity
in people with psychological disorders.
Shaking the
Haystack
It’s bonanza time for
genome-wide analyses.
1
2
Abnormal behaviour is seen in many
mental conditions and presumably
reflects disruptions to normal brain
function. Insight into these
abnormalities is being gathered by
brain imaging – increasing
understanding and raising hopes of
better diagnosis and treatment.
The basis of conditions such as
obsessive–compulsive disorder (OCD)
has been difficult to trace, in part
because human behaviours are tricky to
categorise in a way that makes them
amenable to study. A productive way
forward, being taken by Sam Chamberlain
and colleagues in Cambridge, is to identify
patterns of brain activity that can act as
robust proxies of behavioural traits.
To this end, they looked at brain activity
in people with OCD and their unaffected
relatives, who might be expected to
show similar but less marked
abnormalities. Indeed, compared with
controls, activity in areas within the
frontal lobes – known to be involved in
decision-making – were lower in both
people with OCD and their relatives.
Neural correlates of another mental
disorder, depression, have been
uncovered by Cynthia Fu and colleagues
from the Institute of Psychiatry, London.
Ultimately, this may lead to more
objective diagnosis of depression.
Responses were recorded to faces
manipulated digitally to show varying
degrees of sadness. By analysing activity
across the whole brain, Dr Fu was able to
identify patterns consistently seen in
people with depression but not controls.
Finally, Senior Research Fellow Paul
Fletcher and colleagues in Cambridge
have used brain imaging to explore
susceptibility to schizophrenia, using
ketamine to induce a state of psychosis
in healthy volunteers.
Brain activity was monitored in volunteers
before and after a dose of ketamine.
Some distinctive brain activations seen
before ketamine was administered were
significantly more common in those
reporting psychotic symptoms. Moreover,
activation at certain sites seemed to
predict which types of symptom an
individual experienced.
It may therefore be possible to use brain
imaging to identify vulnerabilities to
particular psychotic symptoms, before
they become clinically apparent.
Chamberlain SR et al. Orbitofrontal dysfunction in
patients with obsessive-compulsive disorder and their
unaffected relatives. Science 2008;321(5887):421–2.
Fu CH et al. Pattern classification of sad facial processing:
toward the development of neurobiological markers in
depression. Biol Psychiatry 2008;63(7):656–62.
Honey GD et al. Individual differences in psychotic
effects of ketamine are predicted by brain function
measured under placebo. J Neurosci
2008;28(25):6295–303.
Last year saw a significant advance in
the genetic analysis of common
diseases, with a flood of papers from
the Wellcome Trust Case Control
Consortium. A further outpouring of
findings has followed this year, as
other groups and consortia have
applied whole-genome approaches
to a range of conditions.
Genome-wide association studies are
taking advantage of high-throughput
genotyping techniques to screen the
entire genome of large numbers of
individuals, to identify sites in the genome
that may be contributing to a disease.
This year saw a whole host of studies
published dissecting conditions as
varied as osteoporosis, ankylosing
spondylitis, psoriasis, Crohn’s disease
and type 2 diabetes.
The latest Crohn’s research identified 21
new risk genes, bringing the total to more
than 30 – though collectively they explain
only about a fifth of the total genetic risk.
This suggests that many additional
genes contribute to Crohn’s, and also
illustrates how complex the condition is.
The studies also picked up unexpected
connections between diseases – one
gene increases susceptibility to both
Crohn’s and psoriasis, another
contributes to both Crohn’s and asthma.
As well as disease, genome-wide studies
have also shed light on other biological
Images
1 Areas of abnormal brain activity (blue) in people with OCD or
their relatives undertaking a cognitive task.
2 Clinical depression may be associated with specific patterns
of brain activity.
3 Large numbers of people can be genotyped in
high-throughput facilities.
4 Embryonic stem cells.