Evolution of Depressive Symptoms Among Depression Subtypes of Clinical and Functional Variables in Primary Care in Chile.

OBJECTIVE: To compare the evolution of depressive symptoms among depressive subtypes based on clinical and functional variables in a sample of primary care in Chile. METHODS: A longitudinal study was conducted in the Maule Region of Chile, focusing on 8 primary care from February 2014 to September 2015. Clinical and functional variables, including Mini International Neuro-psychiatric Interview, Outcome Questionnaire interpersonal and social sub-scales, were applied in a latent class analysis. This analysis categorized 210 patients into 3 subtypes: complex depression (N = 100), recurrent depression (n = 96), and unique depression (n = 14). Complex depression, exhibited a higher probability of suicide attempts, interpersonal and social dysfunction, and association with adverse childhood experiences according the Brief Physical and Sexual Abuse Questionnaire. Patients were monitored over 1 year with the Hamilton scale. The Kruskal-Wallis, non-parametric test, followed by paired Mann-Whitney test evaluated difference in the severity of depressive symptoms between the groups. Additionally, data on mental health interventions were collected. RESULTS: Out of the 210 patients, 89% were women, with a median age of 50 (range 37-58), and 40.1% with only primary education. Sociodemographic characteristics not differ between groups. Significant differences in depressive symptom severity between the groups were found (X2 90.06, P < .001, Kruskal-Wallis test, η2 = 0.084). Post hoc analyses indicated higher depressive symptoms in complex depression compared to recurrent (Z = -9.501, P < .001) and unique (Z = -2.877, P = .004) depression, with no significant difference between recurrent and unique depression (Z = -1.58, P = .113). There were no differences in the number of medical and psychological controls between the groups. The patients with complex depression required greater modifications in the pharmacological prescriptions than those belonging to the other groups. CONCLUSION: These results provide additional evidence of a complex depression subtype in primary care in Chile associated with adverse childhood experiences, that had worse resolution of depressive symptoms. Contrary to expectations, patients belonging to this group did not receive further medical and psychological interventions, probably due to a lack of specific clinical recommendations.

Early Visual Processing and Perception Processes in Object Discrimination Learning.

A brief image presentation is sufficient to discriminate and individuate objects of expertise. Although perceptual expertise is acquired through extensive practice that increases the resolution of representations and reduces the latency of image decoding and coarse and fine information extraction, it is not known how the stages of visual processing impact object discrimination learning (ODL). Here, we compared object discrimination with brief (100 ms) and long (1,000 ms) perceptual encoding times to test if the early and late visual processes are required for ODL. Moreover, we evaluated whether encoding time and discrimination practice shape perception and recognition memory processes during ODL. During practice of a sequential matching task with initially unfamiliar complex stimuli, we find greater discrimination with greater encoding times regardless of the extent of practice, suggesting that the fine information extraction during late visual processing is necessary for discrimination. Interestingly, the overall discrimination learning was similar for brief and long stimuli, suggesting that early stages of visual processing are sufficient for ODL. In addition, discrimination practice enhances perceive and know for brief and long stimuli and both processes are associated with performance, suggesting that early stage information extraction is sufficient for modulating the perceptual processes, likely reflecting an increase in the resolution of the representations and an early availability of information. Conversely, practice elicited an increase of familiarity which was not associated with discrimination sensitivity, revealing the acquisition of a general recognition memory. Finally, the recall is likely enhanced by practice and is associated with discrimination sensitivity for long encoding times, suggesting the engagement of recognition memory in a practice independent manner. These findings contribute to unveiling the function of early stages of visual processing in ODL, and provide evidence on the modulation of the perception and recognition memory processes during discrimination practice and its relationship with ODL and perceptual expertise acquisition.

The Alteration of Neonatal Raphe Neurons by Prenatal-Perinatal Nicotine. Meaning for Sudden Infant Death Syndrome.

