Glial Markers of Suicidal Behavior in the Human Brain-A Systematic Review of Postmortem Studies.

Suicide is a major public health priority, and its molecular mechanisms appear to be related to glial abnormalities and specific transcriptional changes. This study aimed to identify and synthesize evidence of the relationship between glial dysfunction and suicidal behavior to understand the neurobiology of suicide. As of 26 January 2024, 46 articles that met the inclusion criteria were identified by searching PubMed and ISI Web of Science. Most postmortem studies, including 30 brain regions, have determined no density or number of total Nissl-glial cell changes in suicidal patients with major psychiatric disorders. There were 17 astrocytic, 14 microglial, and 9 oligodendroglial studies using specific markers of each glial cell and further on their specific gene expression. Those studies suggest that astrocytic and oligodendroglial cells lost but activated microglia in suicides with affective disorder, bipolar disorders, major depression disorders, or schizophrenia in comparison with non-suicided patients and non-psychiatric controls. Although the data from previous studies remain complex and cannot fully explain the effects of glial cell dysfunction related to suicidal behaviors, they provide risk directions potentially leading to suicide prevention.

Association Between Dementia, Change in Home-Care Use, and Depressive Symptoms During the COVID-19 Pandemic: A Longitudinal Study Using Data from Three Cohort Studies.

Background: The emotional impact of the coronavirus disease 2019 (COVID-19) pandemic on people with dementia has been quantified. However, little is known about the impact of change in home-care use owing to the pandemic. Objective: To determine the longitudinal association between dementia, change in home-care use, and depressive symptoms during the pandemic. Methods: We included data of 43,782 home-dwelling older adults from the English Longitudinal Study of Ageing (ELSA), Study of Health, Ageing and Retirement in Europe (SHARE), and National Health and Aging Trends Study (NHATS). This study considered the latest main wave survey prior to the pandemic as the baseline, and the COVID-19 survey as follow-up. In a series of coordinated analyses, multilevel binomial logistic regression model was used to examine the association between baseline dementia, change in home-care use at follow-up, and presence of depressive symptoms. Results: Dementia, using the ELSA, SHARE, and NHATS datasets, was identified in 2.9%, 2.3%, and 6.5% of older adults, and home-care use reduced in 1.7%, 2.8%, and 1.1% of individuals with dementia, respectively. Dementia was significantly associated with the increased risk of depressive symptoms in all three cohorts. However, the interaction between dementia and period (follow-up) was non-significant in SHARE and NHATS. Across all three cohorts, home-care use during the pandemic, regardless of change in amount, was significantly associated with increased depressive symptoms, compared to the non-use of home care. Conclusions: These results highlight the need for tailoring dementia care at home to promote independence and provide sustainable emotional support.

Place of death from dementia as an underlying cause during the COVID-19 pandemic in Japan: a cross-sectional study from national death certificates.

Background: The coronavirus disease (COVID-19) pandemic has challenged palliative end-of-life care for people with dementia. The site of death can be considered as an end-of-life care quality indicator. Most people with dementia prefer to die at nursing or private homes; however, in Japan, they are often hospitalized in psychiatric hospitals for management of neuropsychiatric symptoms. As palliative end-of-life care for older adults with Alzheimer's disease and related dementias has been further challenged by the COVID-19 pandemic, little is known about its effects on the place of death in patients with dementia. Objectives: This study aimed to investigate the shifts in place of death from dementia during the COVID-19 pandemic in Japan. Changes throughout the pandemic were compared between deaths from dementia and from senility. Design: Cross-sectional. Methods: Death certificate data of individuals aged 65 years or older who died in Japan between 1 January 2018, and 31 December 2021, were used to extract the cause and place of death. Differences in place of death between the periods were estimated using multinomial logistic analysis with reference to death in private homes. Results: Deaths from dementia mostly occurred in hospitals (59%), while deaths from senility were most frequent in nursing homes (37%). After adjusting for patient characteristics, the likelihood of hospital deaths significantly increased for patients with dementia during the pandemic. Meanwhile, the likelihood of senility deaths decreased in hospitals but increased in nursing homes during the pandemic. Conclusion: The shift to hospital deaths since the onset of the COVID-19 pandemic was uniquely observed in deaths from dementia. This hospital shift likely involved increased transfers from nursing and private homes to psychiatric hospitals. Further investigation is needed to examine the association between the pandemic-related change in long-term care workforce and palliative care practice in people with dementia.

