This paper reviews the body of evidence that not only tryptophan and consequent 5-HT depletion, but also induction of indoleamine 2,3-dioxygenase (IDO) and the detrimental effects of tryptophan ...catabolites (TRYCATs) play a role in the pathophysiology of depression. IDO is induced by interferon (IFN)γ, interleukin-6 and tumor necrosis factor-α, lipopolysaccharides and oxidative stress, factors that play a role in the pathophysiology of depression. TRYCATs, like kynurenine and quinolinic acid, are depressogenic and anxiogenic; activate oxidative pathways; cause mitochondrial dysfunctions; and have neuroexcitatory and neurotoxic effects that may lead to neurodegeneration. The TRYCAT pathway is also activated following induction of tryptophan 2,3-dioxygenase (TDO) by glucocorticoids, which are elevated in depression. There is evidence that activation of IDO reduces plasma tryptophan and increases TRYCAT synthesis in depressive states and that TDO activation may play a role as well. The development of depressive symptoms during IFNα-based immunotherapy is strongly associated with IDO activation, increased production of detrimental TRYCATs and lowered levels of tryptophan. Women show greater IDO activation and TRYCAT production following immune challenge than men. In the early puerperium, IDO activation and TRYCAT production are associated with the development of affective symptoms. Clinical depression is accompanied by lowered levels of neuroprotective TRYCATs or increased levels or neurotoxic TRYCATs, and lowered plasma tryptophan, which is associated with indices of immune activation and glucocorticoid hypersecretion. Lowered tryptophan and increased TRYCATs induce T cell unresponsiveness and therefore may exert a negative feedback on the primary inflammatory response in depression. It is concluded that activation of the TRYCAT pathway by IDO and TDO may be associated with the development of depressive symptoms through tryptophan depletion and the detrimental effects of TRYCATs. Therefore, the TRYCAT pathway should be a new drug target in depression. Direct inhibitors of IDO are less likely to be useful drugs than agents, such as kynurenine hydroxylase inhibitors; drugs which block the primary immune response; compounds that increase the protective effects of kynurenic acid; and specific antioxidants that target IDO activation, the immune and oxidative pathways, and 5-HT as well.
► Induction of the tryptophan catabolite (TRYCAT) pathway is associated with the onset of depression. ► Activation of IDO and TDO may induce this pathway and increase the synthesis of detrimental TRYCATs. ► IDO is induced by proinflammatory cytokines, TDO by glucocorticoids, both increased in depression. ► Activation of IDO and TDO deplete plasma tryptophan and consequently brain 5-HT. ► The TRYCAT pathway is new drug target in depression.
Measurements of anisotropic flow coefficients (vn) and their cross-correlations using two- and multiparticle cumulant methods are reported in collisions of pp at s=13 TeV, p−Pb at a center-of-mass ...energy per nucleon pair sNN=5.02 TeV, Xe-Xe at sNN=5.44 TeV, and Pb-Pb at sNN=5.02 TeV recorded with the ALICE detector. The multiplicity dependence of vn is studied in a very wide range from 20 to 3000 particles produced in the midrapidity region |η|<0.8 for the transverse momentum range 0.2<pT<3.0 GeV/c. An ordering of the coefficients v2>v3>v4 is found in pp and p−Pb collisions, similar to that seen in large collision systems, while a weak v2 multiplicity dependence is observed relative to nucleus-nucleus collisions in the same multiplicity range. Using a novel subevent method, v2 measured with four-particle cumulants is found to be compatible with that from six-particle cumulants in pp and p−Pb collisions. The magnitude of the correlation between vn2 and vm2, evaluated with the symmetric cumulants SC(m,n) is observed to be positive at all multiplicities for v2 and v4, while for v2 and v3 it is negative and changes sign for multiplicities below 100, which may indicate a different vn fluctuation pattern in this multiplicity range. The observed long-range multiparticle azimuthal correlations in high multiplicity pp and p−Pb collisions can neither be described by pythia 8 nor by impact-parameter-Glasma, music, and ultrarelativistic quantum molecular dynamics model calculations, and hence, provide new insights into the understanding of collective effects in small collision systems.
