Anxiety, Depression, Perceived Stress, and Burnout Among Chinese Researchers: A Cross-Sectional Nationwide Study.

Purpose: Depression and anxiety have a significant impact on an individuals' work and personal life alike. The mental health of researchers is a significant concern worldwide. This study investigated the mental health status of Chinese researchers specifically and explored the moderating effects of perceived stress on the influence of low self-accomplishment on anxiety and depression. Methods: The online survey platform "Survey Star" was used to create a questionnaire to be distributed to researchers, with 949 questionnaires retrieved. The general information questionnaire, 10-item Perceived Stress Scale (PSS-10), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and Maslach Burnout Inventory General Survey (MBI-GS) were used for this investigation. Pearson's correlation analysis was performed to investigate correlations among the relevant variables. Model 8 of PROCESS 3.3 program was used to analyze the moderating effects of perceived stress. Results: Among the 949 participants, 570 (60.1%) reported symptoms of depression and 431 (45.4%) had symptoms of anxiety, with about one in six reporting symptoms of self-harm or suicidal ideation. Perceived stress was found to moderate the effect of low self-accomplishment on depression and anxiety. Conclusion: Here we show that researchers exhibit a high rate of depression and anxiety symptoms. Perceived stress is also shown to play a moderating role on the influence of low self-accomplishment on anxiety and depression. Thus, reducing perceived stress levels can help to improve the mental health of researchers.

Measuring Sleep Stages and Screening for Obstructive Sleep Apnea with a Wearable Multi-Sensor System in Comparison to Polysomnography.

Objective: To assess the performance of a wearable multi-sensor system (SensEcho) in comparison to polysomnography (PSG) in measuring sleep stages and searching for obstructive sleep apnea (OSA). Methods: Participants underwent overnight simultaneous monitoring using SensEcho and PSG in a sleep laboratory. SensEcho analyzed the recordings spontaneously, and PSG was assessed as per standard guidelines. The degree of snoring was evaluated according to the guidelines for the diagnosis and treatment of OSA hypopnea syndrome (2011 revision). The Epworth Sleepiness Scale (ESS) was used to assess general daytime sleepiness. Results: This study included 103 Han Chinese, 91 of whom (age 39.02 ± 13.84 years, body mass index 27.28 ± 5.12 kg/m2, 61.54% male) completed the assessments. The measures of total sleep time (P = 0.198); total wake time (P = 0.182); shallow sleep (P = 0.297), deep sleep (P = 0.422), rapid eye movement sleep (P = 0.570), and awake (P = 0.336) proportions were similar between SensEcho and PSG. Using an apnea-hypopnea index (AHI) cutoff of ≥ 5 events/h, the SensEcho had 82.69% sensitivity and 89.74% specificity. Almost the same results were obtained at an AHI threshold of ≥ 15 events/h. Although the specificity increased to 94.67%, it decreased to 43.75% at an AHI cutoff of ≥ 30 events/h. Conclusion: This study demonstrated that SensEcho can be used to evaluate sleep status and screen for OSA. Nevertheless, improving the accuracy of its assessment of severe OSA and further testing its effectiveness in community and home environments is necessary.

Correlation Between Aggressive Behavior and Impulsive and Aggressive Personality Traits in Stable Patients with Schizophrenia.

Purpose: To explore the correlation between aggressive behavior and impulsive and aggressive personality traits in inpatients with schizophrenia. Methods: In total, 367 inpatients with schizophrenia were divided into two groups: the aggressive group and the non-aggressive group. We assessed inpatients' psychotic symptoms as well as their aggressive and impulsive personality traits using the Positive and Negative Symptom Scale, the Barratt Impulsiveness Scale, and the Buss-Perry Aggression Questionnaire. Results: Compared with the scores of inpatients in the non-aggressive group, the total Buss-Perry Aggression Questionnaire, subscale, and Barratt Impulsiveness Scale behavioral factor scores in those in the aggressive group were higher (p < 0.05). The results of logistic regression analysis suggested that a high Positive and Negative Symptom Scale positive factor score (odds ratio = 1.07) and a high Buss-Perry Aggression Questionnaire physical aggression score (odds ratio = 1.02) were risk factors for aggressive behavior. Conclusion: Hospitalized patients with schizophrenia with more severe positive symptoms and aggressive traits may be more prone to aggressive behavior.

Reliability and validity of the Chinese version of the Nightmare disorder index in adolescents.

