Short-term serotonergic but not noradrenergic antidepressant administration reduces attentional vigilance to threat in healthy volunteers

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

Cooper and Langton (2006) found a significant bias away from happy faces at 100 ms and a bias towards happy faces at 500 ms.

“Conversely, they found a significant bias away from the happy faces at 100 ms and a bias towards happy faces at 500 ms.”

• cites Cooper and Langton (2006) sourceSupported

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

Cooper and Langton (2006) report opposite patterns of vigilance and avoidance for happy and angry faces across presentation times.

“In support of this, Cooper and Langton (2006) report opposite patterns of vigilance and avoidance for happy and angry faces across presentation times.”

• cites Cooper and Langton (2006) sourceSupported

Classified as probably not a substantial claim.

A range of studies have demonstrated that the amygdala rapidly habituates to repeated presentations of emotional faces and pictures.

“In particular, a range of studies have demonstrated that the amygdala rapidly habituates to repeated presentations of emotional faces (Breiter et al., 1996 ;Whalen et al., 1998 ;Wright et al., 2001) and pictures (Fischer et al., 2000 ;Irwin et al., 1996).”

• cites Breiter et al., 1996 sourceNot checked — no full text of the source
• cites Whalen et al., 1998 sourcePartly supported

  The fMRI data report that amygdala signal increases to masked fearful faces were attenuated to baseline with subsequent presentation epochs, supporting habituation to repeated emotional faces. The ‘Direction of signal changes in the amygdala’ section says the response to happy faces persisted across all epochs, so the finding does not apply to emotional faces generally. The study’s 28-second epochs also do not establish precisely how rapidly habituation occurred. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites Wright et al., 2001 sourceNot checked — no full text of the source

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

Cooper and Langton (2006) report a bias towards angry faces at 100 ms followed by a significant bias away from angry faces at 500 ms.

“They report a bias towards angry faces at 100 ms followed by a significant bias away from angry faces at 500 ms.”

• cites Cooper and Langton (2006) sourceSupported

May combine two claims.

Across all treatment groups and both target valences, volunteers were significantly faster to respond to targets related to the prime compared to unrelated targets, and this facilitation effect was more pronounced for threat than neutral targets.

“As can be seen from Table 3, across all treatment groups and both target valences, volunteers were significantly faster to respond to targets that were related to the prime compared to targets that were unrelated to the prime.This facilitation effect was more pronounced for threat than neutral targets.”

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

Reaction times on the homograph task were not significantly affected by gender and there were no significant interactions between gender and treatment group.

“Reaction times on this task were not significantly affected by gender and there were no significant interactions between gender and treatment group (all p values >0.1).”

May combine two claims.

In the pilot study, the shorter masked timing condition (16 ms target, 84 ms mask) but not the longer produced significant attentional vigilance effects towards fearful faces.

“Similarly, the shorter of the two masked timing conditions (16 ms target, 84 ms mask) but not the longer produced significant attentional vigilance effects towards the fearful faces.”

May combine two claims.

While the placebo and reboxetine groups showed a significant bias towards fearful faces, this was abolished in the citalopram group.

“Whilst both the placebo group and the reboxetine group showed a significant bias towards fearful faces, this was abolished in the citalopram group.”

May combine two claims.

In the pilot study, the 100-ms unmasked condition produced significant attentional vigilance effects towards fearful faces compared with neutral, whereas the 250-ms target unmasked condition did not.

“the 100-ms unmasked condition produced significant attentional vigilance effects towards the fearful faces compared with neutral, whereas there was no significant attentional vigilance to the fearful faces in the 250-ms target unmasked condition.”

May combine two claims.

In the homograph task, there was no significant effect of treatment group on accuracy and no significant interaction between target valence and treatment group.

“There was no significant effect of treatment group on accuracy in this task [F(1, 38)=0.363,p=0.7] and no significant interaction between target valence and treatment group [F(2, 38)= 0.405, p=0.670].”

May combine two claims.

Accuracy rates in the attentional probe task were high (placebo 94%, citalopram 92%, reboxetine 92%) and there were no significant effects of treatment group on accuracy.

“Accuracy rates were very high in this task (placebo, mean 94 % ; citalopram, mean 92 % ; reboxetine, mean 92 %) and there were no significant effects of treatment group on accuracy across any of the task conditions (all comparisons, p>0.2).”

