Developmental changes in functional connectivity between the prefrontal cortex and amygdala following fear extinction.

The amygdala and prefrontal cortex (PFC) undergo dramatic changes in structure, function, and regional connectivity in early life, ultimately stabilizing in early adulthood. Pathways between these two structures underlie many forms of emotional learning, including the extinction of conditioned fear. Here we sought to characterize changes in extinction-related medial PFC (mPFC) â†’ amygdala functional connectivity across development that might explain adolescent impairments in extinction. The retrograde tracer Fluorogold was infused into the amygdala of postnatal day (P)22-23 (juvenile), P31-32 (adolescent), or ≥ P69 (adult) rats, which were then exposed to fear conditioning and extinction training. Brains were collected following extinction or context exposure and processed for expression of pMAPK (as a marker of learning-dependent plasticity) in prelimbic (PL) and infralimbic (IL) amygdala-projecting neurons. Consistent with previous findings, amygdala-projecting mPFC neurons were located primarily in layers (L)II/III and V of the mPFC. We noted that mPFC LII/III projected predominantly to the ipsilateral basolateral amygdala, whereas LV projected bilaterally and targeted multiple amygdalar nuclei. Extinction was not associated with changes in extinction-related plasticity in the PL-amygdala pathways in any age group. No changes were seen in LII/III of the IL, but extinction-related plasticity in LV amygdala-projecting IL neurons decreased linearly across development. These findings suggest that extinction-related functional connectivity between the IL and the amygdala undergoes fundamental changes across development that may contribute to alterations in fear suppression across development.

Inhibition of mGluR1 and IP3Rs impairs long-term memory formation in young chicks.

Calcium (Ca(2+)) is involved in a myriad of cellular functions in the brain including synaptic plasticity. However, the role of intracellular Ca(2+) stores in memory processing remains poorly defined. The current study explored a role for glutamate-dependent intracellular Ca(2+) release in memory processing via blockade of metabotropic glutamate receptor subtype 1 (mGluR1) and inositol (1,4,5)-trisphosphate receptors (IP(3)Rs). Using a single-trial discrimination avoidance task developed for the young chick, administration of the specific and potent mGluR1 antagonist JNJ16259685 (500nM, immediately post-training, ic), or the IP(3)R antagonist Xestospongin C (5microM, immediately post-training, ic), impaired retention from 90min post-training. These findings are consistent with mGluR1 activating IP(3)Rs to release intracellular Ca(2+) required for long-term memory formation and have been interpreted within an LTP2 model. The consequences of different patterns of retention loss following ryanodine receptor (RyR) and IP(3)R inhibition are discussed.

Outcome of suicidal ideation and behavior in a young, help-seeking population over a 2-year period.

Suicidal behavior is associated with negative outcomes, including completed suicide. This study examined the prevalence of suicidal behavior in a sample of referrals to a youth psychiatric service and investigated the stability of suicidality over 2 years. Of the 140 people (mean age 17.8) who were referred to a youth psychiatric service, 82 who were accepted for treatment (RA group) and 58 who were not accepted (RNA group) were assessed; 57% reported considering suicide and 39% reported attempting suicide in the 12 months prior to referral. Participants who reported suicidal ideation were significantly more likely than nonsuicidal participants to have multiple Axis I diagnoses and lower levels of functioning. At the 2-year follow-up there was a significant reduction in suicidality in the RA group, but not in the RNA group. In conclusion, suicidality is prevalent among young people referred to psychiatric services. Even brief contact with services results in a reduction in suicidality over 2 years.

Transcriptional activation of the Drosophila ecdysone receptor by insect and plant ecdysteroids.

A number of insect ecdysteroids, plant ecdysteroids and juvenoids were assayed for their ability to activate Drosophila nuclear receptors in transfected tissue culture cells. Discrete modifications to 20-hydroxyecdysone, the apparent natural ligand for the ecdysone receptor (EcR), conferred dramatic changes on the transcriptional activity of this receptor, suggesting that other biologically relevant EcR ligands may exist. Conversely, none of the compounds tested had a significant effect on the activity of three Drosophila orphan nuclear receptors: DHR38, DHR78 or DHR96. Taken together, these results demonstrate the selectivity of EcR for a series of natural and synthetic ecdysone agonists and suggest that as yet untested compounds may be responsible for activating DHR38, DHR78 and DHR96.

