Figure 1. Bipolar II disorder as a percentage of major depressive episodes. Age:

40/41 years; Zurich Cohort Study. BP-II, bipolar II; UP, unipolar Table I. Mood disorders: MDD and BPD lifetime prevalence. 3-6 MDD, manic-depressive disorder; BPD, bipolar disorder In community studies, the extent of the diagnostic problem is still underestimated, because there are no lifelong prospective studies on mood disorders. The most recent data from large epidemiological studies report, substantially Inhibitors,research,lifescience,medical higher prevalence rates for both major depressive and bipolar disorders compared with 10 to 15 years ago. One source of undcr-recognition in such studies is their cross-sectional design, which relies on subjects’ lifetime memory of hypomania/mania. Epidemiological studies comprising more than one wave report, higher proportions of BPD compared with MDD. We have, then, to assume that, the latest figures still underestimate the problem due to nonreporting. By the age of 20, subjects’ recall of their previous history is Inhibitors,research,lifescience,medical already poor: about, 25% of a random

sample of 1.05 normal subjects could no longer remember documented consultations with MDs, psychiatrists, and psychologists during their school years; there Inhibitors,research,lifescience,medical was no difference between externalizing and internalizing problems.9,10 It can be assumed that cross-sectional community studies underestimate lifetime prevalence rates by 25% to 50%; the dating of the age of onset, must, be equally problematic. However, the main impediment, to accurate measurement of the rates of bipolarity probably remains the overstrict concept, which fails to pick up BP-II and minor bipolar disorders in adults, adolescents, and children. Current diagnostic criteria for bipolarity selleck compound DSM-IV-TR11 gives diagnostic criteria for manic, mixed, and Inhibitors,research,lifescience,medical hypomanic episodes, and for Bipolar I Disorder (B.PI), Bipolar II Disorder (BP-II), Cyclothymic Disorder, and Bipolar Disorder Inhibitors,research,lifescience,medical Not Otherwise Specified (BPNOS). In addition,

there are important specifiers for the course, rapid cycling, seasonal patterns, and type of intcrcpisode recovery. Bipolar I and IT disorders are defined by the presence of depressive disorders associated with manic or hypomanic episodes respectively, which makes the definition of a Isotretinoin hypomanic episode crucial. DSM-IV hypomanic episodes The definition of a hypomanic episode in DSM-IV comprises: (i) experience of a distinct period of expansive, elevated or irritable mood; (ii) a minimum episode duration of 4 days; (iii) the presence of three or more (in the case of irritable mood four or more) of 7 criterial symptoms of mania; (iv) the episode has to be associated with a change in functioning, which is observable by others; and (v) should not. be severe enough to cause marked impairment, hospitalization, or psychotic symptoms. All three criteria (i) to (iii) are to my mind problematic and in need of revision; criterion (iv) may also to be overrestrictive, but, this question needs further investigation.

”23 Janet described how the memories of these traumas tended to return not as stories of what had happened: they were reenacted in the form of intense emotional reactions, aggressive behavior, physical pain, and bodily states that could all be understood as the return of elements of the

traumatic experience. Janet first observed that traumatized patients seemed to react to reminders of the trauma with responses that had been relevant to the original threat, but that currently had no adaptive value. Upon exposure Inhibitors,research,lifescience,medical to reminders, the trauma was reactivated in the form of images, feelings, and physical sensations related to the trauma.21 He proposed that when patients fail to integrate the traumatic experience into the totality of their personal awareness, they seem Inhibitors,research,lifescience,medical to develop problems assimilating new experiences as well. It is … as if their personality

has definitely stopped at a certain point, and cannot enlarge any more by the addition or assimilation of new elements.“23 ”All (traumatized) patients seem to have had the evolution of their lives checked; they are attached to an insurmountable obstacle.“24 Janet proposed that the efforts to keep the fragmented traumatic memories out Inhibitors,research,lifescience,medical of conscious awareness eroded the psychological energy of these patients. This, in turn, interfered with the capacity to engage in focused action and to learn from experience. Unless the dissociated elements of the trauma were integrated into personal consciousness, the patient was likely to experience a

