Functional imaging of emotional memory in bipolar disorder and schizophrenia

Objectives: Although in current diagnostic criteria there exists a distinction between bipolar disorder and schizophrenia, many patients manifest features of both disorders, and it is unclear which aspects, if any, confer diagnostic specificity. In the present study, we investigate whether there are differences in medial temporal lobe (MTL) activation in bipolar disorder and schizophrenia. We also investigate associations between activation levels and symptom severity across the disorders. Methods: Functional magnetic resonance imaging scans were conducted on 14 healthy controls, 14 patients with bipolar disorder, and 15 patients with schizophrenia undergoing an emotional memory paradigm. Results: All groups demonstrated the expected pattern of behavioural responses during encoding and retrieval, and there were no significant group differences in performance. Robust MTL activation was seen in all three groups during viewing of emotional scenes, which correlated significantly with recognition memory for emotional stimuli. The bipolar group demonstrated relatively greater increases in activation for emotional versus neutral scenes in the left hippocampus than both controls and patients with schizophrenia. There was a significant positive correlation between mania scores and activation in the anterior cingulate, and a significant negative correlation between depression scores and activation in the dorsolateral prefrontal cortex. Conclusion: These results provide evidence that there are distinct patterns of activation in the MTL during an emotional memory task in bipolar disorder and schizophrenia. They also demonstrate that different mood states are associated with different neurobiological responses to emotion across the patient groups.     

Affective lability and affect intensity as core dimensions of bipolar disorders during euthymic period

Bipolar disorders are usually defined by alternative mood states, but a more precise characterization of the euthymic period could provide further insights into the pathophysiology of bipolar disorders. Surprisingly, few studies have investigated core affective dimensions in euthymic bipolar patients. In this study, we assessed 179 euthymic bipolar patients (score < 12 on the Montgomery-Åsberg Depression Scale and a score < 6 on the Bech–Rafaelsen Mania Scale) compared with 86 control subjects using French versions of the Affective Lability Scale (ALS) and the Affect Intensity Measure (AIM). Data were analyzed by logistic regression. Our results showed that euthymic bipolar subjects reported having more intense emotions than controls and also had a higher affective lability. High scores in both affective dimensions were associated with a significantly higher risk for psychiatric axis I comorbidity. Moreover, a high affective lability score was associated with an earlier age of onset for bipolar disease. Affective lability and affect intensity might be two core dimensions of bipolar disorder during euthymic periods, suggesting that bipolar disorder is not circumscribed to mood episodes but also affects emotional reactivity between episodes. Both dimensions could account for the stress reactivity of bipolar patients that may lead to relapses.     

The common adolescent bipolar phenotype shows positive biases in emotional processing

Rock PL, Goodwin GM, Harmer CJ. The common adolescent bipolar phenotype shows positive biases in emotional processing.
Bipolar Disord 2010: 12: 606–615. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Bipolar disorder is associated with abnormalities in emotional processing that persist into periods of remission. However, studies of euthymic bipolar disorder patients may be confounded by the experience of mood episodes and medication. We therefore assessed an adolescent group for vulnerability markers associated with the bipolar phenotype. Methods: The Mood Disorder Questionnaire (MDQ) is a screening tool for bipolar disorder that targets mood‐elevation symptoms. We selected 32 high‐scoring students (≥ 7 symptoms) with the adolescent bipolar phenotype and 30 low‐scoring controls (≤ 3 symptoms) and screened them with the Mini International Neuropsychiatric Interview–Plus for bipolar disorder and other psychiatric disorders. We investigated emotional processing by assessing facial expression recognition, emotional memory, emotion‐potentiated startle, and a dot‐probe task. Results: Of the high‐MDQ participants, 12 were in remission from bipolar disorder defined by DSM‐IV‐TR and interview (bipolar II disorder/bipolar disorder not otherwise specified) and 3 from major depressive disorder. High‐MDQ participants had higher levels of neuroticism, low mood, and lifetime anxiety comorbidity and alcohol dependence compared with low‐MDQ participants. The high‐MDQ group showed facilitated recognition of surprised and neutral facial expressions and enhanced processing of positive versus negative information in emotional recognition memory and emotion‐potentiated startle. There were no effects on emotional categorisation/recall memory or attentional bias in the dot‐probe task. Conclusions: These results suggest that students with the common adolescent bipolar phenotype show positive emotional processing biases despite increased levels of neuroticism, low mood, and anxiety. Such effects may represent a psychological vulnerability marker associated with the bipolar phenotype.     

An emotional Stroop functional MRI study of euthymic bipolar disorder

Objective:  To identify the brain regions associated with emotional processing in euthymic bipolar patients.
Methods:  The study examined 12 euthymic bipolar patients using functional magnetic resonance imaging (fMRI) while performing an emotional Stroop (eStroop) task. The task comprised emotionally valent and neutral words presented in alternating blocks that was designed to implicitly induce affect. In conjunction with fMRI, galvanic skin responses (GSR) were measured to monitor arousal.
Results:  Euthymic bipolar patients had diminished activation in response to the affective stimuli in both cortical and subcortical brain regions when compared with healthy subjects. In particular, patients had less activation in the left ventral prefrontal cortex suggesting a potential trait deficit. Patients were slower to react than healthy controls, but did not differ with respect to accuracy.
Conclusions:  Euthymic bipolar patients are perhaps constrained in their ability to engage affective processing. Diminished ventral prefrontal cortex activation corroborates previous reports of a potential trait deficit, suggesting that 'all is not well in euthymia', although the effects of medication cannot be overlooked.     

