Repetitive transcranial magnetic stimulation in combination with citalopram in young patients with first-episode major depressive disorder: a double-blind, randomized, sham-controlled trial.

OBJECTIVES: To evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) started with citalopram in first-episode young major depressive patients. METHODS: In a 2-week double-blind study with a 2-week extended antidepressant phase, 60 first-episode young major depressive patients were randomly assigned to citalopram in combination with 2 weeks of either active or sham rTMS treatment. During the following 2 weeks, the patients continued only the citalopram treatment. The 17-item Hamilton depression rating scale (HAMD-17) and Montgomery-Asberg depression rating scale (MADRS) were used to assess the severity of depression. Moreover, the Wisconsin Card Sorting Test (WCST), Trail-Making Test (TMT), and Stroop Color-Word Test (SCWT) were used to assess executive function. RESULTS: (1) There was a significantly greater number of early improvers (a reduction of HAMD-17 score ≥ 20% within the first 2 weeks) observed in the active rTMS group compared to the sham group (57% vs. 29%, χ(2)=4.667, p=0.031). (2) There was no significant difference observed in responder rates (46% vs. 36%, χ(2)=0.295, p=0.586) or in remission rates (39% vs. 29%, χ(2)=0.319, p=0.572) between the two groups at 4 weeks. (3) There was a significant difference seen in both HAMD-17 and MADRS scores between the two groups at 2 and 4 weeks. The active rTMS group showed a significantly faster score reduction compared to the sham group at 2 weeks (HAMD-17, t=13.444, p=0.001; MADRS, t=30.123, p=0.000), which was maintained at 4 weeks on both scales (HAMD-17, t=46.915, p=0.000; MADRS, t=39.996, p=0.000). (4) The patients did not deteriorate in executive performance, and even improved in categories on WCST and completed TMT faster in the active group. CONCLUSIONS: RTMS accelerated the rapidity of the antidepressant response in first-episode young depressive patients. Our results call for future rTMS studies with larger sample sizes, high intensity of stimuli, and longer duration to draw more definitive conclusions.

[Repetitive transcranial magnetic stimulation combined with antidepressant medication in treatment of first-episode patients with major depression].

OBJECTIVE: To assess the early therapeutic and cognitive effect of repetitive transcranial magnetic stimulation (rTMS) combined with antidepressant medication in treatment of first-episode patients with major depression. METHODS: Sixty first-episode depressed inpatients aged 18-45 y, who met the DSM-IV clinical criteria for major depressive episode were randomly assigned to citalopram treatment (20 mg/d) in combination with a two-week period of either rTMS (study group)or sham procedure (control group) on left dorsal-lateral prefrontal cortex (10 Hz, 90% motor threshold). The Hamilton Depression Rating Scale (HAMD) was used to assess the severity of depression. The Wisconsin Card Sorting Test (WCST) and Continuous Performance Test (CPT) were used to assess cognitive function of depression. RESULT: The response rate was significantly greater in the study group compared to the control group after treatment (57% compared with 29%,P<0.05). The HAMD scores significantly declined after treatment in two groups, and the study group showed lower scores compared to the control group after 2 weeks (P<0.01). Neuropsychological assessments showed that there was no significant difference between the two groups except for the significant improvement in the categories on WCST in study group compared to the baseline (P<0.05) and the control group (P<0.05)after 2 weeks treatment. No serious event occurred in the patients during the rTMS study. CONCLUSION: 10 Hz rTMS enhances early effects of citalopram and improves cognitive function in first-episode major depressive patients.

Changes of Hypocretin (Orexin) System in Schizophrenia: From Plasma to Brain.