Inhibitors,research,lifescience,medical slow decline in personal and JNK-IN-8 purchase occupational functioning.25 As a young physician, during the 1880s, Sigmund Freud did two clinical rotations at the Salpêtrière in Paris. Upon his return to Vienna he attached himself to an older internist, Jospeh Breuer, with whom he started to carefully study the symptoms of ”hysterical“ patients, and the origins of their symptoms, which were often characterized by marked motoric and sensory abnormalities. Inhibitors,research,lifescience,medical They summarized their first set of findings in a paper entitled On the Physical Mechanisms of Hysterical Phenomena.76 these Because of the astuteness of their observations it is useful to quote part of their account: The … memory of the trauma … acts like a foreign body which long after its entry must be regarded as an agent that is still at work. At first sight it seems extraordinary that events experienced so long ago should continue to operate so intensely – that their recollection should not be liable to the wearing away process to which, after all, we see all our memories succumb. The following considerations may perhaps make this a little more intelligible. The fading of a memory or the losing of its affect depends on various factors.

2006). The FIT predates the CMT and was chosen to evaluate its performance. In a developmental study, CMT and FIT were significantly correlated and yielded very similar quantitative working memory capacity scores (Arsalidou et al. 2010). In the current adult data, we also found that correlations between CMT-clown and FIT were very high (0.93) suggesting that these tasks are measures of the same latent variable. Response accuracy decreased with the cognitive demand (difficulty), even though the cortical activity in working memory regions increased with the

items’ cognitive load. Negative Inhibitors,research,lifescience,medical correlations (from −0.65 to −0.89) were obtained with percent signal change and the FIT, which was not studied with fMRI. Inhibitors,research,lifescience,medical This high negative relation using an alternative

measure confirms that the pattern of cortical activity reflects a graded relation of covariation between activity in brain regions and the participants’ use of working memory, which FIT has measured independently. An extended correlation table including all ROIs can be found in Supporting Information (Table S1). Linear trend analyses Carboplatin nmr showed that several regions congruent with working memory processes become progressively active as cognitive load increases. The linear patterns, however, did not show the same signature. Inhibitors,research,lifescience,medical Areas in the prefrontal cortex gradually increase until about D7 and leveled off or decreased at D8, whereas posterior regions, such as the precuneus and fusiform gyri, produced a distinct increase between D4 and D5 with Inhibitors,research,lifescience,medical a more steady increase to D7. The cingulate gyrus, on the other hand, appeared to produce its own pattern with activity progressing gradually up to the highest level of difficulty. We compare these patterns to those produced by areas that showed a decrement in activity as cognitive load increased, related to the default mode. Implications of this finding with reference to working memory capacity measurement are discussed in the Inhibitors,research,lifescience,medical section on capacity limits of working memory. Default mode The coordinated deactivation in regions linked to the control task was also linear, supporting the hypothesis of an inverse

regulation between default-mode and working memory processes (Raichle and Gusnard 2002), and this relation was maintained across increasing difficulty levels (McKiernan et al. 2003). Although our control tasks/baselines do not represent a pure isothipendyl resting state, they carried very limited cognitive demand, and responses induced by sensory processing disrupt only minimal activity in default-mode areas (Greicius et al. 2003). Our obtained linear patterns (Fig. 4) agree with these results. Areas that decreased in activity as a function of difficulty were medial prefrontal cortex, posterior cingulate, and superior temporal gyri, which have been linked with self-relevant thoughts, integrating information, and memory associations, respectively (Buckner et al. 2008).

During a consensus conference supported by the MacArthur Foundation,

Frank and colleagues10 came up with a number of operational definitions to assess the complex course of depressive disorders. Partial MK0683 chemical structure remission is defined as a period of time with some improvement of symptoms, but. not of enough magnitude as to achieve full remission, and with the persistence of some residual symptoms. Inhibitors,research,lifescience,medical This state corresponds to a score of 8 to 15 on the Hamilton Rating Scale for Depression (HAM-D17). Conversely, full remission is obtained where clinical improvement, is such that the patient becomes almost asymptomatic. Clinical remission is usually defined by a score of 7 or less on the HAM-D17 or a score of 1012 or less on the Montgomery Åsberg Depression Rating Scale (MADRS). Zimmerman and Colleagues“ have analyzed the implications of using various cutoff scores on symptom severity scales in order to define clinical remission in depressed patients as part, of the Rhode Island Method to Improve Diagnostic Assessments and Services (MIDAS) project. They also assessed the association Inhibitors,research,lifescience,medical between remission status and psychosocial impairments for different cutoff scores for remission in 303 depressed outpatients using the MADRS, the HAM-D17, and an index of the DSM-IV remission status. For both severity scales, the different,

