NEWS & VIEWS RESEaRch
that such a massive planet as HR 8799e could
have migrated from about 50 to 14.5 au by
means of tidal torques from the residual gas
that had not been used to build up the plan-
ets. The converse theory, by which the planets
all form through core accretion within about
10 au and then slowly move outwards by scat-
tering lesser objects (planetesimals) inwards, is
also problematic because there is probably too
limited a reservoir of planetesimals to move a
7-Jupiter-mass object such as HR 8799b out-
wards some 58 au. So, despite having a clear
view of the system — thanks to the power of
adaptive-optics systems and large ground-
based telescopes — we cannot currently explain
how all four planets formed in a coherent,
coeval fashion.
A key strength of direct imaging is that pho-
tons can be collected from these self-luminous
young planets as they contract, allowing the
planetary spectra to be observed (to calculate
temperatures and luminosities). The observed
brightness of HR 8799b in direct images is
much lower than would be expected from
its observed temperature, given that evolu-
tionary models indicate that HR 8799b must
have a radius larger than that of Jupiter1,2,4.
This ‘under-luminosity’ problem is typical of
around half of the extrasolar planets imaged
to date. One possible explanation is that dusty,
thick, planetary-scale high-latitude cloud
‘bands’ absorb/scatter light when viewing a
young planet over its pole. For example, the
‘under-luminous’ planets in the HR 8799 sys-
tem are probably being viewed close to ‘pole-
on’5, perhaps leading to less light emitted in
the direction of Earth. By contrast, ‘edge-on’
giant planets, such as β-Pictoris b 6, look
brighter because light streams freely from the
brighter equatorial regions between the dark
cloud bands. Clearly, further theoretical (and
direct imaging) work will be needed to identify
the ultimate cause of this under-luminosity
problem.
The future holds much promise for more
surprises in the field of direct imaging of extra-
solar planets. However, it seems unlikely that
any other massive outer planets will be found
around HR 87997. There is always a chance,
though, that low-mass terrestrial planets
lie within the star’s 10-au-radius ‘asteroid’
belt. The next chapter in this story will soon
be written by even more powerful ground-
based, adaptive-optics imagers8,9 and, let us
hope, by more powerful pathfinding, space-
based planet- and disk-imaging telescopes10.
These pathfinders should eventually lead to
a terrestrial-planet-finding telescope even
capable of taking spectra of Earth-like plan-
ets. Such an achievement could address one
of the most pivotal questions in science: how
common are truly Earth-like planets and life in
our Universe? ■
Laird Close is in the Department of Astronomy
and Steward Observatory, University of
© 2010 Macmillan Publishers Limited. All rights reserved
Arizona, Tucson, Arizona 85721, USA.
e-mail lclose@as.arizona.edu
1. Marois, C., Zuckerman, B., Konopacky, Q. M.,
Macintosh, B. & Barman, T. Nature 468,
1080–1083 (2010).
2. Marois, C. et al. Science 322, 1348–1352
(2008).
3. Nero, D. & Bjorkman, J. E. Astrophys. J. 702,
L163–L167 (2009).
4. Bowler, B. P., Liu, M. C., Dupuy, T. J. & Cushing, M. C.
Astrophys. J. 723, 850–868 (2010).
Be Hav Io u r a l n e u r os CI e nCe
A gene for impulsivity
Impulsivity has been linked to various psychiatric disorders and forms of violent
behaviour. A gene mutated in a population of violent Finnish criminal offenders
provides clues to the neural basis of this trait. See Article p.1061
JoHn r. kelsoe
A
n old adage admonishes us to look
before we leap. This bit of common
sense reflects a crucial and complex
brain function that regulates behaviour. To act
without thinking — impulsivity — is to risk
leaping off a cliff. But to excessively delay an
action may lead to inaction or missed oppor-
tunities. Now, using a powerful genomics
approach, Bevilacqua and colleagues1 dissect
elements of the neurotransmitter system in the
brain that mediates impulsivity and show that
the serotonin 2B receptor (HTR2B) has a role
in severe impulsivity, at least in one human
population (page 1061 of this issue).
Impulsivity is generally thought to be a fail-
ure of inhibitory function in the brain2. Clearly,
fine-tuning of such inhibition is important
for an organism to adapt to its environment.
Impulsivity has been linked to a variety of
behavioural and psychiatric syndromes,
including attention deficit hyperactivity dis-
order, mania, drug addiction and borderline
personality disorder (BPD)3,4. It has also been
associated with violent behaviour, as seen in
antisocial personality disorder (ASPD) and
intermittent explosive disorder (IED), and
with suicide. Several neurotransmitters —
serotonin and dopamine in particular — have
been implicated in mediating impulsivity, but
unravelling the underlying mechanisms has
proved challenging.