The Nightmare Disorder Index Questionnaire (NDI) was developed to measure the impact of nightmares. The purpose of this study was to investigate the psychometric properties of NDI among Chinese adolescents. This study investigated the validity and internal consistency of the Nightmare Disorder Index Chinese (NDI-CV) among 6014 Chinese adolescents who completed the NDI-CV, Nightmare Distress Questionnaire-Chinese Version (NDQ-CV), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Chinese Adolescent Daytime Sleepiness Scale (CADSS), Generalized Anxiety Disorder-7 Questionnaire (GAD-7), and Patient Health Questionnaire-9 (PHQ-9). In addition, we investigated the test-retest reliability of the NDI-CV among 423 adolescents who completed a retest of the NDI-CV after a 2-week interval. Finally, NDI-CV demonstrated good psychometric properties in a sample of Chinese adolescents (Cronbach's α coefficient of 0.876), and the 95% confidence interval for the 2-week retest correlation coefficient was 0.675-0.977 (p < 0.001).

Chain mediating effect of insomnia, depression, and anxiety on the relationship between nightmares and cognitive deficits in adolescents.

BACKGROUND: The study explored the differences in nightmare, insomnia, depression, anxiety, and cognitive deficits among adolescents and the chain mediating effects of insomnia, depression, and anxiety on the relationship between nightmares and cognitive deficits in adolescents. METHODS: An online survey was used to collect demographic data of 6014 adolescents and assess nightmare, insomnia, depression, anxiety, and cognitive deficits using the Chinese Version of Nightmare Distress Questionnaire, Insomnia Severity Index, Patient Health Questionnaire 9, Generalized Anxiety Disorder 7, and Perceived Deficits Questionnaire-Depression. Spearman correlation analysis and the SPSS function "PROCESS macro" were used for correlation and mediation analyses, respectively. RESULTS: Female adolescents, senior high school, and poor academic performance had higher nightmare, insomnia, and cognitive deficit scores; those living in the city had higher depression and anxiety scores. Cognitive deficits were positively correlated with nightmares, insomnia, depression, and anxiety. Further, insomnia, depression, and anxiety had a chain mediating effect between nightmares and cognitive deficits in adolescents. Nightmares indirectly affect cognition deficits by affecting insomnia and then depression and anxiety symptoms. LIMITATIONS: As this was a cross-sectional study, the causal relationship between the variables could not be determined. Moreover, reporting bias and volunteer bias might be present. CONCLUSIONS: These findings suggest that clinicians should identify adolescents with frequent nightmares early and provide timely treatment to minimize negative outcomes and possibly limit the chronicity of nightmare disorder. It is significant to maintain the physical and mental health development of adolescents to reduce the risk of insomnia, depression, anxiety, and cognitive deficits.

Nightmare Distress as a Risk Factor for Suicide Among Adolescents with Major Depressive Disorder.

Purpose: Nightmare is common and is also independently implicated in suicide risk among the adolescent population. Adolescents with major depressive disorder (MDD) are at an increased risk of suicide. Therefore, comorbid nightmares may amplify suicide risk among this clinical population. This study aimed to explore the effects of nightmares on suicide risk among adolescents with MDD. Patients and Methods: Subjects were 499 outpatients aged 12-18 in four large psychiatric hospitals clinic of China, from January 1 to October 31, 2021. Simultaneously, we matched 499 healthy controls according to gender and age. All participants underwent affective state (depressive and anxiety symptoms) and sleep variable (nightmare frequency/distress, insomnia symptoms, and daytime sleepiness) evaluation as well as MDD diagnoses and determination of suicide risk by a fully structured diagnostic clinical interview. Results: Adolescents with MDD reported a higher incidence of frequent nightmares (at least one night per week) and level of nightmare distress than healthy controls (22.0% vs 6.1%; 28.85 ± 11.92 vs 17.30 ± 5.61). Over half of the patients with suicide risk (51.6%) experienced frequent nightmares compared with approximately one-third of those at a risk for suicide (30.7%). Patients with suicide risk scored scientifically higher on sleep variables, depressive and anxiety symptoms than those without the risk. Further logistic regression analysis indicated that female gender, junior grade, recurrent depressive episode, severe nightmare distress and severe depressive symptoms were independently and significantly associated with suicide risk. Conclusion: Our study provided evidence that adolescents with MDD experienced a higher prevalence of frequent nightmares and suffered more nightmare distress. Nightmare distress is an independent risk factor for suicide risk.

