***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Selective serotonin reuptake inhibitors ( SSRIs ) are typically thought to have a delay of several weeks in the onset of their clinical effects . However , recent reports suggest they may have a much earlier therapeutic onset . A reduction in amygdala responsivity has been implicated in the therapeutic action of SSRIs . Aims To investigate the effect of a single dose of an SSRI on the amygdala response to emotional faces . Method Twenty-six healthy volunteers were r and omised to receive a single oral dose of citalopram ( 20 mg ) or placebo . Effects on the processing of facial expressions were assessed 3 h later using functional magnetic resonance imaging . Results Volunteers treated with citalopram displayed a significantly reduced amygdala response to fearful facial expressions compared with placebo . Conclusions Such an immediate effect of an SSRI on amygdala responses to threat supports the idea that antidepressants have an earlier onset of therapeutically relevant effects than conventionally thought BACKGROUND Although inflammatory activity is known to play a role in depression , no work has examined whether experimentally induced systemic inflammation alters neural activity that is associated with anhedonia , a key diagnostic symptom of depression . To investigate this , we examined the effect of an experimental inflammatory challenge on the neural correlates of anhedonia-namely , reduced ventral striatum ( VS ) activity to reward cues . We also examined whether this altered neural activity related to inflammatory-induced increases in depressed mood . METHODS Participants ( n = 39 ) were r and omly assigned to receive either placebo or low-dose endotoxin , which increases proinflammatory cytokine levels in a safe manner . Cytokine levels were repeatedly assessed through hourly blood draws ; self-reported and observer-rated depressed mood were assessed regularly as well . Two hours after drug administration , neural activity was recorded as participants completed a task in which they anticipated monetary rewards . RESULTS Results demonstrated that subjects exposed to endotoxin , compared with placebo , showed greater increases in self-reported and observer-rated depressed mood over time , as well as significant reductions in VS activity to monetary reward cues . Moreover , the relationship between exposure to inflammatory challenge and increases in observer-rated depressed mood was mediated by between-group differences in VS activity to anticipated reward . CONCLUSIONS The data reported here show , for the first time , that inflammation alters reward-related neural responding in humans and that these reward-related neural responses mediate the effects of inflammation on depressed mood . As such , these findings have implication s for underst and ing risk of depression in persons with underlying inflammation OBJECTIVE The authors sought to test the causal hypothesis that serotonergic function modulates aspects of the normal spectrum of individual differences in affective experience and social behavior in humans . METHOD A selective serotonin reuptake inhibitor ( SSRI ) , paroxetine , 20 mg/day ( N = 26 ) , or placebo ( N = 25 ) was administered to normal volunteers in a double-blind manner for 4 weeks , and personality variables and social behavior were assessed at baseline and at weeks 1 and 4 of treatment . RESULTS Relative to placebo , SSRI administration reduced focal indices of hostility through a more general decrease in negative affect , yet did not alter indices of positive affect . In addition , SSRI administration increased a behavioral index of social affiliation . Changes in both negative affect and affiliative behavior were significantly related to volunteers ' plasma SSRI levels at the end of the experiment . CONCLUSIONS Central serotonergic function may modulate a dimension of normal personality characterized by reduced negative affective experience and increased affiliative behavior .  SSRI administration has significant and detectable effects on these measures even in the absence of baseline clinical depression or other psychopathology UNLABELLED Neuropsychiatric disorders ( e.g. , autism , schizophrenia ) are partially characterized by social cognitive deficits , including impairments in the ability to perceive others ' emotional states , which is an aspect of social cognition known as theory of mind ( ToM ) . There is also evidence that inflammation may be implicated in the etiology of these disorders , but experimental data linking inflammation to deficits in social cognition is sparse . Thus , we examined whether exposure to an experimental inflammatory challenge led to changes in ToM. One hundred and fifteen ( n=115 ) healthy participants were r and omly assigned to receive either endotoxin , which is an inflammatory challenge , or placebo . Participants completed a social cognition task  , the Reading the Mind in the Eyes ( RME ) test , at baseline and at the peak of the inflammatory response for the endotoxin group . The RME test , a vali date d measure of ToM , evaluates how accurately participants can identify the emotional state of another person