Neuropsychological Functioning in Late-Life Depression.

Neuropsychological functioning in late-life depression.

Front Psychol. 2013; 4: 381
Dybedal GS, Tanum L, Sundet K, Gaarden TL, Bjølseth TM

Background: The literature describing neurocognitive function in patients with late-life depression (LLD) show inconsistent findings in regard to incidence and main deficits. Reduced information processing speed is in some studies found to explain deficits in higher order cognitive function, while other studies report specific deficits in memory and executive function. Our aim was to determine the characteristics of neuropsychological functioning in non-demented LLD patients. Methods: A comprehensive neuropsychological battery was administered to a group of hospitalized LLD patients and healthy control (HC) subjects. Thirty-nine patients without dementia, 60 years or older meeting DSM-IV criteria for current episode of major depression, and 18 non-depressed control subjects were included. The patient group was characterized by having a long lasting current depressive episode of late-onset depression and by being non-responders to treatment with antidepressants. Neurocognitive scores were calculated for the domains of information processing speed, verbal memory, visuospatial memory, executive function, and language. Number of impairments (performance below the 10th percentile of the control group per domain) for each participant was calculated. Results: Nearly half of the patients had a clinically significant cognitive impairment in at least one neurocognitive domain. Relative to HC subjects, LLD patients performed significantly poorer in the domains of information processing speed and executive function. Executive abilities were most frequently impaired in the patient group (39% of the patients). Even when controlling for differences in processing speed, patients showed more executive deficits than controls. Conclusions: Controlling for processing speed, patients still showed impaired executive function compared to HCs. Reduced executive function thus appears to be the core neurocognitive deficit in LLD. Executive function seems to be an umbrella concept for several connected but distinct cognitive functions. Further studies of neuropsychological functioning in LLD patients are needed to characterize more specific what kinds of executive impairments patients have. Additional studies of remitted LLD patients are needed to separate episode-related and persistent impairments. HubMed – depression

Do concomitant pain symptoms in patients with major depression affect quality of life even when taking into account baseline depression severity?

Patient Prefer Adherence. 2013; 7: 463-70
Novick D, Montgomery W, Kadziola Z, Moneta V, Peng X, Brugnoli R, Haro JM

Patients with major depressive disorder (MDD) may suffer from concomitant pain symptoms. The aim of this study is to determine whether the presence of painful physical symptoms (PPS) influences quality of life when taking into account baseline depression severity.Patients with a new or first episode of MDD (n = 909) were enrolled in a 3-month prospective observational study in East Asia. The Hamilton Depression Rating Scale, Clinical Global Impression-Severity score, Somatic Symptom Inventory, and EuroQoL questionnaire-5 Dimensions (EQ-5D) and EQ-Visual Analogue Scale (EQ-VAS) were assessed at baseline and 3 months’ follow-up. The presence of PPS was defined as a mean score of ?2 on the Somatic Symptom Inventory pain-related items. Regression analyses determined predictors of quality of life at 3 months, adjusting for age, sex, depressive symptoms, overall severity, and quality of life at baseline.PPS were present (PPS+) at baseline in 52% of patients. During the 3-month follow-up, EQ-VAS scores improved from 47.7 (standard deviation [SD] 20.6) to 72.5 (SD 20.4), and EQ-5D improved from 0.48 (SD 0.34) to 0.80 (SD 0.26). At 3 months, mean EQ-VAS was 66.4 (SD 21.2) for baseline PPS+ patients versus 78.5 (SD 17.6) for baseline PPS- patients, and mean EQ-5D was 0.71 (SD 0.29) versus 0.89 (SD 0.18). PPS+ at baseline was a significant predictor of quality of life at 3 months after adjusting for sociodemographic and baseline clinical variables.The presence of painful physical symptoms is associated with less improvement in quality of life in patients receiving treatment for major depression, even when adjusting for depression severity. HubMed – depression

Cyclooxygenase-2, PGE2-glycerol, and nitric oxide are involved in muscarine-induced presynaptic enhancement at the vertebrate neuromuscular junction.