Hypocretin (also called orexin) regulates various functions, such as sleep-wake rhythms, attention, cognition, and energy balance, which show significant changes in schizophrenia (SCZ). We aimed to identify alterations in the hypocretin system in SCZ patients. We measured plasma hypocretin-1 levels in SCZ patients and healthy controls and found significantly decreased plasma hypocretin-1 levels in SCZ patients, which was mainly due to a significant decrease in female SCZ patients compared with female controls. In addition, we measured postmortem hypothalamic hypocretin-1-immunoreactivity (ir), ventricular cerebrospinal fluid (CSF) hypocretin-1 levels, and hypocretin receptor (Hcrt-R) mRNA expression in the superior frontal gyrus (SFG) in SCZ patients and controls We observed a significant decrease in the amount of hypothalamic hypocretin-1 ir in SCZ patients, which was due to decreased amounts in female but not male patients. Moreover, Hcrt-R2 mRNA in the SFG was decreased in female SCZ patients compared with female controls, while male SCZ patients showed a trend of increased Hcrt-R1 mRNA and Hcrt-R2 mRNA expression compared with male controls. We conclude that central hypocretin neurotransmission is decreased in SCZ patients, especially female patients, and this is reflected in the plasma.

Discovery of new genetic loci for male sexual orientation in Han population.

Epidemiological studies have demonstrated that the genetic factors partly influence the development of same-sex sexual behavior, but most genetic studies have focused on people of primarily European ancestry, potentially missing important biological insights. Here, we performed a two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in Han Chinese populations and identified two genetic loci (rs17320865, Xq27.3, FMR1NB, Pmeta = 8.36 × 10-8, OR = 1.29; rs7259428, 19q12, ZNF536, Pmeta = 7.58 × 10-8, OR = 0.75) showing consistent association with male sexual orientation. A fixed-effect meta-analysis including individuals of Han Chinese (n = 4791) and European ancestries (n = 408,995) revealed 3 genome-wide significant loci of same-sex sexual behavior (rs9677294, 2p22.1, SLC8A1, Pmeta = 1.95 × 10-8; rs2414487, 15q21.3, LOC145783, Pmeta = 4.53 × 10-9; rs2106525, 7q31.1, MDFIC, Pmeta = 6.24 × 10-9). These findings may provide new insights into the genetic basis of male sexual orientation from a wider population scope. Furthermore, we defined the average ZNF536-immunoreactivity (ZNF536-ir) concentration in the suprachiasmatic nucleus (SCN) as lower in homosexual individuals than in heterosexual individuals (0.011 ± 0.001 vs 0.021 ± 0.004, P = 0.013) in a postmortem study. In addition, compared with heterosexuals, the percentage of ZNF536 stained area in the SCN was also smaller in the homosexuals (0.075 ± 0.040 vs 0.137 ± 0.103, P = 0.043). More homosexual preference was observed in FMR1NB-knockout mice and we also found significant differences in the expression of serotonin, dopamine, and inflammation pathways that were reported to be related to sexual orientation when comparing CRISPR-mediated FMR1NB knockout mice to matched wild-type target C57 male mice.

Rapid membrane effect of estrogens on stimulation of corticotropin-releasing hormone.

BACKGROUND: Classic nuclear-initiated estrogen signaling stimulates corticotropin-releasing hormone (CRH) gene expression as a transcription factor. However, the possible mechanism by which membrane-initiated estrogen signaling (MIES) influences CRH expression remains unclear. There are indications that MIES may upregulate nitric oxide (NO) production through the phosphatidylinositol 3-hydroxy kinase (PI3K) and potentially through the mitogen-activated protein kinase (MAPK) pathway. OBJECTIVES: We investigated the effect of MIES-mediated kinase pathways on CRH expression with or without NO synthesis. METHOD: In SK-N-SH cell culture, estradiol-bovine serum albumin (E2-BSA) was used as the specific membrane estrogen receptor activator, with a specific NO donor, and/or inhibitors for NO synthase (NOS), PI3K, MAPK, protein kinase A (PKA), and protein kinase C (PKC). RESULTS: E2-BSA significantly increased NO and CRH levels in the medium and NOS1-mRNA levels in the cells. In addition, NO donor up-regulated CRH expression, while NOS-inhibitor down-regulated it. When the inhibitor of MAPK and/or the inhibitor of PI3K was added to the medium, only the latter appeared to significantly block the stimulating effect of E2-BSA on NO synthesis, and this was accompanied by an increased CRH expression in the medium. We further studied the effect of the MIES-PKC-mediated pathway on CRH expression, with or without NOS-inhibitor, while the MIES-PKA(-PI3K) pathway served as a control. We found that MIES-PKC upregulated CRH expression independent of NO synthesis. CONCLUSION: MIES can efficiently upregulate CRH expression via various intracellular kinase pathways and may thus be a crucial component in the stress response.

