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Cited by 330Neural and Behavioral Psychology StudiesAnxiety, Depression, Psychometrics, Treatment, Cognitive ProcessesNeurotransmitter Receptor Influence on Behavior

Affective Cognition and its Disruption in Mood Disorders

Open access
Elliott, Rebecca, Zahn, Roland, Deakin, J F William, Anderson, Ian M·2011·Neuropsychopharmacology
DOI 10.1038/npp.2010.77PMC PMC3055516
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Abstract

In this review, we consider affective cognition, responses to emotional stimuli occurring in the context of cognitive evaluation. In particular, we discuss emotion categorization, biasing of memory and attention, as well as social/moral emotion. We discuss limited neuropsychological evidence suggesting that affective cognition depends critically on the amygdala, ventromedial frontal cortex, and the connections between them. We then consider neuroimaging studies of affective cognition in healthy volunteers, which have led to the development of more sophisticated neural models of these processes. Disturbances of affective cognition are a core and specific feature of mood disorders, and we discuss the evidence supporting this claim, both from behavioral and neuroimaging perspectives. Serotonin is considered to be a key neurotransmitter involved in depression, and there is a considerable body of research exploring whether serotonin may mediate disturbances of affective cognition. The final section presents an overview of this literature and considers implications for understanding the pathophysiology of mood disorder as well as developing and evaluating new treatment strategies.

AI snapshot

Written from the paper’s full text.

TL;DR

This review synthesizes behavioral, neuropsychological, and neuroimaging evidence on affective cognition—emotion recognition, attentional and memory bias, and social/moral emotion—and its disruption in mood disorders, with a focus on serotonin. It argues that amygdala–ventromedial prefrontal/cingulate circuitry is central, that depression involves negative biases across cognitive domains, and that serotonergic effects are subtle and often confounded by mood and task factors.

Key findings

  • Affective cognition depends on a distributed network including the amygdala, ventromedial/orbitofrontal cortex, anterior cingulate, hippocampus, insula, and temporal cortices; the amygdala is especially important for emotion recognition and emotional memory, while ventromedial frontal regions are more critical for social and moral emotions. Task demands and inter-regional connectivity strongly shape these responses, and the authors consider a comprehensive neural model premature.
  • Depression is associated with negative biases in face emotion processing, attention, and memory; for example, depressed patients can show slowed responses to happy targets in affective Go/No-Go tasks and enhanced ventral anterior cingulate responses to sad targets with reduced responses to happy targets, opposite to controls. Such biases may persist in remission and appear in at-risk individuals, suggesting trait vulnerability or scarring.
  • Social and moral emotions are clinically relevant: guilt and shame are elevated in major depression, and one cited inpatient study found 75% with severe worthlessness and 20% with high guilt. The subgenual cingulate, implicated in guilt in healthy people, is also a key node in depression models, but direct neuroimaging studies of moral emotions in major depression were lacking at the time.
  • Serotonin manipulations show complex effects: acute tryptophan depletion reduces plasma tryptophan by roughly 70–90%; the 5-HTTLPR S allele is linked to altered affective bias and increased amygdala reactivity, with a meta-analysis of 14 studies suggesting it may account for up to 10% of variance. Behavioral effects of acute 5-HT manipulation are generally subtle, and patient treatment studies are confounded by mood improvement.

Methods

  • Narrative, data-driven review of human affective cognition literature, covering neuropsychological lesion studies, functional neuroimaging in healthy volunteers, behavioral and neuroimaging studies in mood disorders, and pharmacological/genetic studies of serotonin.
  • No primary data collection or formal meta-analysis; the authors synthesize selected studies and include tables/figures summarizing tasks, 5-HT effects, and methodological considerations.
  • Focus is primarily on unipolar depression, with anxiety comorbidity considered together; bipolar depression is largely excluded.

Limitations

  • The paper states that the review is selective, the literature contains inconsistencies and gaps, tasks and primary outcomes are not standardized, secondary measures are often over-interpreted, patient groups are heterogeneous, and treatment studies cannot easily separate pharmacological from mood-related effects.
  • The paper notes that neuropsychological evidence is limited by the rarity of selective lesions, empirical data on basic affective cognition in ventromedial frontal patients are sparse, and direct neuroimaging investigations of moral emotions in major depression were lacking.
  • Evident from the text: many conclusions rest on small, unreplicated, or methodologically varied studies; genotype and 5-HT findings are discrepant; and the authors explicitly state that a comprehensive neuronal model of affective cognition cannot yet be confidently proposed.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/npp.2010.77

Cites

390 of 390 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

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  • Findingcitation

    Goulden et al. (2010a) observed abnormal connectivity associated with sad face processing in remitted depression.

    “Using this approach, we have observed abnormal connectivity associated with sad face processing in remitted depression (Goulden et al., 2010a).”
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  • Findingcitation

    Thomas et al. (submitted) suggests that personality traits conveying vulnerability, such as rumination, may interact with depression history to produce trait-related changes in limbic responses to emotional faces.

    “Recent data from our research suggests that personality traits conveying vulnerability (rumination) may interact with depression history to produce trait related changes in limbic responses to emotional faces (Thomas et al. submitted).”
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  • Interpretationcitation

    Impairments at the cognitive/affective interface may be most specific to mood disorder.

    “impairments at the cognitive/affective interface may be most specific to mood disorder (Clark et al., 2009)”
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  • Interpretationreasoning

    Affective cognition depends critically on the amygdala, ventromedial frontal cortex, and the connections between them.

    “We discuss limited neuropsychological evidence suggesting that affective cognition depends critically on amygdala, ventromedial frontal cortex and the connections between them.”
    • Also stated in: § 3.3. Summary · hedged
      “evidence suggests that amygdala, VMPFC and the connections between them are crucial.”
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  • Interpretationcitation

    Unipolar depression and anxiety should be considered together in a neurobiological context because of comorbidity and commonalities of symptomatology and treatment response.

    “frequent comorbidity with anxiety (Gorman, 1996) and commonalities of symptomatology and treatment response indicate a strong case for considering the disorders together in a neurobiological context (Ressler and Mayberg, 2007).”
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    Interpretationnone given

    Classic neuropsychological evidence points to core roles of the amygdala and ventral prefrontal cortex in affective cognition.

    “Classic neuropsychological evidence will be discussed, pointing to core roles of amygdala and ventral prefrontal cortex in affective cognition.”
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    Premisecitation

    Ekman and Friesen proposed six basic emotional expressions recognisable across species and cultural boundaries.

    “Ekman and Friesen (1971) proposed that six basic emotional expressions could be recognised across both species and cultural boundaries: happy, sad, fearful, angry, disgusted and surprised”
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    Tasks using Ekman stimuli or variants are among the most widely used probes of affective cognition.

    “Tasks using these stimuli, or variants, have emerged as among the most widely used probes of affective cognition.”
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    Interpretationnone given

    Serotonin modulates affective cognition.

