We found that reduced length of the investigated trinucleotide repeat might aggravate craving symptoms. Moreover, an elevated number of repeats might be protective against severe craving. In summary, the presented data points to an underestimated role of the genetic regulation

of androgens in the pathogenesis of alcohol dependence and related disorders. (C) 2009 Elsevier Ltd. All rights reserved.”
“We found a novel type germline mutation at exon 11 of the c-kit gene, which results in a substitution of Tyr to Cys at codon 553 of the c-kit gene product (KIT-Tyr553Cys), in a 68-year-old female patient Wortmannin cost with multiple gastrointestinal stromal tumors (GISTs). In the present study, we carried out mutational analysis in her family members to determine the carriers and characterized the mutation by introducing the corresponding mutation (murine KIT-Tyr552Cys) into expression vector possessing

murine c-kit cDNA. Mutational analysis of peripheral blood leukocytes of her family members revealed that a 44-year-old son had the same mutation, but at MDV3100 present he had neither apparent symptoms nor images of multiple GISTs. By transfection with the expression vector possessing the murine mutant c-kit cDNA, interleukin-3-dependent Ba/F3 murine lymphoid cells started growing autonomously without any growth factors, indicating that the mutation was considered to be of gain-of-function. Imatinib, a small molecule of tyrosine kinase inhibitor, effectively inhibited autophosphorylation of KIT-Tyr552Cys. Nilotinib,

another small molecule of the KIT inhibitor, also effectively inhibited autophosphorylation of KIT-Tyr552Cys. In fact, proliferation of Ba/F3 cells expressing KIT-Tyr552Cys was effectively inhibited by both imatinib and nilotinib. These selleck screening library findings indicate that the novel type human KIT-Tyr553Cys mutation is the cause of the present familial and multiple GISTs, and that both imatinib and nilotinib might effectively inhibit the growth of GISTs developing in the patients of this family. Laboratory Investigation (2012) 92, 451-457; doi:10.1038/labinvest.2011.165; published online 14 November 2011″
“Depression is one of the most common and debilitating psychiatric illnesses around the world, but the current antidepressants used to treat depression have many limitations. Progressively more studies have shown that neuropeptide systems are potential novel therapeutic targets for depression. However, whether the neuropeptide trefoil factor 3 (TFF3) participates in the development of depression has not been examined. In the current experiments, we assessed the antidepressant effects of TFF3 using the forced swim test (FST), tail suspension test (TST), and chronic mild stress (CMS) paradigm. Furthermore, we determined the mechanism that underlies the antidepressant-like effects of TFF3 in the rat FST. TFF3 dose-dependently reduced immobility time in both FST and TST.

We assessed the construct validity of a commercially available, virtual reality transurethral prostate resection simulator.

Materials

and Methods: Participants performed 2, 5-minute transurethral prostate resection exercises on a standardized virtual reality prostate. Data from the first exercise were discarded. Simulator based metrics from the second exercise were tabulated, including tissue resected in gm, number of cuts, coagulation time, number of coagulation attempts, tissue per cut in gm and blood loss. Complications were recorded. selleckchem Performance metrics were compared between groups based on urological training level and prior real-world experience with transurethral prostate resection.

Results: A total of 35 participants with varied levels of transurethral prostate resection experience completed the exercise. Several performance metrics had statistically significant correlations with urology training level and prior experience with transurethral prostate resection. There was a positive correlation of all measures of experience with mass resected, mass resected per cut and blood loss. Number of cuts correlated significantly

with transurethral prostate resection experience in the previous year. Complications were present in most groups with medical students more likely to encounter external urethral sphincter and rectal injuries.

Conclusions:

We report the construct validity of a commercially available, virtual reality transurethral prostate Dinaciclib resection simulator. The more experienced participants resected more BAY 1895344 solubility dmso tissue in a more efficient manner but with increased blood loss. Further investigations are needed before the widespread application of transurethral prostate resection simulators for training, certification and accreditation.”
“Purpose: We evaluated the long-term results and durability of photoselective vaporization and holmium laser ablation as surgical treatment of small to medium prostates in a prospective, randomized study in men with obstructive benign prostatic hyperplasia.

