Jesus Landeira-Fernandez

Different patterns of freezing behavior organized in the periaqueductal gray of rats: Association with different types of anxiety

Freezing defined as the complete absence of body movements is a normal response of animals to unavoidable fear stimuli. The present review presents a series of evidence relating different defensive patterns with specific anxiety disorders. There are at least four different kinds of freezing with specific neural substrates. The immobility induced by stimulation of the ventral column of the periaqueductal gray (vPAG) has been considered a quiescence characteristic of the recovery component of defense-recuperative processes. There is an isomorphism between freezing response to contextual stimuli paired with electrical shocks and generalized anxiety disorder. Besides, two types of freezing emerge with the electrical stimulation of the dorsal aspects of the periaqueductal gray (dPAG): the dPAG-evoked freezing and the dPAG post-stimulation freezing. Evidence is presented in support of the hypothesis that whereas dPAG-evoked freezing would serve as a model of panic attacks, the dPAG post-stimulation freezing appears to be a model of panic disorder. It is also proposed that conditioned freezing plus dPAG electrical stimulation might also mimic panic disorder with agoraphobia. A model of serotoninergic modulation through on- and off-cells of the defense reaction generated in the dPAG is also presented. The understanding of how the periaqueductal gray generates and elaborates different types of freezing is of relevance for our better knowledge of distinct types of anxiety such as panic disorder or generalized anxiety disorder.

Defensive freezing evoked by electrical stimulation of the periaqueductal gray: comparison between dorsolateral and ventrolateral regions

Previous reports indicated that ventrolateral periaqueductal gray (vlPAG) plays a role in the expression of freezing behavior whereas dorsolateral periaqueductal gray (dlPAG) is involved on both freezing and active forms of defensive behaviors. In order to evaluate the role of each of these areas in the occurrence of defensive reactions, rats were electrically stimulated either in the dlPAG or vlPAG with different stimulus frequencies. Stepwise increases in the electrical stimulation of both dlPAG or vlPAG induced initially freezing and then a jumping response. Freezing induced by vlPAG stimulation had a tendency to disappear when the stimulation was turned off whereas freezing induced by dlPAG stimulation remained high in the absence of the stimulation. These results suggest that dlPAG and vlPAG are involved on defensive freezing probably through different neural circuitries.

The Diagnoses of Schizophrenia, Schizoaffective Disorder, Bipolar Disorder and Unipolar Depression: Interrater Reliability and Congruence between DSM-IV and ICD-10

Background: The present study investigated the interrater reliability of the diagnoses of schizophrenia (SCH), schizoaffective disorder (SAD), bipolar disorder (BPD) and unipolar depression (UPD) according to both DSM-IV and ICD-10, as well as the diagnostic congruence between the two classificatory systems. Sampling and Methods: Using the Composite International Diagnostic Interview, two trained psychiatrists simultaneously evaluated 100 inpatients and independently assessed the psychiatric diagnoses. The Cohen’s kappa coefficient was employed to estimate interrater reliability and diagnostic congruence between DSM-IV and ICD-10. Results: SCH was more frequent according to ICD-10 than DSM-IV criteria. Considering both diagnostic systems, all the four nosological categories, but ICD-10 SAD and DSM-IV UPD, were associated with interrater reliability coefficients above 0.50. The coefficient of the diagnostic congruence between DSM-IV and ICD-10 was inferior to 0.50 only for SAD. BPD was associated with the highest degrees of both interrater reliability and diagnostic congruence. Conclusions: The lack of an item excluding the occurrence of an affective syndrome among ICD-10 diagnostic criteria for SCH can account for: the larger frequency of SCH according to ICD-10 than DSM-IV; the unsatisfactory interrater reliability for the diagnosis of ICD-10 SAD, and the low diagnostic congruence for SAD.