Interpersonal psychotherapy-based psychological intervention for patient suffering from COVID-19: A case report.

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) was first found in Wuhan, China, and it has rapidly spread worldwide since the end of 2019. There is an urgent need to treat the physical and psychological aspects of COVID-19. Interpersonal psychotherapy (IPT)-based psychological intervention is an evidence-based therapy for depression and post-traumatic stress disorder. CASE SUMMARY: This report describes a case of COVID-19 in a patient who transmitted the disease to his entire family. The patient received four sessions of IPT-based psychological intervention. We used the Hamilton Rating Scale for Depression and Patient Health Questionnaire to measure depression level, and the Hamilton Anxiety Scale and Generalized Anxiety Disorder to measure anxiety among the patients. CONCLUSION: This case shows that IPT-based therapy can reduce COVID-19 patient depression and anxiety and the advantage of IPT-based therapy.

Dialectical behavior therapy-based psychological intervention for woman in late pregnancy and early postpartum suffering from COVID-19: a case report.

At the end of 2019, a new form of pneumonia disease known as the corona virus disease 2019 (COVID-19) rapidly spread throughout most provinces of China, and the total global number of COVID-19 cases has surpassed 500 000 by Mar. 27, 2020 (WHO, 2020). On Jan. 30, 2020, the World Health Organization (WHO) declared COVID-19 a global health emergency (WHO, 2020). COVID-19 causes most damage to the respiratory system, leading to pneumonia or breathing difficulties. The confirmed case fatality risk (cCFR) was estimated to be 5% to 8% (Jung et al., 2020). Besides physical pain, COVID-19 also induces psychological distress, with depression, anxiety, and stress affecting the general population, quarantined population, medical staff, and patients at different levels (Kang et al., 2020; Xiang et al., 2020). Previous research on patients in isolation wards highlighted the risk of depressed mood, fear, loneliness, frustration, excessive worries, and insomnia (Abad et al., 2010).

[A survey of mental health among transferred injured survivors in Wenchuan earthquake in Sichuan].

OBJECTIVE: To assess the depression and anxious status among transferred injured survivors in Wenchuan earthquake in Sichuan province. METHODS: A total of 43 transferred injured survivors were investigated by questionnaire exploring their trauma symptoms and mental health status. RESULTS: High rates of trauma symptoms were remarkably observed in these survivors. Of all the respondents, 60% had some emotional symptoms and sleeping difficulties. About one third of respondents experienced recurrent and intrusive distressing recollection of event, 16 (37.21%) experienced nightmare, 15 (34.88%) had flashback and 7 (16.28%) of them tried to avoid relative stress. CONCLUSION: Many mental symptoms were observed in transferred injured survivors. The two major factors of mental stress were emotional symptoms and re-experience of the disaster.

[Application of the triage assessment system for a rapid assessment of mental health of the referral wounded and their family members in Wenchuan earthquake].

