THP-1 Monocytic Cells Are Polarized to More Antitumorigenic Macrophages by Serial Treatment with Phorbol-12-Myristate-13-Acetate and PD98059.

Background and Objectives: As modulators of the tumor microenvironment, macrophages have been extensively studied for their potential in developing anticancer strategies, particularly in regulating macrophage polarization towards an antitumorigenic (M1) phenotype rather than a protumorigenic (M2) one in various experimental models. Here, we evaluated the effect of PD98059, a mitogen-activated protein kinase kinase MAPKK MEK1-linked pathway inhibitor, on the differentiation and polarization of THP-1 monocytes in response to phorbol-12-myristate-13-acetate (PMA) under various culture conditions for tumor microenvironmental application. Materials and Methods: Differentiation and polarization of THP-1 were analyzed by flow cytometry and RT-PCR. Polarized THP-1 subsets with different treatment were compared by motility, phagocytosis, and so on. Results: Clearly, PMA induced THP-1 differentiation occurs in adherent culture conditions more than nonadherent culture conditions by increasing CD11b expression up to 90%, which was not affected by PD98059 when cells were exposed to PMA first (post-PD) but inhibited when PD98059 was treated prior to PMA treatment (pre-PD). CD11bhigh THP-1 cells treated with PMA and PMA-post-PD were categorized into M0 (HLA-DRlow and CD206low), M1 (HLA-DRhigh and CD206low), and M2 (HLA-DRlow and CD206high), resulting in an increased population of M1 macrophages. The transcription levels of markers of macrophage differentiation and polarization confirmed the increased M1 polarization of THP-1 cells with post-PD treatment rather than with PMA-only treatment. The motility and cytotoxicity of THP-1 cells with post-PD treatment were higher than THP-1 cells with PMA, suggesting that post-PD treatment enhanced the anti-tumorigenicity of THP-1 cells. Confocal microscopy and flow cytometry showed the effect of post-PD treatment on phagocytosis by THP-1 cells. Conclusions: We have developed an experimental model of macrophage polarization with THP-1 cells which will be useful for further studies related to the tumor microenvironment.

A Case of Unilateral Simultaneous Preauricular Sinus and Postauricular Sinus in an Adult.

Preauricular sinuses are relatively common congenital anomalies of the soft tissues of the ear. By strict definition, when they connect 2 separate spaces, they are referred to as a preauricular fistula. This clinical entity was first described by Heusinger in 1864. Most preauricular sinuses have a small opening located anterior to the root of the helix. In rare cases, they are found posterior to the tragus, near the crus of the helix, and the ear lobule. The latter is the variant type preauricular sinus, also referred to as the "postauricular sinus," as the sinus tract opens posterior to the auricle. Recurrent infections or persistent discharge may require surgical excision which is ideally performed at a time when there is no inflammation. There are a variety of techniques for excision. Regardless of the surgical approach taken, it is of critical importance to remove the subcutaneous sac completely. We present a very rare case involving the co-occurrence of a preauricular sinus and postauricular sinus in a 33-year-old woman. We report this case with a review of the literature.

Temporomandibular joint herniation into the external auditory canal presenting as clicking tinnitus: A case report.

BACKGROUND: Herniation of the temporomandibular joint (TMJ) into the external auditory canal (EAC) due to a bony defect in the EAC is rare. Such bony defects can be secondary to inflammation, neoplasm, trauma. In rare instances, TMJ herniation can occur when the Huschke foramen is constantly exposed. TMJ herniation can induce clicking tinnitus, otalgia, conductive hearing loss, and otorrhea, but can also present with no symptoms. This study reports a case of TMJ herniation. CLINICAL PRESENTATION: A male patient presented with clicking tinnitus that had developed 3 years ago. Dome-shaped soft tissue was found on the anterior EAC wall, which protruded and depressed with mouth movement. The patient underwent surgical reconstruction of the bony defect with titanium mesh, and the symptoms resolved after surgery. CONCLUSION: This case highlights the importance of surgical reconstruction of a bony defect in the EAC using appropriate materials.

Prosthetic Materials Protrusion After Surgical Wall Reconstruction of Temporomandibular Joint Herniation.