Chronic imipramine enhances 5-HT1A and 5-HT2 receptors-mediated inhibition of panic-like behavior in the rat dorsal periaqueductal gray

Electrical stimulation of the dorsal periaqueductal gray (DPAG) has been used to induce panic-like behavior in rats. In the present study, we investigated the effect of chronic imipramine treatment on the sensitivity of different 5-HT receptor subtypes in inhibiting aversion induced by electrical stimulation of this brain area. For that, the effects of intra-DPAG administration of the endogenous agonist 5-HT (20 nmol), the 5-HT(1A) receptor agonist 8-OH-DPAT (8 nmol) and the 5-HT(2A/2C) receptor agonist DOI (16 nmol) were measured in female Wistar rats given either chronic injection of imipramine (15 mg/kg, 3 weeks, ip) or saline. The results showed that the three receptor agonists raised the threshold of aversive electrical stimulation in both groups of animals, but this antiaversive effect was significantly higher in rats treated with imipramine. Treatment with imipramine did not change the basal threshold of aversive electrical stimulation measured before intra-DPAG injection of the 5-HT agonists. The results suggest that sensitization of both 5-HT(1A) and 5-HT(2) receptors within the DPAG may be involved in the beneficial effect of imipramine in panic disorder (PD).

Role of amygdala in conditioned and unconditioned fear generated in the periaqueductal gray

The amygdala and ventral portion of the periaqueductal gray (vPAG) are crucial for the expression of the contextual freezing behavior. However, it is still unclear whether the amygdala also plays a role in defensive behaviors induced by electrical stimulation of the dorsal periaqueductal gray (dPAG). In the present study, rats were implanted with electrodes into dPAG for determination of the thresholds for freezing and escape responses before and after sham or electrolytic lesions in the amygdala. Animals were then submitted to a context fear conditioning procedure. Amygdala lesions disrupted contextual freezing but did not affect defensive behaviors induced by dPAG electrical stimulation. These results indicate that contextual and unconditioned freezing behaviors are mediated by independent neural circuits.

Psychometric properties of the Brazilian-adapted version of the Ages and Stages Questionnaire in public child daycare centers.

Well-designed screening assessment instruments that can evaluate child development in public daycare centers represent an important resource to help improve the quality of these programs, as an early detection method for early developmental delay. The Ages and Stages Questionnaire, 3rd edition (ASQ-3), comprises a series of 21 questionnaires designed to screen developmental performance in the domains of communication, gross motor skills, fine motor skills, problem solving, and personal-social ability in children aged 2 to 66 months. The purpose of the present work was to translate and adapt all of the ASQ-3 questionnaires for use in Brazilian public child daycare centers and to explore their psychometric characteristics with both Classical Test Theory and Rating Scale analyses from the Rasch model family. A total of 18 Ages & Stages Questionnaires - Brazilian translation (ASQ-BR) questionnaires administered at intervals from 6 to 60 months of age were analyzed based on primary caregiver evaluations of 45,640 children distributed in 468 public daycare centers in the city of Rio de Janeiro. The results indicated that most of the ASQ-BR questionnaires had adequate internal consistency. Exploratory factor analyses yielded a one-factor solution for each domain of all of the ASQ-BR questionnaires. The only exception was the personal-social domain in some of the questionnaires. Item Response Theory based on Rating Scale analysis (infit and outfit mean squares statistics) indicated that only 44 of 540 items showed misfit problems. In summary, the ASQ-BR questionnaires are psychometrically sound developmental screening instruments that can be easily administered by primary caregivers.

Amygdaloid lesions produced similar contextual fear conditioning disruption in the Carioca high- and low-conditioned freezing rats

Rats selectively bred for high or low levels of emotionality represent an important and powerful tool to investigate the role of genetic variables in the occurrence of different anxiety disorders. In the present study, albino rats were selectively bred for differences in defensive freezing behavior in response to contextual cues previously associated with footshock, an animal model of general anxiety disorder. The results indicate that these two new lines of rats, which we refer to as Carioca High-Freezing (CHF) and Carioca Low-Freezing (CLF), show a reliable difference in conditioned freezing after three generations of selection. CHF and CLF rats did not present any differences during baseline or post-shock periods. Males from both lines consistently exhibit more conditioned freezing to contextual cues than females. A second experiment used male rats from the fourth generation to investigate the participation of the amygdala during contextual fear conditioning in the CHF and CLF lines. The results indicate that post-training amygdaloid electrolytic lesions lead to similar disruptions in conditioned freezing behavior in both animal lines.