In their search for genes predisposing to
impulsivity, Bevilacqua et al.1 used the well-
studied ‘founder’ population of Finland.
Because of the country’s relative isolation,
the current Finnish population is believed to
be largely derived from two waves of immi-
gration 4,000 and 2,000 years ago5. It has
therefore been argued that, compared with
other, more-outbred populations, there may
be fewer mutations for genetic traits in this
2 3 / 3 0 D E C E m b E R 2 0 1 0 | VO L 4 6 8 | NAT U R E | 1 0 4 9
5. Moro-Martín, A., Rieke, G. H. & Su, K. Y. L. Astrophys.
J. 721, L199–L202 (2010).
6. Lagrange, A.-M. et al. Science 329, 57–59
(2010).
7. Close, L. M. & Males, J. R. Astrophys. J. 709,
342–348 (2010).
8. Beuzit, J.-L. et al. Astron. Soc. Pacif. Conf. Ser. 430,
231 (2010).
9. Macintosh, B. A. et al. Proc. SPIE 7015, 701518
(2008).
10. Green, T. P., Schneider, G. & EXCEDE Mission Team
Bull. Am. Astron. Soc. 39, 975 (2007).
population, and studies of various genetic
disorders support this assumption. To fur-
ther enhance their odds of success, Bevi-
lacqua and co-workers focused on Finnish
subjects with the most extreme manifestation
of impulsivity — violent offenders whom the
authors evaluated in a forensic psychiatric
unit and who had strong lifetime histories of
aggressive acts.
Specifically, Bevilacqua et al. examined
96 individuals for 14 candidate genes, using
next-generation sequencing technology to
identify possible disorder-causing mutations.
They focused on the protein-coding regions
(exons) of the genes as the regions in which
mutations would most probably affect gene
function. They found a variation at a single
nucleotide base — dubbed HTR2B Q20* — in
the HTR2B gene, which results in an errone-
ous stop codon, a signal that ends further pro-
tein extension. The researchers show that this
mutation triggers a process called nonsense-
mediated RNA decay, such that no HTR2B-
receptor protein is expressed.
The HTR2B Q20* mutation was present in
the violent offenders at three times the rate of
that in matched controls (psychiatrically nor-
mal Finnish individuals). It was also inherited,
along with psychiatric illnesses such as ASPD,
IED and BPD, by members of their families. The
17 violent offenders who carried HTR2B Q20*
had all committed an average of five violent
crimes, 94% of which were committed under
the influence of alcohol. These crimes were
largely aggressive reactions to minor events
that lacked premeditation or financial gain
as a goal.
The authors’ results are consistent with
many animal and human studies that impli-
cate serotonin in impulsive behaviour6,7. Previ-
ous studies have in general supported the idea
that low serotonin levels are associated with
impulsive action. For instance, activation
 RESEaRch NEWS & VIEWS
Nucleus
accumbens
HTR2B
mutation
↑ Impulsive
behaviours
↓ Serotonin
Figure 1 | HTR2B and the regulation of impulsivity. Bevilacqua et al.1 find that, in a Finnish
subpopulation, a mutation in the serotonin receptor HTR2B is linked to severe impulsivity. In the
nucleus accumbens region (green) of the brain, projections of neurons that secrete serotonin (red)
interact with those that secrete dopamine (blue). This region has been repeatedly shown to play a
crucial part in choice and impulsivity. Mutations in HTR2B, which modulates the release of dopamine
and serotonin in the nucleus accumbens, may reduce the release of these neurotransmitters, leading
to increased impulsive behaviour.
of the 5-HT1A receptor, which may inhibit
serotonin release, has been linked to impulsiv-
ity in animal models8. Moreover, the levels of
5-hydroxyindoleacetic acid — a metabolite of
serotonin — are reduced in the cerebrospinal
fluid of people who are suicidal9. Further-
more, individuals whose serotonin levels have
been experimentally lowered by diet are more
likely to make impulsive choices10. Nonethe-
less, the role of serotonin is probably com-
plex, not least because the serotonin system
includes 14 different receptors with sometimes
opposing actions.
The HTR2B receptor received little attention
in earlier studies of impulsivity. So, to support
their human data, Bevilacqua et al.1 examined
mice that lack the Htr2b gene. They observed
increased impulsive behaviour in these animals
according to several measures. How exactly
HTR2B deficiency leads to this effect remains
unclear, although the authors find that both
male mice lacking Htr2b and men carrying the
HTR2B Q20* mutation have elevated levels of
the hormone testosterone.