OBJECTIVE: To quickly assess the psychological status of the wounded who were transferred in the earthquake and their family members, as to promoting the system of psychological crisis intervention. METHODS: The triage assessment system was used to the 44 wounded and 37 family members, additionally, the Hamilton Depression Rating Scale (HAMD), and Hamilton Anxiety Rating Scale (HAMA) for related analysis were also administrated to verify the effectiveness of screening of the triage assessment system. RESULTS: Of the 79 wounded and their families in the triage assessment system, the score of emotion in the wounded group was (3.07 +/- 1.38), the score of cognition was (2.34 +/- 1.39), the score of behavior was (2.71 +/- 1.47), and the total score was (8.12 +/- 3.69); the score of emotion in the family group was (2.51 +/- 1.27), the score of cognition was (1.57 +/- 0.85), the score of behavior was (1.71 +/- 1.02), and the total score was (5.80 +/- 2.61). There were significant differences in the family and the wounded group in cognition, behavior and the total (t(cognition) = 2.853, P = 0.006; t(behavior) = 3.366, P = 0.001; t(total) = 3.116, P = 0.003). Both the depression and anxiety symptoms in the Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) were 11.48 +/- 7.62, 9.23 +/- 5.64, and 8.49 +/- 4.87, 9.38 +/- 7.05, respectively. In the emotion, cognition, behavior and total scores of the triage assessment system related to higher with HAMD and HAMA were r(emotion-HAMD) = 0.393, P = 0.001; r(emotion-HAMA) = 0.443, P = 0.000; r(cognition-HAMD) = 0.434, P = 0.000; r(cognition-HAMA) = 0.240, P = 0.037; r(behavior-HAMD) = 0.529, P = 0.000; r(behavior-HAMA) = 0.256, P = 0.026; r(total-HAMD) = 0.517, P = 0.000; r(total-HAMA) = 0.369, P = 0.001. CONCLUSION: The triage assessment system should be the reliable method for an assessment featured by a rapid, accurate and simple one in screening and monitoring.

[Reliability and validity of the self-reporting questionnaire for assessing mental health applied in Wenchuan earthquake].

OBJECTIVE: To detect the reliability and validity of the self-reporting questionnaire (SRQ-20), and to make a rapid assessment on mental health among victims in sudden crisis. METHODS: The SRQ-20 which is on appendix of the Ministry of Health adopted as "emergency psychological crisis intervention guiding principles" was administrated among 1222 victims in Wenchuan earthquake. The reliability of the questionnaire was tested by split-half coefficient and Cronbach's alpha coefficient; the validity was tested by means of principal component factor analysis. RESULTS: The self-reporting questionnaire and split-half coefficient was 0.748, each item of Cronbach's alpha in the reliability coefficient was between in 0.778 to 0.789, overall Cronbach's alpha in the reliability coefficient was 0.792. There were five main components in principal component factor analysis: lacking of power, somatization/biological symptoms, depression thought, emotions and awareness. CONCLUSION: The self-reporting questionnaire (SRQ-20) should have good reliability, and validity, and China's psychological crisis intervention in processing assessment of the mental health should be a fast, accurate and effective screening tool.

[Effect of exogenous androgen on structures of sexually dimorphism nucleus in preoptic area and anteroventral periventricular nucleus before sexual differentiation in female rats].

OBJECTIVE: To investigate the effects of androgen on sexually dimorphism nucleus in preoptic area (SDN-POA) and anteroventral periventricular nucleus (AVPV) before sexual differentiation of the brain in female rats. METHODS: Neonatal female SD rats (n=12) were randomly divided into two groups: androgen group and control group. Twenty-four hours after birth animals were subjected to intraperitoneal injection of 50 microl of testosterone propionate (TP,10.0 g/L) or aseptic oil as control. The rats were sacrificed 60 days after the injection and the brains were collected for crystal violet staining. LEICA Q Win system was applied in detecting the boundaries of SDN-POA and AVPV, then the volumes of SDN-POA and AVPV were calculated. RESULTS: The volumes of SDN-POA in androgen group were significantly larger than those in control group [(16.77+/-2.68) vs (8.99+/-1.42)mm(3)x10(-3), P<0.01], while the volumes of AVPV in androgen group were significantly smaller than those in control group [(9.14+/-1.16) vs (14.62+/-2.80)mm(3)x10(-3), P<0.01]. CONCLUSION: Exogenous androgen rendered before sexual differentiation in female rats results in enlargement of SDN-POA volumes and reduction of AVPV.

