26 Southwick et al27 found that after receiving yohimbine, a subset of PTSD patients not only exhibited physiological arousal such as increased heart rate and blood pressure, but also developed severe anxiety symptoms including acute panic

attacks and increased PTSD symptoms such as intrusive thoughts, flashbacks, and emotional numbing. Yohimbine did not elicit similar responses in trauma-exposed controls without PTSD. Morgan et al28 demonstrated that yohimbine infusion Inhibitors,research,lifescience,medical enhanced acoustic startle responses in combat veterans with PTSD, but did not affect startle responses in combat veterans without PTSD. Consistent with psychophysiologic findings, these result further support the hypothesis that increased noradrenergic responsivity is a core biological feature of PTSD. Neuroendocrine changes in PTSD Baseline neuroendocrine changes In addition to activating the noradrenergic system, exposure to acute stress elicits important neuroendocrine changes that are modulated by the HPA axis. In response Inhibitors,research,lifescience,medical to acute stress, corticotropin-releasing

hormone (CRH) is released from nuclei in the hypothalamus, amygdala, and cortex.29 CRH is a 41-amino-acid peptide that is transported to the anterior lobe of the pituitary gland Inhibitors,research,lifescience,medical where it stimulates pituitary secretion of adrenocorticotropic hormone (ACTH). ACTH enters the Inhibitors,research,lifescience,medical systemic circulation and binds

to cells in the adrenal cortex, thereby stimulating the secretion of Cortisol. Cortisol is the primary stress hormone. Cortisol binds to the type I and type II glucocorticoid receptors that are present on cell membranes and activates a cascade of physiologic stress responses involving altered metabolism, increased cellular uptake of glucose, modulation of immune activity, and induction of hepatic enzymes. This has been reviewed by Michelson et al.30 Cortisol also blocks Inhibitors,research,lifescience,medical further secretion of CRH and ACTH, thereby curtailing the acute stress response once the stress is over. This is a crucial function of Cortisol, since uncontrolled activation of Ketanserin acute stress hormones can significantly harm host tissue. There is clear evidence from animal studies that persistent activation of the HPA axis by chronic and repetitive stress can have deleterious effects such as the acceleration of aging, disruption of reproductive function, immunosuppression, and reduced ability to fight cancers: these findings have been reviewed by Johnson et al.31 Noting that increased HPA axis activity is associated with chronic stress in preclinical studies, investigators CDK inhibitor initially predicted that individuals with PTSD would have elevated plasma Cortisol levels and would fail to suppress Cortisol levels after being administered dexamethasone.

7,86 These findings in drug addiction and OCD beg an important question; if both conditions can be explained, at least in part, by an enhancement

of habit-like learning or a dysregulation of the balance between learning systems, then why are they so manifestly different from a clinical perspective? This is an important question for further study. Inhibitors,research,lifescience,medical Conclusion In this brief review, we have sought to illustrate several instances in which dysregulation of mnemonic processes and the mechanisms of neuroplasticity contribute to prevalent neuropsychiatric diseases. As illustrated in the foregoing discussion, reduced, enhanced, and unbalanced plasticity can all potentially lead to psychopathology. This discussion has by no means been comprehensive—there are other disorders that might be chosen to illustrate the

connections between neuroplasticity Inhibitors,research,lifescience,medical and psychopathology, and each of the individual topics sketched above could be an ample focus for a lengthy review in its own Inhibitors,research,lifescience,medical right. The reader is directed to the various recent references provided for more detail. However, these examples serve to illustrate that advances in the basic science of synaptic plasticity, neurogenesis, memory systems, and related processes may lead very directly to new insight into a number of psychiatric diseases and, potentially, to new therapeutic strategies.
Drug addiction, which Inhibitors,research,lifescience,medical can be defined as the compulsive seeking and taking of drugs despite horrendous consequences or loss of control over drug use, is caused by long-lasting drug-induced changes that occur in certain brain regions.1 Only some individuals, however, succumb to addiction in the face of repeated drug exposure, while Inhibitors,research,lifescience,medical others are capable of using a drug casually and escaping an addiction syndrome. FG-4592 ic50 genetic factors account for roughly 50% of this individual variability in addiction vulnerability, and this degree of heritability holds true for all major classes of addictive drugs, including stimulants, opiates, alcohol, nicotine, and cannabinoids.2

It has not yet been possible to identify most of the genes that comprise this genetic why risk, likely due to the involvement of perhaps hundreds of genetic variations summating in a single individual to confer addiction vulnerability (or, in other individuals, resistance). The other 50% of the risk for addiction is due to a host of environmental factors, occurring throughout a lifetime, that interact with an individual’s genetic composition to render him or her vulnerable to addiction to a greater or lesser extent. Several types of environmental factors have been implicated in addiction, including psychosocial stresses, but by far the most powerful factor is exposure to a drug of abuse itself.