ABSTRACT: Herniation of the temporomandibular joint (TMJ) into the external auditory canal (EAC) is rare. The TMJ and EAC are separated by the anterior bony wall of the EAC. Such a defect can be caused by trauma, infection, neoplasm, inflammation, and in rare cases, congenital bony defects. If asymptomatic or mildly symptomatic, supplemental treatment is primarily given, but if the symptoms are severe enough that the patient regularly feels discomfort, surgical procedure is considered. To our knowledge there are no reports about surgery-related complications and recurrence during the postoperative follow-up period for TMJ herniation in English literature. Here, the authors report the first case of implant protrusion after TMJ herniation surgery along with a literature review.

Altered behavioral and electrophysiological responses to social fairness in manic and euthymic patients with bipolar disorder.

BACKGROUND: Individuals with bipolar disorder show mood instability, including heightened anger and impulsivity. The Ultimatum Game (UG) is a tool used to evaluate emotional and social decision-making strategies. We investigated behavioral and electrophysiological responses to subjectively fair or unfair offers in the UG in patients with bipolar I disorder. METHODS: Twenty-four manic patients, 20 euthymic patients, and 30 healthy controls participated in this study. We analyzed their behaviors and collected electroencephalography data with which to analyze feedback-related negativity (FRN) as they played in the UG as responders. RESULTS: Manic patients exhibited significantly higher rejection rates for unfair offers than euthymic patients and healthy controls. Healthy individuals exhibited a greater (i.e., more negative) FRN amplitude in response to unfair offers than to fair offers, whereas euthymic patients exhibited a greater FRN amplitude in response to fair offers compared with unfair offers. Manic patients exhibited no difference in FRN amplitudes between fair and unfair offers. CONCLUSIONS: The current data suggest that different behavioral responses and FRN amplitude patterns can be associated with characteristic manifestations of mood instability in manic bipolar patients. In addition, electrophysiological alterations in response to unfair offers may be a trait abnormality independent of mood state.

Audiologic outcomes and complications of active middle ear implantation in older adults.

BACKGROUND: A few studies have reported the use of middle ear implants (MEIs) in older adults. OBJECTIVES: To evaluate the audiologic outcomes and postoperative complications of MEIs in older adults. METHODS: This retrospective study reviewed audiologic data and medical records from a single referral centre. We identified 34 patients aged ≥65 years who underwent middle ear implantation using the Vibrant SoundbridgeTM device. Preoperative audiometric testing and postoperative aided audiometric testing were performed to evaluate the functional hearing gain at 1 year postoperatively. Patients were divided into 2 groups depending on whether they underwent explantation because of poor hearing benefit. RESULTS: Follow-up duration ranged from <1 to 5.3 years. The functional gain with MEIs significantly improved relative to the preoperative air conduction thresholds at 0.5, 1, 2, and 4 kHz. Eight patients underwent explantation and 7 lost their external audio processor devices. Those who removed their implants because of the poor hearing (group 1) showed significantly worse hearing thresholds at 1 kHz and speech discrimination scores than the others (group 2). CONCLUSIONS AND SIGNIFICANCE: MEIs for auditory rehabilitation can provide improved speech recognition and significant functional gains in older adults. Patients must be given appropriate preoperative explanations regarding the expected outcomes.

Manipulation ability of internal representation in patients with euthymic bipolar I disorder and schizophrenia using a mental rotation task.

BACKGROUND: A growing body of literature has suggested that effective emotion regulation is influenced by cognitive function. Maintenance and manipulation of internal representations occur in working memory (WM), and impairments of WM have been reported in patients with bipolar disorder. METHODS: We examined the manipulation ability of internal representations in WM using mental rotation (MR) tasks, and compared the task performances of euthymic bipolar I disorder patients to those of schizophrenia patients and healthy controls. In this study, 20 euthymic bipolar I disorder patients, 20 schizophrenia patients, and 38 healthy controls were recruited. People and letter MR tasks were employed to evaluate the ability of WM manipulation. RESULTS: Compared to healthy controls, euthymic bipolar I disorder patients showed substantially higher error rates of people MR task and slower responses in both people and letter MR tasks. Schizophrenia patients showed no difference in error rate and response time in MR tasks compared to healthy controls; however, they showed significantly slower responses in people MR task compared to controls. MR task performance was not different between euthymic bipolar and schizophrenia patients. CONCLUSION: Our study results indicate that manipulation of internal representation, especially in the egocentric MR, is impaired in bipolar disorder even in the emotionally-stable state. We speculate that impaired imagery manipulation might be related to alterations in empathic ability, susceptibility of mental imagery, and emotion regulation strategies observed in bipolar disorder.

Gender differences in social network of cognitive function among community-dwelling older adults.