Professional and paraprofessional group treatments for depression: a comparison of cognitive-behavioral and mutual support interventions.

The relative efficacy of professional and paraprofessional therapists in providing group cognitive-behavioral therapy (CBT) and mutual support group therapy (MSG) was examined. Depressed outpatients (N = 98) were randomly assigned to CBT or MSG led by either 2 professional or 2 paraprofessional therapists. Results suggest that nonprofessionals were as effective as professionals in reducing depressive symptoms and that clients in the CBT and MSG conditions improved equally. Clinically significant improvement was demonstrated for both conditions. However, following treatment, more patients in the professionally led CBT groups were classified as nondepressed and alleviated than in the paraprofessionally led CBT groups. Additionally, therapist adherence to manual-based treatments was associated with greater improvement in clinician-rated depressive symptoms in both conditions and skills in cognitive restructuring were associated with greater improvement among clients in CBT.

Efficient image gradient based vehicle localization.

This paper reports novel algorithms for the efficient localization and recognition of traffic in traffic scenes. The algorithms eliminate the need for explicit symbolic feature extraction and matching. The pose and class of an object is determined by a form of voting and one-dimensional (1-D) correlations based directly on image gradient data, which can be computed "on the fly." The algorithms are therefore very well suited to real-time implementation. The algorithms make use of two a priori sources of knowledge about the scene and the objects expected: (1) the ground-plane constraint and (2) the fact that the overall shape of road vehicles is strongly rectilinear. Additional efficiency is derived from making the weak perspective assumption. These assumptions are valid in the road traffic application domain. The algorithms are demonstrated and tested using routine outdoor traffic images. Success with a variety of vehicles in several traffic scenes demonstrates the efficiency and robustness of context-based image understanding in road traffic scene analysis. The limitations of the algorithms are also addressed in the paper.

Patterns of symptomatic change in depressed patients in a private inpatient mood disorders program.

This naturalistic study of 352 depressed patients admitted to a mood disorders program in a private psychiatric hospital demonstrated that, for the majority of patients, combining cognitive group therapy with ongoing supportive individual, psychoeducational, milieu, and pharmacological interventions resulted in rapid overall improvement and discharge within a few weeks. Improvement was manifested across cognitive and vegetative factor scores of the Beck Depression Inventory. However, patterns of symptom remission differed for subgroups defined by different lengths of stay. For example, patients hospitalized for 4 weeks showed good initial response, followed by a plateau in improvement, and, finally, continued response. These patients eventually reached the same level of functioning at discharge as did more rapidly responding patients with briefer stays. In contrast, a subset of patients (10% of the sample) hospitalized 5 weeks or more showed less overall improvement (especially in vegetative symptoms), plateauing at a moderately symptomatic level. These data suggest that in a minority of depressed individuals, continuing physiological disturbances may underlie dysthymia or residual depression. However, in contrast to the high rates (20-30%) of chronicity reported from tertiary care settings, these data indicate the relatively good initial treatment response of depressed patients admitted to a private psychiatric hospital.

D-Lactate inhibition of memory in a single trial discrimination avoidance task in the young chick.

L-Lactate is a metabolite possibly able to meet some neuronal energy demands. However, a clear role for L-lactate in behaviour remains elusive. Administration of the inactive isomer D-lactate (1.75 mM; ic), immediately post-training, resulted in a persistent retention loss from 40 min post-training when used in conjuction with a single trial discrimination avoidance task designed for the young chick. Furthermore, 1mM noradrenaline (ic) administered 20 min post-training overcame the retention loss induced by D-lactate. Although not directly demonstrated in the current study, it is plausible that D-lactate inhibited memory processing by competing with L-lactate for uptake into neurons. The time of onset of the retention loss induced by D-lactate is in accord with findings where the action of noradrenaline is inhibited. The successful challenge of D-lactate inhibition by a high concentration of noradrenaline may suggest a relationship by some unidentified mechanism.