levels of cutoff scores were associated with different rates of remission. Inhibitors,research,lifescience,medical ‘The Inhibitors,research,lifescience,medical high cutoff scores were also associated with higher rates of psychosocial impairment. These results may suggest, that the lower the cutoff scores used to define remission, the more valid

the results may be in term of clinical relevance and quality of life assessment, after antidepressant therapy. A valuable approach of interest to practising psychiatrists has been proposed by Mclntyre and Colleagues,12 who have designed a shorter version of the HAM-D17 using 7 items out of the 17 items of the original scale, based on frequency and sensitivity to changes after antidepressant Inhibitors,research,lifescience,medical treatment. The authors then attempted to validate this shortened questionnaire, called the Toronto HAM-D7, in a sample of 292 patients with major depression followed up in a depression clinic in Toronto. The results indicate that a score of three or less on the Toronto HAM-.D7 did correlate with the score of seven or less for remission on the 17 items of the HAM-D17. Oxalosuccinic acid If this is confirmed in additional validation studies, the Toronto HAM-D7 Scale could be of practical use for general practitioners and for psychiatrists, as well as for use as a screening tool to be used in some antidepressant trials. An American College of Neuropsychopharmacology (ACNP) Task Force reached consensus guidelines after conducting a critical review of the literature and exchanging expert clinical experience. The ACNP Task Force then made several recommendations, which are, however, generally not. evidence-based, on the concept, of remission in major depressive disorders.

Interestingly, subjective feelings of being high and stimulated were produced solely by expecting to receive MPH. This finding is important to consider when examining initiation and maintenance of nonmedical prescription stimulant use. As motives for nonprescription stimulant

use include the desire to feel high (Barrett et al. 2005), it is likely that individuals who use a stimulant for this purpose will consequently feel high due to these #www.selleckchem.com/products/Fedratinib-SAR302503-TG101348.html keyword# demonstrated placebo effects, which will likely maintain misuse of the drug. Prescription stimulant misuse in athletes ADHD is a controversial problem in sport as participants with this disorder often require banned stimulants while competing. Many of the governing bodies of competitive sports have developed regulations that limit the use of stimulant medications to treat ADHD. In other cases, stimulant use is allowed in the setting of a documented Inhibitors,research,lifescience,medical diagnosis of ADHD. Most sports organizations around the world now follow the guidelines set forth by the World Anti-Doping Agency (WADA). According to this document, the diagnosis of ADHD is to be made by “experienced clinicians” and in accordance to the DSM-IV. Stimulant medications are considered to be a “medical best practice treatment”

that do require the athlete to file a therapeutic use exemption Inhibitors,research,lifescience,medical (TUE). A TUE gives athletes with medical diagnoses an exemption to use a drug normally prohibited by MLB, to treat a legitimately diagnosed medical condition. WADA recommends reassessments of continued treatment every 3–4 months.

Other organizations, such as the National College Athletic Association (NCAA) and individual professional leagues, such as the National Football League (NFL) and Major League Baseball (MLB), Inhibitors,research,lifescience,medical have developed their own regulations. The NCAA does not require Inhibitors,research,lifescience,medical that physicians prescribe a trial of nonstimulant medications before prescribing stimulants, only that the prescribing physician considers nonstimulants first. The NCAA acknowledges that nonstimulant medication may not be as effective as stimulant medications in treating ADHD. In contrast to the NCAA regulations, athletes who are also participating in events governed by the International Olympic Committee (IOC) and/or WADA are not allowed to use stimulant medications, even with a TUE. These organizations require that the athlete with ADHD on stimulant medications stop taking these medication or risk disqualification about (Putukian et al. 2011). It has been reported that MLB players are using an ADHD diagnosis to evade the AMP ban (Associated Press 2009). According to records MLB officials turned over to congressional investigators as part of George Mitchell’s probe into steroid use in baseball, the number of players getting “therapeutic use exemptions” from baseball’s AMP ban jumped in 1 year from 28 to 103 – which means that, suddenly, 7.6% of the 1354 players on major-league rosters have been diagnosed with ADHD. MLB banned AMP in 2006.