Relationship Between Affective Temperaments and Suicide Risk in Patients With First-Onset Major Depressive Disorder.

Background: People may endorse suicidal behavior during a major depressive episode. Affective temperaments may play a role in this risk. We explored the relationship between affective temperaments and suicide and identified some traits that can predict suicide risk in depression. Materials and Methods: We analyzed the results of the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Auto-questionnaire (TEMPS-A) in 284 participants recruited from a psychiatric clinic and the community in Beijing and compared the subscale scores (temperaments of cyclothymic, dysthymic, anxious, irritable, and hyperthymic) among major depressive disorders (MDDs) vs. the general population as well as depressive patients with vs. without suicide risk, using Student's test, chi-square test, rank-sum test, and multivariable regression modeling. Results: The incidence of suicidal risk in depressive subjects was 47.62% (80/168). Being unmarried (p < 0.001), unemployed (p = 0.007), and temperaments of dysthymic, cyclothymic, anxious, and irritable scores (all p < 0.001) were significantly more prevalent in patients with depression than in the general population. Young age (p < 0.001), female sex (p = 0.037), unmarried (p = 0.001), more severe depression (p < 0.001), and dysthymic, anxious, and cyclothymic temperament (all p < 0.05) were significantly more prevalent in patients with depressive disorder than those without suicide risk. The logistic regression analysis showed that younger age (odds ratio [OR] = 0.937, 95% CI 0.905∼0.970), female sex (OR = 2.606, 95% CI 1.142∼5.948), more severe depression (OR = 1.145, 95% CI 1.063∼1.234), cyclothymic temperament (OR = 1.275, 95% CI 1.102∼1.475), and dysthymic temperament (OR = 1.265, 95% CI 1.037∼1.542) were all independently associated with high suicidal risk in patients with first-onset major depression (p < 0.05). Conclusion: Temperament traits differ between the general population and people suffering from MDD. Subjects with MDD who have much more severe depressive symptoms and a cyclothymic or dysthymic temperament were at a high risk of suicide.

Associations between experienced aggression, poor sleep, and suicide risk among Chinese adolescents.

STUDY OBJECTIVES: The physical and mental health of adolescents is an important study area. This study aims to examine the occurrence of aggression, sleep disturbances, and suicide risk among Chinese adolescents, along with the relationships between these factors. METHODS: This is a cross-sectional study conducted through an online survey. Of the original 7011 Chinese adolescent respondents, the analysis included data from 6122 adolescents, aged between 12 and 18 years, from 23 regions, whose average age was 16.12 (±1.44) years, with 48.8% being male. While the chi-square test and t-test were used for analyzing demographic data and continuous variables, respectively, mediation analysis was used to explore the mechanism of experiencing aggression on suicide risk. The respondents' sleep quality, nightmare distress, daytime sleepiness, fatigue, and suicide risk were assessed using the Pittsburgh Sleep Quality Index (PSQI), Nightmare Distress Questionnaire-Chinese version (NDQ-CV), Chinese Adolescent Daytime Sleepiness Scale (CADSS), Multidimensional Fatigue Inventory (MFI-20), and the suicide risk module of the Mini-International Neuropsychiatric Interview (MINI), respectively. Four items were used to assess adolescents' experiences with aggression. RESULTS: Of the respondents, 42% reported experiencing aggression by others, especially parental physical maltreatment. Furthermore, 26.9% of adolescents in school, and in particular, 31.8% in senior high school experienced insomnia symptoms. Adolescents who reported experiences of aggression had more severe insomnia symptoms, nightmare distress, fatigue, and a higher risk of suicide when compared with those who did not (all ps < 0.001). Insomnia symptoms, nightmare distress, and fatigue all mediated the relationship between aggression and suicide risk, and there was a chain of mediating effects between these factors [for total indirect effect ß = 1.1512, 95% CI (0.9671 to 1.3426), direct effect ß = 0.4934, 95% CI (0.1978 to 0.7891), and total effect ß = 1.6446, 95% CI (1.3479 to 1.9414)]. CONCLUSIONS: Our findings indicate that among adolescents, experiencing aggression is associated with an increased suicide risk. In addition to the direct effect of aggression on suicide risk, insomnia, nightmare distress, and fatigue mediate the relationship between aggression and suicide risk. More attention should be paid to adolescents experiencing aggression, and interventions should be implemented and strengthened.