Depression and Anxiety in Older Adults with Dementia During the COVID-19 Pandemic.

This study examined the longitudinal association between dementia, activity participation, the coronavirus disease 2019 pandemic period, and 1-year mental health changes. We obtained data from the National Health and Aging Trends Study in the United States. We included 4,548 older adult participants of two or more survey rounds between 2018 and 2021. We identified baseline dementia status, and assessed depressive symptoms and anxiety at baseline and follow-up. Dementia and poor activity participation were independently associated with an increased prevalence of depressive symptoms and anxiety. Dementia care and support should address emotional and social needs under continued public health restrictions.

Association between advance care planning and depressive symptoms among community-dwelling people with dementia: An observational cross-sectional study during the COVID-19 pandemic in Japan.

Objectives: Advance care planning (ACP) is an increasing priority for people with dementia during the COVID-19 pandemic. This study evaluated the association between ACP initiation and depressive symptoms among home-dwelling people living with dementia. Methods: An internet-based questionnaire survey was conducted with Japanese family caregivers of home-dwelling persons with dementia in June 2021. Family caregivers evaluated the level of depressive symptoms in persons with dementia using the Neuropsychiatric Inventory (NPI). Caregivers also rated the quality of life of persons with dementia using the EQ-5D-5L. Results: A total of 379 family caregivers participated in the survey. Depressive symptoms were reported in 143 persons with dementia (37.7%). A total of 155 persons with dementia (40.9%) had initiated ACP, of which 88 (56.8%) had care professionals involved in ACP conversation. After adjusting for the characteristics of persons with dementia and caregivers, persons with professional involvement showed significantly more severe depressive symptoms compared to those who did not initiate ACP. There was no significant difference in the quality of life of persons with dementia according to ACP initiation. Conclusions: Many home-dwelling persons with dementia experienced depressive symptoms during the COVID-19 pandemic, especially in cases where care professionals were involved in ACP conversations. Optimal and proactive ACP approaches need to be developed to prevent depressive symptoms in newly diagnosed persons.

Quality of End-of-Life Care for Older Adults with Dementia during the COVID-19 Pandemic.

OBJECTIVES: End-of-life (EOL) care during the coronavirus disease 2019 (COVID-19) pandemic has been a concern under the overwhelming pressure of health care service systems. People with dementia often receive suboptimal EOL care; thus, they may be at particular risk of poor care quality during the COVID-19 pandemic. This study investigated the interaction between dementia and pandemic on the proxies' overall ratings and ratings for 13 indicators. DESIGN: A longitudinal study. SETTING AND PARTICIPANTS: Data were collected from 1050 proxies for deceased participants in the National Health and Aging Trends Study, a nationally representative sample of community-dwelling Medicare beneficiaries aged ≥65 years. Participants were included if they had died between 2018 and 2021. METHODS: Participants were categorized into 4 groups depending on the period of death (before vs during the COVID-19 pandemic) and having no vs probable dementia, as defined by a previously validated algorithm. The quality of EOL care was assessed through postmortem interviews with bereaved caregivers. Multivariable binomial logistic regression analyses were performed to examine the main effects of dementia and pandemic period, and the interaction between dementia and pandemic on ratings of quality indicators. RESULTS: A total of 423 participants had probable dementia at the baseline. People with dementia who died were less likely to talk about religion in the last month of life than those without dementia. Decedents during the pandemic were more likely to have an overall rating of care as being not excellent than those before the onset of the pandemic. However, the interaction between dementia and pandemic was not significant in the 13 indicators and the overall rating of EOL care quality. CONCLUSION AND IMPLICATIONS: Most EOL care indicators preserved the level of quality, regardless of dementia and the COVID-19 pandemic. Disparities in spiritual care may exist across people with and without dementia.

Decreased ß-hydroxybutyrate and ketogenic amino acid levels in depressed human adults.