118-120 To summarize, if inflammatory activation of astrocytes

unquestionably has consequences for neuronal function and viability, it must be emphasized that the overall effect is dependent on the fine balance between a number of factors including the type, duration, and severity of the insult, the complex interplay between the various cytokines released by NLG919 mouse astrocytes and surrounding cells, and the receptors for cytokines and growth factors expressed by these neighboring cells. Alzheimer’s disease Inhibitors,research,lifescience,medical Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder, is characterized by the progressive decline of cognitive functions including memory and mental processing, and by disturbances in behavior and personality.121 Typical histopathological features of the Inhibitors,research,lifescience,medical AD brain are amyloid-β (Aβ) plaques which may contain dystrophic neurites, intracellular neurofibrillary tangles, vascular amyloidosis, neuronal and synaptic loss, and reactive gliosis.

Though the exact pathophysiological mechanisms Inhibitors,research,lifescience,medical leading to synaptic loss and the resulting cognitive decline have not been fully elucidated, a central role of Aβ peptides in concert with neuroinflammation is generally accepted.122 Alois Alzheimer himself in 1910 suggested that glial cells may participate in the pathogenesis of dementia123; however, their exact role is still a matter of debate, as available Inhibitors,research,lifescience,medical evidence can argue both for neuroprotective or neurotoxic effects. Reactive astrocytes, like microglia, are observed in close association with Aβ plaques in the brains of AD patients,124,125 and both cell types have been shown to be capable of internalizing and degrading Aβ peptides.126-128 This is thought to be a neuroprotective mechanism

by contributing to the clearance of Aβ from the extracellular space, thus avoiding the accumulation of toxic extracellular Aβ. Several observations support an active role of astrocytes in Aβ clearance. Inhibitors,research,lifescience,medical For example, astrocytes surrounding plaques in autopsy material from the brain of AD patients contain intracellular Aβ deposits.128,130 In addition, when exogenous astrocytes were Endonuclease transplanted into the brain of Aβ plaque-bearing transgenic mice, they migrated towards Aβ deposits and internalized Appositive material.129 Similarly in ex vivo studies, binding, internalization, and degradation of Aβ could be observed when cultured astrocytes were seeded on top of plaque-bearing sections prepared either from the brains of AD patients or transgenic mice models of AD.127,129 The physiological importance of Aβ clearance by glial cells in vivo is evidenced by the increased Ap accumulation and premature death observed in a transgenic mouse model of AD when microglial activation was impaired.

In addition, it might be just the results of ASM, not cause, which is very important limitation of this study. Nevertheless, we could confirm that ASM was not caused by myocardial ischemia. According to a large scale review of 3923 cases by Reynolds et al.,5) the incidence of ASM was 40%, and valve surgery was more likely to cause ASM compared to CBS. In the present study, the incidence of ASM was 74%, almost

two-fold what was previously Inhibitors,research,lifescience,medical reported, but we did not observe an association between the type of surgery and the occurrence of ASM. The same mechanism may be responsible for ASM in both CBS and HVS. In the literature, it is described that ASM occurs immediately after surgery and usually tends to resolve with time, Inhibitors,research,lifescience,medical although it can persist indefinitely in some patients.23) In consensus with this statement, our data showed ASM disappeared over time in most patients without clinically detectable pericardial constriction. Only 3 patients in our study sample had clinically significant transient constrictions probably because of the use of steroids; in 2 of these patients, ASM disappeared over time. In summary, ASM is frequent after OHS, however, ASM does not seem to have any clinical significance and will likely disappear over time. Further, we demonstrated that decreased postoperative

Inhibitors,research,lifescience,medical systolic VRad of the Cisplatin clinical trial antero-septum and anterior wall is associated with the occurrence of ASM. Limitations Echocardiographic Inhibitors,research,lifescience,medical views are relatively poorer after HVS than those after CBS. Therefore, the occurrence of ASM after HVS might be underestimated. Although data from all the patients

were available immediately after the operation, data from the 3–6-month and 1-year follow-up visits were only available for 40–45% of the patients each group. In addition, we performed VVI analysis Inhibitors,research,lifescience,medical before and immediately after surgery in only a limited number of patients (approximately 40 patients), and we were unable to identify reversal of systolic VRad of the antero-septum and anterior wall when ASM disappeared. Lastly, we usually use diuretics peri-OHS; thus, some patients with constrictive physiology may not have been revealed. However, this limitation may not be clinically Thymidine kinase relevant, even in patients with ASM, because the majority of study patients did not require prolonged diuretic administration after OHS. Conclusion Even though ASM was common in patients immediately after cardiac surgery, it disappeared over time without causing clinically detectable pericardial constriction. Furthermore, ASM might not be caused by myocardial ischemia, but we demonstrated that a decreased postoperative systolic VRad of the antero-septum and anterior wall is associated with ASM after cardiac surgery. Acknowledgements This study was supported by the Korean National Research Foundation and funded with a grant from the Korean Government (MEST) (No. 2012027176).

