Systematic review of the neural basis of social cognition in patients with mood disorders

In the paper

“studies examining patients with bipolar disorder in a depressed phase of illness reveal a mood congruent bias in emotion perception tasks, including difficulties labelling happy faces 97,102 and a tendency to misinterpret neutral facial stimuli as sad 144,183 and happy faces as angry.”

What the sources say

• Partly supported

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  cites [97] sourceExperimental — accuracy not yet measured
• Partly supported

  The Results (Face Emotion Labeling Accuracy; page not available) report that depressed bipolar participants were less accurate than healthy controls when labeling faces in the happy-face experiment. The Discussion describes a possible attentional bias toward sad expressions, but it does not report that participants mislabeled neutral faces as sad or happy faces as angry. Elevated amygdala activity to neutral faces in the sad-face experiment is not evidence of those specific misinterpretations. (LLM, conf=0.86)

  cites [102] sourceExperimental — accuracy not yet measured
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  cites [144] sourceExperimental — accuracy not yet measured
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In the paper

“Neuroimaging studies conducted in children and adolescents with MDD also show heightened activation in the amygdala 56,60,74 and OFC 74 in response to emotional facial expressions (for conflicting findings, see Thomas and colleagues 42 ).”

What the sources say

• Partly supported

  In Results > Imaging, adolescents with MDD showed greater amygdala activation than healthy peers for the fearful-afraid versus fearful-passive contrast. The OFC analysis found only a nonsignificant trend for MDD versus controls on that contrast, and no difference for fearful-passive versus happy-passive; the latter contrast also showed amygdala hypoactivation in MDD. Thus, this paper does not support a general claim of heightened activation in both regions. (LLM, conf=0.88)

  cites [56] sourceExperimental — accuracy not yet measured
• Partly supported

  The Results (fMRI Data; page unavailable) report greater amygdala activity in patients than controls while viewing facial expressions. The Methods describe the patient group as adolescents with anxiety or depressive disorders, or both, so the finding is not specific to adolescents with MDD. The study’s reported fMRI analyses focus on the amygdala; the citing sentence attaches multiple references to that finding and separately cites reference 74 for OFC activation. (LLM, conf=0.86)

  cites [60] sourceExperimental — accuracy not yet measured
• Not checked yetcites [74]

In the paper

“Taken together, neuroimaging studies of social cognition in patients with mood disorders reveal enhanced activation in limbic and emotion-related structures and attenuated activity within frontal regions associated with emotion regulation and higher cognitive functions.”

In the paper

“The neural networks under lying higher-order social cognitive processes, including empathy, remain unexplored in patients with mood disorders.”

In the paper

“However, the same study group found that amygdala-DLPFC connectivity was significantly associated with illness severity, indicating that patients with MDD with reduced connectivity between these regions had a more pervasive and severe course of illness.58”

What the sources say

• Not checked yetcites [58] source

In the paper

“A recent study by Victor and colleagues, 73 however, found that remitted patients with MDD showed exaggerated responses in the amygdala to masked sad faces and a lack of amygdalar response to masked happy faces compared with controls.”

What the sources say

• Not checked yetcites [73] source

In the paper

“For example, a recent study by Fu and colleagues 43 examined responding to positive stimuli in patients with MDD compared with matched controls and found reduced activation in subcortical (basal ganglia), limbic (hippocampus) and extrastriate regions among acutely ill patients with MDD; this pattern was attenuated following treatment with fluoxetine.”

What the sources say

• Not checked yetcites [43] source

In the paper

“Preliminary findings by Norbury and colleagues 68 demonstrate elevated DLPFC activation in response to fearful faces in euthymic patients compared with controls.Levels of amygdala activation did not differ between patients and matched controls during the presentation of fearful faces.”

What the sources say

• Not checked yetcites [68] source

In the paper

“Similarly, Keedwell and colleagues 61 found that severely depressed patients showed increased visual cortex responses to sad faces and reduced neural response in these same regions to happy faces in the early stages of antidepressant treatment.Following continued antidepressant therapy and clinical improvement, these patterns were reversed.”

What the sources say

• Not checked yetcites [61] source

In the paper

“to date, few studies have included separate groups with MDD and with bipolar disorder and have directly compared patterns of neural activation between these groups; most studies included relatively small samples of patients with MDD or bipolar disorder.”

In the paper

“On average, neural activityis most commonly decreased in the DLPFC 30,59,68,76 and increased in the left amygdala, 55,74,76,79,98,99 the fusiform gyrus 82,93,98 and the inferior frontal gyrus 82,90,98 in patients with mood disorders.”