Depression, Anxiety, and Suicidal Ideation in Chinese University Students During the COVID-19 Pandemic.

Coronavirus disease-2019 (COVID-19) pandemic has seriously threatened the global public health security and caused a series of mental health problem. Current research focuses mainly on mental health status and related factors in the COVID-19 pandemic among Chinese university students. Data from 11133 participants was obtained through an online survey. The Patient Health Question-9 (PHQ-9) was used to assess depressive symptoms, the Social Support Rate Scale (SSRS) was used to assess social support. We also used 7-item Generalized Anxiety Disorder Scale (GAD-7) to assess anxiety symptoms. Totally, 37.0% of the subjects were experiencing depressive symptoms, 24.9% anxiety symptoms, 20.9% comorbid depressive and anxiety symptoms, and 7.3% suicidal ideation. Multivariable logistic regression analysis revealed an increased presence of mental health problems in female students, graduate students, and those with personal COVID-19 exposure. Awareness of COVID-19, living with family were protective factors that reduced anxiety and depression symptoms. In addition, male, personal COVID-19 exposure, depressive and anxiety symptoms were risk factors for suicidal ideation. Social support, COVID-19 preventive and control measures, prediction of COVID-19 trends, living with family and graduate students are protective factors for reducing suicidal ideation.

The Effect of Social Support on Mental Health in Chinese Adolescents During the Outbreak of COVID-19.

PURPOSE: The coronavirus disease 2019 (COVID-19) outbreak impacts physical and mental health. The purpose of this study was to explore the association between the levels of social support and mental health among Chinese adolescents during the outbreak. METHODS: A total of 7,202 adolescents aged 14-18 years completed online survceys from March 8 to 15, 2020, in China. Researchers assessed the associations between depression symptoms (Patient Health Questionnaire-9), anxiety symptoms (Chinese version of the 7-item Generalized Anxiety Disorder scale), and social support (Social Support Rate Scale). RESULTS: COVID-19 exposure was associated with a higher prevalence of depression symptoms (odds ratio [OR] = 1.38, 95% confidence interval [CI]: 1.14-1.66) and anxiety symptoms (OR = 1.26, 95% CI: 1.04-1.52). Only 24.6% of adolescents reported high levels of social support. Most adolescents (70%) reported medium levels of support, and 5.4% reported low support. Low support was associated with higher prevalence of depression (OR = 4.24, 95% CI: 3.38-5.33) and anxiety symptoms (OR = 3.18, 95% CI: 2.54-3.98), while controlling for gender, grade, living situation, and COVID-19 exposure; similarly, medium support was associated with higher prevalence of depression (OR = 2.79, 95% CI: 2.48-3.15) and anxiety (OR = 2.19, 95% CI: 1.94-2.48) symptoms. CONCLUSIONS: This study indicates there is a higher prevalence of mental health problems among adolescents with medium and low levels of social support in China during the outbreak of COVID-19.

Sleep problems among Chinese adolescents and young adults during the coronavirus-2019 pandemic.

OBJECTIVE: To assess the prevalence and sociodemographic correlates of insomnia symptoms among Chinese adolescents and young adults affected by the outbreak of coronavirus disease-2019 (COVID-19). METHODS: This cross-sectional study included Chinese adolescents and young adults 12-29 years of age during part of the COVID-19 epidemic period. An online survey was used to collect demographic data, and to assess recognition of COVID-19, insomnia, depression, and anxiety symptoms using the Pittsburgh Sleep Quality Index (PSQI), the Patient Health Questionnaire (PHQ-9), and the Generalized Anxiety Disorder (GAD-7) questionnaires, respectively. The Social Support Rate Scale was used to assess social support. RESULTS: Among 11,835 adolescents and young adults included in the study, the prevalence of insomnia symptoms during part of the COVID-19 epidemic period was 23.2%. Binomial logistic regression analysis revealed that female sex and residing in the city were greater risk factors for insomnia symptoms. Depression or anxiety were risk factors for insomnia symptoms; however, social support, both subjective and objective, was protective factors against insomnia symptoms. Furthermore, anxiety and depression symptoms were mediators of social support and insomnia symptoms. CONCLUSIONS: Results of this study revealed a high prevalence of sleep problems among adolescents and young adults during the COVID-19 epidemic, especially senior high school and college students, which were negatively associated with students' projections of trends in COVID-19. The adverse impact of COVID-19 was a risk factor for insomnia symptoms; as such, the government must devote more attention to sleep disorders in this patient population while combating COVID-19.