Cardiac MRI (CMR) is a particularly flexible imaging modality that offers excellent soft tissue contrast, well

characterized gadolinium enhancement techniques for myocardial scar visualization, 3-D imaging of complex cardiovascular anatomy, real-time 2-D imaging along arbitrary imaging planes, and the ability to quantify cardiac motion and blood-flow. This article will review the application of CMR to current clinical procedures and on-going advances toward full CMR guidance of electrophysiology procedures. THE PRESENT: ABLATION PLANNING AND GUIDANCE USING PRE-PROCEDURAL CMR ATRIAL FIBRILLATION MRI has been used most extensively to assist planning and guidance of atrial fibrillation (AF) Inhibitors,research,lifescience,medical ablation procedures. AF is the most Idarubicin common clinically relevant arrhythmia affecting 0.4% of the general population.6 The principal morbidities related to AF are stroke due to embolization of atrial thrombus and symptoms related to poor heart rate regulation with resting heart rates commonly Inhibitors,research,lifescience,medical over 110 beats per minute. In the early Inhibitors,research,lifescience,medical 1990s surgical modification

of the atria with a series of linear incisions was found to be effective at controlling AF, but a minimally invasive catheter-based procedure could not replicate these results.7,8 It was later recognized that the triggering foci for AF frequently arise from one or more pulmonary veins (PVs).9 The ability to cure AF by ablating PV triggers or ablating conduction pathways exiting the PVs was promising but hampered by the risk of pulmonary vein Inhibitors,research,lifescience,medical stenosis

due to injury of the vessels.8 Electrospatial mapping technology led to the development of purely anatomic circumferential ablation strategies in which circular lesions are created further from the PV ostia to block the exit of PV triggers4 (Figure 1A). Using this technique alone or in combination with PV isolation, a 70% to 80% success rate has been achieved.8 However, repeat procedures are often needed to achieve Inhibitors,research,lifescience,medical this success, and the success rate drops to 50% or less for the more chronic forms of AF associated with next ischemic, hypertensive, and valvular heart disease.8 There also remains a 5% risk of major complications including cardiac perforation, pulmonary vein stenosis, and the rare but potentially lethal risk of atrioesophageal fistula formation.8 In an effort to improve procedural success and reduce complications, 3-D MRI angiography (MRA) has been used to assist planning of AF ablation. Kato and colleagues used MRA to study left atrial anatomy in normal subjects and patients with paroxysmal atrial fibrillation and found that 38% of people had pulmonary vein anatomic variants.10 Identification of these variants is important because AF-triggering foci can be located within additional veins (Figure 2A).

RF energy is delivered to the tissue between the jaws of the clamp at 75 volts and 750 milliamps (mA).20 The RF generator monitors voltage, current, temperature, time, and tissue conductance. Energy delivery is continued until tissue conductance between electrodes in the jaws of the clamp decreases and reaches a steady state for 2 seconds.21,22 Current studies have found that bipolar radiofrequency is superior to unipolar radiofrequency.19,21 Bipolar RF is able more consistently to create transmural lesions especially when working only with the ablation of Inhibitors,research,lifescience,medical the pulmonary veins since the shape of the clamp

allows easy placement around the pulmonary veins. Endocardial blood flow has also not been shown to influence the ablation lesion depth.22 Microwave and ultrasound energy sources have been used as well in surgical ablation.23 Inhibitors,research,lifescience,medical However, studies have shown that these energy sources in the current state do not create transmural lesions consistently so the long-term efficacy in achieving a return to sinus rhythm is very low.20,21 In fact, the Federal Food and Drug Administration (FDA) recently removed its approval for the use of ultrasound in surgical ablation procedures. ABLATION PROBES Table 1 displays the ablation probes that are in use today. The cryothermy probes are produced by Medtronic (Minneapolis, MN, USA),

and the radiofrequency probes are produced by Atricure (Schiphol, The Netherlands) (Figure 1).15,16 Inhibitors,research,lifescience,medical The Cardioblate® CryoFlex™ Surgical Ablation System is Inhibitors,research,lifescience,medical intended for minimally invasive cardiac surgical procedures, including the treatment of cardiac arrhythmias. The Cardioblate Imatinib in vitro CryoFlex 7-cm, 10-cm, and 10-S probes plus the Cardioblate CryoFlex Clamp and Cardioblate CryoFlex Surgical