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

There was no significant three-way interaction between group, valence, and masking status.

“There was no significant three-way interaction between grouprvalencermasking status.”

May combine two claims.

In the homograph task, there was a significant main effect of target type and a significant interaction between target valence and target type.

“This revealed a significant main effect of target type [F(1, 36)=28.83,p<0.001] and a significant interaction between target valence and target type [F(1, 36)=4.96,p=0.032].”

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

Attentional vigilance scores were not significantly affected by gender and there were no significant interactions between gender and treatment group.

“Attentional vigilance scores on this task were not significantly affected by gender and there were no significant interactions between gender and treatment group (all p values >0.09).”

May combine two claims.

In the masked condition, there were no significant effects of valence or group on attentional vigilance.

“In the masked condition there were no significant effects of valence or group on attentional vigilance (all p values >0.2).”

May combine two claims.

As predicted, the noradrenergic antidepressant reboxetine did not significantly affect attentional vigilance to threat or the threat-related interpretation of ambiguous homographs.

“As predicted, the noradrenergic antidepressant reboxetine did not significantly affect attentional vigilance to threat or the threat-related interpretation of ambiguous homographs.”

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

The participants used in this study were generally young, high-functioning students.

“However, it is important to note that the participants used in this study were generally young, high-functioning students.”

May combine two claims.

The three groups all showed a relatively increased priming effect for threat-related primes compared with neutral-related primes, suggesting a threat-related interpretative bias that was not modulated by antidepressant treatment.

“In addition, the three groups all showed a relatively increased priming effect for the threat-related primes compared with the neutral-related primes, suggesting a threatrelated interpretative bias that was not modulated by antidepressant treatment.”

May combine two claims.

All three treatment groups showed faster responses to targets that were related to the homograph primes, indicating that the priming was effective.

“All three treatment groups showed faster responses to targets that were related to the homograph primes, indicating that the priming was effective.”

May combine two claims.

There was a significant difference in attentional vigilance between citalopram and placebo groups and between reboxetine and citalopram groups (p<0.05).

“Error bars represent standard error of mean (* p<0.05 for comparison between citalopram and placebo groups and between reboxetine and citalopram groups).”

May combine two claims.

Both citalopram and reboxetine positively bias emotional processing but have a different profile of effects on response to threat as measured by the emotion-potentiated startle response.

“we have previously reported that whilst both of these classes of antidepressants positively bias emotional processing, they have a different profile of effects on response to threat as measured by the emotion-potentiated startle response”

• cites Harmer et al., 2004 sourceNot checked — no full text of the source

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

Short-term (7 d) administration of citalopram and reboxetine reduces processing of negative emotional material and increases perception and memory for positively valenced emotional material in healthy volunteers.

“short-term (7 d) administration of the selective serotonin reuptake inhibitor (SSRI), citalopram, and the selective noradrenaline reuptake inhibitor (SNRI), reboxetine, has been shown to reduce the processing of negative emotional material, such as fearful and angry faces, and to increase the perception of and memory for positively valenced emotional material in healthy volunteers”

• cites Harmer et al., 2004 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

There is a considerable body of empirical data demonstrating heightened attentional vigilance towards threatening stimuli in individuals with high trait anxiety and individuals with a range of clinical anxiety disorders.

“There is a considerable body of empirical data demonstrating heightened attentional vigilance towards threatening stimuli in individuals with high levels of trait anxiety and individuals with a range of clinical anxiety disorders”

• cites Koster et al., 2005 sourceNot checked — no full text of the source
• cites MacLeod et al., 1986Not matched

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

• cites Mogg and Bradley, 2002 sourceNot checked — no full text of the source

May combine two claims.

7 d citalopram administration reduces the potentiation of the startle response by negative pictures in healthy volunteers, while reboxetine has no effect on this paradigm.

“while 7 d citalopram administration reduces the potentiation of the startle response by negative pictures in healthy volunteers, reboxetine has no effect on this paradigm”

• cites Harmer et al., 2004 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

Participants were randomly allocated to double-blind intervention with placebo, citalopram, or reboxetine for 7 d.

“Volunteers were randomly allocated to double-blind intervention with one of the three following oral treatments for a period of 7 d : placebo, citalopram (20 mg/ d) or reboxetine (4 mg b.i.d.).”

Classified as probably not a substantial claim.

SSRIs have therapeutic value in the treatment of a range of anxiety disorders.