Prevalence and socio-demographic correlates of psychological health problems in Chinese adolescents during the outbreak of COVID-19.

Psychological health problems, especially emotional disorders, are common among adolescents. The epidemiology of emotional disorders is greatly influenced by stressful events. This study sought to assess the prevalence rate and socio-demographic correlates of depressive and anxiety symptoms among Chinese adolescents affected by the outbreak of COVID-19. We conducted a cross-sectional study among Chinese students aged 12-18 years during the COVID-19 epidemic period. An online survey was used to conduct rapid assessment. A total of 8079 participants were involved in the study. An online survey was used to collect demographic data, assess students' awareness of COVID-19, and assess depressive and anxiety symptoms with the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) questionnaire, respectively. The prevalence of depressive symptoms, anxiety symptoms, and a combination of depressive and anxiety symptoms was 43.7%, 37.4%, and 31.3%, respectively, among Chinese high school students during the COVID-19 outbreak. Multivariable logistic regression analysis revealed that female gender was the higher risk factor for depressive and anxiety symptoms. In terms of grades, senior high school was a risk factor for depressive and anxiety symptoms; the higher the grade, the greater the prevalence of depressive and anxiety symptoms. Our findings show there is a high prevalence of psychological health problems among adolescents, which are negatively associated with the level of awareness of COVID-19. These findings suggest that the government needs to pay more attention to psychological health among adolescents while combating COVID-19.

Patients With Drug-Naive Bipolar Disorder in Remission After 8 Weeks of Treatment Had Decreased Serum Uric Acid Concentrations.

Background: Evidence indicates that the serum concentration of uric acid (UA) in patients may relate both to the pathophysiology and therapeutics of bipolar disorder (BPD). The purpose of this study was to examine the changes and clinical significance of serum UA concentrations in first-episode manic patients suffering from BPD. Methods: Seventy-six drug-naive patients with first-episode bipolar mania and 76 age- and gender-matched healthy subjects were recruited. Young Mania Rating Scale and Hamilton Depression Rating Scale were used to assess clinical symptoms. We tested serum UA concentrations by sandwich enzyme-linked immunosorbent assay at baseline and at the end of 8-week treatment in BPD patients and in the control group. Results: After 8-week quetiapine and sodium valproate treatment, this study revealed that the serum UA concentrations in remitted patients were significantly lower than nonremitted patients; however, those remitted patients still had higher serum UA than healthy controls. We discovered that the baseline UA concentration was higher in nonremitted than remitted patients after 8 weeks of treatment. Finally, a positive association was found between serum UA and symptom relief in the first episode of manic disorder patients. Conclusion: Patients with first-episode BPD had high levels of serum UA, which responds to treatment mainly in remitted patients. Our results suggest that serum UA concentrations might present potentially a trait marker in bipolar patients.

Prevalence and clinical-demographic correlates of hyperhomocysteinemia in inpatients with bipolar disorder in a Han Chinese population.

Recent studies have reported that hyperhomocystinemia (HHcy) is highly prevalent in patients with bipolar disorder (BD), placing them at greater risk of cardiovascular disease and possibly serving as a disease biomarker. However, the correlation of HHcy with demographic or clinical parameters is not well known. In this study, we examined the prevalence of HHcy and its association with these parameters in a sample of Chinese BD patients. Fasting plasma homocysteine (Hcy) levels were determined in 198 BD inpatients and 84 healthy controls. HHcy was defined when Hcy concentration exceeded 15.0µmol/L. Affective symptomatology was assessed by the Young Mania Rating Scale, Hamilton Depression Rating Scale and the Clinical Global Impressions severity scale. Compared to healthy controls, BD patients had a significantly higher prevalence (34.85% vs. 19.05%) of HHcy and a higher absolute level of homocysteine. Logistic regression analysis demonstrated that BD patients with HHcy were more likely to be male, have elevated BMI, more frequent treatment on lithium but less on valproate. These results suggest that Chinese inpatients with bipolar disorder have a higher rate of HHcy than the general population, and those at greatest risk are male, have an elevated BMI, and take more lithium but less valproate therapy.

Psychopathology and personality traits associated with driving while intoxicated in Beijing, China: Implications for interventions.