Nicotine may link maternal cigarette smoking with respiratory dysfunctions in sudden infant death syndrome (SIDS). Prenatal-perinatal nicotine exposure blunts ventilatory responses to hypercapnia and reduces central respiratory chemoreception in mouse neonates at Postnatal Days 0 (P0) to P3. This suggests that raphe neurons, which are altered in SIDS and contribute to central respiratory chemoreception, may be affected by nicotine. We therefore investigated whether prenatal-perinatal nicotine exposure affects the activity, electrical properties, and chemosensitivity of raphe obscurus (ROb) neurons in mouse neonates. Osmotic minipumps, implanted subcutaneously in 5- to 7-day-pregnant CF1 mice, delivered nicotine bitartrate (60 mg kg(-1) d(-1)) or saline (control) for up to 28 days. In neonates, ventilation was recorded by head-out plethysmography, c-Fos (neuronal activity marker), or serotonin autoreceptors (5HT1AR) were immunodetected using light microscopy, and patch-clamp recordings were made from raphe neurons in brainstem slices under normocarbia and hypercarbia. Prenatal-perinatal nicotine exposure decreased the hypercarbia-induced ventilatory responses at P1-P5, reduced both the number of c-Fos-positive ROb neurons during eucapnic normoxia at P1-P3 and their hypercapnia-induced recruitment at P3, increased 5HT1AR immunolabeling of ROb neurons at P3-P5, and reduced the spontaneous firing frequency of ROb neurons at P3 without affecting their CO2 sensitivity or their passive and active electrical properties. These findings reveal that prenatal-perinatal nicotine reduces the activity of neonatal ROb neurons, likely as a consequence of increased expression of 5HT1ARs. This hypoactivity may change the functional state of the respiratory neural network leading to breathing vulnerability and chemosensory failure as seen in SIDS.

Odorant recognition using biological responses recorded in olfactory bulb of rats.

In this study we applied pattern recognition (PR) techniques to extract odorant information from local field potential (LFP) signals recorded in the olfactory bulb (OB) of rats subjected to different odorant stimuli. We claim that LFP signals registered on the OB, the first stage of olfactory processing, are stimulus specific in animals with normal sensory experience, and that these patterns correspond to the neural substrate likely required for perceptual discrimination. Thus, these signals can be used as input to an artificial odorant classification system with great success. In this paper we have designed and compared the performance of several configurations of artificial olfaction systems (AOS) based on the combination of four feature extraction (FE) methods (Principal Component Analysis (PCA), Fisher Transformation (FT), Sammon NonLinear Map (NLM) and Wavelet Transform (WT)), and three PR techniques (Linear Discriminant Analysis (LDA), Multilayer Perceptron (MLP) and Support Vector Machine (SVM)), when four different stimuli are presented to rats. The best results were reached when PCA extraction followed by SVM as classifier were used, obtaining a classification accuracy of over 95% for all four stimuli.

Neural sensitivity to odorants in deprived and normal olfactory bulbs.

Early olfactory deprivation in rodents is accompanied by an homeostatic regulation of the synaptic connectivity in the olfactory bulb (OB). However, its consequences in the neural sensitivity and discrimination have not been elucidated. We compared the odorant sensitivity and discrimination in early sensory deprived and normal OBs in anesthetized rats. We show that the deprived OB exhibits an increased sensitivity to different odorants when compared to the normal OB. Our results indicate that early olfactory stimulation enhances discriminability of the olfactory stimuli. We found that deprived olfactory bulbs adjusts the overall excitatory and inhibitory mitral cells (MCs) responses to odorants but the receptive fields become wider than in the normal olfactory bulbs. Taken together, these results suggest that an early natural sensory stimulation sharpens the receptor fields resulting in a larger discrimination capability. These results are consistent with previous evidence that a varied experience with odorants modulates the OB's synaptic connections and increases MCs selectivity.

Astrocytic αVß3 integrin inhibits neurite outgrowth and promotes retraction of neuronal processes by clustering Thy-1.