“Given the growing evidence of the therapeutic value of SSRIs in the treatment of a range of anxiety disorders”

• cites Dhillon et al., 2006 sourceNot checked — no full text of the source
• cites Kent et al., 1998 sourceNot checked — no full text of the source
• cites Pae and Patkar, 2007 sourceNot checked — no full text of the source

May combine two claims.

These changes in emotional processing occur in the absence of significant differences in subjective mood and more rapidly than the therapeutic effects of these drugs would typically be seen clinically.

“Importantly, these changes in emotional processing occur in the absence of significant differences in subjective mood and more rapidly than the therapeutic effects of these drugs would typically be seen clinically.”

• cites Harmer et al., 2004 sourceNot checked — no full text of the source

May combine two claims.

Mogg et al. (2004) reported that patients with generalized anxiety disorder produced significantly fewer threat-related spellings of homophones following 4 wk SSRI treatment compared to before treatment, and this reduction was positively correlated with clinical improvement.

“Mogg and colleagues (2004) reported that patients with generalized anxiety disorder produced significantly fewer threat-related spellings of homophones following 4 wk treatment with a SSRI compared to before treatment.”

• Also stated in: § Introduction Contemporary cognitive psychology models emphasize the role that biases in threat processing play in the aetiology and maintenance of clinical states of anxiety (e.g.Beck et al., 1985 ;Eysenck, 1992Eysenck, , 1997 ; ;MacLeod et al., 2004 ;Mogg and Bradley, 1998 ;Williams et al., 1988Williams et al., , 1997 ; ;Yiend and Mackintosh, 2004).Individuals with high trait anxiety and patients with a range of clinical anxiety disorders have been shown to have threat-related biases in selective attention.For example, studies using the attentional probe paradigm have demonstrated that individuals with high levels of anxiety are relatively faster to respond to probes that replace threatening stimuli than probes that replace neutral stimuli compared with low-anxiety controls, indicating increased attentional vigilance to the location of the threat stimuli (Koster et al., 2005 ;Mogg et al., 1994Mogg et al., , 1997 ; ;Yiend and Mathews, 2001).There is also good evidence that interpretative biases favouring threat also play an important role in a wide range of anxiety disorders (e.g.Clark et al., 1997 ;Eysenck et al., 1991 ;Huppert et al., 2007 ;Stoler and McNally, 1991).For example, when presented with a homograph that has both a threat meaning and a non-threat meaning (such as ' patient'), individuals with high levels of trait anxiety and patients with anxiety disorders are typically faster to report whether a word is a real word or a non-word in response to an associate of the threat interpretation (e.g.'hospital ') than an associate of the neutral interpretation (e.g.'calm ') compared with low-anxious controls (Richards and French, 1992). Reducing threat-related processing biases is a major focus of cognitive-behavioural therapeutic interventions for the treatment of anxiety disorders (Beck et al., 1985).Recently, evidence has emerged to suggest that pharmacological treatments for mood disorders may also influence emotional processing.For example, short-term (7 d) administration of the selective serotonin reuptake inhibitor (SSRI), citalopram, and the selective noradrenaline reuptake inhibitor (SNRI), reboxetine, has been shown to reduce the processing of negative emotional material, such as fearful and angry faces, and to increase the perception of and memory for positively valenced emotional material in healthy volunteers (Harmer et al., 2004).Importantly, these changes in emotional processing occur in the absence of significant differences in subjective mood and more rapidly than the therapeutic effects of these drugs would typically be seen clinically.This suggests that antidepressants may directly modulate the neural processing of emotional and social information, rectifying the maladaptive processing biases seen in depression.This may represent an important mechanism by which these pharmacological agents exert their therapeutic effects. Given the growing evidence of the therapeutic value of SSRIs in the treatment of a range of anxiety disorders (Dhillon et al., 2006 ;Kent et al., 1998 ;Pae and Patkar, 2007), an outstanding question is whether SSRIs have effects on emotional processing biases that are particularly relevant to anxiety.There is some evidence from clinical studies to support this notion.For example, Mogg and colleagues (2004) reported that patients with generalized anxiety disorder produced significantly fewer threat-related spellings of homophones following 4 wk treatment with a SSRI compared to before treatment.Furthermore, this reduction in threat-related interpretative bias was positively correlated with clinical improvement, suggesting that it was relevant to the therapeutic action of the drug.The major difficulty with interpreting such effects, however, is that it is not possible to distinguish the direct action of the drug on threat processing from non-specific effects of symptom change produced by the SSRI treatment.Assessment of the cognitive effects of short-term antidepressant administration to healthy volunteers is one method of circumventing this problem, as it allows the direct effect of the drug to be assessed in the absence of symptom change and in comparison with a placebo control group.The current study therefore assessed the effect of a SSRI on anxiety-related emotional processing paradigms in healthy volunteers. Unlike SSRIs, selective noradrenaline reuptake inhibitors (SNRIs), while effective antidepressants, are not commonly used in the treatment of anxiety.Consistent with this, we have previously reported that whilst both of these classes of antidepressants positively bias emotional processing, they have a different profile of effects on response to threat as measured by the emotion-potentiated startle response (Harmer et al., 2004).Thus, while 7 d citalopram administration reduces the potentiation of the startle response by negative pictures in healthy volunteers, reboxetine has no effect on this paradigm (Harmer et al., 2004).On the basis of this, we have previously hypothesized that whilst citalopram influences emotional processing biases that are relevant to both anxiety and depression, the effect of reboxetine is expressed more specifically on the elaborative and explicit processes that are particularly implicated in depression.In order to test this hypothesis, a reboxetine-treated group was included in the present study as an additional contrast. The current study therefore assessed the effect of 7 d treatment with the SSRI, citalopram, and the SNRI, reboxetine, on anxiety-related threat processing paradigms in healthy volunteers.This treatment period was chosen because, as mentioned above, 7 d administration of antidepressants to healthy volunteers has previously been shown to have significant effects on emotional processing (Harmer et al., 2004).A 7-d treatment period also has the particular advantage of allowing the effects of the drug on emotional processing to be measured before the full therapeutic effect would typically be seen in clinical populations.Threat processing was assessed with a commonly used test of attentional vigilance to threat (the attentional probe task, using emotional facial expressions as stimuli) and a commonly used test of interpretative bias (the homograph primed lexical decision task).It was predicted that citalopram would reduce attentional and interpretative threat-relevant biases compared with placebo but that reboxetine would have no effect on these anxiety-related emotional processing paradigms. · plain