BACKGROUND AND OBJECTIVES: Driving while intoxicated (DWI) represents an area of grave concern in China, yet little research has focused on it or on the personality traits and psychiatric disorders among these drivers. METHODS: We enrolled 325 of 382 residents charged with DWI in a compulsory detention center in Beijing, China. And 351 male drivers who had never had any alcohol arrests as control participants. All were screened for Axis I disorders using the Chinese version of the Structured Clinical Interview for the Diagnostic Statistical Manual of Mental Disorders IV-TR (SCID), the Minnesota Multiphasic Personality Inventory (MMPI-2), and the Sixteen Personality Factor Questionnaire (16PF). RESULTS: The subjects were all males with a mean (±SD) age of 34.41 ± 8.48 years, and almost 30% met DSM-IV criteria for alcohol abuse or dependence (n = 92). Compared to normal controls they showed greater Social Boldness, Abstractedness, Apprehension, Liveliness and Tension, and poorer Reasoning, Vigilance, Openness to Change, and Self-reliance. On the MMPI-2, DWI subjects showed greater Hypochondriasis, Psychopathic Deviate, Paranoia, Psychasthenia, Schizophrenia and Hypomania; and lower Social introversion. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Severe alcohol problems are more common in Beijing's drunk drivers than in the Chinese general population. These DWI drivers also have a broad variety of traits that increase their tendency to be venturesome and socially bold while enjoying excitement and risk-taking. (Am J Addict 2017;26:374-378).

The new pattern of drug abuse in China.

PURPOSE OF REVIEW: Drug abuse has resulted in a huge burden on public health and the economy in China. Since the reemergence of drug abuse in China in the 1980s, the number of drug addicts has increased dramatically, especially the proportion of users of synthetic drugs, such as amphetamine-type stimulant (ATS). Further, the proportion of opiate addicts has decreased among the new initiates. This review describes the new pattern of drug abuse and the resultant intervention strategy in China. RECENT FINDINGS: The demographics regarding drug abuse in China point to a trend of younger users, and indicate that Internet and telephone are facilitating drug trafficking. Furthermore, polydrug use is common. Many heroin addicts have used ATS and other synthetic drugs, and some synthetic drug abusers have used opiate drugs too. HIV infection and psychosis comorbidity are primarily associated with drug abuse in China. SUMMARY: Although opiate drug use and its associated harm have been controlled effectively in some areas, the synthetic drugs and new designer drugs have complicated the drug abuse scene. A national system of management and intervention for synthetic drugs and associated diseases urgently needs to be established in China.

Hippocampal CLOCK protein participates in the persistence of depressive-like behavior induced by chronic unpredictable stress.

RATIONALE: Circadian disturbances are strongly linked with major depression. The circadian proteins CLOCK and BMAL1 are abundantly expressed but function differently in the suprachiasmatic nucleus (SCN) and hippocampus. However, their roles in depressive-like behavior are still poorly understood. OBJECTIVES: To investigate the alterations of CLOCK and BMAL1 in the SCN and hippocampus in rats subjected to chronic unpredictable stress (CUS) and to explore the relationship of circadian protein and the depressive-like behavior. RESULTS: Together with depressive-like behavior induced by CUS, CLOCK and BMAL1 in the SC were inhibited during the light period, and the peak expression of CLOCK in the hippocampus was shifted from the dark to light period. BMAL1 expression in the hippocampus was not significantly changed. Two weeks after the termination of CUS, abnormalities of CLOCK in the CA1 and CA3 endured, with unchanged depressive-like behavior, but the expression of CLOCK and BMAL1 in the SCN recovered to control levels. Knockdown of the Clock gene in CA1 induced depressive-like behavior in normal rats. CLOCK in the SCN and hippocampus may participate in the development of depressive-like behavior. However, CLOCK in the hippocampus but not SCN was involved in the long-lasting effects of CUS on depressive-like behavior. BMAL1 in the hippocampus appeared to be unrelated to the effects of CUS on depressive-like behavior. CONCLUSION: CLOCK protein in the hippocampus but not SCN play an important role in the long-lasting depressive-like behavior induced by CUS. These findings suggest a novel therapeutic target in the development of new antidepressants focusing on the regulation of circadian rhythm.

NMDA receptor glycine modulatory site in the ventral tegmental area regulates the acquisition, retrieval, and reconsolidation of cocaine reward memory.