by looking only at their eyes . We found that endotoxin ( vs. placebo ) led to decreases in performance on the RME test from baseline to the peak of inflammatory response , indicating that acute inflammation can lead to decreases in the ability to accurately and reliably comprehend emotional information from others . Given that deficits in ToM are implicated in neuropsychiatric disorders , including those which may have an inflammatory basis , these results may have implication s for underst and ing the links between inflammation , social cognition , and neuropsychiatric disorders . CLINICAL TRIALS REGISTRATION Clinical Trials.gov NCT01671150 OBJECTIVE Antidepressants that inhibit the reuptake of serotonin ( SSRIs ) or norepinephrine ( SNRIs ) are effective in the treatment of disorders such as depression and anxiety . Cognitive psychological theories emphasize the importance of correcting negative biases of information processing in the nonpharmacological treatment of these disorders , but it is not known whether antidepressant drugs can directly modulate the neural processing of affective information . The present study therefore assessed the actions of repeated antidepressant administration on perception and memory for positive and negative emotional information in healthy volunteers . METHOD Forty-two male and female volunteers were r and omly assigned to 7 days of double-blind intervention with the SSRI citalopram ( 20 mg/day ) , the SNRI reboxetine ( 8 mg/day ) , or placebo . On the final day , facial expression recognition , emotion-potentiated startle response , and memory for affect-laden words were assessed . Question naires monitoring mood , hostility , and anxiety were given before and after treatment . RESULTS In the facial expression recognition task , citalopram and reboxetine reduced the identification of the negative facial expressions of anger and fear . Citalopram also abolished the increased startle response found in the context of negative affective images . Both antidepressants increased the relative recall of positive ( versus negative ) emotional material . These changes in emotional processing occurred in the absence of significant differences in ratings of mood and anxiety . However , reboxetine decreased subjective ratings of hostility and elevated energy . CONCLUSIONS Short-term administration of two different antidepressant types had similar effects on emotion-related tasks in healthy volunteers , reducing the processing of negative relative to positive emotional material . Such effects of antidepressants may ameliorate the negative biases in information processing that characterize mood and anxiety disorders . They also suggest a mechanism of action potentially compatible with cognitive theories of anxiety and depression Background Inflammation rapidly impairs mood and cognition and , when severe , can appear indistinguishable from major depression . These sickness responses are characterized by an acute reorientation of motivational state ; pleasurable activities are avoided , and sensitivity to negative stimuli is enhanced . However , it remains unclear how these rapid shifts in behavior are mediated within the brain . Methods Here , we combined computational modeling of choice behavior , experimentally induced inflammation , and functional brain imaging ( functional magnetic resonance imaging ) to describe these mechanisms . Using a double-blind , r and omized crossover study design , 24 healthy volunteers completed a probabilistic instrumental learning task on two separate occasions , one 3 hours after typhoid vaccination and one 3 hours after saline ( placebo ) injection . Participants learned to select high probability reward ( win £ 1 ) and avoid high probability punishment ( lose £ 1 ) stimuli . An action-value learning algorithm was fit to the observed behavior , then used within functional magnetic resonance imaging analyses to identify neural coding of prediction error signals driving motivational learning . Results Inflammation acutely biased behavior , enhancing punishment compared with reward sensitivity , through distinct actions on neural representations of reward and punishment prediction errors within the ventral striatum and anterior insula . Consequently , choice options leading to potential rewards were less behaviorally attractive , and those leading to punishments were more aversive . Conclusions Our findings demonstrate the neural mediation of a rapid , state-dependent reorientation of reward versus punishment sensitivity during inflammation . This mechanism may aid the adaptive reallocation of metabolic re sources during acute sickness but might also account for maladaptive , motivational changes that underpin the association between chronic inflammation and depression Substantial evidence demonstrates that inflammatory processes may underlie depression for a subset of patients , including work showing that healthy subjects exposed to an inflammatory challenge show increases in depressed mood and feelings of social disconnection . However , despite the fact that depression is two times as likely to occur in females than males , the vast majority of this work has been carried out