AIM: A social network, which is a set of people connected through socially meaningful relationships, is considered protective for neurocognitive disorders. Men and women have been found to have different opportunities for social participation and it is possible social networks do not form the same way. We hypothesized, male and female social networks would have different protective influences on cognitive function. METHODS: The Korean Social Life, Health, and Aging Project, a cohort study involving health examination and social network survey among adults aged ≥60 years in South Korea was conducted from 2014 to 2015. In total, 501 participants (208 men and 293 women) were included in the study. Through face-to-face sessions, participants were asked to answer questionnaires about general characteristics, depressive symptoms, instrumental activities of daily living (IADL), social activity, cognitive function and social network variables (degree, betweenness, and closeness centrality and brokerage roles). Multiple linear regression models were used to investigate whether cognitive functions of men and women are differently influenced by their social networks, and path analysis was used to find the direct/indirect influence of social networks on cognitive function. RESULTS: Out-degree centrality and social activity scores were positively correlated with Mini-Mental State Examination (MMSE) scores only in women. In both genders, age and IADL scores were negatively associated with MMSE scores, while educational level was positively correlated. CONCLUSIONS: Cognitive function of women was influenced by social activity and the number of members they considered friends. This finding suggests the influence of social networks on cognitive function differ by gender. Geriatr Gerontol Int 2020; 20: 467-473.

Maxillary Sinus Pneumocele Presenting as Aesthetic Deformity: A Case Report With Literature Review.

We report an interesting case of maxillary sinus pneumocele that presented with aesthetic deformity and completely treated with Caldwell-Luc approach and thoroughly review all of the past literature focusing on clinical symptoms and surgical approach. Based on our comprehensive review of maxillary sinus pneumocele, we found 2 important characteristics. First, maxillary sinus pneumocele may be asymptomatic but cause various symptoms owing to the displacement of neighboring structures, such as facial symptoms, eye symptoms, and nasal obstruction. Second, there is no standard operation technique for maxillary sinus pneumocele, but surgical approach should be individualized depending on patient's symptoms and needs. Therefore, more case studies are needed to confirm this.

Low working memory capacity in euthymic bipolar I disorder: No relation to reappraisal on emotion regulation.

BACKGROUND: Emotion regulation (ER) applies behavioral and cognitive strategies to modify the appearance and intensity of emotions. Working memory capacity (WMC) plays an important role in the ER process, particularly through its influence on the efficiency of ER strategies. METHODS: We investigated interactions between WMC and three ER strategies, namely cognitive reappraisal, expressive suppression, and rumination, in 43 euthymic patients with bipolar I disorder and 48 healthy control subjects. We used the Korean versions of the Operation Span Task, Emotion Regulation Questionnaire, Ruminative Response Scale, and Difficulties in Emotion Regulation Scale. RESULTS: WMC modulated the efficacy of cognitive reappraisal in healthy controls with high WMC, but not in patients with bipolar disorder. There were no significant interactions between WMC and expressive suppression or rumination in either group. LIMITATIONS: These include the small sample size, use of neutral words to evaluate negative emotion, use of self-administered questionnaires, and relatively high cut-off for the definition of euthymic states. A number of uncontrolled factors may have influenced our results including patients' duration of remission, number of episodes, psychiatric family history, and current psychiatric medications. CONCLUSIONS: Our findings suggest that working memory does not function effectively in the reappraisal process during ER in patients with bipolar disorder. This may indicate that top-down regulation of emotion is impaired in bipolar disorder. Cognitive interventions aimed at improving ER in such patients may be ineffective.

Losartan Prevents Maladaptive Auditory-Somatosensory Plasticity After Hearing Loss via Transforming Growth Factor-ß Signaling Suppression.

