Faster speed of onset of the depressive episode is associated with lower cytokine serum levels (IL-2, -4, -6, -10, TNF-α and IFN-γ) in patients with major depression.

INTRODUCTION: Cytokines might play a key role in the pathophysiology of major depressive disorder (MDD). The speed of onset of depressive episodes has been discussed as an important clinical parameter in MDD. The aim of this study was to investigate a potential influence of the speed of onset of the depressive episode on cytokine serum levels. METHOD: Serum level of the cytokines interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ) granulocyte and monocyte colony stimulating factor (GM-CSF) were measured in a total of 92 patients with MDD that did not respond to at least one previous antidepressant treatment. Patients were retrospectively divided in two groups: Faster (≤4 weeks) and slower (>4 weeks) onset of the depressive episode defined as the time passing from the first depressive symptoms to a full-blown depressive episode by using information from a clinical interview. RESULTS: We found significantly lower serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ in patients with a faster onset compared to patients with a slower onset of the depressive episodes. Furthermore, lower cytokine serum levels of IL-2, IL-8, IL-10 and IFN-γ were found in patients with a shorter duration (less than 6 months) compared to a longer duration (6-24 months) of the current depressive episode. This effect on cytokines was independent from the effect of the speed of onset of the depressive episode. CONCLUSIONS: Patients with faster onset of the depressive episode might represent a biological subtype of MDD with lower serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ.

Reward- and attention-related biasing of sensory selection in visual cortex.

Attention to task-relevant features leads to a biasing of sensory selection in extrastriate cortex. Features signaling reward seem to produce a similar bias, but how modulatory effects due to reward and attention relate to each other is largely unexplored. To address this issue, it is critical to separate top-down settings defining reward relevance from those defining attention. To this end, we used a visual search paradigm in which the target's definition (attention to color) was dissociated from reward relevance by delivering monetary reward on search frames where a certain task-irrelevant color was combined with the target-defining color to form the target object. We assessed the state of neural biasing for the attended and reward-relevant color by analyzing the neuromagnetic brain response to asynchronously presented irrelevant distractor probes drawn in the target-defining color, the reward-relevant color, and a completely irrelevant color as a reference. We observed that for the prospect of moderate rewards, the target-defining color but not the reward-relevant color produced a selective enhancement of the neuromagnetic response between 180 and 280 msec in ventral extrastriate visual cortex. Increasing reward prospect caused a delayed attenuation (220-250 msec) of the response to reward probes, which followed a prior (160-180 msec) response enhancement in dorsal ACC. Notably, shorter latency responses in dorsal ACC were associated with stronger attenuation in extrastriate visual cortex. Finally, an analysis of the brain response to the search frames revealed that the presence of the reward-relevant color in search distractors elicited an enhanced response that was abolished after increasing reward size. The present data together indicate that when top-down definitions of reward relevance and attention are separated, the behavioral significance of reward-associated features is still rapidly coded in higher-level cortex areas, thereby commanding effective top-down inhibitory control to counter a selection bias for those features in extrastriate visual cortex.

Role of the somatostatin system in contextual fear memory and hippocampal synaptic plasticity.

Somatostatin has been implicated in various cognitive and emotional functions, but its precise role is still poorly understood. Here, we have made use of mice with somatostatin deficiency, based upon genetic invalidation or pharmacologically induced depletion, and Pavlovian fear conditioning in order to address the contribution of the somatostatin system to associative fear memory. The results demonstrate an impairment of foreground and background contextual but not tone fear conditioning in mice with targeted ablation of the somatostatin gene. These deficits were associated with a decrease in long-term potentiation in the CA1 area of the hippocampus. Both the behavioral and the electrophysiological phenotypes were mimicked in wild-type mice through application of the somatostatin-depleting substance cysteamine prior to fear training, whereas no further deficits were observed upon application in the somatostatin null mutants. These results suggest that the somatostatin system plays a critical role in the acquisition of contextual fear memory, but not tone fear learning, and further highlights the role of hippocampal synaptic plasticity for information processing concerning contextual information.