    “we consider the role of serotonin (5-hydroxytryptamine, 5-HT) in modulating affective cognition, which has important implications for understanding the pathophysiology of depression and mechanisms of effective antidepressants.”
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    • Rests on an assumption: Serotonin is a key neurotransmitter involved in depression.

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    Premisecitation

    Arguments that affective cognition is a central efficacy marker for antidepressant treatment are gathering momentum.

    “Arguments that affective cognition represents a central efficacy marker for antidepressant treatment are gathering momentum (Harmer et al., 2010)”
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    Interpretationnone given

    Functional neuroimaging in healthy subjects elaborates the roles of the amygdala, ventral prefrontal cortex, and other structures in affective cognition.

    “We will then consider the functional neuroimaging literature in healthy subjects which elaborates the roles of these, and other, structures in affective cognition.”
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    Premisecitation

    Bipolar depression is a distinct disorder.

    “Bipolar depression is a distinct disorder largely beyond our scope (Phillips et al., 2008 for an excellent recent review).”
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    Premisecitation

    IAPS pictures have been extensively standardised using valence and arousal and used to assess emotion perception in neuroimaging.

    “the International Affective Pictures Series (IAPS: Lang et al., 2008) are a set of pictures which have been extensively standardised using the dimensional measures of valence and arousal and used to assess emotion perception in neuroimaging contexts.”
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    Interpretationnone given

    Disturbances of affective cognition are a core and specific feature of mood disorders.

    “Disturbances of affective cognition are a core and specific feature of mood disorders and we discuss the evidence supporting this claim, both from behavioural and neuroimaging perspectives.”
    • Also stated in: § 1.3 Affective function and mood disorder · plain
      “Disturbance of affective cognition constitutes a core aspect of the symptomatology of many psychiatric disorders, in particular depression and anxiety.”
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    Premisecitation

    Moral emotions are cognitively multi-faceted and entail complex causal attributions.

    “Moral emotions are cognitively multi-faceted (Eisenberg, 2000) and entail complex causal attributions (Weiner, 1985), such as who caused an outcome.”
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    There is evidence for transcultural ubiquity of moral emotions.

    “There is evidence for transcultural ubiquity of moral emotions (Fessler, 1999)”
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    The exact actions and values for which a moral emotion such as guilt is felt vary across socio-cultural groups and individuals.

    “the exact actions and values for which we feel a certain moral emotion such as guilt greatly varies across socio-cultural groups and individuals”
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    Premisecitation

    Phineas Gage suffered VMPFC damage in 1848 and showed emotional and social changes without significant cognitive impairment.

    “The seminal neuropsychological case from an affective processing standpoint is Phineas Gage who suffered VMPFC damage in 1848 and was reported to show emotional and social changes in the absence of significant cognitive impairment (Damasio et al., 1994).”
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    Premisecitation

    More cognitive aspects of empathy are differentially sensitive to ventromedial lesions while emotional aspects depend on inferior frontal gyrus.

    “Shamay-Tsoory et al. (2009) suggest that more cognitive aspects of empathy are differentially sensitive to ventromedial lesions while emotional aspects depend on inferior frontal gyrus.”
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    Shame-proneness has been measured implicitly, circumventing social desirability biases in self-report.

    “More recently, shame-proneness has been measured implicitly (Rusch et al., 2007) circumventing social desirability biases classically encountered in self-report measures.”
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    Premisecitation

    Individual differences in proneness to guilt and shame have been classically measured using self-report questionnaires.

    “Individual differences in proneness to certain moral emotions, such as guilt (O'Connor et al., 1997;Tangney, 1990) and shame (Tangney, 1990) have been classically measured using self-report questionnaires.”
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    Premisenone given

    Moral sentiments enable people to overcome self-interest and benefit others or enforce moral rules and values.

    “Moral sentiments enable people to overcome self-interest and benefit other people directly”
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    Interpretationreasoning

    Neuropsychology has provided far less information about emotional processing and affective cognition than about non-affective cognition, largely due to the rarity of selective lesions.

    “However, neuropsychology has provided far less information about emotional processing and affective cognition, largely due to the rarity of lesions with selective effects on affective processing.”
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    Premisecitation

    Emotional moral decisions depend on VMPFC; when it is damaged, the cognitive dorsal frontal system can more easily enforce rational moral decisions.

    “One explanation for this finding is that emotional moral decisions depend on the VMPFC and when this is damaged, the cognitive dorsal frontal system can more easily enforce rational moral decisions that lead to overall greater moral benefit (Greene et al., 2004).”
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    Premisecitation

    Moral emotion deficits are not unique to ventromedial lesions; mesolimbic and basal forebrain lesions may also cause morally inappropriate behaviour.

    “Moral emotion deficits are not unique to patients with ventromedial lesions.Patients with lesions to mesolimbic and basal forebrain regions may also exhibit morally inappropriate behaviour (Moll et al, 2005).”
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    Premisecitation

    The lower fear ratings in amygdala patients generalised to other negative emotions to some extent but not to happiness.

    “This finding generalised to other negative emotions to some extent, but not to happiness (Adolphs et al., 2004).”
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    Interpretationcitation

    The amygdala plays a critical role in face emotion processing, perhaps via control of response in posterior perceptual regions.

    “These findings suggest that the amygdala plays a critical role in face emotion processing, perhaps via control of response in posterior perceptual regions (Vuilleumier et al., 2004).”
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    Premisecitation

    Amnesic patients with varying lesion types showed mild to moderate verbal recall deficits but still enhanced recall of emotional versions of the Cahill story.

    “Hamann et al. (1997) showed that a group of amnesic patients with varying lesion types presented mild to moderate memory deficits on measures of verbal recall, but still showed enhanced recall of emotional versions of the Cahill story task.”
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    Premisecitation

    Patients with amygdala damage can recognise faces and generate a normal range of facial expressions.

    “Patients with amygdala damage can recognise faces and generate a normal range of facial expressions (Anderson and Phelps, 2000).”
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    Interpretationreasoning

    The amygdala plays a central role in emotion recognition and categorisation as well as emotional biasing of memory.

    “Neuropsychological studies indicate that the amygdala plays a central role in emotion recognition and categorisation as well as emotional biasing of memory.”
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    Premisecitation

    Many studies focus on the amygdala's role in perception of both negative and positive emotions.

    “Many studies focus on the role of the amygdala in perception of both negative (e.g.Wang et al., 2005;Stark et al., 2007) and positive (e.g.Garavan et al., 2001;Kensinger and Schachter, 2006) emotions.”
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    Premisecitation

    Left lateralised amygdala damage abolishes the normal enhancement of verbal memory by emotional valence, while the right amygdala may mediate a similar effect for visual information.

    “Further evidence suggests that specifically left lateralised damage abolishes the normal enhancement of verbal memory by emotional valence (Buchanan et al., 2001;Edith Frank and Tomaz, 2003) while the right amygdala may mediate a similar effect for visual information (Markowitsch, 1998).”
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    Interpretationreasoning

    Patients with VMPFC damage do not appear to demonstrate deficits in basic affective cognition, but their impairments are in the social emotional domain.