Sex hormones affect acute and chronic stress responses in sexually dimorphic patterns: Consequences for depression models.

BACKGROUND: Alterations in peripheral sex hormones may play an important role in sex differences in terms of stress responses and mood disorders. It is not yet known whether and how stress-related brain systems and brain sex steroid levels fluctuate in relation to changes in peripheral sex hormone levels, or whether the different sexes show different patterns. We aimed to investigate systematically, in male and female rats, the effect of decreased circulating sex hormone levels following gonadectomy on acute and chronic stress responses, manifested as changes in plasma and hypothalamic sex steroids and hypothalamic stress-related molecules. METHOD: Experiment (Exp)-1: Rats (14 males, 14 females) were gonadectomized or sham-operated (intact); Exp-2: gonadectomized and intact rats (28 males, 28 females) were exposed to acute foot shock or no stressor; and Exp-3: gonadectomized and intact rats (32 males, 32 females) were exposed to chronic unpredictable mild stress (CUMS) or no stressor. For all rats, plasma and hypothalamic testosterone (T), estradiol (E2), and the expression of stress-related molecules were determined, including corticotropin-releasing hormone, vasopressin, oxytocin, aromatase, and the receptors for estrogens, androgens, glucocorticoids, and mineralocorticoids. RESULTS: Surprisingly, no significant correlation was observed in terms of plasma sex hormones, brain sex steroids, and hypothalamic stress-related molecule mRNAs (p > 0.113) in intact or gonadectomized, male or female, rats. Male and female rats, either intact or gonadectomized and exposed to acute or chronic stress, showed different patterns of stress-related molecule changes. CONCLUSION: Diminished peripheral sex hormone levels lead to different peripheral and central patterns of change in the stress response systems in male and female rats. This has implications for the choice of models for the study of the different types of mood disorders which also show sex differences.

Abnormal parietal encephalomalacia associated with schizophrenia: A case report.

RATIONALE: It is widely believed that structural abnormalities of the brain contribute to the pathophysiology of schizophrenia. The parietal lobe is a central hub of multisensory integration, and abnormities in this region might account for the clinical features of schizophrenia. However, few cases of parietal encephalomalacia associated with schizophrenia have been described. PATIENT CONCERNS AND DIAGNOSES: In this paper, we present a case of a 25-year-old schizophrenia patient with abnormal parietal encephalomalacia. The patient had poor nutrition and frequently had upper respiratory infections during childhood and adolescence. She showed severe schizophrenic symptoms such as visual hallucinations for 2 years. After examining all her possible medical conditions, we found that the patient had a lesion consistent with the diagnosis of encephalomalacia in her right parietal lobe and slight brain atrophy. INTERVENTIONS: The patient was prescribed olanzapine (10 mg per day). OUTCOMES: Her symptoms significantly improved after antipsychotic treatment and were still well controlled 1 year later. LESSONS: This case suggested that parietal encephalomalacia, which might be caused by inflammatory and infectious conditions in early life and be aggravated by undernutrition, might be implicated in the etiology of schizophrenia.

Aromatase changes in depression: A postmortem and animal experimental study.