in males . Thus , the objective of this study was to determine whether females ( vs males ) would show greater increases in proinflammatory cytokines , depressed mood , and social disconnection in response to an inflammatory challenge . One hundred and fifteen healthy participants ( 69 female ) completed this double-blind , placebo-controlled , r and omized clinical trial in which participants were r and omly assigned to receive either a single infusion of low-dose endotoxin ( derived from Escherichia coli ; 0.8 ng/kg of body weight ) or placebo ( same volume of 0.9 % saline ) . Interleukin-6 ( IL-6 ) , tumor necrosis factor-α ( TNF-α ) , depressed mood , and feelings of social disconnection were assessed hourly . Results showed that endotoxin ( vs placebo ) led to increases in proinflammatory cytokines ( TNF-α , IL-6 ) , depressed mood , and feelings of social disconnection . Females exposed to endotoxin showed greater increases in depressed mood and feelings of social disconnection . Furthermore , increases in TNF-α and IL-6 were correlated with increases in social disconnection for females but not for males . These sex differences in the relationships between inflammatory and socioemotional responses to an inflammatory challenge may be particularly important for underst and ing why females are two times as likely as males to develop depressive disorders Background Systemic infections commonly cause sickness symptoms including psychomotor retardation . Inflammatory cytokines released during the innate immune response are implicated in the communication of peripheral inflammatory signals to the brain . Methods We used functional magnetic resonance brain imaging ( fMRI ) to investigate neural effects of peripheral inflammation following  typhoid vaccination  in 16 healthy men , using a double-blind , r and omized , crossover-controlled design . Results Vaccination had no global effect on neurovascular coupling but markedly perturbed neural reactivity within substantia nigra during low-level visual stimulation . During a cognitive task , individuals in whom typhoid vaccination engendered higher levels of circulating interleukin-6 had significantly slower reaction time responses . Prolonged reaction times and larger interleukin-6 responses were associated with evoked neural activity within substantia nigra . Conclusions Our findings provide mechanistic insights into the interaction between inflammation and neurocognitive performance , specifically implicating circulating cytokines and midbrain dopaminergic nuclei in mediating the psychomotor consequences of systemic infection Rationale Acute tryptophan depletion ( ATD ) decreases levels of central serotonin . ATD thus enables the cognitive effects of serotonin to be studied , with implication s for the underst and ing of psychiatric conditions , including depression . Objective To determine the role of serotonin in conscious ( explicit ) and unconscious/incidental processing of emotional information . Material s and methods A r and omized , double-blind , cross-over design was used with 15 healthy female participants . Subjective mood was recorded at baseline and after 4 h , when participants performed an explicit emotional face processing task , and a task eliciting unconscious processing of emotionally aversive and neutral images presented subliminally using backward masking . Results ATD was associated with a robust reduction in plasma tryptophan at 4 h but had no effect on mood or autonomic physiology . ATD was associated with significantly lower attractiveness ratings for happy faces and attenuation of intensity/arousal ratings of angry faces . ATD also reduced overall reaction times on the unconscious perception task , but there was no interaction with emotional content of masked stimuli . ATD did not affect breakthrough perception ( accuracy in identification ) of masked images . Conclusions ATD attenuates the attractiveness of positive faces and the negative intensity of threatening faces , suggesting that serotonin contributes specifically to the appraisal of the social salience of both positive and negative salient social emotional cues . We found no evidence that serotonin affects unconscious processing of negative emotional stimuli . These novel findings implicate serotonin in conscious aspects of active social and behavioural engagement and extend knowledge regarding the effects of ATD on emotional perception BACKGROUND Infectious , autoimmune , and neurodegenerative diseases are associated with profound psychological disturbances . Studies in animals clearly demonstrate that cytokines mediate illness-associated behavioral changes . However , the mechanisms underlying the respective psychological alterations in humans have not been established yet . Therefore , we investigated the effects of low-dose endotoxemia , a well-established and safe model of host-defense activation , on emotional , cognitive , immunological , and endocrine parameters . METHODS In a double-blind , crossover study , 20 
    Output:
    
Acute experimental inflammation causes negative biases in social and emotional processing that could explain observed associations between inflammation and depression