The production rates and the transverse momentum distribution of strange hadrons at mid-rapidity (
y
<
0.5
) are measured in proton-proton collisions at
s
= 13 TeV as a function of the charged ...particle multiplicity, using the ALICE detector at the LHC. The production rates of
K
S
0
,
Λ
,
Ξ
, and
Ω
increase with the multiplicity faster than what is reported for inclusive charged particles. The increase is found to be more pronounced for hadrons with a larger strangeness content. Possible auto-correlations between the charged particles and the strange hadrons are evaluated by measuring the event-activity with charged particle multiplicity estimators covering different pseudorapidity regions. When comparing to lower energy results, the yields of strange hadrons are found to depend only on the mid-rapidity charged particle multiplicity. Several features of the data are reproduced qualitatively by general purpose QCD Monte Carlo models that take into account the effect of densely-packed QCD strings in high multiplicity collisions. However, none of the tested models reproduce the data quantitatively. This work corroborates and extends the ALICE findings on strangeness production in proton-proton collisions at 7 TeV.
This paper presents the measurements of
π
±
,
K
±
,
p
and
p
¯
transverse momentum (
p
T
) spectra as a function of charged-particle multiplicity density in proton–proton (pp) collisions at
s
=
13
TeV
...with the ALICE detector at the LHC. Such study allows us to isolate the center-of-mass energy dependence of light-flavour particle production. The measurements reported here cover a
p
T
range from 0.1 to 20
GeV
/
c
and are done in the rapidity interval
|
y
|
<
0.5
. The
p
T
-differential particle ratios exhibit an evolution with multiplicity, similar to that observed in pp collisions at
s
=
7
TeV
, which is qualitatively described by some of the hydrodynamical and pQCD-inspired models discussed in this paper. Furthermore, the
p
T
-integrated hadron-to-pion yield ratios measured in pp collisions at two different center-of-mass energies are consistent when compared at similar multiplicities. This also extends to strange and multi-strange hadrons, suggesting that, at LHC energies, particle hadrochemistry scales with particle multiplicity the same way under different collision energies and colliding systems.
The study of (anti-)deuteron production in pp collisions has proven to be a powerful tool to investigate the formation mechanism of loosely bound states in high-energy hadronic collisions. In this ...paper the production of
(anti-)deuterons
is studied as a function of the charged particle multiplicity in inelastic pp collisions at
s
=
13
TeV using the ALICE experiment. Thanks to the large number of accumulated minimum bias events, it has been possible to measure (anti-)deuteron production in pp collisions up to the same charged particle multiplicity (
d
N
ch
/
d
η
∼
26
) as measured in p–Pb collisions at similar centre-of-mass energies. Within the uncertainties, the deuteron yield in pp collisions resembles the one in p–Pb interactions, suggesting a common formation mechanism behind the production of light nuclei in hadronic interactions. In this context the measurements are compared with the expectations of coalescence and statistical hadronisation models (SHM).
A
bstract
The inclusive J/
ψ
elliptic (
v
2
) and triangular (
v
3
) flow coefficients measured at forward rapidity (2
.
5
< y <
4) and the
v
2
measured at midrapidity (|
y
|
<
0
.
9) in Pb-Pb ...collisions at
s
NN
= 5
.
02 TeV using the ALICE detector at the LHC are reported. The entire Pb-Pb data sample collected during Run 2 is employed, amounting to an integrated luminosity of 750
μ
b
−
1
at forward rapidity and 93
μ
b
−
1
at midrapidity. The results are obtained using the scalar product method and are reported as a function of transverse momentum
p
T
and collision centrality. At midrapidity, the J/
ψ v
2
is in agreement with the forward rapidity measurement. The centrality averaged results indicate a positive J/
ψ v
3
with a significance of more than 5
σ
at forward rapidity in the
p
T
range 2
< p
T
<
5 GeV/
c
. The forward rapidity
v
2
,
v
3
, and
v
3
/v
2
results at low and intermediate
p
T
(
p
T
≲ 8 GeV/
c
) exhibit a mass hierarchy when compared to pions and D mesons, while converging into a species-independent curve at higher
p
T
. At low and intermediate
p
T
, the results could be interpreted in terms of a later thermalization of charm quarks compared to light quarks, while at high
p
T
, path-length dependent effects seem to dominate. The J/
ψ v
2
measurements are further compared to a microscopic transport model calculation. Using a simplified extension of the quark scaling approach involving both light and charm quark flow components, it is shown that the D-meson
v
n
measurements can be described based on those for charged pions and J/
ψ
flow.
A
bstract
The inclusive J
/ψ
production in Pb–Pb collisions at the center-of-mass energy per nucleon pair
s
NN
= 5
.