  “Furthermore, this reduction in threat-related interpretative bias was positively correlated with clinical improvement”

• cites Mogg et al., 2004 sourceNot checked — no full text of the source

May combine two claims.

The three groups were matched in gender, verbal IQ, and age, with no significant differences between groups on these measures.

“The three groups were matched in terms of gender, verbal IQ (assessed with the National Adult Reading Test) and age (see Table 1).”

• Also stated in: § Attentional probe task · plain

  “There were no significant differences between the three groups on any of these measures”

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

Medication was given in identical capsules twice a day to maintain blinding.

“Medication was given in identical capsules twice a day to maintain blinding.”

May combine two claims.

There was no significant effect of treatment group on average overall reaction times or on reaction times on the neutral-neutral trials, suggesting no baseline reaction time differences between the three groups.

“There was no significant effect of treatment group on average overall reaction times or on reaction times on the neutral-neutral trials (all p values >0.2), suggesting no baseline reaction time differences between the three groups.”

Probably not a substantial claim: may not pass S2 (checkable).

The finding that citalopram reduces attentional orienting to threatening stimuli is highly relevant to its clinical use in the treatment of anxiety disorders.

“which is highly relevant to its clinical use in the treatment of anxiety disorders.”

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

The use of a between-subjects design has the disadvantage of variability across the treatment groups generated by individual differences.

“Second, the use of a between-subjects design has the disadvantage of variability across the treatment groups generated by individual differences.”

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

The previous study (Mogg et al., 2004) did not have a placebo control group, so it is possible that the posttreatment reduction in threat-related interpretative bias reflects practice effects rather than a specific effect of the drug on interpretation.

“This previous study did not have a placebo control group so it is possible that the posttreatment reduction in threat-related interpretative bias reflects practice effects rather than a specific effect of the drug on interpretation.”

• cites Mogg et al., 2004 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.

Whilst the early effects of SSRIs may relate specifically to selective attention to threat, over time it is possible that they may generalize to influence a broader spectrum of emotional and social processing.

“Whilst the early effects of SSRIs may relate specifically to selective attention to threat, over time it is possible that they may generalize to influence a broader spectrum of emotional and social processing.”