Ablation Console freeze target tissue and block the electrical conduction pathways by creating an inflammatory response Inhibitors,research,lifescience,medical and cryonecrosis. Atricure developed a new cryoprobe that is being used with the nitric oxide platform; the new probe is semi-flexible and can be used to apply all lesions required for the maze procedure. Unlike the CryoFlex, the Cryo1 probe has a defrost feature that facilitates quick removal of the probe from the tissue (Figure 2). All ablation devices may induce complications due to their potential damage the cardiac tissue.15,16 Table 1 Ablation Devices. Photos courtesy of the respective manufacturers. only Figure 1 Atricure®Radiofrequency Ablation Probe. Figure 2 Atricure®CryoFlex Probe 1. Estech (San Ramon, CA, USA), a leader in minimally invasive and endoscopic cardiac ablation, has recently gained FDA conditional Investigational Device Exemption (IDE) approval to start a trial study (Figure 3). The IDE trial has been designed to evaluate the treatment of atrial fibrillation (AF) utilizing a multiple temperature-controlled radiofrequency (TCRF) device used to treat non-paroxysmal AF. The Estech device is called the COBRA® Surgical System.

). Moreover, the dose, concentrations, and the time of exposure of a nanomaterial employed are essential. In effect, the efficiency of cellular uptake of nanomaterials and the resultant intracellular concentration may determine the cytotoxic potential. Elucidating the molecular mechanisms by which nanosized particles induce activation of cell death signalling pathways will be critical for the development of prevention strategies to minimize the cytotoxicity of nanomaterials. Unfortunately, in the literature, there are many conflicting data; the most plausible reason is certainly the discrepancy of nanomaterials

and experimental models Inhibitors,research,lifescience,medical engaged. Although some authors have recently alerted colleagues on these issues [3, 5, Inhibitors,research,lifescience,medical 8, 9, 150–152], it has not yet been put in place a guideline, generally accepted by the scientific community in the field, to address these matters. In fact, harmonization of protocols for material characterization and for cytotoxicity testing of nanomaterials Inhibitors,research,lifescience,medical is needed. In addition, parallel profiling of several classes of nanomaterials, combined with detailed characterization of their physicochemical properties,

could buy 3-MA provide a model for safety assessment of novel nanomaterials [153]. During the past decade, owing to major technological advances in the field of combinatorial chemistry Inhibitors,research,lifescience,medical in addition to the sequencing of an ever increasing number of genomes, high-content chemical and genetic libraries have become available, raising the need for high-throughput screening (HTS) and high-content screening (HCS) approaches. In response to this demand, multiple conventional cell death detection methods have been adapted to HTS/HCS, and many novel HTS/HCS-amenable Inhibitors,research,lifescience,medical techniques have been developed [37, 154]. In the last years, several authors started to study the nanotoxicity with this tools and highlighted the potential of these approaches [9, 60, 75, 155–161]. An overall aim should identify HTS/HCS assays that

can be used routinely Oxygenase to screen nanomaterials for interaction with the cell death modalities system. HTS/HCS may accelerated the analysis on a scale that commensurates with the rate of expansion of new nanomaterials but in any case is a first validation step, then it remains to confirm whether the same identified mechanisms in vitro are responsible for their in vivo toxicity. In conclusion, a multilevel-integrated uniform and consistent approach should contemplate for nanomaterial toxicity characterization. In spite of the recent advances in our understanding of cell death mechanisms and associated signalling networks, much work remains to be done before we can fully elucidate the toxicological behaviour of the nanomaterials as well as understand their participation in the determination of cell fate.