A hyperactive hypothalamo-pituitary-adrenal (HPA) axis is a prominent feature in depression. It has been shown that androgens inhibit HPA activity and that estrogens stimulate it. We have therefore investigated, in human postmortem hypothalamus, whether depression features an increase in aromatase, which is the rate-limiting enzyme for the conversion of androgens to estrogens. In addition, we have tested the effect of an aromatase inhibitor on depression-like symptoms in a frequently used animal model for depression. At first, aromatase immunoreactivity (ir) was quantified in the central part of the hypothalamic paraventricular nucleus (PVN) of 10 major depressive disorder (MDD) patients and 10 well-matched control subjects. Subsequently an animal experimental study was performed using the chronic unpredictable mild stress (CUMS) rats as depression model. The effect of administration of 1,4,6-androstatriene-3,17-dione (ATD), an aromatase inhibitor, was investigated by silastic capsule implantation. In the postmortem study, the amount of PVN aromatase-ir decreased significantly in the MDD group compared to the controls (P=0.029). In the animal study, ATD was found to cause significantly increased testosterone (T) levels, both in plasma and in the hypothalamus. However, ATD administration did not show significant effects on the depression-like behaviors or plasma corticosterone levels in CUMS rats. Based on our observations in human postmortem material and the animal experiment, we have to conclude that alterations in aromatase in adulthood do not seem to play a major role in the pathogenesis of the symptoms of depression.

Relationships between dorsolateral prefrontal cortex metabolic change and cognitive impairment in first-episode neuroleptic-naive schizophrenia patients.

The present study aimed to explore the possible associations between the dorsolateral prefrontal cortex (DLPFC) metabolites and the cognitive function in first-episode schizophrenia (FES).This study included 58 patients with FES (29 males and 29 females; mean age, 22.66 ±â€Š7.64 years) recruited from the First Affiliated Hospital, College of Medicine, Zhejiang University, and 43 locally recruited healthy controls (16 males and 27 females; mean age, 23.07 ±â€Š7.49 years). The single-voxel proton magnetic resonance spectroscopy was used to measure the levels of N-acetylaspartate (NAA); complex of glutamate, glutamine, and γ-aminobutyric acid (Glx); choline-containing compounds; and myo-inositol in the DLPFC. The ratios of metabolites to creatine (Cr) were calculated. The cognitive function was assessed by Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). Correlation analysis was used to assess the relationships between the DLPFC metabolites and the cognitive function.Compared with the healthy controls, the patients with FES showed significantly reduced scores in each part of the MCCB, significantly reduced NAA/Cr, and significantly increased Glx/Cr in the left DLPFC. Poor performance in verbal learning and visual learning was correlated to the reduced NAA/Cr ratio in the left DLPFC.These findings suggest that a lower NAA/Cr ratio in the left DLPFC is associated with the cognitive deficits in patients with FES, and may be an early biochemical marker for the cognitive impairment in schizophrenia.

Circulating T lymphocyte subsets, cytokines, and immune checkpoint inhibitors in patients with bipolar II or major depression: a preliminary study.

This study aimed to investigate the less known activation pattern of T lymphocyte populations and immune checkpoint inhibitors on immunocytes in patients with bipolar II disorder depression (BD) or major depression (MD). A total of 23 patients with BD, 22 patients with MD, and 20 healthy controls (HCs) were recruited. The blood cell count of T lymphocyte subsets and the plasma level of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were selectively investigated. The expression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), programmed cell death protein 1 (PD-1) and its ligands, PD-L1 and PD-L2, on T lymphocytes and monocytes, was detected. In results, blood proportion of cytotoxic T cells significantly decreased in BD patients than in either MD patients or HCs. The plasma level of IL-6 increased in patients with BD and MD. The expression of TIM-3 on cytotoxic T cells significantly increased, whereas the expression of PD-L2 on monocytes significantly decreased in patients with BD than in HCs. These findings extended our knowledge of the immune dysfunction in patients with affective disorders.

Efficacy of repetitive transcranial magnetic stimulation with quetiapine in treating bipolar II depression: a randomized, double-blinded, control study.

