Psychiatric problems in fibromyalgia : clinical and neurobiological links between mood disorders and fibromyalgia

Objective. To review the literature addressing the relationship between mood disorders and fibromyalgia/chron-ic pain and our current understanding of overlapping pathophysiological processes and pain and depression circuitry. Methods. We selectively reviewed articles on the co-occurrence of mood disorders and fibromyalgia/chronic pain published between 1990 and July 2012 in PubMed. Bibliographies and cross references were considered and included when appropriate. Results. Forty-nine out of 138 publications were retained for review. The vast majority of the studies found an association between depression and fibromyalgia. There is evidence that depression is often accompanied by symptoms of opposite polarity characterised by heights of mood, thinking and behaviour that have a considerable impact on pharmacological treatment. Recent developments support the view that the high rates of fibromyalgia and mood disorder comorbidity is generated by largely overlapping pathophysiological processes in the brain, that provide a neurobiological basis for the bidirectional, mutually exacerbating and disabling relationship between pain and depression. Conclusions. The finding of comparable pathophysiological characteristics of pain and depression provides a framework for understanding the relationship between the two conditions and sheds some light on neurobio-logical and therapeutic aspects

Somatoform disorders and rheumatic diseases : from DSM-IV to DSM-V

Medically unexplained symptoms are considered 'somatoform disorders' in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). The introduction of this nosographic category has been helpful in drawing attention to a previously neglected area, but has not been successful in promoting an understanding of the disorders' biological basis and treatment implications, probably because of a series of diagnostic shortcomings. The newly proposed DSM-V diagnostic criteria try to overcome the limitations of the DSM-IV definition, which was organised centrally around the concept of medically unexplained symptoms, by emphasising the extent to which a patient's thoughts, feelings and behaviours concerning their somatic symptoms are disproportionate or excessive. This change is supported by a growing body of evidence showing that psychological and behavioural features play a major role in causing patient disability and maintaining high level of health care use. Pain disorders is the sub-category of DSM-IV somatoform disorders that most closely resembles fibromyalgia. Regardless of the diagnostic changes recently brought about by DSM-V, neuroimaging studies have identified important components of the mental processes associated with a DSM- IV diagnosis of pain disorder

Consequences of a unified, anarchical model of fermion masses and mixings

We show that most features of the mass and mixing pattern of the second and third SM fermion families can be accounted for without making use of flavour symmetries or other types of flavour dynamics. We discuss the implications for flavour phenomenology, in particular for the tau -> mu gamma decay rate, and comment on LFV effects at colliders. We show that the model can be embedded in a full SO(10) supersymmetric GUT in 5 dimensions that preserves the successful MSSM gauge coupling unification prediction for alpha(s). Interesting features of this embedding are i) the connection of one of the hierarchy parameters with the strong coupling assumption, ii) the absence of KK threshold effects on the alpha(s) prediction at one loop, and iii) the shift of the GUT scale up to about 10(17) GeV. Proton decay is under control, also due to the larger GUT scale. A large atmospheric angle for normal hierarchical neutrinos is obtained in an unusual way

Underground Neutrino Detectors for Particle and Astroparticle Science: the Giant Liquid Argon Charge Imaging ExpeRiment (GLACIER)

The current focus of the CERN program is the Large Hadron Collider (LHC), however, CERN is engaged in long baseline neutrino physics with the CNGS project and supports T2K as recognized CERN RE13, and for good reasons: a number of observed phenomena in high-energy physics and cosmology lack their resolution within the Standard Model of particle physics; these puzzles include the origin of neutrino masses, CP-violation in the leptonic sector, and baryon asymmetry of the Universe. They will only partially be addressed at LHC. A positive measurement of $\sin^22\theta_{13}>0.01$ would certainly give a tremendous boost to neutrino physics by opening the possibility to study CP violation in the lepton sector and the determination of the neutrino mass hierarchy with upgraded conventional super-beams. These experiments (so called ``Phase II'') require, in addition to an upgraded beam power, next generation very massive neutrino detectors with excellent energy resolution and high detection efficiency in a wide neutrino energy range, to cover 1st and 2nd oscillation maxima, and excellent particle identification and $\pi^0$ background suppression. Two generations of large water Cherenkov detectors at Kamioka (Kamiokande and Super-Kamiokande) have been extremely successful. And there are good reasons to consider a third generation water Cherenkov detector with an order of magnitude larger mass than Super-Kamiokande for both non-accelerator (proton decay, supernovae, ...) and accelerator-based physics. On the other hand, a very massive underground liquid Argon detector of about 100 kton could represent a credible alternative for the precision measurements of ``Phase II'' and aim at significantly new results in neutrino astroparticle and non-accelerator-based particle physics (e.g. proton decay).Comment: 31 pages, 14 figure