    “Patients with VMPFC damage do not appear to demonstrate deficits in basic affective cognition (although there is a paucity of empirical data) rather their impairments are in the social emotional domain.”
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    Interpretationreasoning

    Functional neuroimaging provides a tool to test and develop the hypothesis that the amygdala, VMPFC and their connections are crucial.

    “Functional neuroimaging provides a tool to test and develop this hypothesis.”
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    Premisecitation

    Amygdala response is specific to perception of emotional content, while hippocampal and prefrontal responses are associated with subjective experience.

    “A more direct attempt to separate perception of emotional content from subjective experience of emotion found that amygdala response was specific to perception, while hippocampal and prefrontal responses were associated with subjective experience (Garrett and Maddock, 2006).”
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    Premisecitation

    Valence and arousal interact in critical emotion-processing regions.

    “it has recently been suggest that valence and arousal interact in critical emotion-processing regions (Lewis et al, 2007;Nielen et al, 2009.”
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    Premisecitation

    The relationship between subjective valence ratings and BOLD response is complex; responses correlate positively with unpleasant valence ratings and negatively with pleasant ratings in partially overlapping regions.

    “Response in a number of regions correlated positively with valence ratings of unpleasant pictures and response in partially overlapping regions correlated negatively with ratings of pleasant pictures, suggesting that the relationship between rating valence and BOLD response is a complex one.”
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    Premisecitation

    Amygdala response to fearful faces has been widely reported.

    “Amygdala response to fearful faces has been widely reported (Whalen et al., 2001)”
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    Premisecitation

    Surprise is the least investigated of the six basic emotions and has distinct qualities; it is a transitory emotion.

    “Of the six basic emotions, surprise is the least investigated and has distinct qualities.Specifically, surprise can be described as a 'transitory emotion'; it is briefly experienced and changes into other expressions depending upon the nature of the surprise (Posamentier and Abdi, 2003).”
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    Disgust is associated with response in basal ganglia and reliable insula response correlating with increasing intensity of disgust.

    “Disgust is associated with response in areas of the basal ganglia (Posamentier and Abdi, 2003) as well as reliable response in the insula, correlating with increasing intensity of disgust (Phillips et al., 1997).”
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    Amygdala response to faces is suppressed as attentional resources are diverted elsewhere, and this effect is specific to fearful faces.

    “Brassen et al (2010) also reported suppression of amygdala response to faces as attentional resources were diverted elsewhere, and in this study the effect was specific to fearful faces.”
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    Responses to fearful and angry faces are associated with reciprocal connections between amygdala and ventral cingulate and connections between amygdala and OFC.

    “Stein et al. (2007) reported that responses to fearful and angry faces were associated with reciprocal connections between amygdala and ventral cingulate and also connections between amygdala and OFC.”
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    Premisecitation

    Negative ratings of surprised faces elicit right amygdala response, while positive ratings are associated with signal changes in ventral prefrontal cortex.

    “Kim et al. (2003) investigated brain responses to surprise in relation to valence ratings; negative ratings of surprised faces elicited right amygdala response, while positive ratings were associated with signal changes in ventral prefrontal cortex.”
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    Interpretationreasoning

    Different face tasks will differentially engage emotional regions; overt categorisation of emotion likely engages emotional processing regions differently from covert tasks.

    “they indicate that different faces tasks will differentially engage emotional regions.In particular the studies suggest that overt categorisation of emotion is likely to engage emotional processing regions differently from covert tasks.”
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    Premisecitation

    Subsequent memory for negative or high arousal information is associated with occipital and temporal activity, whereas memory for positive or low arousal information is associated with frontal activity.

    “Mickley et al. (2009) showed that subsequent memory for negative or high arousal information was associated with occipital and temporal activity, whereas memory for positive or low arousal information was associated with frontal activity.”
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    Premisecitation

    The neural basis of memory for neutral pictures is modulated by the emotional context in which they were encoded; amygdala and OFC are critical regions.

    “Smith et al. (2004) showed that the neural basis of memory for neutral pictures was modulated by the emotional context in which they had been encoded, an incidental task in which emotional content is not the focus of cognition.Again, amygdala and OFC were critical regions.”
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    Premisecitation

    When retrieval of emotional material is relevant to current behaviour, enhanced connectivity between amygdala and hippocampus is bi-directional and modulated by OFC.

    “When retrieval of emotional material was relevant to current behaviour, enhanced connectivity between amygdala and hippocampus was bi-directional and modulated by OFC.”
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    Interpretationcitation

    The amygdala is a central structure in emotional processing, and the ACC and OFC are also critical substrates of the affective-cognitive interface.

    “while the amygdala is a central structure in emotional processing (Costafreda, 2008), ACC and OFC are also critical substrates of the affectivecognitive interface.”
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    Premisecitation

    Emotional words are better remembered, associated with differential responses in prefrontal cortex sub-regions; right VLPFC correlates with correct retrieval of negative words, right VMPFC and OFC show enhanced responses to positive words.

    “Kuchinke et al. (2006) examined prefrontal cortex responses to word recognition.Emotional words were better remembered, associated with differential responses in sub-regions of prefrontal cortex.Right ventrolateral prefrontal cortex correlated with correct retrieval of negative words, whereas right VMPFC and OFC showed enhanced responses to positive words.”
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    Premisecitation

    In a Go/No-Go task with affective facial expressions, slowed responses to fearful expressions are associated with amygdala activation, and difficulty inhibiting happy faces is inversely related to caudate nucleus activity.

    “Another study of healthy adults that used a Go/No-Go task with affective facial expressions as cues found slowed responses to fearful expressions that were associated with amygdala activation and difficulty inhibiting responses to happy faces that was inversely related to caudate nucleus activity (Hare et al., 2005).”
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    Premisecitation

    Rostral ACC is involved in emotional Stroop performance, with a critical function in resolving emotional conflict.

    “Etkin et al. (2006) also highlighted a role of rostral ACC in emotional Stroop performance, suggesting that the critical function of this region is in resolving emotional conflict.”
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    Interpretationcitation

    Understanding interactions between emotion and cognition requires connectivity approaches, not just region-specific responses; the strength of connectivity between regions and their modulatory control of other regions are important.

    “more recent studies emphasise the importance of connectivity approaches to understanding critical interactions between emotion and cognition (Pessoa, 2008).Thus, it is not just region-specific responses of amygdala, ACC or OFC that are important, but rather the strength of connectivity between these regions, and their modulatory control of other regions.”
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    Anxiety symptoms often precede the onset of depressive symptoms and outlast them.

    “anxiety symptoms often precede the onset of depressive symptoms and outlast them (Wittchen et al., 2003).”
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    Neuroticism is a personality trait of emotional lability with a strong genetic component that greatly amplifies the risk of depression with increasing levels of life stress.