OBJECTIVES: Hearing loss disrupts the balance of auditory-somatosensory inputs in the cochlear nucleus (CN) of the brainstem, which has been suggested to be a mechanism of tinnitus. This disruption results from maladaptive auditory-somatosensory plasticity, which is a form of axonal sprouting. Axonal sprouting is promoted by transforming growth factor (TGF)-ß signaling, which can be inhibited by losartan. We investigated whether losartan prevents maladaptive auditory-somatosensory plasticity after hearing loss. METHODS: The study consisted of two stages: determining the time course of auditory-somatosensory plasticity following hearing loss and preventing auditory-somatosensory plasticity using losartan. In the first stage, rats were randomly divided into two groups: a control group that underwent a sham operation and a deaf group that underwent cochlea ablation on the left side. CNs were harvested 1 and 2 weeks after surgery. In the second stage, rats were randomly divided into either a saline group that underwent cochlear ablation on the left side and received normal saline or a losartan group that underwent cochlear ablation on the left side and received losartan. CNs were harvested 2 weeks after surgery. Hearing was estimated with auditory brainstem responses (ABRs). Western blotting was performed for vesicular glutamate transporter 1 (VGLUT1), reflecting auditory input; vesicular glutamate transporter 2 (VGLUT2), reflecting somatosensory input; growth-associated protein 43 (GAP-43), reflecting axonal sprouting; and p-Smad2/3. RESULTS: Baseline ABR thresholds before surgery ranged from 20 to 35 dB sound pressure level. After cochlear ablation, ABR thresholds were higher than 80 dB. In the first experiment, VGLUT2/VGLUT1 ratios did not differ significantly between the control and deaf groups 1 week after surgery. At 2 weeks after surgery, the deaf group had a significantly higher VGLUT2/VGLUT1 ratio compared to the control group. In the second experiment, the losartan group had a significantly lower VGLUT2/VGLUT1 ratio along with significantly lower p-Smad3 and GAP-43 levels compared to the saline group. CONCLUSION: Losartan might prevent axonal sprouting after hearing loss by blocking TGF-ß signaling thereby preventing maladaptive auditory-somatosensory plasticity.

Behavioral and Electrophysiological Alterations for Reinforcement Learning in Manic and Euthymic Patients with Bipolar Disorder.

AIMS: Bipolar disorder is characterized by behavioral changes such as risk-taking and increasing goal-directed activities, which may result from altered reward processing. Patients with bipolar disorder show impaired reward learning in situations that require the integration of reinforced feedback over time. In this study, we examined the behavioral and electrophysiological characteristics of reward learning in manic and euthymic patients with bipolar disorder using a probabilistic reward task. METHODS: Twenty-four manic and 20 euthymic patients with bipolar I disorder and 24 healthy control subjects performed the probabilistic reward task. We assessed response bias (RB) as a preference for the stimulus paired with the more frequent reward and feedback-related negativity (FRN) to correct identification of the rich stimulus. RESULTS: Both manic and euthymic patients showed significantly lower RB scores in the early learning stage (block 1) in comparison with the late learning stage (block 2 or block 3) of the task, as well as significantly lower RB scores in the early stage compared to healthy subjects. Relatively more negative FRN amplitude is elicited by no presentation of an expected reward, compared to that elicited by presentation of expected feedback. The FRN became significantly more negative from the early (block 1) to the later stages (blocks 2 and 3) in both manic and euthymic patients, but not in healthy subjects. Changes in RB scores and FRN amplitudes between blocks 2 and 3 and block 1 correlated positively in healthy controls, but correlated negatively in manic and euthymic patients. The severity of manic symptoms correlated positively with reward learning scores and negatively with the FRN. CONCLUSIONS: These findings suggest that patients with bipolar disorder during euthymic or manic states have behavioral and electrophysiological alterations in reward learning compared to healthy subjects. This dysfunctional reward processing may be related to the abnormal decision-making or altered goal-directed activities frequently seen in patients with bipolar disorder.

Facial reanimation using hypoglossal-facial nerve anastomosis after schwannoma removal.

CONCLUSION: In this series, the split type hypoglossal-facial nerve anastomosis resulted in more favorable outcomes in terms of both facial function and tongue atrophy. OBJECTIVE: This study compared surgical techniques for hypoglossal-facial nerve anastomosis after schwannoma removal and evaluated which technique achieves better facial outcomes and less tongue morbidity. METHOD: This study included 14 patients who underwent hypoglossal-facial nerve anastomosis after schwannoma removal and were followed for more than 1 year. Three surgical techniques were performed: end-to-end, end-to-side, and split anastomoses. Facial palsy and tongue atrophy after anastomosis were evaluated using the scales suggested by House-Brackmann and Martins, respectively. Tumor volume and the time to surgery were also evaluated, and the effects on facial outcomes were analyzed. RESULTS: Overall, nine of 14 (64.3%) patients had favorable facial outcomes, and eight of 14 (57.1%) had favorable tongue outcomes. Regarding facial palsy, five of seven (71.4%) end-to-end, three of four (75%) split, and only one of three (33.3%) end-to-side patients had favorable facial function. Regarding tongue atrophy, all three (100%) end-to-side, three of four (75%) split, and two of seven (28.6%) end-to-end patients had favorable tongue outcomes. The effects of tumor volume and time to surgery on facial outcome were not significant.

