A new chronobiological approach to discriminate between acute and chronic depression using peripheral temperature, rest-activity, and light exposure parameters.

BACKGROUND: Circadian theories for major depressive disorder have suggested that the rhythm of the circadian pacemaker is misaligned. Stable phase relationships between internal rhythms, such as temperature and rest/activity, and the external day-night cycle, are considered to be crucial for adapting to life in the external environmental. Therefore, the relationship and possible alterations among (i) light exposure, (ii) activity rhythm, and (iii) temperature rhythm could be important factors in clinical depression. This study aimed to investigate the rhythmic alterations in depression and evaluate the ability of chronobiological parameters to discriminate between healthy subjects and depressed patients. METHODS: Thirty female subjects, including healthy subjects, depressed patients in the first episode, and major recurrent depression patients. Symptoms were assessed using Hamilton Depression Scale, Beck Depression Inventory and Montgomery-Äsberg Scale. Motor activity, temperature, and light values were determined for 7 days by actigraph, and circadian rhythms were calculated. RESULTS: Depressed groups showed a lower amplitude in the circadian rhythm of activity and light exposure, but a higher amplitude in the rhythm of peripheral temperature. The correlation between temperature and activity values was different in the day and night among the control and depressed groups. For the same level of activity, depressed patients had lowest temperature values during the day. The amplitudes of temperature and activity were the highest discriminant parameters. CONCLUSIONS: These results indicate that the study of rhythms is useful for diagnosis and therapy for depressive mood disorders.

Laboratory validation of confirmatory tests for rabies diagnosis: Approaches to reduce animal use and facilitate sample collection.

Rabies is an encephalitis caused by rabies virus, whose transmission occurs upon contact with infected animals' saliva. The diagnosis is usually performed post-mortem through a direct fluorescent antibody test (DFAT). If the DFAT results are negative, they must be confirmed with an isolation test, usually the mouse inoculation test (MIT), which implies the suffering and death of the animals, high costs and most importantly, up to 28 days to confirm a negative result. Another issue related to rabies diagnosis is the sample collection and storage, which is critical for the rabies virus' RNA genome. Thus, this study aimed to evaluate (i) reverse transcriptase polymerase chain reaction (RT-PCR) and Rabies Tissue Culture Infection Tests (RTCIT) in comparison to DFAT and MIT and (ii) FTA® cards as an alternative sample collection and preservation method. Eighty animal samples were evaluated through DFAT, RTCIT and RT-PCR; MIT was performed only in DFAT-negative samples. FTA® cards were evaluated with a subset of 64 samples, with sufficient material for imprinting. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV), agreement and Cohen's kappa were calculated for each test combination. RTCIT had higher sensitivity (92.5%) and RT-PCR had higher specificity (92.3%) compared to DFAT. The combination of tests enhanced sensitivity, NPV and Cohen's kappa (considering positive results by RTCIT or RT-PCR), and specificity and PPV (when both tests were concordant). The PCR based on FTA® cards as sample source was specific (84.6%-96.2%) but presented lower sensitivity (29.7%-73.0%), although it could detect as positive four DFAT-negative samples. RTCIT and RT-PCR may be used as confirmatory tests in DFAT-negative samples. Moreover, FTA® cards may be helpful for sample collection in field situations where a long time is needed until the sample undergoes laboratory testing.

6­Sulfatoxymelatonin as a predictor of clinical outcome in depressive patients.

OBJECTIVES: This study established the value of the 6­sulfatoxymelatonin (aMT6s) urine concentration as a predictor of the therapeutic response to noradrenaline reuptake inhibitors in depressive patients. METHODS: Twenty-two women aged 18-60 years were selected. Depressive symptoms were assessed by using the Hamilton Depression Scale. Urine samples were collected at 0600-1200 h, 1200-1800 h, 1800-2400 h, and 2400-0600 h intervals, 1 day before and 1 day after starting on the nortriptyline treatment. Urine aMT6s concentration was analyzed by a one-way analysis of variance/Bonferroni test. Spearman's rank correlation coefficient was used to analyze the correlation between depressive symptoms after 2 weeks of antidepressant treatment and the increase in aMT6s urine concentration. RESULTS: Higher and lower size effect groups were compared by independent Student's t-tests. At baseline, the 2400­ to 0600­h interval differed from all other intervals presenting a significantly higher aMT6s urine concentration. A significant difference in aMT6s urine concentrations was found 1 day after treatment in all four intervals. Higher size effect group had lower levels of depressive symptoms 2 weeks after the treatment. A positive correlation between depressive symptoms and the delta of aMT6s in the 2400-0600 h interval was observed. CONCLUSION: Our results reinforce the hypothesis that aMT6s excretion is a predictor of clinical outcome in depression, especially in regard to noradrenaline reuptake inhibitors.