ß-hydroxybutyrate (BHB) is a major ketone body synthesized mainly in the liver mitochondria and is associated with stress and severity of depression in humans. It is known to alleviate depressive-like behaviors in mouse models of depression. In this study, plasma BHB, ketogenic and glucogenic amino acids selected from the Tohoku Medical Megabank Project Community-Based Cohort Study were analysed and measured using nuclear magnetic resonance spectroscopy. The Center for Epidemiologic Studies Depression Scale (CES-D) was utilized to select adult participants with depressive symptoms (CES-D ≥ 16; n = 5722) and control participants (CES-D < 16; n = 18,150). We observed significantly reduced plasma BHB, leucine, and tryptophan levels in participants with depressive symptoms. Using social defeat stress (SDS) mice models, we found that BHB levels in mice sera increased after acute SDS, but showed no change after chronic SDS, which differed from human plasma results. Furthermore, acute SDS increased mitochondrial BHB levels in the prefrontal cortex at 6 h. In contrast, chronic SDS significantly increased the amount of food intake but reduced hepatic mitochondrial BHB levels in mice. Moreover, gene transcriptions of voltage-dependent anion-selective channel 1 (Vdac1) and monocarboxylic acid transporter 1 (Mct1), major molecules relevant to mitochondrial biogenesis and BHB transporter, significantly decreased in the liver and PFC after chronic SDS exposure. These results provide evidence that hepatic and prefrontal mitochondrial biogenesis plays an important role in BHB synthesis under chronic stress and in humans with depressive symptoms.

N-Acetylcysteine Suppresses Microglial Inflammation and Induces Mortality Dose-Dependently via Tumor Necrosis Factor-α Signaling.

N-acetylcysteine (NAC) is an antioxidant that prevents tumor necrosis factor (TNF)-α-induced cell death, but it also acts as a pro-oxidant, promoting reactive oxygen species independent apoptosis. Although there is plausible preclinical evidence for the use of NAC in the treatment of psychiatric disorders, deleterious side effects are still of concern. Microglia, key innate immune cells in the brain, play an important role in inflammation in psychiatric disorders. This study aimed to investigate the beneficial and deleterious effects of NAC on microglia and stress-induced behavior abnormalities in mice, and its association with microglial TNF-α and nitric oxide (NO) production. The microglial cell line MG6 was stimulated by Escherichia coli lipopolysaccharide (LPS) using NAC at varying concentrations for 24 h. NAC inhibited LPS-induced TNF-α and NO synthesis, whereas high concentrations (≥30 mM) caused MG6 mortality. Intraperitoneal injections of NAC did not ameliorate stress-induced behavioral abnormalities in mice, but high-doses induced microglial mortality. Furthermore, NAC-induced mortality was alleviated in microglial TNF-α-deficient mice and human primary M2 microglia. Our findings provide ample evidence for the use of NAC as a modulating agent of inflammation in the brain. The risk of side effects from NAC on TNF-α remains unclear and merits further mechanistic investigations.

Microarray dataset of gene transcription in mouse microglia and peripheral monocytes in contextual fear conditioning.

The transcription profile of microglia related to fear conditioning remains unclear. Here, we used Illumina MouseWG-6v2 microarrays to investigate the gene transcription changes in microglia and peripheral monocytes after contextual fear conditioning of C57BL/6 J mice. Mice were trained with or without a single minimized footshock stimulation (0-s or 2-s, 0.4 mA) and re-exposed to the training context without footshock for three different durations 24 h later: 0 min (FS0), 3 min (FS3), or 30 min (FS30). Whole brain microglia and peripheral monocytes were prepared 24 h after re-exposure using a neural tissue dissociation kit, including non-footshock controls for two re-exposure durations (Con3 and Con30). The data can be valuable for researchers interested in glial cells and neurotransmission studies and are related to the research article "Contextual fear conditioning regulates synapse-related gene transcription in mouse microglia".

Sex-Specific Differences in the Transcriptome of the Human Dorsolateral Prefrontal Cortex in Schizophrenia.

Schizophrenia presents clinical and biological differences between males and females. This study investigated transcriptional profiles in the dorsolateral prefrontal cortex (DLPFC) using postmortem data from the largest RNA-sequencing (RNA-seq) database on schizophrenic cases and controls. Data for 154 male and 113 female controls and 160 male and 93 female schizophrenic cases were obtained from the CommonMind Consortium. In the RNA-seq database, the principal component analysis showed that sex effects were small in schizophrenia. After we analyzed the impact of sex-specific differences on gene expression, the female group showed more significantly changed genes compared with the male group. Based on the gene ontology analysis, the female sex-specific genes that changed were overrepresented in the mitochondrion, ATP (phosphocreatine and adenosine triphosphate)-, and metal ion-binding relevant biological processes. An ingenuity pathway analysis revealed that the differentially expressed genes related to schizophrenia in the female group were involved in midbrain dopaminergic and γ-aminobutyric acid (GABA)-ergic neurons and microglia. We used methylated DNA-binding domain-sequencing analyses and microarray to investigate the DNA methylation that potentially impacts the sex differences in gene transcription using a maternal immune activation (MIA) murine model. Among the sex-specific positional genes related to schizophrenia in the PFC of female offspring from MIA, the changes in the methylation and transcriptional expression of loci ACSBG1 were validated in the females with schizophrenia in independent postmortem samples by real-time PCR and pyrosequencing. Our results reveal potential genetic risks in the DLPFC for the sex-dependent prevalence and symptomology of schizophrenia.