2001). Similarly, wall-following behavior in Periplaneta americana relies on both thigmotactic stimulation of the antenna and visual guidance (Creed and Miller 1990). The presence of coupled thigmotactic and visual components has also been proposed

for Drosophila open-field behavior (Besson and Martin 2005; Liu et al. 2007). To determine the environmental features that elicit exploratory and wall-following behaviors, we examined wild type and visually impaired mutants in arenas with different environments. Herein, we show that Drosophila actively explore the arena boundary over other internal environments. Wild-type Drosophila also display Inhibitors,research,lifescience,medical a significant preference for darkened corners. The boundary exploration overrides the preference for darkened corners. We propose this preference for darkened corners represents shelter seeking. Materials

and Methods Fly stocks and husbandry All stocks were raised Inhibitors,research,lifescience,medical and maintained on standard yeast-cornmeal agar food at room temperature. Flies that were used in behavioral KU-0063794 in vivo assays were two- to five-day-old males raised on standard Inhibitors,research,lifescience,medical food at 25°C, 60% humidity, with 12 h of light/day. The norpA7 mutants were obtained from the Bloomington Stock Center. Behavior assays The base and walls of all the open-field arenas were made from clear polycarbonate. The ceiling of the arena was made from the lid of a 15-cm polystyrene petri plate (Fisher Scientific, Pittsburgh, PA). A 2-mm hole was drilled in the top of the arena, near the side to allow for the aspiration of a fly into the arena. Since the top of the arena was larger than the bottom, the hole could be shifted out of the active arena area after the fly was added. The Inhibitors,research,lifescience,medical flies were typically aspirated into the arena ~2–3 cm from the boundary, with the starting positions rotated between the four Inhibitors,research,lifescience,medical quadrant positions of the arena. The arenas were illuminated by two 23 W compact fluorescent flood lights

(R40, 1200 lumens, 5100 K), located 1.15 m above the arena. Arenas were set up in a laboratory that was maintained between 22°C and 24°C. The movement of the fly within the arena was tracked with Ethovision XT v5.0 (Noldus Information Technology, Leesburg, VA). The recording rate of the tracker was set to 30 frames per second. All the arenas were 0.7 cm in height. Statistical analysis The collected data were analyzed with others Ethovision XT v5.0 (Noldus Information Technology). Before beginning the experiments, it was determined that Canton-S had no significant preferences for individual arena quadrants. To eliminate any biased results due to the starting position of the fly, the starting locations of the fly were equally distributed across different zones used in the analysis. The measured variables included total path length, distance from center, the percentage of time spent in different zones defined by the investigator using the tracking software.

64 Specifically, the G allele (a perfect proxy for the C allele at rs6313) tends to be associated

with reduced expression of the receptor. It can therefore be inferred that reduced availability of the 5-HT2A receptor is a risk factor for tardive dyskinesia. Notably, 5-HT2A receptors are strongly expressed in the caudate and putamen,65 and recent evidence obtained from dopamine-depleted rodents suggests a complex interplay of subcortical dopamine and 5-HT in the regulation of motor behavior.66 Two genes outside of the dopamine and 5-HT systems have received sufficient attention in the pharmacogenetics of TD to merit meta-analysis (Table I). Many commonly prescribed APDs, including FGAs (haloperidol, perphenazine, thioridazine), Inhibitors,research,lifescience,medical as well as SGAs (risperidone and aripiprazole), are metabolized in the liver by check details CYP2D6 (debrisoquine hydroxylase).67 The CYP2D6 gene is highly polymorphic, with over 70 known variants (for a current classification, view the allele nomenclature at http://www.imm.ki.se/CYPalleles/).

