Objective the cognitive neuropsychological model of depression proposes that negative biases in the processing of emotionally salient information have a central role in the development and maintenance of depression. We have conducted a systematic review to determine whether acute experimental inflammation is associated with changes to cognitive and emotional processing that are thought to cause and maintain depression. Methods We identified experimental studies in which healthy individuals were administered an acute inflammatory challenge (bacterial endotoxin/vaccination) and standardised tests of cognitive function were performed. Results Fourteen references were identified, reporting findings from 12 independent studies on 345 participants. Methodological quality was rated strong or moderate for 11 studies. Acute experimental inflammation was triggered using a variety of agents (including endotoxin from E. coli, S. typhi, S. abortus Equi and Hepatitis B vaccine) and cognition was assessed over hours to months, using cognitive tests of i) attention/executive functioning, ii) memory and iii) social/emotional processing. Studies found mixed evidence that acute experimental inflammation caused changes to attention/executive functioning (2 of 6 studies showed improvements in attention executive function compared to control), changes in memory (3 of 5 studies; improved reaction time: reduced memory for object proximity: poorer immediate and delayed memory) and changes to social/emotional processing (4 of 5 studies; reduced perception of emotions, increased avoidance of punishment/loss experiences, and increased social disconnectedness). Conclusions Acute experimental inflammation causes negative biases in social and emotional processing that could explain observed associations between inflammation and depression.

Objective Depression is common in people with long term conditions, and is associated with worse medical outcomes. Previous research shows perseverative negative thinking (e.g. worry, rumination) predicts subsequent depression and worse medical outcomes, suggesting interventions targeting perseverative negative thinking could improve depression and medical outcomes. Previous studies recruited healthy individuals, however. This review aimed to determine the temporal relationship and strength of prospective association of perseverative negative thinking with depression, anxiety and emotional distress in people with long term conditions. Method Four electronic databases were searched for studies including standardised measures of perseverative negative thinking and depression, anxiety or emotional distress, and which presented prospective associations. Findings were narratively synthesized. Results Thirty studies were identified in a range of long term conditions. Perseverative negative thinking and subsequent depression, anxiety or emotional distress were significantly correlated in the majority of studies (bivariate r = 0.23 to r = 0.73). 25 studies controlled for confounders, and in 15 perseverative negative thinking predicted subsequent depression, anxiety or emotional distress. Results varied according to condition and study quality. Six of 7 studies found bivariate associations between depression, anxiety or emotional distress and subsequent perseverative negative thinking, though 2 studies controlling for key covariates found no association. Few studies assessed the impact of perseverative negative thinking on medical outcomes. Conclusion Strongest evidence supported perseverative negative thinking predicting subsequent depression, anxiety and emotional distress in people with long term conditions. Further prospective research is warranted to clarify the association of perseverative negative thinking with subsequent poor medical outcomes.

BACKGROUND: Depression is common in people with long term conditions (LTCs) and is associated with worse medical outcomes. Understanding the mechanisms underpinning this relationship could help predict who is at increased risk of adverse medical outcomes, and lead to the development of novel interventions. Perseverative negative cognitive processes, such as worry and rumination, involve repetitive and frequent thoughts about oneself and one's concerns. These processes have been associated with negative affect, and also adverse medical outcomes. The results of prospective studies, which would allow causal inferences to be drawn, are more equivocal however. Furthermore, the majority of studies have been conducted in physically healthy individuals, and we do not know to what extent these findings will generalise to people with LTCs. METHODS/DESIGN: Electronic databases will be searched using a search strategy including controlled vocabulary and text words related to perseverative negative cognitive processes (such as worry and rumination) and negative affect (including depression and anxiety). Records will be hand-searched for terms related to LTCs. Citation and bibliography searching will be conducted, and authors of included studies will be contacted to identify unpublished studies. Studies will be included if they contain a standardised measure of the prospective association between perseverative negative cognitive processes and negative affect, or vice versa, in people with LTCs. Narrative and meta-analytic methods will be used to synthesize the data collected. DISCUSSION: This review will identify and synthesise studies of the prospective association between perseverative negative cognitive processes and negative affect among people with LTCs. The findings will help to identify whether worry and rumination could cause depression and anxiety in people with LTCs, and might indicate whether perseverative negative cognitive processes are appropriate targets for treatment.