Plasma metabolic disturbances during pregnancy and postpartum in women with depression.

Examining plasma metabolic profiling during pregnancy and postpartum could help clinicians understand the risk factors for postpartum depression (PPD) development. This analysis targeted paired plasma metabolites in mid-late gestational and 1 month postpartum periods in women with (n = 209) or without (n = 222) PPD. Gas chromatogram-mass spectrometry was used to analyze plasma metabolites at these two time points. Among the 170 objected plasma metabolites, principal component analysis distinguished pregnancy and postpartum metabolites but failed to discriminate women with and without PPD. Compared to women without PPD, those with PPD exhibited 37 metabolites with disparate changes during pregnancy and the 1-month postpartum period and an enriched citrate cycle. Machine learning and multivariate statistical analysis identified two or three compounds that could be potential biomarkers for PPD prediction during pregnancy. Our findings suggest metabolic disturbances in women with depression and may help to elucidate metabolic processes associated with PPD development.

Suicide rates during the COVID-19 pandemic in Japan from April 2020 to December 2021.

This study estimated the excess suicidal mortality during the COVID-19 pandemic in Japan. A Poisson regression model was used to assess the association between unemployment rates, expenditure for alcohol, eating out, and suicide, from January 2008 to March 2020. The excess suicidal mortality was assessed by applying the identified model to data from April 2020 to December 2021. The number of estimated excess deaths during COVID-19 was 3397 in men and 2390 in women. COVID-19 may have caused unprecedented psychological distress among people, owing to restricted social gatherings and prolonged uncertainties.

Contextual fear conditioning regulates synapse-related gene transcription in mouse microglia.

Microglia have been suggested to be involved in the underlying mechanism of conditional fear memory formation by regulating inflammatory cytokines. However, the mechanism linking microglia and neuronal activity related to fear conditioning remains unclear. This study characterized the transcription profile of microglia in a fear memory conditional mouse model. Compared with those in control mice microglia, the most significantly induced genes were synapse-related, whereas immune-related genes were reduced due to fear memory consolidation. Whilst the increased expression of synapse-related genes was reversed after fear memory extinction, that of immunological genes was not, strongly suggesting a connection between microglia, neurons, and a dysregulated immune response following contextual fear conditioning. Furthermore, in the hippocampal microglia, we found that the expression of neurotransmitter release regulators, γ-aminobutyric acid (GABA) receptor GABRB3 and synapsin 1/2, increased under fear memory consolidation and restored (decreased) after extinction. In addition, compared with the transcription profile in peripheral monocytes, few overlapping genes were not enriched in biological processes. Taken together, the identified conditional fear stress-induced changes in mouse microglial transcription profiles suggest that microglia-neuron communication mediates contextual fear conditioning.

The Association Between COVID-19 Information Sources and Stigma Against Health Care Workers Among College Students: Cross-sectional, Observational Study.

BACKGROUND: The COVID-19 pandemic has triggered stigmatic attitudes against health care workers. Some forms of social media may play a role in disseminating stigmatizing messages. OBJECTIVE: We aimed to investigate the association between COVID-19 information sources and stigma against health care workers among college students during the pandemic. METHODS: A cross-sectional, observational study was conducted using a web-based platform in the Tohoku region of Japan. College students aged ≥20 years were asked to complete the questionnaire between August 18 and October 31, 2020. Stigma against health care workers was evaluated using a modified Japanese version of the Social Distance Scale. Participants were also asked to rate their perceived vulnerability to infection using the Japanese version of the Perceived Vulnerability to Disease scale. RESULTS: A total of 281 students from 8 colleges completed the web-based survey. There were 139 (49.5%) participants who used Twitter, 187 (66.5%) who used news websites, and 46 (16.4%) who used the websites of public health agencies as COVID-19 information sources. After adjusting for age, sex, department, and Perceived Vulnerability to Disease scores, the level of stigma did not differ between students who used Twitter and those who did not. Students who used the websites of public health agencies showed a significantly less stigmatic attitude than those who did not. CONCLUSIONS: Fact-checking and directing visitors to credible information sources from public health agencies may have prevented the formation of stigmatic attitudes toward health care workers. An effective strategy to enable easy access to information provided by public agencies should be integrated into widespread web-based platforms.