    “Neuroticism is a personality trait of emotional lability with a strong genetic component which greatly amplifies the risk of depression with increasing levels of life stress (Kendler et al. 2004).”
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    Anxiety disorders and depression commonly co-exist.

    “Anxiety disorders and depression commonly co-exist (Kessler et al., 2003)”
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    Premisecitation

    Depressed patients exhibit negative biases in identifying facial emotions; they are more likely to interpret neutral faces as sad and happy faces as neutral, resulting in an overall negative bias compared to controls.

    “others have argued that depressed patients exhibit negative biases in identifying facial emotions; patients are more likely to interpret neutral faces as sad and happy faces as neutral, resulting in an overall negative bias compared to controls (Gur et al., 1992;Surguladze et al. 2004).”
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    • cites Gur et al., 1992 source

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    • cites Surguladze et al. 2004 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Vulnerability to depression involves many genetic and psychosocial factors that, if present together at critical periods, combine to produce cognitive and neurochemical vulnerability to the state of depression.

    “It is clear that vulnerability involves many genetic and psychosocial factors each potentially contributing to a variety of mood, anxiety and personality disorders but if present together at critical periods, they combine to produce cognitive and neurochemical vulnerability to the state of depression.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Cognitive and emotional personality styles antedate the onset of depression.

  • May combine two claims.

    Interpretationcitation

    Distinct cognitive and emotional styles may outlast recovery and predict risk of relapse.

    “Distinct cognitive and emotional styles may also outlast recovery to predict risk of relapse.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    Guilt-proneness seems to be associated with depressive symptoms in patients with current major depression only, but not in healthy people.

    “Guilt-proneness seems to be associated with depressive symptoms in patients with current major depression only, but not in healthy people.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Depressed patients seem to show decreased sensitivity to emotional faces, but within that context, a negative bias.

    “Thus depressed patients seem to show decreased sensitivity to emotional faces, but within that context, a negative bias.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Depression is associated with a pattern of cognition biased towards negative information, with depressed individuals tending to remember negative items and rate experiences or stimuli as more negative than controls.

    “Depression has long been associated with a pattern of cognition biased towards negative information, with depressed individuals showing a tendency to remember negative items and to rate experiences or stimuli as more negative than do controls (e.g.Gur et al., 1992;Mogg et al., 1995).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Gur et al., 1992 source

      Not checked in the free run.

    • cites Mogg et al., 1995 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    There are marked discrepancies between studies of emotional picture processing in depression, which may reflect differences in patient characteristics or paradigms.

    “Clearly there are marked discrepancies between studies which may reflect differences in patient characteristics or paradigms.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The Mayberg model has value in both diagnosis and prediction of treatment response.

    “This model has subsequently been developed and shown to have value in both diagnosis and prediction of treatment response (Mayberg et al., 2002;2003;Ressler and Mayberg, 2007).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Mayberg et al., 2002;2003

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Ressler and Mayberg, 2007 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Biases of attention may reflect either impairments of top-down cognitive control over affective responses or enhanced bottom-up responses to affective stimuli (or a combination).

    “Biases of attention may reflect either impairments of top-down cognitive control over affective responses or enhanced bottom-up responses to affective stimuli (or potentially a combination of the two).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Limbic overactivity during initial evaluation of emotional stimuli, combined with a failure of cortical control (prefrontal hypoactivity), causes negative biases observed in depression.

    “Phillips et al. (2003) have argued that limbic overactivity during initial evaluation of emotional stimuli, combined with a failure of cortical control (reflected by prefrontal hypoactivity), cause negative biases observed in depression.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Phillips et al. (2003) source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Deficits at the interface between affect and cognition may be more specific to depression than generalised performance deficits and may represent an important target for treatment.

    “It has been argued that these deficits at the interface between affect and cognition may be more specific to depression than generalised performance deficits (Clark et al., 2009, Chamberlain andSahakian 2006) and may represent an important target for treatment (Clark et al., 2009;Harmer et al., 2010).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Clark et al., 2009 source

      Not checked in the free run.

    • cites Chamberlain andSahakian 2006

      Not checked in the free run.

    • cites Harmer et al., 2010

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Liotti et al. (2000) demonstrated that sad mood induction in remitted depressed participants produced rCBF changes similar to those in current depression, with decreases in medial OFC extending to anterior medial PFC and anterior thalamus, and increases in VLPFC and lateral OFC.

    “Liotti et al. (2000) demonstrated that when a sad mood was induced, rCBF changes in remitted depressed participants were similar to those seen in current depression, with decreases observed in medial OFC, extending to anterior medial PFC, and the anterior thalamus, and increases in VLPFC and lateral OFC.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Liotti et al. (2000) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Matthews et al. (2008) reported reduced functional coupling of the amygdala and supragenual ACC during emotion processing, and this reduction increased with severity of depression.

    “Matthews et al. (2008) reported reduced functional coupling of the amygdala and supragenual ACC during emotion processing that increased with severity of depression.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Matthews et al. (2008) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Neumeister et al. (2006) demonstrated enhanced rCBF in the amygdala and reduced rCBF in the left ventral striatum in remitted participants viewing sad faces.

    “Neumeister et al. (2006) demonstrated rCBF to be enhanced in the amygdala and reduced in left ventral striatum in remitted participants viewing sad faces.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Neumeister et al. (2006) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ATD typically leads to a 70-90% reduction in plasma tryptophan over 4-6 hours, resulting in reduced CNS 5-HT synthesis, turnover and neurotransmission.

    “This ingenious experimental method involves administration of an amino acid drink without the essential amino acid precursor of 5-HT, tryptophan, and typically leads to a 70-90% reduction in plasma tryptophan concentration over the next 4-6 hours which results in reduced CNS 5-HT synthesis, turnover and neurotransmission (Hood et al., 2005).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Hood et al., 2005 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Other studies reported a lower density of 5-HT transporters in depressed patients.

    “Some studies have reported a higher density of transporters in depressed patients (Cannon et al., 2007) while others have reported lower density (Selvaraj et al. 2009).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Selvaraj et al. 2009

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The advanced monoamine hypothesis proposes that the density of monoamine transporters modulates the degree to which synaptic monoamines, through re-uptake, are exposed to raised intraneuronal MAO.

    “The authors have evolved a novel conceptual reorientation (the advanced monoamine hypothesis) that the density of monoamine transporters modulates the degree to which synaptic monoamines, through the re-uptake mechanism, are exposed to raised intraneuronal MAO.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Meyer et al.,2006 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Impaired 5-HT function may not be a sufficient condition for depression, implicating other vulnerability factors.

    “2) impaired 5-HT function may not be a sufficient condition for depression, implicating other vulnerability factors;”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Low synaptic 5-HT content, caused by increased uptake and indexed by up-regulated 5-HT 2A receptor binding, negatively colours the perception of self, life and the future.