Morningness-eveningness, use of stimulants, and minor psychiatric disorders among undergraduate students.

Morningness-eveningness dimension in humans have been indicated to influence social behavior and individual health. The aim of the present study was to investigate the association of the morningness-eveningness dimension with behavioral and health aspects in a sample of undergraduate students. We assessed demographic data; the Pittsburgh Sleep Quality Index was used to evaluate sleep quality; the Morningness/Eveningness Questionnaire to determine morningness-eveningness, and the Self-Reporting Questionnaire to assess minor psychiatric disorders. A total of 372 students (66.7% females), on average 21.6 years old, participated in this study. Among them, 92.2% did not smoke, 58.9% engaged in physical activities, and 19.7% were night-shift workers. In regard to morningness-eveningness, 55.9% of the participants were intermediate between evening (39.5%) and morning (4.6%) types. Poor sleep quality (OR = 1.89), minor psychiatric disorders (OR = 1.92), and tobacco consumption (OR = 3.65) predominated among evening types. Evening types were predominantly males (OR = 1.72). This study suggests that evening types are more vulnerable to sleep and psychiatric disturbances, and tend to smoke more than morning types.

Long-term effect of morphine administration in young rats on the analgesic opioid response in adult life.

Neonates, infants and children are often exposed to pain from invasive procedures during intensive care and during the post-operative period. Opioid anesthesia and post-operative opioid analgesia have been used in infants and result in clinical benefits. The objectives of this study were to verify the effect of repeated 5 microg morphine administration (subcutaneous), once a day for 7 days in 8-day-old rats, at P8 until P14. To verify the long-term effect of morphine, the animals were submitted to a second exposure of 5mg/kg (intraperitoneal) of morphine at P80 until P86. Animals that received morphine for 7 days, at P14 did not develop tolerance, however at P80, rats demonstrated greater morphine analgesia. At P86, after 7 days of morphine administration, animals showed classical tolerance. These findings may have important implications for the human neonate, suggesting a possible explanation for the differences in the requirements of morphine observed in the youngest patients.

Methylprednisolone administration alters adenine nucleotide hydrolysis in rat blood serum.

The effect of methylprednisolone on the hydrolysis of adenine nucleotides by rat blood serum enzymes was studied. Adult male Wistar rats were submitted to three different treatments with synthetic steroid methylprednisolone: one dose of 50 mg/kg, i.p. (acute); or oral doses of 6 mg/kg dissolved in drinking water for 15 (sub-chronic) or 30 (chronic) days. Decreased ADP hydrolysis was observed after acute and sub-chronic treatments. Furthermore, ATP, ADP and AMP hydrolysis decreased after chronic treatment. These alterations may constitute one of the mechanisms that mediate the development of some of the side effects associated with corticosteroid use.

Long-lasting delayed hyperalgesia after chronic restraint stress in rats-effect of morphine administration.

Different effects upon the nociceptive response have been observed with exposure to acute and chronic stress in rats. In the present study we repeatedly submitted rats to restraint for 40 days, inducing hyperalgesia using the tail-flick test. A new session of acute stress was applied at the end of 40 days period, and the chronically-stressed animals demonstrated analgesia after forced swimming, but not after restraint. The effect of stress interruption for 14 or 28 days on the nociceptive threshold was then investigated. The basal tail-flick latency remained decreased for at least 28 days (hyperalgesic effect). Following the periods of suspension, the animals were submitted to new session of acute restraint, and stress-induced analgesia was observed only after 28 days of stress interruption. Thus, the mechanisms involved in the long-lasting hyperalgesia presented in this study are not exactly the same as those responsible for the analgesia induced by acute stressors. After 40 days of chronic stress treatment, morphine was injected i.p. (1.0, 5.0 mg/kg or saline). The repeatedly stressed rats displayed decreased morphine effects on nociception compared to unstressed controls. The tolerance of the response to morphine agrees with previous studies suggesting that chronic restraint stress could modify the activity of opioid systems.