Depression and anxiety among nursing students during the COVID-19 pandemic in Tohoku region, Japan: A cross-sectional survey.

AIM: Restrictions such as physical distancing and online learning for college students were implemented due to the COVID-19 pandemic. Owing to this, students may experience psychological distress from social isolation and loneliness. Nursing students are subjected to an exacerbated level of distress during the pandemic due to their role as health professionals. Therefore, the present study aimed to investigate the level of anxiety and depression among Japanese nursing students, according to their perceived vulnerability to COVID-19. METHODS: A total of 281 college students (104 nursing students and 177 other college students) responded to a web-based anonymous questionnaire survey from 18 August to 31 October 2020. The Hospital Anxiety and Depression Scale was used to evaluate anxiety (HADS-A) and depression (HADS-D). Perceived vulnerability to COVID-19 was assessed using the Perceived Vulnerability to Disease Scale. RESULTS: In both groups of students, the prevalence of both anxiety (30.5% in nursing students; 69.5% in others) and depressive symptoms (31.1% in nursing students; 68.9% in others) were remarkably high. There were no significant differences in anxiety and depression between nursing and other students after adjusting for perceived vulnerability to COVID-19 plus socio-demographic characteristics and stress coping styles. Perceived vulnerability and its interactions with nursing did not show a significant association with either depression or anxiety. CONCLUSION: This study highlights the need for greater support and preventive strategies for mental health problems for college students during the COVID-19 pandemic regardless of perceived vulnerability.

Adolescent Carers' Psychological Symptoms and Mental Well-being During the COVID-19 Pandemic: Longitudinal Study Using Data From the UK Millennium Cohort Study.

PURPOSE: During the COVID-19 pandemic, adolescent carers in the UK may have experienced psychological distress owing to increased caring burden and loss of a break from their caring role. This study investigated longitudinal association between adolescents' caring status and mental health outcomes from 2018/2019 to February-March 2021. METHODS: The participants (n = 3,927) answered mental health questions in both the Millennium Cohort Study sweep 7 survey (age 17 years in 2018/2019) and at least one of three waves of the COVID-19 survey from May 2020 to February-March 2021. Caring status at the age of 17 years was assessed using a single question regarding whether the participant regularly looked after anyone who needed care, without being paid. Outcome measures were psychological symptoms, measured using the Kessler Distress Scale, and mental well-being, measured using the Warwick-Edinburgh Mental Well-being Scale. RESULTS: Compared with 3,616 noncarers, 311 (7.9%) adolescent carers reported significantly higher Kessler Distress Scale and lower Warwick-Edinburgh Mental Well-being Scale scores during the pandemic. These associations were largely explained by psychosocial risk factors. Worse outcomes were associated with poor sleep quality, attempted suicide at baseline, low social support, and a strong feeling of loneliness during the pandemic. These factors were significantly more likely to be observed among adolescent carers than noncarers. DISCUSSION: UK adolescent carers exhibited worsened mental health outcomes one year after the first national lockdown. This increased distress may be attributable to psychosocial risk factors during the pre-COVID-19 and current COVID-19 periods, and they require psychosocial support.

Deficient Autophagy in Microglia Aggravates Repeated Social Defeat Stress-Induced Social Avoidance.

Major depressive disorder (MDD) is associated with repeated exposure to environmental stress. Autophagy is activated under various stress conditions that are associated with several diseases in the brain. This study was aimed at elucidating the autophagy signaling changes in the prefrontal cortex (PFC) under repeated social defeat (RSD) to investigate the involvement of microglial autophagy in RSD-induced behavioral changes. We found that RSD stress, an animal model of MDD, significantly induced initial autophagic signals followed by increased transcription of autophagy-related genes (Atg6, Atg7, and Atg12) in the PFC. Similarly, significantly increased transcripts of ATGs (Atg6, Atg7, Atg12, and Atg5) were confirmed in the postmortem PFC of patients with MDD. The protein levels of the prefrontal cortical LC3B were significantly increased, whereas p62 was significantly decreased in the resilient but not in susceptible mice and patients with MDD. This indicates that enhanced autophagic flux may alleviate stress-induced depression. Furthermore, we identified that FKBP5, an early-stage autophagy regulator, was significantly increased in the PFC of resilient mice at the transcript and protein levels. In addition, the resilient mice exhibited enhanced autophagic flux in the prefrontal cortical microglia, and the autophagic deficiency in microglia aggravated RSD-induced social avoidance, indicating that microglial autophagy involves stress-induced behavioral changes.