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

The homogeneity of this sample has the advantage of increasing the power to detect drug-related differences between treatment groups.

“Whilst the homogeneity of this sample has the advantage of increasing the power to detect drugrelated differences between treatment groups”

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

A more interesting explanation for the divergent findings relates to the longer SSRI treatment period (4 wk) used in the previous study compared to the present study (1 wk).

“A more interesting explanation for the divergent findings relates to the longer SSRI treatment period (4 wk) used in the previous study compared to the present study (1 wk).”

Classified as probably not a substantial claim.

Animal and human studies suggest that the amygdala is critically involved in the fast, automatic appraisal of threat stimuli and directing attention towards emotionally salient, biologically relevant events.

“Such a proposal is also consistent with evidence from animal and human studies suggesting that the amygdala is critically involved in the fast, automatic appraisal of threat stimuli and directing attention towards emotionally salient, biologically relevant events”

• cites Davis and Whalen, 2001 sourceNot checked — no full text of the source
• cites LeDoux, 1995 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

It is difficult to draw any conclusions about the effect of citalopram on attentional vigilance to happy faces from the present study.

“It should be noted that it is difficult to draw any conclusions about the effect of citalopram on attentional vigilance to happy faces from the present study”

Classified as probably not a substantial claim.

No assessment of awareness of the masked stimuli was carried out in the present study.

“Second, no assessment of awareness of the masked stimuli was carried out.”

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

The between-subjects design necessitated careful matching of the groups on a range of factors (such as age, gender, baseline subjective mood ratings) in order to ensure internal validity.

“However, the between-subjects design did necessitate careful matching of the groups on a range of factors (such as age, gender, baseline subjective mood ratings) in order to ensure internal validity.”

Classified as probably not a substantial claim.

Several models suggest that anxiety biases attention towards threat-related stimuli by increasing the output from an amygdala-centred threat evaluation system.

“Several models suggest that anxiety biases attention towards threat-related stimuli by increasing the output from an amygdala-centred threat evaluation system”

• cites Mathews and Mackintosh, 1998 sourceNot checked — no full text of the source
• cites Öhman and Wiens, 2004 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

Threat-related cognitive biases are reduced following successful psychological intervention.

“there is evidence that threat-related cognitive biases are reduced following successful psychological intervention”

• cites Mathews et al., 1995 sourceNot checked — no full text of the source

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

There was no physiological measure of compliance with the drug treatment in the present study.

“First, we did not have a physiological measure of compliance with the drug treatment.”

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

UK guidelines on the treatment of anxiety disorders recommend pharmacological treatment with SSRIs and tricyclic antidepressants, but do not recommend treatment with SNRIs, such as reboxetine.

“Indeed, UK guidelines on the treatment of anxiety disorders recommend pharmacological treatment with SSRIs and tricyclic antidepressants, but do not recommend treatment with SNRIs, such as reboxetine (NICE, 2007).”

• cites NICE, 2007Not matched

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

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

Preconscious attentional biases to threat are reduced following cognitive behavioural therapy.

“Such preconscious attentional biases to threat have been shown to be reduced following cognitive behavioural therapy (e.g.Mogg et al., 1995a).”

• cites Mogg et al., 1995a sourceNot checked — no full text of the source

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

In an attentional probe paradigm, anxious individuals orient to the position of previously presented threat-related stimuli even when they are backwardly masked and presented below the level of conscious awareness.

“For example, in an attentional probe paradigm anxious individuals have been shown to orient to the position of previously presented threat-related stimuli, even when they were backwardly masked and therefore presented below the level of conscious awareness (Mogg et al., 1995b).”

• cites Mogg et al., 1995b sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S2 (checkable).

Studying the mechanisms of antidepressant drugs in healthy volunteers has the advantage that the behavioural effects of the drugs can be explored unconfounded by changes in clinical state or symptom remission.

“Studying the mechanisms of antidepressant drugs in healthy volunteers has the advantage that the behavioural effects of the drugs can be explored unconfounded by changes in clinical state or symptom remission.”

Classified as probably not a substantial claim.

If stimuli are presented very close to awareness thresholds, the pre-attentive effects of masked stimuli may be reduced.

“Mogg and Bradley (1999) note that if stimuli are presented very close to awareness thresholds, the pre-attentive effects of masked stimuli may be reduced.”

• cites Mogg and Bradley (1999) sourceNot checked — no full text of the source