This was demonstrated experimentally [14]. The course of the selleck inhibitor metabolites and the enzymes are shown in Figure 6. Based on the model structure and the estimated parameters, all enzymes and metabolites show an increasing behavior while PEP is nearly constant over the growth rate. Figure 6 Left (plot A): Course of the enzymes PfkA (solid), lumped glycolysis

(dashed), and Pyk (dash-dotted) with the growth rate. Right (plot B): Course of the metabolites glucose-6-phosphate (solid), fructose-1,6-bisphosphate (dashed), PEP (dash-dotted), and … 2.4. Dynamic Model Having the model parameters for the uptake Inhibitors,research,lifescience,medical systems available, the complete system including PtsG induction kinetics (see Appendix) was simulated with fine-tuned parameters (empirical tuning of the parameters). First, time course data with

simulated Inhibitors,research,lifescience,medical and experimental data are shown in Figure 7 for selected values of IPTG. Figure 7 Dynamic model simulation and comparison with experimental data. A: optical density, B: glucose in g/l, C: PtsG in arbitrary units, D: degree of phosphorylated EIIA (dimensionless). Left: IPTG 0 μM; Right IPTG 140 μM. Shown are data for optical density (plot A), extracellular glucose concentration (plot B), PtsG (plot C), and EIIA phosphorylated (plot D) for no IPTG (left) and maximal IPTG concentration (right). The calculation of the optical density in plot A shows a very good agreement with the experimental data; glucose uptake for Inhibitors,research,lifescience,medical high concentrations of IPTG could not be reproduced accurately as the yield coefficients for each experiment were different and in the calculations, a mean value was used. Furthermore, Inhibitors,research,lifescience,medical the fit of the parameters for glucose uptake (Figure 5) also shows differences between simulated and experimental values that can be seen here again. For a high value of IPTG, the

value of PtsG measured in the exponential phase could be described as well as the degree of phosphorylation of EIIA. Steady state values (taken in the exponential phase) are considered and compared with simulation results (Figure Inhibitors,research,lifescience,medical 8). Plot A shows simulation results for growth on non-PTS (upper curve) and PTS (lower curve) carbohydrates. For small uptake rates, both curves converge. For large others growth rates, the PTS reaches its capacity limit since the energy for the transport is generated in the glyoclysis itself. Figure 8 Left (plot A): Degree of phosphorylation of EIIA versus growth rate. Shown are simulation results for growth on non-PTS carbohydrates (upper solid line) and for growth on PTS carbohydrates (lower solid line). Values for the experiments 1–7 are … For increasing values of IPTG, the system moves from one curve to the other, indicating a change of the uptake system based on the induction of PtsG: the degree of phosphorylation decreases while the growth rate increases. A comparison of the experimental data with the simulation data reveals differences in the growth rate.

For major trauma patients: Use of LMWH or unfractionated heparin or mechanical prophylaxis indicated over no prophylaxis. For major trauma patients in whom LMWH and unfractionated heparin are contraindicated: Use of mechanical prophylaxis indicated over no mechanical prophylaxis. For major trauma patients: Use of inferior Inhibitors,research,lifescience,medical vena cava filter for primary VTE prevention not indicated. Abbreviations: DVT deep venous thrombosis GCS Glasgow coma score ICH intracerebral hemorrhage LMWH low-molecular-weight heparin PE pulmonary

embolism PT prothrombin time PTT partial thrombin time SAH subarachnoid hemorrhage TBI traumatic brain injury TF tissue factor UFH unfractionated heparin VTE venous

thromboembolic events. Footnotes Conflict of interest: No potential conflict of interest relevant to this article Inhibitors,research,lifescience,medical was reported.
Approximately 22,000 new cases of ovarian cancer are diagnosed each year in the United States, and around 16,000 women die each year from ovarian cancer.1 A woman’s lifetime chance of being diagnosed with ovarian cancer Inhibitors,research,lifescience,medical is 1/72 with a 1% chance of dying from this disease. Platinum-based chemotherapy drugs against ovarian cancer were introduced almost 30 years ago, and the last big breakthrough was the introduction of the taxane drugs in the early 1990s. These drugs increased the mean survival rate from 24 to 38 months,2 that is, they did not cure the disease but rather increased the patient’s life-span by several months. Currently, the GSK1363089 price common course of treatment for ovarian cancer is to perform a complete debulking in which the woman’s internal reproductive organs are removed. Debulking is Inhibitors,research,lifescience,medical followed by chemotherapy with drugs such as carboplatin and taxol. Roughly 80% of the women