Previous work2 suggests that HTR2B may
function by modulating both serotonin and
dopamine in the nucleus accumbens — a brain
region involved in impulsive behaviour (Fig. 1).
For instance, the ‘club drug’ ecstasy has been
shown11 to stimulate the release of both sero-
tonin and dopamine in the nucleus accumbens
by directly activating HTR2B. It could there-
fore be that depletion of the HTR2B receptor
results in increased impulsive behaviour by
reducing the release of both serotonin and
dopamine in the nucleus accumbens. However,
much more work is required to elucidate how
HTR2B regulates impulsive behaviour through
1 0 5 0 | NAT U R E | VO L 4 6 8 | 2 3 / 3 0 D E C E m b E R 2 0 1 0
its modulation of the interaction between
pathways involving serotonin and dopamine.
Bevilacqua and colleagues’ observation1 that
the HTR2B Q20* mutation is unique to Finns
serves as yet another reminder of the high level
of heterogeneity likely to be seen in complex
D r uG D I sC ov e rY
Reader’s block
Protein factors can regulate gene expression by binding to specifically modified
DNA-associated proteins. Small molecules that selectively interfere with such
interaction may be of therapeutic value. See Article p.1067 & Letter p.1119
s e a n D . tav e r n a & P H I l I P a . C o l e
P
rotein factors are crucial for control-
ling gene expression. One group of such
factors affects gene activity by ‘reading’
epigenetic marks — reversible modifications
such as the addition of phosphate, acetyl or
methyl groups — on proteins after their trans-
lation from RNA. The factors’ target proteins
are histones, which associate with DNA to form
chromatin. The reading ability of these protein
factors is a result of specific, well-folded sub-
domains, sometimes called readers, which can
distinguish between the post-translationally
modified state of their binding partner and its
unmodified state. Two papers1,2 in this issue
describe highly potent and selective inhibi-
tor molecules that compete with acetylated
histones for binding to a set of such readers.
© 2010 Macmillan Publishers Limited. All rights reserved
genetic traits and the importance of population
history. But although this specific mutation is
absent in non-Finnish populations, different
mutations in the HTR2B gene might operate
in other populations.
Bevilacqua and colleagues’ paper also illus-
trates the power of exon-based sequencing in
founder populations, and suggests that exonic
mutations of strong functional effect do play a
part in complex behavioural traits. ■
John R. Kelsoe is in the Department
of Psychiatry, University of California,
San Diego, and the VA San Diego Healthcare
System, La Jolla, California 92014, USA.
e-mail: jkelsoe@ucsd.edu
1. Bevilacqua, L. et al. Nature 468, 1061–1066
(2010).
2. Cardinal, R. N. Neural Netw. 19, 1277–1301 (2006).
3. Moeller, F. G., Barratt, E. S., Dougherty, D. M.,
Schmitz, J. M. & Swann, A. C. Am. J. Psychiatry 158,
1783–1793 (2001).
4. Swann, A. C., Lijffijt, M., Lane, S. D., Steinberg, J. L. &
Moeller, F. G. Bipolar Disord. 11, 280–288 (2009).
5. Peltonen, L., Jalanko, A. & Varilo, T. Hum. Mol. Genet.
8, 1913–1923 (1999).
6. Robbins, T. W. Psychopharmacology 163, 362–380
(2002).
7. Pattij, T. & Vanderschuren, L. J. M. J. Trends
Pharmacol. Sci. 29, 192–199 (2008).
8. Winstanley, C. A., Theobald, D. E., Dalley, J. W. &
Robbins, T. W. Neuropsychopharmacology 30,
669–682 (2005).
9. Träskman, L., Åsberg, M., Bertilsson, L. & Sjüstrand,
L. Arch. Gen. Psychiatry 38, 631–636 (1981).
10. Rogers, R. D. et al. Psychopharmacology 146,
482–491 (1999).
11. Doly, S. et al. J. Neurosci. 28, 2933–2940 (2008).
These data have therapeutic implications.
Post-translational modifications can
often influence transient protein–protein
interactions by creating or disrupting bind-
ing surfaces on the molecules. Among such
modifications, acetylation on lysine amino-
acid residues has been centre stage: originally
discovered3 more than 40 years ago as a regula-
tor of chromatin structure, this modification
has now been detected in thousands of other
proteins4. Acetyl-lysine modifications facili-
tate the interaction of the protein with proteins
that contain bromodomains — evolutionarily
conserved subdomains that can specifically
bind, or read, the acetylated form of the lysine
during regulatory processes5. Such interactions
are thought to regulate transcription and to
be involved in various diseases, including
cancer.