Differential diagnosis of lipoma and atypical lipomatous tumor/well-differentiated liposarcoma by cytological analysis.

BACKGROUND: Adipocytic tumors are the most common soft tissue tumors, with lipomas and atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDL), which comprise most cases. Preoperative differential diagnosis of lipoma or ALT/WDL can provide important information for decisions regarding treatment. We evaluated the cytological findings of 20 cases of lipoma and ALT/WDL. METHODS: Fluorescence in situ hybridization (FISH) was performed on formalin-fixed paraffin-embedded specimens (FFPE) to examine mouse double minute 2 homolog (MDM2) amplification in all cases. Tissue samples were collected from the center of the surgical materials, stained with Pap, and evaluated for 12 cytological parameters by six cytotechnologists. RESULTS: The findings regarding large atypical cells, multinucleated cells, and nuclear pleomorphism were highly concordant among the cytotechnologists and were associated with MDM2 amplification. Large atypical cells, considered a highly specific feature of ALT/WDL, were not observed in lipoma cases. However, the sensitivity of the large atypical cell findings was not high (67%); therefore, comprehensive evaluation of multinucleated cells and pleomorphism is crucial for predicting ALT/WDL diagnosis. FISH of MDM2 on Pap-stained specimens was performed in four cases. In two, the results were similar to those of MDM2 FISH performed on FFPE sections and were reproducible, whereas in the other two, the signal could not be evaluated because of the strong background coloration. CONCLUSIONS: Cytology specimens may be useful for the preoperative diagnosis of adipocytic tumors, particularly if the FISH conditions for Pap-stained specimens and the detection accuracy of MDM2 amplification can be improved.

A single nucleotide polymorphism (-250 A/C) of the GFAP gene is associated with brain structures and cerebral blood flow.

AIM: Glial fibrillary acidic protein (GFAP), the intermediate filament protein expressed in astrocytes, plays a key role in many aspects of brain function through communication with neurons or blood vessels. A common single nucleotide polymorphism (SNP), GFAP -250 C/A (rs2070935), is associated with the transcriptional regulation of GFAP, which can potentially result in the genotype-specific brain structure. This study aimed to verify the biological effects of the GFAP variants on brain structure and function. METHODS: We investigated the associations between the GFAP variants and magnetic resonance imaging findings, including gray and white matter volumes, white matter integrity, and resting arterial blood flow, from 1212 healthy Japanese subjects. RESULTS: The GFAP -250 C/A genotype was significantly associated with total gray matter volume, total white matter volume, average mean diffusivity, and mean cerebral blood flow. In voxel-by-voxel analyses, the GFAP genotype showed significant associations with the regional gray and white matter volumes in the inferior frontal lobe and corpus callosum, the regional mean diffusivity in the left posterior region, and the regional cerebral blood flow throughout the brain. CONCLUSION: This study revealed a common SNP that is significantly associated with multiple global brain structure parameters.

Cooperation in bottlenose dolphins: bidirectional coordination in a rope-pulling task.

In comparison with terrestrial animals, such as primates, there is limited empirical evidence for cooperative behavior in marine mammals under experimental conditions. In this study, we used a cooperative rope-pulling task to investigate how bottlenose dolphins (Tursiops truncatus) coordinate their behavior with a partner. Dolphins successfully learned and were able to perform the task, even when one subject started after the other. In the no-delay condition (i.e., both subjects sent at the same time), one pair of dolphins showed coordinated behaviors. When pairs were successful in solving the task in the delay condition (i.e., one individual sent later than the other), the initiators (i.e., first individual sent) were likely to wait for the follower to arrive, and the follower was likely to swim faster when the initiator did not wait and started pulling the rope alone. These coordinated behaviors might help resolve the given cooperative task. Our results suggest that bottlenose dolphins learn to coordinate their behaviors via trial and error and recognize the necessity of performing simultaneous actions with a partner to successfully accomplish cooperative tasks. In addition, both partners showed behavioral changes over many trials of no-delay and delay conditions, suggesting that bidirectional coordination occurred in the cooperative task.