    “The inference is that low synaptic 5HT content, caused by increased uptake and indexed by up-regulated 5HT 2A receptor binding, negatively colours the perception of self, life and the future.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    The relationship between 5-HT and DAS scores may be direct and mediated by decreased 5-HT 2A receptor stimulation.

    “That this may be a surprisingly direct relationship and mediated by decreased 5-HT 2A receptor stimulation is suggested by one study in healthy volunteers in which DAS scores decreased one hour after acute administration of fenfluramine, a drug which releases 5-HT with effects mediated by 5HT 2 receptors (Meyer et al. 2003).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Meyer et al. 2003 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Some studies reported a higher density of 5-HT transporters in depressed patients.

    “Some studies have reported a higher density of transporters in depressed patients (Cannon et al., 2007) while others have reported lower density (Selvaraj et al. 2009).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Cannon et al., 2007 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Meyer et al. (2006) suggested that impaired 5-HT function in depression may come about through depletion of synaptic 5-HT by raised amounts of intraneuronal monoamine oxidase A.

    “A recent series of studies (Meyer et al.,2006) has suggested a possible resolution to these discrepancies by arguing that impaired 5-HT function in depression may come about through depletion of synaptic 5-HT by raised amounts of the intraneuronal enzyme mono-amine oxidase A.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Meyer et al.,2006 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    L-alleles of 5-HTTLPR have been associated with a better treatment response to SSRIs, although discrepant findings exist.

    “L-alleles result in greater mRNA transcription and more active 5-HTT function (Parsey et al., 2006) and have been associated with a better treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants although discrepant findings exist (Serretti et al., 2007).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Serretti et al., 2007 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In children, S-allele carriers have attentional bias towards sad but not happy or angry faces, which interacted with maternal history of depression.

    “increased selective attention towards fear-related pictures (spiders) in women (Osinsky et al., 2008) and in children, attentional bias towards sad but not happy or angry faces which interacted with a maternal history of depression (Gibb et al., 2009).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Gibb et al., 2009 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    L-alleles of 5-HTTLPR result in greater mRNA transcription and more active 5-HTT function.

    “L-alleles result in greater mRNA transcription and more active 5-HTT function (Parsey et al., 2006) and have been associated with a better treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants although discrepant findings exist (Serretti et al., 2007).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Parsey et al., 2006 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    S-allele carrier status had no direct effect on an emotional memory task, but interacted with stressful life events to produce significant emotional biases.

    “For example, Lemogne et al. (2009) reported that S-allele carrier status had no direct effect on an emotional memory task, but interacted with stressful life events to produce significant emotional biases.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lemogne et al. (2009) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A low-dose ATD study found no effect on fear recognition but an increase in happiness recognition.

    “The other study, using low-dose ATD, found no effect on fear recognition but an increase in happiness recognition (Hayward et al., 2005).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Hayward et al., 2005 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Most studies of 5-HT manipulations find some effect on face emotion recognition, but the picture is not fully consistent.

    “Most studies of 5-HT manipulations find some effect but the picture is not fully consistent, reflecting several factors including pharmacological mode of action.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Of 3 studies using ATD to decrease 5-HT function, 2 found a decrease in fear recognition with no effect on recognising other emotions.

    “Of 3 studies using ATD to decrease 5-HT function, 2 found a decrease in fear recognition with no effect on recognising other emotions; in one it occurred in females but not males (Harmer et al., 2003c) and the other only in S-allele carriers of the 5-HT transporter (5-HTT) (Marsh et al., 2006).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Harmer et al., 2003c

      Not checked in the free run.

    • cites Marsh et al., 2006 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    5-HT neuronal makeup influences affective cognition, presumably through developmental influences.

    “These studies provide strong support for 5-HT neuronal makeup influencing affective cognition, presumably through developmental influences, although discrepancies between studies suggest that intervening variables such as life stress may also be crucial.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    5-HT does not appear to selectively alter short-term encoding or recall of emotional material but may facilitate longer term forgetting of negative events.

    “5-HT does not appear to selectively alter short-term encoding or recall of emotional material but may facilitate longer term forgetting of negative events.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Repeated tryptophan decreased recognition of disgust but increased recognition of happiness.

    “Repeated administration of tryptophan (Murphy et al., 2006) decreased recognition of disgust but increased recognition of happiness.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Murphy et al., 2006 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    In healthy volunteers, there is a possible acute facilitatory effect of 5-HT on fear recognition, and less consistently happiness recognition, in women; the effect in men is less clear.

    “In summary, in healthy volunteers, there is a possible acute facilitatory effect of 5-HT on fear recognition, and less consistently happiness recognition, in women; the effect in men is less clear.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Acute mirtazapine decreased rather than increased fear recognition with no effect on other emotions.

    “Acute treatment with the antidepressant mirtazapine, which has multiple effects on 5-HT as well as noradrenaline function, decreased rather than increased fear recognition with no effect on other emotions (Arnone et al., 2009).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Arnone et al., 2009 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Duloxetine failed to increase fear recognition but increased happiness and disgust recognition.

    “Duloxetine, which inhibits both 5-HT and noradrenaline reuptake, failed to increase fear recognition (Harmer et al., 2008) but increases in happiness and disgust recognition were found.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Harmer et al., 2008 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Chronic treatment with 5-HT agents may result in different alterations in emotion recognition compared to acute manipulations, shifting the balance toward positive and away from negative emotions.

    “The effect of chronic treatment with 5-HT agents may result in different alterations in emotion recognition compared to acute manipulations, shifting the balance toward positive and away from negative emotions.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In the Cahill task, ATD generally impaired recall after one week but with relative sparing of unpleasant compared with neutral scenes.

    “Using the Cahill task we similarly found participants who received ATD had generally impaired recall after one week but with relative sparing of unpleasant compared with neutral scenes (Richell and Anderson, 2001).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Richell and Anderson, 2001 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Shorter-term emotional memory is not greatly influenced by 5-HT, but the rate of memory decay for negative information over longer periods is more sensitive.

    “One possibility therefore is that shorter-term emotional memory is not greatly influenced by 5-HT but the rate of memory decay for negative information over longer periods is more sensitive.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Seven days of citalopram treatment resulted in a trend to faster categorisation and an increase in recall of positive compared with negative traits.

    “but 7 days of citalopram treatment resulted in a trend to faster categorisation and an increase in the recall of positive compared with negative traits.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Harmer et al., 2004 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In an affective version of the Rey Auditory Verbal Learning Test, ATD generally impaired recall, most strongly for neutral words after 30 minutes, but after 18 hours there was less forgetting of negative compared with positive and neutral words.

    “In one study using an affective version of the Rey Auditory Verbal Learning Test there was generally impaired recall under ATD, most strongly for neutral words after 30 minutes but after 18 hours there was less forgetting of negative compared with positive and neutral words (Klaassen et al., 2002).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Klaassen et al., 2002 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Patients with generalised anxiety disorder had increased negative bias to ambiguous homophones compared with controls, which decreased with SSRI treatment.