Homozygosity Inhibitors,research,lifescience,medical for null alleles gives rise to the “poor metabolizer” phenotype characterized by no enzyme activity while null allele heterozygosity gives rise to an intermediate Inhibitors,research,lifescience,medical debrisoquine hydroxylase metabolic phenotype characterized by impaired – but not absent – enzyme activity.68 Reduced CYP2D6 activity can be expected to result in higher effect dose as measured by blood levels of active drug, with Inhibitors,research,lifescience,medical potential for increased dose-dependent side effects. Consistent with this pharmacokinetic prediction, a metaanalysis of 8 studies demonstrated a moderate effect of (any) loss of function alleles on risk for TD (OR=1.43), while homozygotes (poor metabolizers) had 1.64-fold greater odds of suffering tardive dyskinesia.44 A recent small study further confirms these results.69 A similar

effect has been studied for SOD2, the gene encoding manganese superoxide dismutase, a mitochondrial enzyme involved in oxidative metabolism. A functional SNP (Ala9Val), affecting efficiency of MnSOD Inhibitors,research,lifescience,medical transport, has been associated with TD risk; counterintuitively, the less efficient val allele is protective.39 Homozygotes for the Ala (T) allele are about twice Oxalosuccinic acid as likely to develop TD compared with val carriers (Table I). Extrapyramidal symptoms Compared with the relative plethora of studies on tardive dyskinesia, pharmacogenetic studies of EPS are lacking. However, a few studies have reported allelic effects on acute side effects that are consistent with those reported for TD. For example, Eichammer et al70 reported increased incidence of akathisia amongst DRD3 Gly carriers; however, two studies of extrapyramidal symptoms have been negative.71,72 One additional study identified another DRD3 SNP (rs167771) which was associated with EPS in a study of 270 risperidonetreated patients,73 but this result awaits replication.

The smallest sample size in such trials is 12,42 and in some studies as many as 30 volunteers are tested.43 The following trials all used the classic 2×2 factorial design, and found clear effects of alcohol but no potential of the study compounds to produce interactions. Four used young volunteers, no interaction being found for the anticpileptic tiagabinc,42 the N.M.DA antagonist, remacemide,43 the antiobesity compound sibutramine,44 lorazepam, or the β-carboline abecarnil.21 In a trial

with elderly volunteers, no interactions were Inhibitors,research,lifescience,medical detected for the muscarinic agonist, SB-202026.45 The multiple-dosing design was employed in a crossover study to evaluate the interaction potential of alcohol and the selective serotonin reuptake inhibitor (SSRI) Inhibitors,research,lifescience,medical fluvoxamine in young volunteers.46 No signs of an interaction were identified in this trial. In an unusual design, the effects of two doses of moclobemide (100 and 300 mg), trazodone

150 mg, and placebo were evaluated in elderly volunteers.28,47 Twelve of the volunteers had the four dose conditions in a crossover design, on each occasion receiving a placebo alcohol dose. Twelve further volunteers had the same four study compound conditions, but also received alcohol 0.5 g/kg on each occasion. No interactions Inhibitors,research,lifescience,medical with alcohol were identified for either compound. Drug-drug interaction trials follow the same basic design as alcohol

interaction trials and the same basic design rules generally apply, with the added complication that in some trials it is desirable for both drugs to reach steady state. In a series of trials looking for interactions with the SSRI sertraline, parallel-group designs were employed. Inhibitors,research,lifescience,medical In one trial, phenytoin was administered to all volunteers for 24 days.48 From day 8 onwards, sertraline Inhibitors,research,lifescience,medical was administered to half the volunteers and placebo sertraline to the other half. Cognitive testing was performed prior to dosing and repeatedly postdosing on days 0, 7, and 24. There was no evidence that nearly phenytoin alone impaired performance or that when dosed with sertraline any cognitive effects www.selleckchem.com/products/purmorphamine.html appeared. In a second trial, carbamazepine was administered to all volunteers for 32 days.49 From day 16 onwards, sertraline was administered to half of the volunteers and placebo sertraline to the other half. Cognitive testing with the CDR system was performed repeatedly on days 1, 15, and 32. Carbamazepine impaired attentional efficiency, slowing performance on simple reaction time, choice reaction time, and digit vigilance. These effects were still evident after 32 days of dosing. There was no evidence that sertraline had an influence on this disruption to attention, nor did any other effects emerge when sertraline was codosed with carbamazepine.