The clinical and cognitive responses to repetitive transcranial magnetic stimulation (rTMS) in bipolar II depressed patients remain unclear. In this study, thirty-eight bipolar II depressed patients were randomly assigned into three groups: (i) left high-frequency (n = 12), (ii) right low-frequency (n = 13), (iii) sham stimulation (n = 13), and underwent four-week rTMS with quetiapine concomitantly. Clinical efficacy was evaluated at baseline and weekly intervals using the 17-item Hamilton Depression Rating Scale (HDRS-17) and Montgomery-Asberg Depression Rating Scale (MADRS). Cognitive functioning was assessed before and after the study with the Wisconsin Card Sorting Test (WCST), Stroop Word-Color Interference Test (Stroop), and Trail Making Test (TMT). Thirty-five patients were included in the final analysis. Overall, the mean scores of both the HDRS-17 and the MADRS significantly decreased over the 4-week trial, which did not differ among the three groups. Exploratory analyses revealed no differences in factor scores of HDRS-17s, or in response or remission rates. Scores of WCST, Stroop, or TMT did not differ across the three groups. These findings indicated active rTMS combined with quetiapine was not superior to quetiapine monotherapy in improving depressive symptoms or cognitive performance in patients with bipolar II depression.

Sex differences in the stress response in SD rats.

Sex differences play an important role in depression, the basis of which is an excessive stress response. We aimed at revealing the neurobiological sex differences in the same study in acute- and chronically-stressed rats. Female Sprague-Dawley (SD) rats were randomly divided into 6 groups: chronic unpredictable mild stress (CUMS), acute foot shock (FS) and controls, animals in all 3 groups were sacrificed in proestrus or diestrus. Male SD rats were randomly divided into 3 groups: CUMS, FS and controls. Comparisons were made of behavioral changes in CUMS and control rats, plasma levels of corticosterone (CORT), testosterone (T) and estradiol (E2), and of the hypothalamic mRNA-expression of stress-related molecules, i.e. estrogen receptor α and ß, androgen receptor, aromatase, mineralocorticoid receptor, glucocorticoid receptor, corticotropin-releasing hormone, arginine vasopressin and oxytocin. CUMS resulted in disordered estrus cycles, more behavioral and hypothalamic stress-related molecules changes and a stronger CORT response in female rats compared with male rats. Female rats also showed decreased E2 and T levels after FS and CUMS, while male FS rats showed increased E2 and male CUMS rats showed decreased T levels. Stress affects the behavioral, endocrine and the molecular response of the stress systems in the hypothalamus of SD rats in a clear sexual dimorphic way, which has parallels in human data on stress and depression.

Effect of pentobarbital and isoflurane on acute stress response in rat.

BACKGROUND: Anesthesia administration before sacrificing animals is a common practice in stress-related studies, but the effect of anesthesia on the results remains understudied. We aimed to reveal the interference of different anesthetics, i.e. intraperitoneal (i.p.) sodium-pentobarbital injection or isoflurane inhalation, with the acute stress responses in rats. METHODS: Rats were randomly divided into foot shock (FS) and non-stressed control groups, and further grouped according to the sacrificing procedure: direct decapitation, decapitation after i.p. sodium-pentobarbital injection, or isoflurane inhalation. There was also a non-stressed group sacrificed by decapitation following i.p. saline injection. Plasma levels of corticosterone (CORT), testosterone and estradiol, hypothalamic stress-related molecule mRNA expression of corticotropin-releasing hormone, arginine vasopressin and oxytocin, and frontal lobe stress-related molecule mRNA expression of NMDA receptor subunit NR2B, GABAA receptor and the neuronal-type nicotinic acetylcholine receptor were measured. RESULTS: FS significantly increased plasma CORT levels in direct decapitation and isoflurane groups, while this stress response 'disappeared' following i.p. sodium-pentobarbital injection. In control animals, both the injection of saline and pentobarbital caused a significant increase of plasma CORT. Neither the sex hormone levels nor the mRNA expression of stress-related molecules in the brain showed significant differences among the groups. CONCLUSION: The injection of the anesthetic compound rather than the compound itself may cause extra stress which interferes with the plasma CORT levels, but not with plasma sex hormone levels nor with the brain mRNA expression. Isoflurane inhalation leaves the stress response intact and is also optimal from an ethical point of view.