    “Patients with generalised anxiety disorder (GAD) had increased negative bias to ambiguous homophones compared with controls which decreased with SSRI treatment (Mogg et al., 2004); the change in bias correlated with clinical improvement suggesting a mood rather than pharmacological effect.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Mogg et al., 2004 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a dot-probe paradigm, citalopram decreased reaction time when the probe replaced a positive rather than neutral word, not seen on placebo, with no effect on negative words.

    “In a dot-probe paradigm, citalopram decreased the reaction time when the probe replaced a positive rather than neutral word which was not seen on placebo although no effect was seen with negative words (Browning et al., 2007).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Browning et al., 2007 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The change in bias in GAD correlated with clinical improvement, suggesting a mood rather than pharmacological effect.

    “the change in bias correlated with clinical improvement suggesting a mood rather than pharmacological effect.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    None of these changes correlated with clinical outcome and there was no difference between drugs.

    “none of these changes correlated with clinical outcome and there was no difference between drugs.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Tranter et al., 2009 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Drug-free remitted depressed women had more accurate recognition of fearful faces, but not other emotions, compared with controls, and this decreased after a single dose of citalopram.

    “Bhagwagar et al. (2004) found that drug-free remitted depressed women had more accurate recognition of fearful faces, but not other emotions, compared with controls and this decreased ('normalised') after a single dose of citalopram, opposite to the increased recognition seen in controls (discussed above).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Bhagwagar et al. (2004) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In medicated and unmedicated remitted depressed patients, low dose ATD had no effect on mood or emotional Stroop interference in unmedicated participants or controls, but slower colour naming of negative words compared to neutral words in remitted depressed patients on antidepressants.

    “A study using an emotional Stroop task in medicated and unmedicated remitted depressed patients found there was no effect of low dose ATD on mood or emotional Stroop interference in unmedicated participants (or controls) but slower colour naming of negative words compared to neutral words in remitted depressed patients on antidepressants (Munafo et al., 2006).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Munafo et al., 2006 source

      Not checked in the free run.

  • May combine two claims.

    Premiseown data

    Drug-free patients show decreased discrimination of face emotions which was not present in those on antidepressants.

    “The lack of a control group makes interpretation difficult, but, consistent with the literature, we have found that drug-free patients show decreased discrimination of face emotions which was not present in those on antidepressants (unpublished data).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites unpublished data

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the same study, there was no effect of ATD at either dose on an affective Go/No-Go task or an emotional implicit association task.

    “In the same study there was no effect of ATD at either dose on an affective Go/No-Go task or an emotional implicit association task.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Merens et al., 2008 source

      Not checked in the free run.

  • May combine two claims.

    Premiseown data

    Patients tended to improve more on citalopram, and improvement in recognition of happiness at 2 weeks predicted clinical outcome at 6 weeks, accounting for 21% of the variance.

    “However patients tended to improve more on citalopram and improvement in recognition of happiness at 2 weeks predicted clinical outcome at 6 weeks, accounting for 21% of the variance.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Tranter et al., 2009 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Affective cognition appears to normalise with antidepressant treatment in depressed and anxious patients, but the role of 5-HT in these improvements is not clear.

    “In summary affective cognition appears to 'normalise' with antidepressant treatment in depressed and anxious patients but the role of 5-HT in these improvements is not clear.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    These data support a role for 5-HT neurones in modulating amygdala reactivity to emotional stimuli but cannot directly determine the functional dynamic effects of 5-HT.

    “These data, along with the genetic data describe above, support a role for 5-HT neurones in modulating amygdala reactivity to emotional stimuli but cannot directly determine the functional dynamic effects of 5-HT.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premiseown data

    Unmedicated people with remitted depression have an increase in bias to identification of face emotions, not confined to fear, which was not present in those on antidepressants.

    “In partial support of this we have also found an increase in bias to identification of face emotions (but not confined to fear) in unmedicated people with remitted depression which was not present in those on antidepressants (unpublished data).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites unpublished data

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    mPFC 5-HT2A receptor density measured using [18F]-altanserin correlated negatively with right amygdala fMRI activity and positively with mPFC-amygdala functional coupling.

    “and that medial prefrontal cortex (mPFC) 5-HT 2A receptor density, measured using [ 18 F]-altanserin, correlated negatively with right amygdala fMRI activity and positively with mPFC-amygdala functional coupling (Fisher et al., 2009).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Fisher et al., 2009 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A third study reported no effect of ATD but found an interaction between threat sensitivity and positive modulation by ATD of right amygdala activation.

    “A third study reported no effect (Cools et al., 2005) but did find an interaction between the personality trait of threat sensitivity and positive modulation by ATD of right amygdala activation.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Cools et al., 2005 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Repeated administration of citalopram or escitalopram for 1-3 weeks decreased amygdala activation to fearful faces in 2 studies, but on different sides, with no effect in a third.

    “Repeated administration of citalopram or escitalopram for 1-3 weeks has been reported to decrease amygdala activation to fearful faces in 2 studies (Arce et al., 2008;Harmer et al., 2006a), but on different sides, with no effect in a third (Norbury et al., 2009) which instead found enhanced amygdala responses to happy faces.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Arce et al., 2008 source

      Not checked in the free run.

    • cites Harmer et al., 2006a

      Not checked in the free run.

    • cites Norbury et al., 2009 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    If effects of 5-HT manipulations in healthy volunteers are subtle, such differences may be critical.

    “If, as argued above, effects of 5-HT manipulations in healthy volunteers are subtle, such differences may be critical.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    At baseline, depressed patients had increased activation compared with controls to sad faces in a range of areas including amygdala, hippocampus, caudate, insula and ACC, with no difference seen for happy faces.

    “At baseline, patients had increased activation compared with controls to sad faces in a range of areas including amygdala, hippocampus, caudate, insula and ACC with no difference seen for happy faces.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Fu et al., 2004

      Not checked in the free run.

    • cites Fu et al., 2007

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Imaging evidence in healthy volunteers taken as a whole supports a role for 5-HT in the neuronal basis of affective cognition, particularly emotion categorisation, with insufficient evidence to draw conclusions about affective bias.

    “To summarise the imaging evidence in healthy volunteers taken as a whole supports a role for 5-HT in the neuronal basis of affective cognition, particularly emotion categorisation with insufficient evidence to draw conclusions about affective bias.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisecitation

    Patients had lower activation of the ACC at baseline compared with controls, but those with relatively greater activation had better symptomatic outcomes at 8 weeks.

    “Although patients had lower activation of the ACC at baseline compared with controls, those with relatively greater activation had better symptomatic outcomes at 8 weeks.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Davidson et al., 2003 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In an affective Go/No-Go task, ATD resulted in altered responses in a variety of areas including enhanced activation of amygdala and hippocampus on the left and thalamus, anterior insula and parahippocampal gyrus on the right for emotional compared with neutral targets, whereas decreased activity was seen in the ACC.