respond to chemotherapy, but the relapse rate is very high with a 60% relapse rate within 1 year and 80% within 5 years.3 When a relapse occurs, the disease is usually resistant to chemotherapy and spreads throughout the abdomen. When the disease Inhibitors,research,lifescience,medical reaches this stage, there is no weapon in medicine’s arsenal that can save such a patient. For this reason, epithelial ovarian cancer is considered the most lethal type of gynecological cancers today.4 As in many cancers, early detection is critical for survival. Resveratrol If ovarian cancer is detected early, during stages I and II, the survival rate is quite good. However, the majority of ovarian cancers are detected at stages III and IV, where the 10-year survival rate is between 10% and 20%.5 Early detection of ovarian cancer is difficult, partly due to its non-specific symptoms and lack of a screening test for the general population. As a result, diagnosis often occurs when the disease is at an advanced stage and when the prognosis is poor.

v. injection. Therefore the authors concluded that although PAMAM polyplexes were trapped within the lung due to charge interactions, the occlusion of capillaries might not be effective enough to induce effects similar to LPEI in lung, and transfection signals are

not detectable. At any rate, the PAMAM-G5 dendrimer could be a potential candidate for loading pDNA onto echogenic PLGA NP since, as PEI, it promises to have highly desirable characteristics of enhanced gene delivery that is restricted to tumors and a reduced off-target (lung) reporter gene expression in vivo. Inhibitors,research,lifescience,medical Finally, another promising new cationic polymer that could be a great candidate for complexing with PLGA is one containing a branched oligoethyleneimine (OEI, 800Da) core, diacrylate esters as linkers, and oligoamines as surface modifications [48]. Although complex in structure, these are also promising since they exhibit low cytotoxicity in vivo Inhibitors,research,lifescience,medical and were shown to transfect tumor tissue at levels comparable to those with PEI but were better tolerated Inhibitors,research,lifescience,medical with no change in liver histology or liver enzymes, while LPEI and BPEI resulted in an increase in liver enzyme levels, suggesting

early necrotic stages in liver 24h after treatment. OEI also exhibited a more tumor-specific gene expression profile than when PEI was used, with lower lung transgene expression. Finally, dendrimers also can be used to target nucleic acid delivery to particular cells or tissues Inhibitors,research,lifescience,medical using cell-penetrating peptides. For example, PAMAM-G5 dendrimers displaying cyclic RGD targeting peptides (PAMAM-RGD) improved transport

[49] and also could deliver siRNA in polyplex complexes of ~200nm, mediating more efficient nucleic acid delivery through multicellular Inhibitors,research,lifescience,medical 3D U87 glioma spheroids than that of native PAMAM dendrimers, presumably by interfering with integrin-ECM contacts present in a three-dimensional tumor model [50]. Figure 5 PAMAM-dendrimer-based complexes may be an alternative to PEI for pDNA delivery in vivo using NP. (a) PLGA:PAMAM-G5 gives higher tumor expression of reporter Thiamine-diphosphate kinase pDNA and lower nonspecific lung transfection for a more favorable biocompatible profile in vivo … Although highly efficient nonviral gene carriers, one common Syk inhibitor drawback of LPEI, PLL, and PAMAM dendrimer cationic polymers is that these may present a high toxicity in vivo, even if a relatively low cytotoxicity is initially observed in vitro. Therefore, some solutions have included surface modification to significantly help reduce their toxicity [51–53]. For example, to help expand the in vivo applications of PAMAM, one study attempted to improve characteristics of this polymer as a gene delivery carrier by incorporation of polyethylene glycol (PEG, molecular weight 5,000).

The increase in autophagic vacuoles in response to nanomaterials may be an adaptive cellular response. There is evidence that autophagy can selectively compartmentalize nanomaterials. In fact, nanoparticles are commonly observed within the autophagosome

compartment, suggesting that activation of autophagy is a targeted exertion to sequester and degrade these materials following entrance into the cytoplasm [104]. It is possible that the cells might perceive nanomaterials as an endosomal pathogen or an aggregation-prone protein (both commonly degraded by the autophagy machinery). Recent evidence Inhibitors,research,lifescience,medical supports ubiquitination of nanomaterials directly Inhibitors,research,lifescience,medical or indirectly via colocalization with ubiquitinated protein aggregates, suggesting that cells may indeed select nanomaterials for autophagy through a pathway similar to invading pathogens [13, 98, 105]. Additionally, ubiquitinated proteins accumulate concomitantly with nanomaterial-induced autophagic vacuoles [106]. It is important to underlie that Inhibitors,research,lifescience,medical nanoscale was a significant factor in eliciting the autophagic response. Autophagy was not induced by quantum dots that had a tendency to aggregate to Caspase activity assay microscale particles into the cells [107]. Nanoscale size dependence was also reported