Thy-1 is a membrane glycoprotein suggested to stabilize or inhibit growth of neuronal processes. However, its precise function has remained obscure, because its endogenous ligand is unknown. We previously showed that Thy-1 binds directly to α(V)ß(3) integrin in trans eliciting responses in astrocytes. Nonetheless, whether α(V)ß(3) integrin might also serve as a Thy-1-ligand triggering a neuronal response has not been explored. Thus, utilizing primary neurons and a neuron-derived cell line CAD, Thy-1-mediated effects of α(V)ß(3) integrin on growth and retraction of neuronal processes were tested. In astrocyte-neuron co-cultures, endogenous α(V)ß(3) integrin restricted neurite outgrowth. Likewise, α(V)ß(3)-Fc was sufficient to suppress neurite extension in Thy-1(+), but not in Thy-1(-) CAD cells. In differentiating primary neurons exposed to α(V)ß(3)-Fc, fewer and shorter dendrites were detected. This effect was abolished by cleavage of Thy-1 from the neuronal surface using phosphoinositide-specific phospholipase C (PI-PLC). Moreover, α(V)ß(3)-Fc also induced retraction of already extended Thy-1(+)-axon-like neurites in differentiated CAD cells as well as of axonal terminals in differentiated primary neurons. Axonal retraction occurred when redistribution and clustering of Thy-1 molecules in the plasma membrane was induced by α(V)ß(3) integrin. Binding of α(V)ß(3)-Fc was detected in Thy-1 clusters during axon retraction of primary neurons. Moreover, α(V)ß(3)-Fc-induced Thy-1 clustering correlated in time and space with redistribution and inactivation of Src kinase. Thus, our data indicates that α(V)ß(3) integrin is a ligand for Thy-1 that upon binding not only restricts the growth of neurites, but also induces retraction of already existing processes by inducing Thy-1 clustering. We propose that these events participate in bi-directional astrocyte-neuron communication relevant to axonal repair after neuronal damage.

Simultaneous single unit recording in the mitral cell layer of the rat olfactory bulb under nasal and tracheal breathing.

Odor perception depends on the odorant-evoked changes on Mitral/Tufted cell firing pattern within the olfactory bulb (OB). The OB exhibits a significant "ongoing" or spontaneous activity in the absence of sensory stimulation. We characterized this ongoing activity by simultaneously recording several single neurons in the mitral cell layer (MCL) of anesthetized rats and determined the extent of synchrony and oscillations under nasal and tracheal breathing. We recorded 115 neurons and found no significant differences in the mean firing rates between both breathing conditions. Surprisingly, nearly all single units exhibited a long refractory period averaging 14.4 ms during nasal respiration that was not different under tracheal breathing. We found a small incidence (2% of neurons) of gamma band oscillations and a low incidence (8.1%) of correlated firing between adjacent MCL cells. During nasal respiration, a significant oscillation at the respiratory rate was observed in 12% of cells that disappeared during tracheal breathing. Thus, in the absence of odorants, MCL cells exhibit a long refractory period, probably reflecting the intrinsic OB network properties. Furthermore, in the absence of sensory stimulation, MCL cell discharge does not oscillate in the gamma band and the respiratory cycle can modulate the firing of these cells.

Simultaneous Single Unit Recording in the Mitral Cell Layer of the Rat Olfactory Bulb under Nasal and Tracheal Breathing

Odor perception depends on the odorant-evoked changes on Mitral/Tufted cell firing pattern within the olfactory bulb (OB). The OB exhibits a significant "ongoing" or spontaneous activity in the absence of sensory stimulation. We characterized this ongoing activity by simultaneously recording several single neurons in the mitral cell layer (MCL) of anesthetized rats and determined the extent of synchrony and oscillations under nasal and tracheal breathing. We recorded 115 neurons and found no significant differences in the mean firing rates between both breathing conditions. Surprisingly, nearly all single units exhibited a long refractory period averaging 14.4 ms during nasal respiration that was not different under tracheal breathing. We found a small incidence (2% of neurons) of gamma band oscillations and a low incidence (8.1%) of correlated firing between adjacent MCL cells. During nasal respiration, a significant oscillation at the respiratory rate was observed in 12% of cells that disappeared during tracheal breathing. Thus, in the absence of odorants, MCL cells exhibit a long refractory period, probably reflecting the intrinsic OB network properties. Furthermore, in the absence of sensory stimulation, MCL cell discharge does not oscillate in the gamma band and the respiratory cycle can modulate the firing of these cells.