What the sources say

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In the paper

“To date, studies examining the neural correlates of ToM processing in patients with mood disorders have been confined to investigations of patients with bipolar disorder; 2 prelim inary investigations have examined euthymic patients with bipolar disorder.”

In the paper

“Findings concerning the impact of symptom severity among actively ill patients have been less consistent and, on average, have failed to reveal a relation between severity of active illness and patterns of neural activation”

In the paper

“The effect of illness burden and age on neuronal activation during ToM performance in patients with mood disorders remains an underexplored area of research.”

In the paper

“which may result in the misdiag nosis of bipolar depression as MDD, 37,38”

What the sources say

• Not checked yetcites [37] source
• Not checked yetcites [38] source

In the paper

“These models posit that prefrontal regions, such as the lateral prefrontal cortex, mPFC, OFC and dorsal anterior cingulate, modulate activity in subcortical (e.g., amygdala) and limbic regions.106,113”

What the sources say

• Not checked yetcites [106] source
• Not checked yetcites [113] source

In the paper

“Where possible, neuroimaging findings involving patients with mood disorders are contextualized based on several key variables, including illness burden (e.g., number of affective episodes), illness state (e.g., active v. remitted), medication status, age, cognitive load and comorbidity, thought to moderate cognitive performance in patients with mood disorders.29”

What the sources say

• Not checked yetcites [29] source

In the paper

“Critically, key variables, including illness burden, symptom severity, comorbidity, medication status and cognitive load may moderate this pattern of neural activation.”

In the paper

“For example, theoretical models propose that the ability to recognize another's emotion is critical to ToM, 8 with empirical evidence supporting this view.”

What the sources say

• Not checked yetcites [8] source
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In the paper

“Given the dearth of papers investigating the domains of ToM in patients with mood disorders, we adopted a liberal approach to the inclusion of relevant articles in these domains.”

In the paper

“These studies were likely not able to detect a relation between this illness variable and neuronal response because of their limited sample sizes and the inclusion of patients with varying levels of depression.”

In the paper

“Overall, these studies point toward a processing bias involving enhanced attention to and recognition of negatively valenced faces during active states of depression that may be accompanied by a tendency to mislabel positively valenced faces as sad and to misjudge (i.e., amplify) the amount of negative emotion conveyed in faces.”

In the paper

“Given the ubiquitous nature of facial expressions, the ability to recognize facial expressions is crucial for intact interpersonal functioning.123”

What the sources say

• Not checked yetcites [123]

In the paper

“it is possible that this null finding stemmed from the inclusion of first-episode patients in the mood disorders group.”

What the sources say

• Not checked yetcites [69] source

In the paper

“whereas implicit processing of sad faces was associated with enhanced activation in the amygdala, anterior cingulate cortex, lateral temporal cortex and mPFC, explicit processing of sad faces was associated with attenuation of these same regions.”

What the sources say

• Not checked yetcites [188] source

In the paper

“a contrasting pattern of reduced amygdala and subgenual cingulate activation in response to sad but not happy facial expressions has been reported in conjunction with a mood-congruent deficit in recognizing sad facial affect.”

What the sources say

• Not checked yetcites [77] source

In the paper

“Depressed patients with bipolar disorder have also shown elevated activity in the amygdala 102 and attenuated responses in the OFC and DLPFC to neutral and negative (e.g., angry, fearful, sad) faces.”

What the sources say

• Not checked yetcites [102] source
• Not checked yetcites [30] source

In the paper

“In euthymic patients with bipolar disorder compared with healthy controls, studies have demonstrated increased hippocampal activity 82 along with enhanced amygdala activity 76 and diminished DLPFC activation when viewing fearful faces 76,82,86”

What the sources say

• Not checked yetcites [82] source
• Not checked yetcites [76] source
• Not checked yetcites [86] source

In the paper

“Overall, these results suggest that conventional antidepressants and novel treatments may dampen hyperactive responses to negative stimuli and enhance the salience of positive stimuli.”

In the paper

“Foland and colleagues 84 also found reduced functional connectivity between the ventrolateral prefrontal cortex and the amygdala during a facial emotional labelling task in line with reduced inhibitory frontal control over amygdala reactivity.”

What the sources say

• Not checked yetcites [84] source

In the paper

“It is plausible that the discrepant findings in subcortical activations in both actively ill and euthymic patients may stem from failure to account for comorbid disorders.”

In the paper

“Severity of depressive or manic symptoms may influence neural response to affective facial stimuli in patients with bipolar disorder, although the evidence is inconsistent.”

In the paper

“Evidence of greater left amygdala-OFC connectivity in response to sad faces and reduced bilateral connectivity between these same regions in response to happy faces has also been reported in depressed but not euthymic patients with bipolar disorder.”