for neodymium oxide nanoparticle, with larger particles inducing less autophagy [108]. Apparently, modifications of the Inhibitors,research,lifescience,medical surface properties

might be able to alter the autophagy-inducing activity of the nanomaterials. Cationic PAMAM dendrimers elicited autophagy more than anionic ones in vitro [94]. Carbon nanotubes with carboxylic acid group could induce autophagy, while those functionalized with poly-aminobenzene sulfonic acid and polyethylene glycol Inhibitors,research,lifescience,medical groups were not [100]. Recently, it has been published that a short synthetic peptide, RE-1, binds to lanthanide-based nanocrystals, forms a stable coating layer on the nanoparticles surface, and significantly abolishes their autophagy-inducing activity. Furthermore, the addition of an arginine-glycine-aspartic acid motif to RE-1 enhances autophagy induced mafosfamide by lanthanide-based nanocrystals [109]. It is also possible that nanomaterials cause a state of autophagic dysfunction, correlated with a blockade of autophagy flux, and this may be involved in their mechanism of toxicity [110, 111]. Nanoparticles could give rise to autophagy dysfunction by overloading or directly inhibiting lysosomal enzymes or disrupting cytoskeleton-mediated vesicle trafficking, resulting in diminished autophagosome-lysosome fusion [112].

4,95% CI=2.6-11.3) compared with individuals with neither insomnia or psychiatric disorders. The authors suggested that the early diagnosis and treatment of insomnia may prevent subsequent depression. In a longitudinal study of 979 young adults,24 insomnia increased the relative risk for depression fourfold (95% 0=2.2-7.0) over a 3-year period, even after controlling for baseline depression symptoms. In another longitudinal study in 591 young adults, depression and insomnia symptoms were assessed six times Inhibitors,research,lifescience,medical over 21 years.25 The presence of insomnia either with or without comorbid depression tended to be highly stable over time. Between

17% and 50% of cases without depression but Inhibitors,research,lifescience,medical with 2 weeks or more of insomnia in the past 6 months developed a major depressive episode at a subsequent time point. The presence of insomnia (without depression) and depression (without insomnia) were not longitudinally related to each other. Insomnia comorbid

with depression, however, was longitudinally related to having both. Two other studies have similarly identified insomnia as a risk factor for depression over long follow-up periods. One ABT-263 research buy study26 followed Inhibitors,research,lifescience,medical over 1000 male medical students for a median of 34 years (range 1-45). Both insomnia and difficulty sleeping under stress in medical school increased the risk for subsequent depression (relative risk and 95% CI, respectively, 1.9, 1.2-3.2 and 1.7, 1.1-2.5). Another study followed 1244 middle-aged adults for 12 years.27 Chronic insomnia was reported in a third of women and a quarter of men; three Inhibitors,research,lifescience,medical quarters of those with insomnia at baseline also had insomnia at the 12year follow-up. Only women who reported insomnia at baseline were significantly more likely to report feeling depressed at follow-up Inhibitors,research,lifescience,medical “(QR=4.1, 95% CI=2.1-7.2), whereas the relationship in men was not significant. (OR=1.3, 95% 0=0.8-2.3). Similar risk relationships have been identified in older

adults. In a study28 involving 147 older adults without, a prior history of mental illness, the presence of insomnia (scoring 1 or higher on any of the Hamilton Rating Scale for Depression sleep items) was assessed at two time points separated by 1 year. Participants with insomnia that persisted at both time points were more likely to develop a first episode of depression during the Levetiracetam 1-year follow-up period (OR=6.9,95% 0=1.3-36.1) compared with participants who scored 0 on the three sleep items at both time points. In a larger longitudinal study of 524 older adults,29 sleep disturbances at baseline predicted depression 2 to 3 years later (odds ratio=3.2, 95% CI=1 .5-6.8), after adjusting for other risk factors. Individuals with persistent sleep disturbances were more likely to be depressed than individuals whose insomnia had resolved at follow-up or individuals who developed insomnia during follow-up.