    “By contrast, in an elaborately analysed study using the affective Go/No-Go task, Roiser et al. (Roiser et al., 2008;Roiser et al., 2009) found that ATD resulted in altered responses in a variety of areas including enhanced activation of amygdala and hippocampus on the left and thalamus, anterior insula and parahippocampal gyrus on the right for emotional compared with neutral targets whereas”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Roiser et al., 2008 source

      Not checked in the free run.

    • cites Roiser et al., 2009 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Inconsistencies in the literature may reflect critical differences in paradigms used, as well as differences between different pharmacological manipulation protocols.

    “Inconsistencies in the literature may reflect critical differences in paradigms used, as well as differences between different pharmacological manipulation protocols.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Treatment with venlafaxine led to increased activation in left insula cortex within 2 weeks in depressed patients compared with a decrease over time seen in controls when viewing negative relative to neutral pictures, with a similar pattern seen by 8 weeks in the ACC.

    “Treatment with the dual serotonin and noradrenaline reuptake inhibitor venlafaxine (Davidson et al., 2003) led to increased activation in left insula cortex within 2 weeks in depressed patients compared with a decrease over time seen in controls when viewing negative relative to neutral pictures with a similar pattern seen by 8 weeks in the ACC.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Davidson et al., 2003 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Patients had an increased dynamic range in the ACC and decreased dynamic range in the lateral PFC to sad faces and a decreased dynamic range to happy faces in bilateral thalamus and hippocampus.

    “Patients had an increased dynamic range (the difference in activation between low and high intensity emotion) in the ACC and decreased dynamic range in the lateral PFC to sad faces and a decreased dynamic range to happy faces in bilateral thalamus and hippocampus.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Fu et al., 2004

      Not checked in the free run.

    • cites Fu et al., 2007

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationnone given

    A more integrative model may ultimately provide a better explanation of affective cognition.

    “however affective cognition may ultimately be better explained by a more integrative model.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationnone given

    Behavioural and fMRI results broadly support an effect of 5-HT manipulation on affective cognition in depression, but such findings are usually confounded by shifts in depressed mood caused by 5-HT modulation.

    “Both behavioural and fMRI results broadly support an effect of 5-HT manipulation on affective cognition in depression, however these results are typically confounded by changes in the depressed state in response to 5-HT modulation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Within these networks, response patterns vary by emotion: basic emotions such as fear rely more on limbic regions, while complex emotions such as guilt rely more on medial prefrontal regions.

    “The pattern of responses within these networks is dependent on specific emotions, with more emphasis on limbic regions for basic emotions like fear and more emphasis on medial prefrontal regions for complex emotions like guilt.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    Response patterns also vary with task demands: emotion perception tasks engage posterior and subcortical components more, whereas prefrontal regions become more involved when greater integration with cognitive processes is needed.

    “The pattern also depends on task demands, with emotion perception tasks preferentially engaging posterior and subcortical components of the network and prefrontal regions becoming more involved as more integration with cognitive processes is required.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    Relative to controls, depressed patients tend to show biases toward negative material and/or away from positive material.

    “In broad terms, depressed patients show biases towards negative material and/or away from positive material relative to controls.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    fMRI evidence more consistently supports that 5-HT modulation affects normal affective cognition, suggesting that neuronal changes can occur without measurable performance effects.

    “fMRI results more consistently support the view that 5-HT modulation impacts normal affective cognition, indicating that there may be neuronal changes in the absence of measurable performance effects.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Comparable models can be developed for reward learning and emotional decision-making.

    “Although we have not discussed reward learning or emotional decision-making here, similar models can be derived to describe these processes (Dolan, 2007).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Dolan, 2007 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    Neuropsychological studies point to the amygdala's role in emotion recognition and emotional memory, and to the VMPFC's role in social and moral emotions.

    “Neuropsychological studies highlight roles of amygdala (particularly in the recognition of emotion and emotional memory) and VMPFC (particularly in social and moral emotions).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    In healthy controls, the behavioural effects of 5-HT on affective function are small and depend on the specific manipulation and task used.

    “5-HT effects on affective function in healthy controls are subtle at a behavioural level and appear to depend critically on both the exact manipulation and the task used.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Symptomatic improvement was associated with reduction of dynamic range to sad faces in pregenual ACC and an increase in activation to happy faces in left hippocampus and extrastriate regions.

    “Symptomatic improvement was associated with reduction of dynamic range to sad faces in pregenual ACC and an increase in activation to happy faces in left hippocampus and extrastriate regions.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Fu et al., 2004

      Not checked in the free run.

    • cites Fu et al., 2007

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Over time depressed patients showed a reduction in activation to sad faces in left amygdala which correlated with an increase in dynamic range in left lateral PFC.

    “Over time depressed patients showed a reduction in activation to sad faces in left amygdala which correlated with an increase in dynamic range in left lateral PFC.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Fu et al., 2004

      Not checked in the free run.

    • cites Fu et al., 2007

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    Several factors may be important, including current mood, personality traits, gender, and genotype, all of which have been shown to interact with 5-HT effects.

    “However a number of intervening factors may be critical, including current mood, personality traits, gender and genotype, all of which have been shown to interact with 5-HT effects.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In an affective Go/No-Go study, remitted depressed women differed from controls: they showed no increased activation to emotional versus neutral targets, but an increased rather than decreased response to emotional distractors in the dorsal ACC.

    “Remitted depressed subjects differed significantly from controls with no increase in activation to emotional compared with neutral targets but an increased, rather than decreased, response to emotional distractors in the dorsal ACC.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Roiser et al., 2009 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Mayberg's model emphasizes that amygdala responses to emotional stimuli are enhanced during depression and normalize with recovery.

    “Various iterations of Helen Mayberg's influential model emphasise enhanced amygdala response to emotional stimuli in the depressed state that normalises on recovery.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    After eight weeks of SSRI treatment, the differences normalized; other areas with significant patient-control differences did not change significantly over time in patients, except for decreased activation to fearful face distractors in the right DLPFC, which increased with treatment.

    “After eight weeks treatment with a variety of SSRIs these differences normalised; other areas where there were significant differences between patients and controls did not show significant changes over time in patients except for a decreased activation to fearful face distractors in the right DLPFC which increased with treatment.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Fales et al., 2009 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Fales et al. reported that depressed patients had greater left amygdala activation than controls when fearful faces were distractors, but less activation when those faces were targets.

    “depressed patients showed a number of differences from controls including activating left amygdala more than controls when fearful faces were presented as distractors, but less than controls when they were targets.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Fales et al., 2009 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The dorsal ACC has been linked to conflict adjustment and error correction, and the altered response may indicate changed 5-HT control of neurons there when irrelevant emotional information is present.