Materials and Methods: From March 2005 to April 2007 we randomly allocated 109 patients with a prostate gland of less than 60 cc to prostate photoselective vaporization (52) or holmium laser ablation (57) and evaluated them 1, 2 and 3 years postoperatively. Functional followup included measurement of maximum urinary flow rate, post-void residual urine, International Prostate Symptom Score, quality of life, International Index of Erectile Function and prostate specific antigen.

Results: Mean +/- SD preoperative prostate volume was 33.1 +/- 14.5 and 37.3 +/- 13.6 in the laser ablation and vaporization groups, respectively. All functional parameters improved significantly compared to baseline values in each group.

IGF-1R expression

correlated with endogenous HoxA9 expression in a small panel of mixed lineage leukemia (MLL)/AF4 cell lines. siRNA knockdown of endogenous HoxA9 expression in the MLL/AF4-positive cell line RS4;11 resulted in loss of IGF-1R expression. These data indicate that HoxA9 overexpression induces IGF- 1R expression and subsequently promotes leukemic cell growth.”
“Thalamo-cortical networks generate specific patterns of oscillations during distinct vigilance states and epilepsy, well characterized by electroencephalography (EEG). Oscillations depend on recurrent synaptic loops, which are controlled by GABAergic Paclitaxel cost transmission. In particular, GABA(A) receptors containing the alpha 3 subunit are expressed predominantly in cortical layer VI and thalamic reticular nucleus (nRT)

learn more and regulate the activity and firing pattern of neurons in relay nuclei. Therefore, ablation of these receptors by gene targeting might profoundly affect thalamo-cortical oscillations. Here, we investigated the role of alpha 3-GABA(A) receptors in regulating vigilance states and seizure activity by analyzing chronic EEG recordings in alpha 3 subunit-knockout (alpha 3-KO) mice. The presence of postsynaptic alpha 3-GABA(A) receptors/gephyrin clusters in the nRT and GABA(A)-mediated synaptic currents in acute thalamic slices was also examined.

EEG spectral analysis showed JQ-EZ-05 solubility dmso no difference between genotypes during non rapid-eye movement (NREM) sleep or at waking-NREM sleep transitions. EEG power in the spindle frequency range (10-15 Hz) was significantly lower at NREM-REM sleep transitions in mutant compared with wild-type mice. Enhancement of sleep pressure by 6 h sleep deprivation did not reveal any differences in the regulation of EEG activities between genotypes. Finally, the waking EEG showed a slightly larger power in the 11-13-Hz band in alpha 3-KO mice. However, neither behavior nor the waking EEG showed alterations suggestive of absence seizures. Furthermore, alpha 3-KO mice did not differ in seizure susceptibility in a model

of temporal lobe epilepsy. Strikingly, despite the disruption of postsynaptic gephyrin clusters, whole-cell patch clamp recordings revealed intact inhibitory synaptic transmission in the nRT of alpha 3-KO mice. These findings show that the lack of alpha 3-GABA(A) receptors is extensively compensated for to preserve the integrity of thalamo-cortical function in physiological and pathophysiological situations. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“(Very) severe acquired aplastic anemia ((v)SAA) and myelodysplastic syndrome (MDS) are rare diseases in childhood. (V) SAA is a bone marrow (BM) failure syndrome characterized by immune-mediated destruction of hematopoietic progenitors.

DRG neurons were cultured for 48 hours and then exposed to CAP (2 mu mol/L), capsazepine (CPZ) (2 mu mol/L) plus CAP (2 mu

mol/L), or extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor PD98059 (10 mu mol/L) plus CAP (2 mu mol/L) for an additional 24 hours. The DRG neurons were continuously exposed to culture media as a control. After that, the levels of Gal mRNA and CGRP mRNA of DRG neurons were determined using real time-PCR analysis. Gal and CGRP expression in CH5183284 situ was detected by an immunofluorescent labeling technique. The levels of phosphorylated-ERK1/2 (pERK1/2) protein were detected using a Western blot assay. The results showed that CAP evoked increases of Gal and its mRNA and decreases of CGRP and its mRNA in DRG neurons. Administration of either CPZ or PD98059 blocked the effects of CAP. These data indicate that Gal and CGRP shared different responses to CAP stimulation. Gal and CGRP may have different

effects in nociceptive processing during neurogenic inflammation. (C) 2013 Elsevier B.V. All rights reserved.”
“Whether leptin targets the hypothalamic serotonergic system to inhibit food intake is 5-Fluoracil datasheet not established. We examined the effect of a short-term i.c.v. leptin treatment on serotonin microdialysate levels in rat lateral hypothalamus. Adipose tissue gene expression was also evaluated.