Chronic stress effects on adenine nucleotide hydrolysis in the blood serum and brain structures of rats.

We have previously observed that adenosine 5'-diphosphate (ADP) hydrolysis was decreased 25% in spinal cord synaptosomes of chronically stressed male rats, while no changes were observed in ATPase activity. In the present study, we investigated the effect of chronic stress on the hydrolysis of adenine nucleotides in two cerebral structures (frontal cortex and hypothalamus) and in the blood serum of male rats. Adult male Wistar rats were submitted to 1-h restraint stress/day for 45 days (chronic) and were sacrificed 24 h after the last session of stress. Adenosine 5'-triphosphate (ATP) or ADP hydrolysis was assayed in the synaptosomal fraction obtained from the frontal cortex and hypothalamus of control and chronically stressed animals. No effects on ADP or ATP hydrolysis were observed in any of the cerebral structures analyzed after chronic stress. On the other hand, reduced ADP hydrolysis was observed in the blood serum of chronic stressed rats. It is possible that the effects observed in the blood serum may represent an adaptation to chronic stress and may reflect different functions of nucleotides and/or enzymes in these tissues. It is possible that altered levels of ADPase activity in the serum may be a biochemical marker for chronic stress situations.

Impact of the time in an animal model of mood disorder.

UNLABELLED: The objective of the study is to evaluate whether intervening and testing in different rest-activity periods of the day would produce different measurements in animal behavior studies. METHODOLOGY: Thirty-five, 60-day-old male Wistar rats were submitted to an inescapable foot shock (IFS) stress model and behavioral tests (Light-Dark Box test). The animals received intervention and were tested in both light and dark phases, resulting in the following groups: control L (tested in the light), control D (tested in the dark), LL (IFS and tested in the light), LD (IFS in the light and tested in the dark), DL (IFS in the dark and tested in the light), and DD (IFS and tested in the dark). RESULTS: The Light-Dark Box test showed that control L was not significantly different from other groups in any of the parameters. However, when comparing control D with the intervention groups, we observed a difference in the mean length of time spent in the light compartment (t=2.56; p=0.045). A significant difference in the number of crossings into the light compartment was only observed between the control D and the LL and LD groups (t=-2.608; p=0.028; t=-2.571; p=0.030, respectively). The latency time for the control D group was significantly lower than that of the DD group (t=-2.556; p=0.043). CONCLUSIONS: These results show that behavior testing during the animal's period of highest activity (dark period) revealed differences caused by the intervention, whereas no differences were apparent when the control group was observed during the day.

Depression scores associate with chronotype and social jetlag in a rural population.

In public health, mood disorders are among the most important mental impairments. Patients with depressive episodes exhibit daily mood variations, abnormal patterns in sleep-wake behavior, and in the daily rhythms of several endocrine-metabolic parameters. Although the relationship between the sleep/circadian processes and mood disorders is poorly understood, clock-related therapies, such as light therapy, sleep deprivation, and rigid sleep schedules, have been shown to be effective treatments. Several studies investigated the relationship between circadian phenotype (chronotype) and depression. These focused mainly on urban populations and assessed diurnal preferences (Morningness-Eveningness score) rather than the actual timing of sleep and activity. Here, we used the Beck Depression Inventory (BDI) in an essentially rural population (N?=?4051), and investigated its relation to circadian phenotype (chronotype and social jetlag), assessed with the Munich Chronotype Questionnaire (MCTQ). In our study design, we (i) normalized both chronotype and BDI scores for age and sex (MSF(sas) and BDI(as), respectively); (ii) calculated individual social jetlag (misalignment of the biological and social time); and (iii) investigated the relationship between circadian phenotypes and BDI scores in a population homogeneous in respect to culture, socioeconomic factors, and daily light exposure. A 15.65% (N?=?634) of the participants showed mild to severe depressive BDI scores. Late chronotypes had a higher BDI(as) than intermediate and early types, which was independent of whether or not the participants were smokers. Both chronotype and BDI(as) correlated positively with social jetlag. BDI(as) was significantly higher in subjects with >2?h of social jetlag than in the rest of the population?again independent of smoking status. We also compared chronotype and social jetlag distributions between BDI categories (no symptoms, minimal symptoms, and mild to severe symptoms of depression) separately for men and women and for four age groups; specifically in the age group 31?40 yrs, subjects with mild to severe BDI scores were significantly later chronotypes and suffered from higher social jetlag. Our results indicate that misalignment of circadian and social time may be a risk factor for developing depression, especially in 31- to 40-yr-olds. These relationships should be further investigated in longitudinal studies to reveal if reduction of social jetlag should be part of prevention strategies. (Author correspondence: karla.allebrandt@med.uni-muenchen.de ).