What the sources say

• Not checked yetcites [97] source

In the paper

“In a sample of patients with bipolar disorder with mixed illness states, amygdala activity in response to happy faces was greater in unmedicated patients but lower in medicated patients compared with controls.”

What the sources say

• Not checked yetcites [80] source

In the paper

“emotionspecific impairments in the identification of sadness, 77 disgust 181 and fear 181 as well as a more generalized deficit in facial emotion recognition have been reported in actively manic patients.”

What the sources say

• Not checked yetcites [77] source
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In the paper

“These findings indicate that the negative bias toward sad faces improves and a positive bias toward happy faces emerges with antidepressant treatment.”

In the paper

“Recent work has demonstrated significant associations between an earlier illness onset and both amygdala hyperactivity 86 and decreased activity within the DLPFC.”

What the sources say

• Not checked yetcites [86] source
• Not checked yetcites [76] source

In the paper

“Thomas and colleagues 42 found that during passive viewing of fearful versus neural faces, patients with MDD showed hypoactivation of the right amygdala, whereas hyperactivation of this region was observed in patients with heterogeneous anxiety disorders (generalized anxiety disorder and/or panic disorder).”

What the sources say

• Not checked yetcites [42] source

In the paper

“Hyperactivity in the amygdala in response to negative facial stimuli has been demonstrated across numerous studies of patients with MDD, and a small number of studies indicate hypoactivity in this region in response to positive facial stimuli.”

In the paper

“Moreover, neuroimaging evidence also implicates the posterior superior temporal sulcus, which is involved in biological motion perception, 223,224 including socially relevant directional cues such as the eye gaze of others, 225,226 and the adjacent temporoparietal junction, which is involved in the attribution of beliefs to others, 227 as critical for ToM ability.7,228,229”

What the sources say

• Not checked yetcites [223] source
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In the paper

“as neuroimaging studies are inherently under temporal constraint, a decreased number of trials may be used to shorten the scan duration, consequently decreasing the statistical power during between-and within-group comparisons.”

In the paper

“although patients with mood disorders may perform comparably to controls on behavioural measures, the neural processing of that information is extensively altered”

What the sources say

• Not checked yetcites [64] source
• Not checked yetcites [76] source

In the paper

“During passive viewing paradigms, patients with bipolar disorder and those with MDD demonstrate hypoactivity in the DLPFC and OFC and hyperactivity in the amygdala and anterior cingulate (subgenual and pregenual), although evidence is less consistent for subcortical regions such as the amygdala and paralimbic regions.”

What the sources say

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In the paper

“Recognition of emotional prosody is thought to draw on multiple processing resources mediated by a complex neural network found primarily in the right superior temporal region.”

What the sources say

• Not checked yetcites [198] source
• Not checked yetcites [199] source

In the paper

“Taken together, these different paradigms tend to converge on a pattern of decreased activation in prefrontal cortical regions associated with emotion regulation and cognitive control (e.g., DLPFC) and increased activation in prefrontal, limbic and subcortical regions associated with affective processing.”

In the paper

“Overall, these data suggest that patients with bipolar depression may be biased toward negative mood-congruent facial expressions, whereas those with unipolar depression have an attentional bias away from positive expressions.”

What the sources say

• Not checked yetcites [102] source

In the paper

“Rela tively small sample sizes and variable emotion processing paradigms employed in these studies may also have contributed to discrepant findings observed in subcortical regions, such as the amygdala, across mood states.”

In the paper

“A nascent literature suggests that youth with MDD and with bipolar disorder show impaired performance on tests of facial emotion processing, a finding underscored by studies demonstrating early alterations in the neuronal circuitry under lying social cognitive processing in these samples.”

In the paper

“Taken together, these results point toward an overall lack of inhibition by higher-order cognitive structures on limbic and emotion-related structures during social cognitive processing in patients with mood disorders that is consistent across different social cognitive tasks, including recognition of emotion in faces and prosody, as well as ToM.”

In the paper

“patients with bipolar disorder do not show this normalization of function despite recovery (for exceptions following treatment with a mood stabilizer, see Hassel and colleagues 86 and Robinson and colleagues 90”

What the sources say

• Not checked yetcites [86] source
• Not checked yetcites [90] source

In the paper

“social cognitive tasks that place high demands on cognitive processing resources (e.g., executive functioning, working memory) may engage higherorder cognitive regions to a greater extent than those social cognitive tasks having lower-order processing demands”

In the paper

“the inclusion of heterogeneous samples of patients with comorbid diag noses, particularly anxiety disorders, may limit the interpretability of findings.”