RATIONALE AND OBJECTIVES: Accumulating clinical and preclinical studies have shown that the memories of the rewarding effects of drugs and their paired cues may contribute to relapse and persistent cocaine use. Glutaminergic actions in the ventral tegmental area (VTA) have been shown to regulate the rewarding effect of drugs and conditioned responses to drug-associated cues, but the role of the VTA in the acquisition, retrieval, and reconsolidation of cocaine cues is not yet known. METHODS: In the present study, we used 7-chlorothiokynurenic acid (7-CTKA), an N-methyl-D-aspartate (NMDA) receptor glycine modulatory site antagonist with no rewarding effects, to examine the role of the NMDA receptor glycine modulatory site in the acquisition, retrieval, and reconsolidation of cocaine-related reward memory using the conditioned place preference (CPP) paradigm. RESULTS: Separate groups of Sprague-Dawley rats were trained to acquire cocaine-induced CPP. Vehicle or 7-CTKA was microinjected into the VTA or substantia nigra (SN) (5 µg/µl) at different time points: 10 min before each CPP training session (acquisition), 10 min before the reactivation of CPP (retrieval), and immediately after the reactivation of CPP (reconsolidation). Cocaine-induced CPP was retested 24 h and 1 and 2 weeks after 7-CTKA administration. 7-CTKA microinjected into the VTA, but not SN, significantly impaired the acquisition, retrieval, and reconsolidation of cocaine-induced CPP without affecting cocaine-induced locomotion. CONCLUSIONS: Our findings suggest that the NMDA receptor glycine modulatory site in the VTA plays a major role in cocaine reward memory, and NMDA receptor glycine site antagonists may be potential pharmacotherapies for the management of relapse.

Chronic unpredictable stress induces a reversible change of PER2 rhythm in the suprachiasmatic nucleus.

Many clinical studies have shown that circadian rhythm abnormalities are strongly associated with major depression. The master clock of the circadian system in mammals is located in the suprachiasmatic nucleus (SCN) within the anterior hypothalamus, where Per1 and Per2 are essential core components of circadian rhythm oscillation. Chronic unpredictable stress (CUS) is a reliable animal model of depression with good face, predictive, and constructive validity. In the present study, we investigated the effects of CUS on the circadian expression of PER1 and PER2 in the SCN. We found that CUS led to depressive-like behavior and reduced the amplitude of PER2 oscillation in the SCN, which were blocked by 3 weeks of desipramine (DMI) treatment. 2 weeks after termination of CUS, the decreased peak of PER2 expression returned to control levels, whereas depressive-like behavior remained unchanged. Our findings suggest that the dampened amplitude of PER2 expression in the SCN may participate in the development of depressive-like behavior induced by CUS but is unlikely involved in the long-lasting effects of CUS on depressive-like behavior.

Effects of cannabinoid CB1 receptor antagonist rimonabant on acquisition and reinstatement of psychostimulant reward memory in mice.

Drug addiction processes are considered to be mainly controlled by the mesocorticolimbic dopamine system. Cannabinoids, a class of psychoactive drugs of abuse, elicit their rewarding and pharmacological effects through the endocannabinoid system. Previous research has indicated that dopaminergic neurons in the mesocorticolimbic system are also under the control of the endocannabinoid system. Recently, evidence has suggested that the endocannabinoid system may also participate in the modulation of the common reward system. The present study examined whether rimonabant, a cannabinoid CB1 receptor antagonist, disrupts the acquisition and reinstatement of psychostimulant reward memory measured by conditioned place preference (CPP). Mice were trained to acquire methamphetamine or cocaine-induced CPP. A priming injection of methamphetamine (0.5 mg/kg, i.p.) or cocaine (5 mg/kg, i.p.) was respectively given to reinstate methamphetamine or cocaine-induced CPP after extinction. Vehicle or rimonabant (1 or 3 mg/kg, i.p.) was administered at different time-points: 30 min before each CPP training session (acquisition) or 30 min before the priming injection (reinstatement). Rimonabant at doses of 1 and 3 mg/kg significantly inhibited the acquisition of methamphetamine- and cocaine-induced CPP. At the high dose (3 mg/kg), rimonabant disrupted the reinstatement of extinguished methamphetamine- or cocaine-induced CPP. These findings indicate that cannabinoid CB1 receptors play a major role in psychostimulant reward memory, and rimonabant may be a potential pharmacotherapy for psychostimulant addiction.