Attentional capture and behavioral control by conditioned stimuli have been dissociated in animals. The current study assessed this dissociation in humans. Participants were trained on a Pavlovian schedule in which 3 visual stimuli, A, B, and C, predicted the occurrence of an aversive noise with 90%, 50%, or 10% probability, respectively. Participants then went on to separate instrumental training in which a key-press response canceled the aversive noise with a. 5 probability on a variable interval schedule. Finally, in the transfer phase, the 3 Pavlovian stimuli were presented in this instrumental schedule and were no longer differentially predictive of the outcome. Observing times and gaze dwell time indexed attention to these stimuli in both training and transfer. Aware participants acquired veridical outcome expectancies in training--that is, a > B > C, and these expectancies persisted into transfer. Most important, the transfer effect accorded with these expectancies, a > B > C. By contrast, observing times accorded with uncertainty--that is, they showed B > a = C during training, and B < a = C in the transfer phase. Dwell time bias supported this association between attention and uncertainty, although these data showed a slightly more complicated pattern. Overall, the study suggests that transfer is linked to outcome prediction and is dissociated from attention to conditioned stimuli, which is linked to outcome uncertainty.

BACKGROUND: the ability to abstain from drinking, despite incentives to imbibe, is essential to recovery from alcoholism. METHODS: We used an incentive conflict task to investigate ability to abstain from responding during presentations of incentive cues. Both alcoholic (n = 23) and healthy subjects (n = 22) were required to withhold responding during the simultaneous presentation of two visual stimuli in which the individual presentation allowed responding for monetary reward. Brain structures activated during performance of the task were studied using functional magnetic resonance imaging in healthy volunteers (n = 8), and changes in gray matter volume were studied in a separate group of patients (n = 29) compared with control subjects (n = 31) in regions of interest identified on functional magnetic resonance imaging. RESULTS: Abstinent alcoholic patients were severely impaired on the incentive conflict task. The impairment was greater in patients with experience of several versus a single detoxification. Healthy volunteers, during the same incentive conflict task, showed distinct patterns of brain activation (including gyrus rectus, ventromedial prefrontal cortex, and superior frontal gyrus). Reduction of gray matter volume in ventromedial prefrontal cortex and superior frontal gyrus of patients was more extensive in those with multiple detoxifications. CONCLUSIONS: Performance deficits in alcoholics are associated with withdrawal-induced impairments in prefrontal subfields, which are exacerbated following repeated episodes of detoxification. Detoxification thus compromises functional and structural integrity of prefrontal cortex and may thus impair the ability to control future drinking. Performance in the incentive conflict task is a sensitive biomarker for such deficits.

To investigate the efficacy and cognitive and psychomotor effects of venlafaxine and dothiepin in elderly patients with moderate major depression. A prospective, randomized, double-blind, parallel-group, active comparator controlled study was conducted. Eighty-eight patients (aged > or = 60 years) were enrolled. Each patient received either venlafaxine (immediate release formulation) 37.5 mg twice per day or dothiepin 25 mg mane followed by 50 mg nocte for 26 weeks. Efficacy was assessed with the Montgomery-Asberg Depression Rating Scale and the Hamilton Depression Rating Scale. A psychometric test battery to assess cognitive function, activities of daily living and sleep consisted of Critical Flicker Fusion (CFF), Short-term Memory--Kim's Game, Cognitive Failures Questionnaire, Milford Epworth Sleepiness Scale, Leeds Sleep Evaluation Questionnaire, and an Accident Scoring Questionnaire. Quality of Life Questionnaires (Short Form 36 and Quality of Life in Depression Scale) were also administered. Venlafaxine significantly (p < 0.05) raised CFF scores compared to baseline but had no effect on any other measure. Dothiepin significantly (p < 0.05) lowered CFF threshold, and increased ratings of both sedation and difficulty in waking. The results showed that venlafaxine at doses of 37.5 mg b.i.d. in elderly depressed patients is free from disruptive effects on cognitive function and psychomotor performance.