Male rats received four daily injections of leptin (5 mu g) or vehicle (with pair-feeding to leptin-induced intake) and a fifth injection during collection

of LH microdialysates. We found that serotonin and 5-HIAA levels were not affected by the leptin pre-treatment, as basal levels were similar between the leptin and the pair-fed group. These levels remained unaltered after the acute leptin injection.

For gene expression studies, rats were pre-treated with five daily injections of either leptin (5 mu g) or vehicle (with either pair-feeding or ad libitum intake). mRNA levels of resistin, adiponectin, lipoprotein lipase, and PPAR-gamma were unaltered by either leptin or pair-feeding. Leptin gene expression was significantly reduced by leptin but not by pair-feeding, in both the retroperitoneal (- 74%) and the epididymal (- 99%) depots while no differences were observed in the subcutaneous depot.

The observations confirmed the absence of an acute stimulatory effect of central selleckchem leptin on serotonin release in the lateral hypothalamus and showed that the pre-treatment with leptin failed to modify this pattern. This indicates that components of the serotonergic system are probably not directly affected by leptin. Additionally, the central effect of leptin was able to downregulate its own adipose tissue gene expression in a depot-specific manner while other adipokine genes were not affected. (C) 2013 Elsevier B.V. All rights reserved.”
“Vascular Endothelial Growth Factor (VEGF) is a potent angiogenic factor, which also regulates bone remodeling.

001). Although significant associations were found between ambient temperature, selleckchem atmospheric pressure and hours of sunshine vis-A-vis monthly urinary calculi attack rates for the total population, after adjustment for trends and seasonality, ambient temperature was found to be the sole major factor having

any positive association with the monthly attack rates.

Conclusions: We conclude that seasonal variations do exist in the monthly urinary calculi attack rates for all age and gender populations, and that following time series statistical adjustment, only ambient temperature had any consistent association with monthly attack rates.”
“The hepatic transporter Mdr2 is an ATP-binding cassette transporter which excretes phosphatidylcholine into the bile. We showed that the level of Mdr2 mRNA oscillated in circadian fashion in mouse liver whereas such oscillation HKI272 was dampened in the liver of Clock mutants. To examine transcriptional regulation of the Mdr2 gene we performed luciferase reporter assays using plasmid constructs containing the 5′-flanking region of the Mdr2 gene. Reporter assays using deletion constructs demonstrated that E4BP4 represses the transcriptional activity of the promoter including the D1 and D2 sites within four putative E4BP4-binding sites. Chromatin

immunoprecipitation and gel shift assays showed that E4BP4 binds to the D2 site, but not to the D1 site. These data suggested that E4BP4 is a negative transcription factor for circadian Mdr2 mRNA expression. (C) 2007 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“Purpose: Recent studies have suggested an increased prevalence of urolithiasis and recurrence associated with obesity. We assessed the influence of obesity on stone risk factors as well as on stone recurrence.

Materials and Methods: A database of patient history, body mass index, and serum and urine chemistry was analyzed for 704 consecutive stone formers (467 first time stone formers

and 247 recurrent stone formers). Obesity was defined as body mass index greater than 25 kg/m(2). The effect of obesity on stone risk factors and recurrence were stratified Crenolanib ic50 according to stone episodes. Of these, 163 (23.2%) patients who had been followed for more than 36 months (median 54, range 5 to 148) were included in recurrence analysis.

Results: Obesity was significantly associated with stone episodes (p = 0.043). Obese stone formers excreted increased amounts of sodium, calcium, uric acid and citrate, while the urinary pH in a 24-hour urine sample was decreased compared to nonobese stone formers (p < 0.05, respectively). Stone analysis revealed that uric acid stone was significantly more commonly found in the obese patients (p = 0.046). Multivariate Cox regression model stratified by stone episodes revealed that obesity (HR 2.572, 95% CI 1.376-4.807, p = 0.