Prevalencia de transtornos mentais menores e subdiagnóstico de sintomas depressivos em mulheres na atenção primária / Prevalence of minor mental disorders and underdiagnosis of depressive symptoms in women in primary care

Introdução: transtornos mentais representam 13% da carga de doença no mundo. Apesar destasconstatações, a lacuna entre a oferta e a procura de cuidados de saúde mental é grande. Um dosfatores principais que contribuem para esta situação é o subdiagnóstico de transtornos mentais.Objetivos: esse estudo descreve a prevalência de sintomas psiquiátricos menores e depressivosem mulheres na atenção primária.Métodos: 201 mulheres foram recrutadas. Utilizou-se Self Reporting Questionnaire - 20>8 eduas perguntas do Manual Diagnóstico e Estatístico de Transtornos Mentais (DSM-IV-TR) paradiagnóstico de depressão.Resultados: cinquenta e três por cento das pacientes apresentaram SRQ> 8. Pacientes que responderam“sim” às perguntas 1 e 2 apresentaram maior escore no SRQ-20 (10,7+0,38; 11,01+0,41 respectivamente;P<0,01). 24,7% responderam “sim” a uma questão; 43,7% responderam “SIM” à ambas. Entre as não-usuáriasde psicofármacos, 40,5% têm SRQ>8. Entre aquelas com SRQ-20>8, 70,8% não usavam psicofármacos.Conclusão: mais da metade das pacientes apresentou sintomas depressivos e menos de 20%estavam utilizando antidepressivo no momento da entrevista, evidenciando subtratamento dotranstorno. Estes resultados podem estar relacionados à falta de mecanismos adequados para omanejo da depressão na atenção primária.

Mental disorders account for 13% of disease burden worldwide. Despite these findings, the gap between supply and demand for mental health care is great. One of the main factors contributing to this situation is the underdiagnosis of mental disorders. Aims: to describe the prevalence of minor psychiatric symptoms and depression in women in primary care. Methods: two-hundred and one women were recruited. We used the Self Reporting Questionnaire 20 (SRQ-20) > 8 and two questions of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) for depression diagnosis. Results: fifty-three percent of patients had SRQ-20 ¡Ý 8. Patients who answered ¡°YES¡± to questions 1 and 2 had higher scores on the SRQ-20 (10.7¡À0.38; 11.01¡À0.41, respectively; p < 0.01); 24.7% answered ¡°YES¡± to one question; and 43.7% answered ¡°YES¡± to both. Among non-users of psychotropic drugs, 40.5% had SRQ-20 ¡Ý 8. Among those with SRQ-20 ¡Ý 8, 70.8% were not using psychotropic drugs. Conclusion: more than half of the patients had depressive symptoms and less than 20% were using antidepressants at the time of the interview, showing undertreatment of the disorder. These results may be related to lack of adequate mechanisms for the management of depression in primary care.

Repeated restraint stress reduces opioid receptor binding in different rat CNS structures.

Different effects of exposure to acute or to repeated stress have been observed upon the nociceptive response in rats. In the present study, we repeatedly submitted Wistar rats to restraint for 40 days, a treatment known to induce an increase in the nociceptive response in the tail-flick test. Afterwards, the effect of repeated restraint stress on the density of opioid receptors in rat spinal cord, frontal cortex, and hippocampus was investigated. Results showed that repeatedly stressed rats displayed a significant decrease in opioid receptors density in all structures studied; cortex (141.3 +/- 5.7 for control and 103.3 +/- 15.9 for stressed rats), hippocampus (92.4 +/- 7.2 for control and 64.8 +/- 7.7 for stressed rats), and spinal cord (122.2 +/- 12.8 for control and 79.7 +/- 9.7 for stressed rats). These findings suggest opioid mediation of the altered responses observed in these repeatedly-stressed animals, although the participation of non-opioid mechanisms in this phenomenon cannot be ruled out.