A realistic pattern of fermion masses from a five-dimensional SO(10) model

We provide a unified description of fermion masses and mixing angles in the framework of a supersymmetric grand unified SO(10) model with anarchic Yukawa couplings of order unity. The space-time is five dimensional and the extra flat spatial dimension is compactified on the orbifold $S^1/(Z_2 \times Z_2')$, leading to Pati-Salam gauge symmetry on the boundary where Yukawa interactions are localised. The gauge symmetry breaking is completed by means of a rather economic scalar sector, avoiding the doublet-triplet splitting problem. The matter fields live in the bulk and their massless modes get exponential profiles, which naturally explain the mass hierarchy of the different fermion generations. Quarks and leptons properties are naturally reproduced by a mechanism, first proposed by Kitano and Li, that lifts the SO(10) degeneracy of bulk masses in terms of a single parameter. The model provides a realistic pattern of fermion masses and mixing angles for large values of $\tan\beta$. It favours normally ordered neutrino mass spectrum with the lightest neutrino mass below 0.01 eV and no preference for leptonic CP violating phases. The right handed neutrino mass spectrum is very hierarchical and does not allow for thermal leptogenesis. We analyse several variants of the basic framework and find that the results concerning the fermion spectrum are remarkably stable.Comment: 30 pages, 7 figures, 4 table

Chronic widespread pain in spondyloarthritis

The pain associated with spondyloarthritis (SpA) can be intense, persistent and disabling. It frequently has a multifactorial, simultaneously central and peripheral origin, and may be due to currently active inflammation, or joint damage and tissue destruction arising from a previous inflammatory condition. Inflammatory pain symptoms can be reduced by non-steroidal anti-inflammatory drugs, but many patients continue to experience moderate pain due to alterations in the mechanisms that regulate central pain, as in the case of the chronic widespread pain (CWP) that characterises fibromyalgia (FM). The importance of distinguishing SpA and FM is underlined by the fact that SpA is currently treated with costly drugs such as tumour necrosis factor (TNF) inhibitors, and direct costs are higher in patients with concomitant CWP or FM than in those with FM or SpA alone. Optimal treatment needs to take into account symptoms such as fatigue, mood, sleep, and the overall quality of life, and is based on the use of tricyclic antidepressants or selective serotonin reuptake inhibitors such as fluoxetine, rather than adjustments in the dose of anti-TNF agents or disease-modifying drugs

Gauge coupling unification, the GUT scale, and magic fields

We consider field sets that do not form complete SU(5) multiplets, but exactly preserve the one-loop MSSM prediction for $\alpha_3(M_Z)$ independently of the value of their mass. Such fields can raise the unification scale in different ways, through a delayed convergence of the gauge couplings, a fake unified running below the GUT scale, or a postponed unification after a hoax crossing at a lower scale. The $\alpha_3(M_Z)$ prediction is independent of the mass of the new fields, while the GUT scale often is not, which allows to vary the GUT scale. Such "magic" fields represent a useful tool in GUT model building. For example, they can be used to fix gauge coupling unification in certain two step breakings of the unified group, to suppress large KK thresholds in models with extra dimensions, or they can be interpreted as messengers of supersymmetry breaking in GMSB models.Comment: 14 pages, 3 figures. Typos corrected in text and equations, reference adde