    “This area has been implicated in adjustment to conflict and error correction and may suggest altered 5-HT control of neurones in the region in response to extraneous emotional information.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    Altered connectivity between the amygdala and ventral ACC, and also the OFC, may be a key substrate of disrupted affective cognition in depression.

    “Exciting recent research suggests that connectivity between amygdala and ventral ACC, as well as OFC, may be a critical substrate of disrupted affective cognition in depression.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationnone given

    Studies most often use tasks involving perception or recognition of facial emotions, and their results are summarized in Table 2, which illustrates limitations and gaps in the data.

    “Most frequently, studies using tasks involving the perception or recognition of face emotions have been used and the results are summarised in Table 2 illustrating limitations and gaps in the data set.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    According to Phillips et al., emotional stimuli produce heightened limbic responses, including in the amygdala, while reduced prefrontal responses reflect a failure of cortical regulation of emotion.

    “Phillips et al. (2003Phillips et al. ( , 2008) ) argue that emotional stimuli elicit heightened responses in limbic regions including the amygdala and that hypo-response in prefrontal regions reflects a failure of cortical systems to regulate emotional responses.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Phillips et al., 2003 source

      Not checked in the free run.

    • cites Phillips et al., 2008 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Mayberg places the subgenual ACC at the center of the dysfunctional network and proposes that this region is critical for emotion regulation.

    “Critically, she places the subgenual ACC at the epicentre of the dysfunctional network, hypothesising a critical role for this region in emotion regulation (Ressler and Mayberg, 1997)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Ressler and Mayberg, 1997

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The effects of acute tryptophan depletion on memory may depend critically on the delay of recall.

    “Shows that effects of ATD on memory may critically depend on delay of recall.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Klaassen et al., 2002 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Emotional memory, measured behaviorally or by fMRI, may be a biomarker for effective antidepressant action.

    “Harmer et al. (2010) have argued that emotional memory, assessed either behaviourally or (perhaps more robustly) by fMRI response, may represent a biomarker for effective antidepressant drug action.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Harmer et al., 2010

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Symptoms of feelings of worthlessness and guilt occur consistently across cultures in depressive disorders.

    “shows that symptoms of feelings of worthlessness and guilt consistently occur across cultures”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Sartorius et al., 1980 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Moral emotions depend critically on the mechanisms of social attachment.

    “This review links recent work on the neurobiology and neurochemistry of attachment with insights into the neuroanatomical basis of moral emotions which critically depend on social attachment mechanisms.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Moll, Schulkin, 2009 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Direct electrical stimulation of the anterior cingulate cortex markedly improves mood in patients with treatment-resistant depression.

    “This seminal study shows that direct stimulation of ACC dramatically improves depressed mood.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Mayberg et al., 2005 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Guilt-related script-driven imagery activates the anterior cingulate cortex dorsally to the genu of the corpus callosum.

    “shows activation of the anterior cingulate dorsally to the genu of the corpus callosum”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Shin et al., 2000 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Guilt is confined to only a certain proportion of patients with depressive disorders.

    “but that the latter is confined to only a certain proportion of patients”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Sartorius et al., 1980 source

      Not checked in the free run.

141 of 141

  • The paper relies on this without support.

    Ekman-type face stimuli typically do not elicit discernible changes in emotional state.

    “Typically these stimuli do not elicit discernible changes in emotional state.”

  • The paper relies on this without support.

    Affective cognition is at the heart of successful social function, which is compromised in psychiatric disorder.

    “Affective cognition is at the heart of successful social function, which is compromised in psychiatric disorder.”

  • The paper relies on this without support.

    Serotonin is a key neurotransmitter involved in depression.

    “Serotonin is thought to be a key neurotransmitter involved in depression”

  • The paper relies on this without support.

    Affective processing is fundamental to human behaviour.

    “Affective processing is fundamental to human behaviour.”

  • The paper relies on this without support.

    All actions and decisions take place in an emotional context and cognitive functions are coloured by emotional state.

    “All our actions and decisions take place in an emotional context and therefore cognitive functions are coloured by emotional state.”

  • The paper relies on this without support.

    Cognitive factors critically modulate affective responses.

    “Conversely, cognitive factors critically modulate affective responses”

  • The paper relies on this without support.

    Feelings of inadequacy, self-blame, worthlessness and hopelessness are core, specific and distinctive symptoms of severe depression.

    “Feelings of inadequacy, self-blame, worthlessness and hopelessness are core, specific and distinctive symptoms of severe depression.”

  • The paper relies on this without support.

    Cognitive and emotional personality styles antedate the onset of depression.

    “There is good evidence that cognitive and emotional personality styles antedate the onset of depression.”

  • The paper relies on this without support.

    Nearly all commonly used antidepressant drugs work by enhancing 5-HT neurotransmission.

    “Nearly all commonly used antidepressant drugs work by enhancing 5-HT neurotransmission.”

  • The paper relies on this without support.

    In-vivo studies of 5-HT far outnumber those of other neurotransmitters.

    “Furthermore, in-vivo studies of 5-HT far outnumber those of other neurotransmitters.”

  • The paper relies on this without support.

    Citalopram and tryptophan act through presynaptic 5-HT neurones.

    “These drugs both act through presynaptic 5-HT neurones and this would be compatible with impaired 5-HT neuronal function in depression.”
11 of 11

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

Research works printed but not linked: 3

  1. Goulden N (2010). Connectivity Techniques in Psychiatry. University of Manchester. PhD Thesis, Manchester, UK.
  2. Thomas EJ (2009). Interactions between rumination and cognition in depression. University of Manchester PhD thesis.
  3. Welt L (1888). Über Charakterveränderungen des Menschen. Dtsch Arch Klin Med 42: 339–390.

Cited by

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Related

Authors
Elliott, R., Zahn, R., Deakin, J. F. W., & Anderson, I. M.
Affiliations
University of Manchester (GB)
Corresponding author
Elliott, Rebecca
ORCID
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2010-06-23
Volume
36
Issue
1
Pages
153-182
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/npp.2010.77
PMC
PMC3055516
OpenAlex
W2140443081
Cited by
330
References
390
Citations by year
2026: 8 · 2025: 15 · 2024: 39 · 2023: 11 · 2022: 15 · 2021: 21 · 2020: 20 · 2019: 23 · 2018: 24 · 2017: 20 · 2016: 9 · 2015: 28 · 2014: 25 · 2013: 29 · 2012: 29
FWCI
1.65
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Neuropsychopharmacology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (publishedVersion, other-oa)
  • Research Explorer (The University of Manchester) (submittedVersion, other-oa)
Funders
Medical Research Council
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
affective cognition, mood disorders, depression, emotion classification, attentional bias, social emotions, moral emotions, amygdala, ventromedial prefrontal cortex, serotonin, treatment options
MeSH terms
Affect, Animals, Brain, Brain Chemistry, Cognition, Depressive Disorder, Humans, Limbic System, Neural Pathways, Serotonin, Prefrontal Cortex, Mood Disorders

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