Adjunctive α-lipoic acid reduces weight gain compared with placebo at 12 weeks in schizophrenic patients treated with atypical antipsychotics: a double-blind randomized placebo-controlled study.

α-Lipoic acid (ALA) has been reported to be effective in reducing body weight in rodents and obese patients. Our previous open trial showed that ALA may play a role in reducing weight gain in patients with schizophrenia on atypical antipsychotics. The present study evaluated the efficacy of ALA in reducing weight and BMI in patients with schizophrenia who had experienced significant weight gain since taking atypical antipsychotics. In a 12-week, double-blind randomized placebo-controlled study, 22 overweight and clinically stable patients with schizophrenia were randomly assigned to receive ALA or placebo. ALA was administered at 600-1800 mg, as tolerated. Weight, BMI, abdomen fat area measured by computed tomography, and metabolic values were determined. Adverse effects were also assessed to examine safety. Overall, 15 patients completed 12 weeks of treatment. There was significant weight loss and decreased visceral fat levels in the ALA group compared with the placebo group. There were no instances of psychopathologic aggravation or severe ALA-associated adverse effects. ALA was effective in reducing weight and abdominal obesity in patients with schizophrenia who had experienced significant weight gain since beginning an atypical antipsychotic regimen. Moreover, ALA was well tolerated throughout this study. ALA might play an important role as an adjunctive treatment in decreasing obesity in patients who take atypical antipsychotics.

P600 alteration of syntactic language processing in patients with bipolar mania: Comparison to schizophrenic patients and healthy subjects.

BACKGROUND: Disturbances in thought, speech, and linguistic processing are frequently observed in bipolar manic patients, but the underlying neurophysiological mechanisms are not well understood. P600 is a distinct, positive event-related potential component elicited by syntactic violations. Using the P600 ERP, we examined neural processing of syntactic language comprehension in patients with bipolar mania compared to patients with schizophrenia and healthy people. METHOD: P600s were recorded from 21 manic patients with bipolar disorder, 26 patients with schizophrenia, and 29 healthy subjects during the presentation of 120 auditory sentences with syntactic violations or non-violations. Subjects were asked to judge whether each sentence was correct or incorrect. RESULTS: Patients with mania and schizophrenia had significantly smaller P600 amplitudes associated with syntactic violations compared with healthy subjects. There was no difference in P600 amplitude between patient groups. For behavioral performance, patients with schizophrenia had significantly less accurate rates and longer reaction times compared with healthy subjects, whereas manic patients exhibited no significant differences in accuracy and only showed increased reaction times in comparison with healthy subjects. LIMITATIONS: Psychotropic drug usage and small sample size. CONCLUSION: Patients with bipolar mania have reduced P600 amplitude, comparable to patients with schizophrenia. Our findings may represent the first neurophysiological evidence of abnormal syntactic linguistic processing in bipolar mania.

Perceptions of social dominance through facial emotion expressions in euthymic patients with bipolar I disorder.

The ability to accurately perceive dominance in the social hierarchy is important for successful social interactions. However, little is known about dominance perception of emotional stimuli in bipolar disorder. The aim of this study was to investigate the perception of social dominance in patients with bipolar I disorder in response to six facial emotional expressions. Participants included 35 euthymic patients and 45 healthy controls. Bipolar patients showed a lower perception of social dominance based on anger, disgust, fear, and neutral facial emotional expressions compared to healthy controls. A negative correlation was observed between motivation to pursue goals or residual manic symptoms and perceived dominance of negative facial emotions such as anger, disgust, and fear in bipolar patients. These results suggest that bipolar patients have an altered perception of social dominance that might result in poor interpersonal functioning. Training of appropriate dominance perception using various emotional stimuli may be helpful in improving social relationships for individuals with bipolar disorder.

The Significance of Rhinologic Evaluation and Pretreatment for Patients Undergoing Two-Jaw Surgery Through Nasotracheal Intubation.