Previous

results have suggested that a key function of pp28 in the envelopment of infectious HCMV is expressed after the protein localizes in the assembly compartment (AC). In this study, we investigated the potential this website role of pp28 multimerization in the envelopment of the infectious virion. Our results indicated that pp28 multimerized during viral infection and that interacting domains responsible for self-interaction were localized in the amino terminus of the protein (amino acids [aa] 1 to 43). The results from transient-expression and/or infection assays indicated that the self-interaction took place in the AC. A mutant pp28 molecule containing only the first 35 aa failed to accumulate in the AC, did not interact with pp28 in the AC, and could not support virus replication. In contrast, the first 50 aa of pp28 was sufficient for the self-interaction within the AC and the assembly of infectious virus. Recombinant viruses

encoding an in-frame deletion of aa 26 to 33 of pp28 were replication competent, whereas infectious virus was not recovered from HCMV BACs lacking aa 26 SHP099 to 43. These findings suggested that the accumulation of pp28 was a prerequisite for multimerization of pp28 within the AC and that pp28 multimerization in the AC represented an essential step in the envelopment and production of infectious virions.”
“The pathophysiological underpinnings of bipolar disorder are not fully understood. However, they may be due in part to changes in the phosphatidylinositol second messenger system selleck chemical (PI-cycle) generally, or changes in myo-inositol concentrations more specifically. Dextroamphetamine has been used as a model for mania in several human studies as it causes similar subjective and

physiological symptoms. We wanted to determine if dextro-amphetamine altered myo-inositol concentrations in vivo as it would clearly define a mechanism linking putative changes in the PI-cycle to the subjective psychological changes seen with dextro-amphetamine administration. Fifteen healthy human volunteers received a baseline scan, followed by second scan 75 min after receiving a 25 mg oral dose of dextro-amphetamine. Stimulated echo proton magnetic resonance spectroscopy (MRS) scans were preformed at 3.0 Tesla (T) in the dorsal medial prefrontal cortex (DMPFC). Metabolite data were adjusted for tissue composition and analyzed using LCModel. Twelve adult male rats were treated acutely with a 5-mg/kg intraperitoneal dose of dextro-amphetamine. After 1 h rats were decapitated and the brains were rapidly removed and frozen until dissection. Rat brains were dissected into frontal, temporal, and occipital cortical areas, as well as hippocampus. Tissue was analyzed using a Varian 18.8 T spectrometer. Metabolites were identified and quantified using Chenomx Profiler software.

“
“The detection of social threat is crucial for adaptive behaviour. Previous studies have shown that angry faces capture attention and are processed more efficiently than happy faces. While this anger superiority effect has been found in typical and atypical development, it is unknown whether it exists in individuals with Williams syndrome (WS),

who show reduced social fear and atypical sociability. In this study, children with WS searched for angry or happy target faces surrounded by 2, 5 or 8 distracters (happy or angry faces, respectively). Performance was compared to that of mental age-matched controls. Results revealed no group differences for happy faces, however for angry faces, the WS, but not the control group, showed a significant performance

decrease for the 8-distracters condition, indicating the absence of an anger superiority effect, in good agreement with evidence for abnormal structure and function in brain areas for Selleck Tozasertib social threat processing in WS. (C) 2009 Elsevier Ltd. All rights reserved.”
“Objective: Analysis of congenital heart surgery results requires a reliable method CB-5083 research buy of estimating the risk of adverse outcomes. Two major systems in current use are based on projections of risk or complexity that were predominantly subjectively derived. Our goal was to create an objective, empirically based index that can be used to identify the statistically estimated risk of in-hospital mortality by procedure and to group procedures into risk categories.

Methods: Mortality risk was estimated for 148 types of operative procedures using data from 77,294 operations entered into the European Association for Cardiothoracic Surgery (EACTS) Congenital Heart Surgery Database (33,360 operations) and the Society of Thoracic Surgeons (STS) Congenital Heart Surgery Database (43,934 patients) between 2002 and 2007. EPZ004777 cost Procedure-specific mortality rate estimates were calculated using a Bayesian model that adjusted for small denominators.