Awareness of Disease in Dementia: Factor Structure of the Assessment Scale of Psychosocial Impact of the Diagnosis of Dementia

Despite the growing understanding of the conceptual complexity of awareness, there currently exists no instrument for assessing different domains of awareness in dementia. In the current study, the psychometric properties of a multidimensional awareness scale, the Assessment Scale of Psychosocial Impact of the Diagnosis of Dementia (ASPIDD), are explored in a sample of 201 people with dementia and their family caregivers. Cronbachs alpha was high (α = 0.87), indicating excellent internal consistency. The mean of corrected item-total correlation coefficients was moderate. ASPIDD presented a four-factor solution with a well-defined structure: awareness of activities of daily living, cognitive functioning and health condition, emotional state, and social functioning and relationships. Functional disability was positively correlated with total ASPIDD, unawareness of activities of daily living, cognitive functioning, and with emotional state. Caregiver burden was correlated with total ASPIDD scores and unawareness of cognitive functioning. The results suggest that ASPIDD is indeed a multidimensional scale, providing a reliable measure of awareness of disease in dementia. Further studies should explore the risk factors associated with different dimensions of awareness in dementia.

Effect of dorsal and ventral hippocampal lesions on contextual fear conditioning and unconditioned defensive behavior induced by electrical stimulation of the dorsal periaqueductal gray.

The dorsal (DH) and ventral (VH) subregions of the hippocampus are involved in contextual fear conditioning. However, it is still unknown whether these two brain areas also play a role in defensive behavior induced by electrical stimulation of the dorsal periaqueductal gray (dPAG). In the present study, rats were implanted with electrodes into the dPAG to determine freezing and escape response thresholds after sham or bilateral electrolytic lesions of the DH or VH. The duration of freezing behavior that outlasted electrical stimulation of the dPAG was also measured. The next day, these animals were subjected to contextual fear conditioning using footshock as an unconditioned stimulus. Electrolytic lesions of the DH and VH impaired contextual fear conditioning. Only VH lesions disrupted conditioned freezing immediately after footshock and increased the thresholds of aversive freezing and escape responses to dPAG electrical stimulation. Neither DH nor VH lesions disrupted post-dPAG stimulation freezing. These results indicate that the VH but not DH plays an important role in aversively defensive behavior induced by dPAG electrical stimulation. Interpretations of these findings should be made with caution because of the fact that a non-fiber-sparing lesion method was employed.

Antinociception induced by stimulation of ventrolateral periaqueductal gray at the freezing threshold is regulated by opioid and 5-HT2A receptors as assessed by the tail-flick and formalin tests.

It has been suggested that antinociception is part of the animals defensive reaction to threatening situations. Chemical or electrical stimulation of the ventrolateral portion of the periaqueductal gray (vlPAG) produces both defensive freezing behavior and antinociception, supporting the view that the vlPAG is a critical structure in the coordination of the defensive reaction. The present study indicated that electrical stimulation of the vlPAG, at a current intensity sufficient to induce defensive freezing, caused a decrease in reactivity to a phasic escapable noxious stimulus (as measured in the tail-flick test) and to a tonic, inescapable noxious stimulus (as measured in the formalin test). These antinociceptive effects were reversed by microinjections of the opioid antagonist naltrexone or the specific 5-HT2A receptor antagonist ketanserin into the stimulation sites. These results suggest that (a) activation of neural circuits of the vlPAG, responsible for the production of freezing behavior, reduces the reactivity to nociceptive stimuli (as evaluated by the tail-flick and formalin tests) and that (b) opioid- and 5-HT2A-mediated mechanisms are called into action for regulating the antinociceptive response that accompanies the freezing behavior induced by vlPAG stimulation.