J Physiol. 2013 Jul 1;
Lindgren CA, Newman ZL, Morford JJ, Ryan SB, Battani KA, Su Z

Previous work has demonstrated that activation of muscarinic acetylcholine receptors at the lizard neuromuscular junction (NMJ) induces a biphasic modulation of evoked neurotransmitter release: an initial depression followed by a delayed enhancement. The depression is mediated by the release of the endocannabinoid 2-arachidonylglycerol (2-AG) from the muscle and its binding to CB1 receptors on the motor nerve terminal. The work presented here suggests that the delayed enhancement of neurotransmitter release is mediated by cyclooxygenase-2 (COX-2) as it converts 2-AG to the glycerol ester of prostaglandin E2 (PGE2-G). Using immunofluorescence, COX-2 was detected in the perisynaptic Schwann cells (PSCs) surrounding the NMJ. Pre-treatment with either of the selective COX-2 inhibitors, Nimesulide or DuP 697, prevents the delayed increase in endplate potential (EPP) amplitude normally produced by muscarine. In keeping with its putative role as a mediator of the delayed muscarinic effect, PGE2-G enhances evoked neurotransmitter release. Specifically, PGE2-G increases the amplitude of EPPs without altering that of spontaneous miniature EPPs (MEPPs). As shown previously for the muscarinic effect, the enhancement of evoked neurotransmitter release by PGE2-G depends on nitric oxide (NO) since the response is abolished by application of either L-NAME, an inhibitor of NO synthesis, or carboxy-PTIO, a chelator of NO. Intriguingly, the enhancement is not prevented by AH6809, a prostaglandin receptor antagonist but is blocked by capsazepine, a TRPV1 and TRPM8 receptor antagonist. Taken together, these results suggest that the conversion of 2-AG to PGE2-G by COX-2 underlies the muscarine-induced enhancement of neurotransmitter release at the vertebrate NMJ. HubMed – depression

Cholinergic modulation of neuronal excitability and recurrent excitation-inhibition in prefrontal cortex circuits: implications for gamma oscillations.

J Physiol. 2013 Jul 1;
Pafundo DE, Miyamae T, Lewis DA, Gonzalez-Burgos G

Cholinergic neuromodulation in neocortical networks is required for gamma oscillatory activity associated with working memory and other cognitive processes. Importantly, the cholinergic agonist carbachol (CCh) induces gamma oscillations in vitro, via mechanisms that may be shared with in vivo gamma oscillations and that are consistent with the pyramidal-interneuron-network-gamma (PING) model. In PING oscillations, pyramidal cells (PCs), driven by asynchronous excitatory input, recruit parvalbumin-positive fast spiking interneurons (FSNs), which then synchronize the PCs via feedback inhibition. Whereas the PING model is favored by current data, how cholinergic neuromodulation contributes to gamma oscillation production is poorly understood. We thus studied the effects of cholinergic modulation on circuit components of the PING model in mouse medial prefrontal cortex (mPFC) brain slices. CCh depolarized and evoked action potential firing in a fraction of PCs and increased excitatory synaptic input onto FSNs. In synaptically-connected pairs, CCh reduced the short-term depression at FSN-PC and PC-FSN synapses, equalizing synaptic strength during repetitive presynaptic firing while simultaneously increasing the failure probability. Interestingly, when PCs or FSNs fired in response to gamma frequency oscillatory inputs, CCh increased the firing probability per cycle. Combined with the equalization of synaptic strength, an increase by CCh in the fraction of neurons recruited per oscillation cycle may support oscillatory synchrony of similar strength during relatively long oscillation episodes such as those observed during working memory tasks, suggesting a significant functional impact of cholinergic modulation of mPFC circuit components crucial for the PING model. HubMed – depression