Each procedure was assigned a numeric score (the STS-EACTS Congenital Heart Surgery Mortality Score [2009]) ranging from 0.1 to 5.0 based on the estimated mortality rate. Procedures were also sorted by increasing risk and grouped into 5 categories (the STS-EACTS Congenital Heart Surgery Mortality Categories [2009]) that were chosen to be optimal with respect to minimizing within-category variation and maximizing between-category variation. Model performance was subsequently assessed in an independent validation sample (n = 27,700) and compared with 2 existing methods: Risk Adjustment for Congenital Heart Surgery (RACHS-1) categories and Aristotle Basis Complexity scores.

Results: Estimated mortality rates ranged across procedure types from 0.3% (atrial septal defect repair with patch) to 29.8% (truncus plus interrupted aortic arch repair). The proposed STS-EACTS score and STS-EACTS categories demonstrated good discrimination for predicting mortality in the validation sample (C-index = 0.784 and 0.

“
“Early-onset familial Alzheimer’s disease (EOFAD) has been associated with mutations in three genes, of which presenilin

1 (PSEN1) mutations are the most https://www.selleckchem.com/products/10058-f4.html frequent. Here we report a novel PSEN1 mutation in a Chinese family with autosomal dominant Alzheimer’s disease with an onset age in the early 40s. Molecular genetic analysis showed a 507-509delATC mutation at codon 169, leading to the deletion of serine in residue 169 (Ser169del). The amnestic presentation and absence of other features contrast with the other two mutations at codon 169 which have been associated with myoclonic jerks and seizures. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“Purpose: Ureteral replacement with interposition of a bowel segment has traditionally required 4SC-202 order a large incision with substantial associated morbidity and prolonged time to convalescence. During the last 7 years a technique for laparoscopic assisted ileal interposition has evolved that mimics our open approach. We present a comparative analysis of functional and perioperative outcomes between patients undergoing laparoscopic or open ileal ureter replacement at our institution.

Materials

and Methods: A search of all procedures from 1980 to the present revealed 7 patients undergoing laparoscopic and 7 undergoing open ileal interposition. Functional and perioperative data from these patients are compared, and a detailed description of technique for the laparoscopic procedure is presented.

Results: Narcotic analgesic use in morphine equivalents (median

38.9 vs 322.2 mg, p = 0.035) and time to convalescence (median 4 vs 5.5 weeks, p = 0.03) were significantly less in the laparoscopic group. A trend toward shorter hospital stay (median 5 vs 8 days, p = 0.101) was also noted in patients in the laparoscopic check details group. There was no evidence of anastomotic stricture for patients in either group at last followup.

Conclusions: Despite the small number of subjects involved a significant advantage was noted for postoperative recovery after laparoscopic compared to open ileal interposition. A detailed understanding of this complicated procedure can help prevent inherent pitfalls.”
“Oxidative stress is associated with the aging process, a risk factor for neurodegenerative diseases, and decreased by reduced energy intake. Oxidative modifications can affect protein function: the sulfur-containing amino acids, including methionine, are particularly susceptible to oxidation. A methionine sulfoxide can be enzymatically reduced by the methionine sulfoxide reductase (Msr) system. Previously, we have shown that MsrA(-/-) mice exhibit altered locomotor activity and brain dopamine levels as function of age. Previous studies have demonstrated that a caloric restriction enhances antioxidant defense and reduces the action of reactive oxygen species.

The inclusion of additional endpoints beyond traditional reflexive find more behaviours further supports the value of rodent neuropathic pain models, such as the SNI, as behavioural assays to detect new chemical entities to treat this pain condition. (C) 2013 Elsevier Ltd. All rights reserved.”
“Metabotropic glutamate 5 (mGlu5) receptor antagonists reduce L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesias (LID) in Parkinson’s disease (PD). The aim of this study was to investigate the long-term effect of the prototypal mGlu5 receptor antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) on glutamate receptors known to be involved

in the development of LID in the de novo chronic treatment of monkeys lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP monkeys were treated for one month with L-DOPA and developed dyskinesias