02 TeV, measured with the ALICE detector at the CERN LHC, is reported. The J
/ψ
...meson is reconstructed via the dimuon decay channel at forward rapidity (2
.
5
< y <
4) down to zero transverse momentum. The suppression of the J
/ψ
yield in Pb–Pb collisions with respect to binary-scaled pp collisions is quantified by the nuclear modification factor (
R
AA
). The
R
AA
at
s
NN
= 5
.
02 TeV is presented and compared with previous measurements at
s
NN
= 2
.
76 TeV as a function of the centrality of the collision, and of the J
/ψ
transverse momentum and rapidity. The inclusive J
/ψ R
AA shows a suppression increasing toward higher transverse momentum, with a steeper dependence for central collisions. The modification of the J
/ψ
average transverse momentum and average squared transverse momentum is also studied. Comparisons with the results of models based on a transport equation and on statistical hadronization are carried out.
A
bstract
Anisotropic flow coefficients,
v
n
, non-linear flow mode coefficients,
χ
n,mk
, and correlations among different symmetry planes,
ρ
n,mk
are measured in Pb-Pb collisions at
s
NN
= 5
.
02 ...TeV. Results obtained with multi-particle correlations are reported for the transverse momentum interval 0
.
2
< p
T
<
5
.
0 GeV/
c
within the pseudorapidity interval 0
.
4
<
|
η
|
<
0
.
8 as a function of collision centrality. The
v
n
coefficients and
χ
n,mk
and
ρ
n,mk
are presented up to the ninth and seventh harmonic order, respectively. Calculations suggest that the correlations measured in different symmetry planes and the non-linear flow mode coefficients are dependent on the shear and bulk viscosity to entropy ratios of the medium created in heavy-ion collisions. The comparison between these measurements and those at lower energies and calculations from hydrodynamic models places strong constraints on the initial conditions and transport properties of the system.
A
bstract
Inclusive J
/ψ
production is studied in minimum-bias proton-proton collisions at a centre-of-mass energy of
s
= 5
.
02 TeV by ALICE at the CERN LHC. The measurement is performed at ...mid-rapidity (
|y| <
0
.
9) in the dielectron decay channel down to zero transverse momentum
p
T
, using a data sample corresponding to an integrated luminosity of
L
int
= 19
.
4
±
0
.
4 nb
−
1
. The measured
p
T
-integrated inclusive J
/ψ
production cross sec- tion is d
σ/
d
y
= 5
.
64
±
0
.
22(stat.)
±
0
.
33(syst.)
±
0
.
12(lumi.)
μ
b. The
p
T
-differential cross section d
2
σ/
d
p
T
d
y
is measured in the
p
T
range 0–10 GeV
/c
and compared with state-of- the-art QCD calculations. The J
/ψ
〈
p
T
〉 and
p
T
2
are extracted and compared with results obtained at other collision energies.
In 1874, Karl Kahlbaum described catatonia as an independent syndrome characterized by motor, affective, and behavioral anomalies. In the following years, various catatonia concepts were established ...with all sharing the prime focus on motor and behavioral symptoms while largely neglecting affective changes. In 21st century, catatonia is a well-characterized clinical syndrome. Yet, its neurobiological origin is still not clear because methodological shortcomings of hitherto studies had hampered this challenging effort. To fully capture the clinical picture of catatonia as emphasized by Karl Kahlbaum, 2 decades ago a new catatonia scale was developed (Northoff Catatonia Rating Scale NCRS). Since then, studies have used NCRS to allow for a more mechanistic insight of catatonia. Here, we undertook a systematic review searching for neuroimaging studies using motor/behavioral catatonia rating scales/criteria and NCRS published up to March 31, 2019. We included 19 neuroimaging studies. Studies using motor/behavioral catatonia rating scales/criteria depict cortical and subcortical motor regions mediated by dopamine as neuronal and biochemical substrates of catatonia. In contrast, studies relying on NCRS found rather aberrant higher-order frontoparietal networks which, biochemically, are insufficiently modulated by gamma-aminobutyric acid (GABA)-ergic and glutamatergic transmission. This is further supported by the high therapeutic efficacy of GABAergic agents in acute catatonia. In sum, this systematic review points out the difference between motor/behavioral and NCRS-based classification of catatonia on both neuronal and biochemical grounds. That highlights the importance of Kahlbaum's original truly psychomotor concept of catatonia for guiding both research and clinical diagnosis and therapy.
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