SUSY GUT Model Building

I discuss an evolution of SUSY GUT model building, starting with the construction of 4d GUTs, to orbifold GUTs and finally to orbifold GUTs within the heterotic string. This evolution is an attempt to obtain realistic string models, perhaps relevant for the LHC. This review is in memory of the sudden loss of Julius Wess, a leader in the field, who will be sorely missed.Comment: 24 pages, 14 figures, lectures given at PiTP 2008, Institute for Advanced Study, Princeton, to be published in the European Physical Journal

Nucleon Decay Searches with large Liquid Argon TPC Detectors at Shallow Depths: atmospheric neutrinos and cosmogenic backgrounds

Grand Unification of the strong, weak and electromagnetic interactions into a single unified gauge group is an extremely appealing idea which has been vigorously pursued theoretically and experimentally for many years. The detection of proton or bound-neutron decays would represent its most direct experimental evidence. In this context, we studied the physics potentialities of very large underground Liquid Argon Time Projection Chambers (LAr TPC). We carried out a detailed simulation of signal efficiency and background sources, including atmospheric neutrinos and cosmogenic backgrounds. We point out that a liquid Argon TPC, offering good granularity and energy resolution, low particle detection threshold, and excellent background discrimination, should yield very good signal over background ratios in many possible decay modes, allowing to reach partial lifetime sensitivities in the range of 1034−1035 years with exposures up to 1000 kton×year, often in quasi-background-free conditions optimal for discoveries at the few events level, corresponding to atmospheric neutrino background rejections of the order of 105. Multi-prong decay modes like e.g. p→μ−π+K+ or p→e+π+π− and channels involving kaons like e.g. p→K+ν¯, p→e+K0 and p→μ+K0 are particularly suitable, since liquid Argon imaging (...)This work was in part supported by ETH and the Swiss National Foundation. AB, AJM and SN have been supported by CICYT Grants FPA-2002-01835 and FPA-2005-07605-C02-01. SN acknowledges support from the Ramon y Cajal Programme. We thank P. Sala for help with FLUKA while she was an ETH employee

Transdiagnostic subgroups of cognitive impairment in early affective and psychotic illness

Abstract: Cognitively impaired and spared patient subgroups were identified in psychosis and depression, and in clinical high-risk for psychosis (CHR). Studies suggest differences in underlying brain structural and functional characteristics. It is unclear whether cognitive subgroups are transdiagnostic phenomena in early stages of psychotic and affective disorder which can be validated on the neural level. Patients with recent-onset psychosis (ROP; N = 140; female = 54), recent-onset depression (ROD; N = 130; female = 73), CHR (N = 128; female = 61) and healthy controls (HC; N = 270; female = 165) were recruited through the multi-site study PRONIA. The transdiagnostic sample and individual study groups were clustered into subgroups based on their performance in eight cognitive domains and characterized by gray matter volume (sMRI) and resting-state functional connectivity (rsFC) using support vector machine (SVM) classification. We identified an impaired subgroup (N ROP = 79, N ROD = 30, N CHR = 37) showing cognitive impairment in executive functioning, working memory, processing speed and verbal learning (all p < 0.001). A spared subgroup (N ROP = 61, N ROD = 100, N CHR = 91) performed comparable to HC. Single-disease subgroups indicated that cognitive impairment is stronger pronounced in impaired ROP compared to impaired ROD and CHR. Subgroups in ROP and ROD showed specific symptom- and functioning-patterns. rsFC showed superior accuracy compared to sMRI in differentiating transdiagnostic subgroups from HC (BACimpaired = 58.5%; BACspared = 61.7%, both: p < 0.01). Cognitive findings were validated in the PRONIA replication sample (N = 409). Individual cognitive subgroups in ROP, ROD and CHR are more informative than transdiagnostic subgroups as they map onto individual cognitive impairment and specific functioning- and symptom-patterns which show limited overlap in sMRI and rsFC. Clinical trial registry name: German Clinical Trials Register (DRKS). Clinical trial registry URL: https://www.drks.de/drks_web/ . Clinical trial registry number: DRKS00005042