Cl-amidine purchase while those treated with L-DOPA and MPEP (10 mg/kg) developed significantly less. Normal control and saline-treated MPTP monkeys were also included. All MPTP monkeys were extensively and similarly denervated. The basal ganglia [H-3]ABP688 specific binding (mGlu5 receptors) was elevated in L-DOPA-treated MPTP monkeys compared to controls but not in those treated with L-DOPA and MPEP; dyskinesia scores of these monkeys correlated positively with their [H-3]ABP688 specific binding. Striatal density (B-max) of [H-3]ABP688 specific binding increased in L-DOPA-treated MPTP monkeys compared to other groups and affinity (K-d) remained unchanged. Striatal mGlu5 receptor mRNA remained unchanged following treatments. Elevated basal ganglia specific binding of [H-3]Ro 25-6981 (NMDA NR1/NR2B receptors), [H-3]Ro 48-8587 (AMPA receptors) but not [H-3]CGP-39653 (NMDA NR1/NR2A receptors) was observed only in L-DOPA-treated MPTP monkeys; dyskinesias scores correlated with binding. By contrast, basal ganglia [H-3]LY341495 specific binding (mGlu2/3 receptors) decreased in L-DOPA-treated click here MPTP monkeys

compared to controls, saline and L-DOPA + MPEP treated MPTP monkeys; dyskinesias scores correlated negatively with this binding. Hence, chronic MPEP treatment reduces the development of LID and is associated with a normalization of glutamate neurotransmission. (C) 2013 Elsevier Ltd. All rights reserved.”
“The known interactions between the serotonergic and neurokinin systems suggest that serotonin re-uptake inhibitor (SSRIs) efficacy may be improved by neurokinin-1 receptor (NK1R) antagonism. In the current studies combination of a subeffective dose of an SSRI (0.3 mg/kg fluoxetine or 0.03 mg/kg citalopram) with a subeffective dose of an NK1R antagonist (0.3 mg/kg aprepitant or 1 mg/kg CP-122,721) produced efficacy in the gerbil forced swim test (FST).

Methods: Data regarding preoperative condition, mortality, and morbidity Necrostatin-1 nmr have been reviewed and analyzed.

Results: From January 1993 to December 2009, 101 patients had bridge to transplant procedures with the SynCardia Total Artificial Heart. Ninety-one percent of cases were Interagency Registry for Mechanically Assisted Circulatory Support profile 1, and the remaining 9% of cases were failing medical therapy on multiple inotropic medications. The mean support time was 87 days (median,

53 days; range, 1-441 days). Pump outputs during support were 7 to 9 L/min. Adverse events included strokes in 7.9% of cases and take-back for hemorrhage in 24.7% of cases. Survival to transplantation was 68.3%. Causes of death of 32 patients on device support included multiple organ failure (13), pulmonary failure (6), and neurologic injury (4). Survival after transplantation at 1, 5, and 10 years was 76.8%, 60.5%, and 41.2%, respectively. The longest-term survivor is currently alive 16.4 years postimplantation.

Conclusions: These patients were not candidates for left ventricular assist device therapy and were expected to die. The SynCardia Total Artificial Heart offers a real alternative for survival

with a reasonable complication rate in appropriate candidates who otherwise might have been assigned to hospice care. (J Thorac Cardiovasc Surg 2012;143:727-34)”
“Background. see more Mood lability is a concept widely used. However, data on its prevalence and morbid associations are scarce.

We sought to establish the occurrence and importance of mood lability in a large community sample of cildren and adolescents by testing a priori hypotheses.

Method. Cross-sectional data were taken from a national mental health survey including 5326 subjects aged 8-79 years in the UK. The outcomes were prevalence and characteristics of mood lability and its associations with psychopathology and overall impairment.

Results. Mood lability occurred in more than 5% of the population of children and adolescents, both by parent and self-report. Mood lability was strongly associated with a wide range of psychopathology Cyclopamine and was linked to significant impairment even in the absence of psychiatric disorders. Mood lability was particularly strongly associated with co-morbidity between internalizing and externalizing disorders, even when adjusting for the association with individual disorders. The pattern of results did not change after excluding youth with bipolar disorder or with episodes of elated mood.

Conclusions. Clinically significant mood lability is relatively common in the community. Our findings indicate that mood lability is not a mere consequence of other psychopathology in that it is associated with significant impairment even in the absence of psychiatric diagnoses. Moreover, the pattern of association of mood lability with co-morbidity suggests that it could be a risk factor shared by both internalizing and externalizing disorders.