The aim of this study is to determine whether rhinologic preoperative evaluation and pretreatments reduce intranasal trauma and decrease postoperative complications, such as nasal obstruction and epistaxis, in patients undergoing 2-jaw surgery with nasotracheal intubation. This study included 360 patients with malocclusion (Class III) who underwent 2-jaw surgery under general anesthesia via nasotracheal intubation in our hospital from January to December 2013 and categorized into 3 groups. Nasotracheal intubation was performed according to the nasal cavity the patient was able to breathe comfortably (Group I). The site of nasotracheal intubation was decided by 1 rhinologic specialist who evaluated preoperative dental computed tomography (Group II). The site of nasotracheal intubation was decided upon nasal endoscopic findings, dental computed tomography evaluation, and rhinologic pretreatment (Group III).Group II and Group III showed less damage to the nasal mucosa compared with the nasal status of Group I. Upon comparing Group II and Group III, Group III showed better overall status of the nasal mucosa compared with Group II. Visual analogue scale scores for nasal obstruction were pretty similar for all groups on the first postoperative day. In Group III, the nasal mucosa, however, was improved to that of preoperative status on the third postoperative day.In conclusion, it may be useful to pre-evaluate the mucosal and anatomical status of the nasal cavity to select patients requiring rhinologic pretreatment and decide the site for nasotracheal intubation to minimize complications arising from nasotracheal intubation.

Internalized stigma and its psychosocial correlates in Korean patients with serious mental illness.

We aimed to examine internalized stigma of patients with mental illness in Korea and identify the contributing factors to internalized stigma among socio-demographic, clinical, and psychosocial variables using a cross-sectional study design. A total of 160 patients were recruited from a university mental hospital. We collected socio-demographic data, clinical variables and administered self-report scales to measure internalized stigma and levels of self-esteem, hopelessness, social support, and social conflict. Internalized stigma was identified in 8.1% of patients in our sample. High internalized stigma was independently predicted by low self-esteem, high hopelessness, and high social conflict among the psychosocial variables. Our finding suggests that simple psychoeducation only for insight gaining cannot improve internalized stigma. To manage internalized stigma in mentally ill patients, it is needed to promote hope and self-esteem. We also suggest that a relevant psychosocial intervention, such as developing coping skills for social conflict with family, can help patients overcome their internalized stigma.

Manic patients exhibit more utilitarian moral judgments in comparison with euthymic bipolar and healthy persons.

Both emotional and cognitive processes are involved in moral judgments. Ventromedial prefrontal lesions are related to impaired prosocial emotions and emotional dysregulation, and patients with these lesions exhibit increased utilitarian judgments of emotionally salient personal moral dilemmas. Bipolar patients experiencing manic episode also have impaired emotional regulation and behavioral control. We investigated the characteristics of moral judgment in manic and euthymic patients with bipolar disorder using the 50 hypothetical moral dilemma task (17 non-moral, 20 personal, and 13 impersonal). Our study included 27 manic bipolar patients, 26 euthymic bipolar patients, and 42 healthy controls. Subjects were instructed to determine whether or not each dilemma was morally acceptable, and their reaction times were recorded. Manic patients showed significantly greater utilitarian judgment than euthymic patients and normal controls for personal moral dilemmas. However, there were no significant between-group differences for the non-moral and impersonal moral dilemmas. Our results suggest that increased utilitarian judgments of personal moral dilemmas may be a state-related finding observed only in manic patients. This difference in moral judgment assessments may reflect the decision-making characteristics and underlying neurobiological mechanisms of bipolar disorder, especially during the manic state.

Effects of emotional stimuli on time perception in manic and euthymic patients with bipolar disorder.

BACKGROUND: Time perception, which plays a fundamental role in decision-making and the evaluation of the environment, is also influenced by emotions. Patients with bipolar disorder have impairments in emotional processing as well as interval timing. We investigated the effects of emotional stimuli on time estimation and reproduction in manic and euthymic bipolar patients compared with healthy controls. METHODS: We recruited 22 manic bipolar patients, 24 euthymic bipolar patients and 24 healthy controls. Each subject performed time estimation and reproduction tasks using standardized affective pictures that were classified into 4 stimulus groups according to valence and level of arousal and presented for durations of 2, 4, and 6s. We analyzed temporal performance on these tasks using transformed data expressed as a proportion of the target period. RESULTS: The interactions between arousal and valence were different in manic patients compared with euthymic patients and healthy controls in both time estimation and reproduction tasks. Manic patients showed no effect of positive valence low arousal stimuli in the time estimation task compared to euthymic patients and healthy controls. In the time reproduction task, the effect of emotional stimuli was reversed in manic patients compared to euthymic patients and healthy controls. Significant correlations between the severity of manic symptoms or illness severity and average temporal performance scores were found in manic patients. CONCLUSION: Our results suggest that altered emotion-related time judgments may be a state-dependent phenomenon observed in manic patients only. This difference in time perception for emotional stimuli may be related to the underlying neurobiological mechanisms of the manic state.