The moderating impact of emotional intelligence on free cortisol responses to stress

The construct of trait emotional intelligence (trait EI) refers to the individual differences in the perception, processing, regulation and utilization of emotional information. Several studies have found that trait EI was a significant moderator of subjective responses (e.g., mood deterioration, emotional intensity, action tendencies, bodily sensations) to both natural and laboratory stressors. The present study aims at extending these findings by examining whether trait EI also moderates the biological (i.e., cortisol) response to stress. To this end, 56 participants were assigned to either a neutral or a stressful condition (public speech task) and psychological and cortisol reactivity were examined. Results revealed that higher trait EI scores were associated with significantly lower reactivity to stress at both psychological (i.e., mood deterioration) and biological (i.e., salivary cortisol) levels. Additional analyses revealed that trait EI had incremental validity to predict stress reactivity over and above social desirability, alexithymia and the five-factor model of personality.     

Hoarding and emotional reactivity: The link between negative emotional reactions and hoarding symptomatology

Hoarding disorder (HD) is characterized by difficulty discarding, clutter, and frequently excessive acquiring. Theories have pointed to intense negative emotional reactions (e.g., sadness) as one factor that may play a critical role in HD's etiology. Preliminary work with an analogue sample indicated that more intense negative emotions following emotional films were linked with greater hoarding symptoms. Symptom provocation imaging studies with HD patients have also found evidence for excessive activation in brain regions implicated in processing emotions. The current study utilized a sample with self-reported serious hoarding difficulties to examine how hoarding symptoms related to both general and hoarding-related emotional reactivity, taking into account the specificity of these relationships. We also examined how two cognitive factors, fear of decision-making and confidence in memory, modified this relationship. 628 participants with self-identified hoarding difficulties completed questionnaires about general emotional reactivity, depression, anxiety, decision-making, and confidence in memory. To assess hoarding-related emotional reactivity, participants reported their emotional reactions when imagining discarding various items. Heightened general emotional reactivity and more intense emotional reactions to imagined discarding were associated with both difficulty discarding and acquisition, but not clutter, controlling for age, gender, and co-occurring mood and anxiety symptoms. Fear of decision-making and confidence in memory interacted with general emotional reactivity to predict hoarding symptoms. These findings provide support for cognitive-behavioral models of hoarding. Experimental research should be conducted to discover whether emotional reactivity increases vulnerability for HD. Future work should also examine whether emotional reactivity should be targeted in interventions for hoarding.     

Neural correlates of impaired emotional discrimination in borderline personality disorder: An fMRI study

A common approach to study neuronal aspects of emotional reactivity of borderline personality disorder (BPD) is to study the brain response to emotional faces with functional magnetic resonance imaging (fMRI). 10 BPD patients and 10 matched controls were submitted to an emotional discrimination task in which subjects had to identify an emotional face from a neutral face while fMRI data was acquired. BPD patients made more mistakes than controls in the discrimination task when negative faces were involved. The emotional discrimination task activated brain areas that are known to participate in processing of emotional faces (fusiform gyrus, insula and amygdala) regardless of the psychiatric condition. Additionally, BPD showed higher activation than controls in the middle and inferior temporal cortical areas, brain areas that participate in the processing of face features that carry emotional value. Furthermore, activity at this site correlated with impulsivity score in the Zuckerman–Kuhlman Personality Questionnaire. Our findings may be related to cognitive impairment that may be characteristic of the disorder.     

Trait and state corticostriatal dysfunction in bipolar disorder during emotional face processing

Liu J, Blond BN, van Dyck LI, Spencer L, Wang F, Blumberg HP. Trait and state corticostriatal dysfunction in bipolar disorder during emotional face processing.
Bipolar Disord 2012: 14: 432–441. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: Convergent evidence supports limbic, anterior paralimbic, and prefrontal cortex (PFC) abnormalities in emotional processing in bipolar disorder (BD) and suggests that some abnormalities are mood‐state dependent and others persist into euthymia. However, few studies have assessed elevated, depressed, and euthymic mood states while individuals processed emotional stimuli of varying valence to investigate trait‐ and state‐related neural system responses. Here, regional brain responses to positive, negative, and neutral emotional stimuli were assessed in individuals with BD during elevated, depressed, and euthymic mood states. Methods: One hundred and thirty‐four subjects participated in functional magnetic resonance imaging scanning while processing faces depicting happy, fearful, and neutral expressions: 76 with BD (18 in elevated mood states, 19 depressed, 39 euthymic) and 58 healthy comparison (HC) individuals. Analyses were performed for BD trait‐ and mood state‐related features. Results: Ventral anterior cingulate cortex (VACC), orbitofrontal cortex (OFC), and ventral striatum responses to happy and neutral faces were decreased in the BD group, compared to the HC group, and were not influenced by mood state. Elevated mood states were associated with decreased right rostral PFC activation to fearful and neutral faces, and depression was associated with increased left OFC activation to fearful faces. Conclusions: The findings suggest that abnormal VACC, OFC, and ventral striatum responses to happy and neutral stimuli are trait features of BD. Acute mood states may be associated with additional lateralized abnormalities of diminished right rostral PFC responses to fearful and neutral stimuli in elevated states and increased left OFC responses to fearful stimuli in depressed states.     

Insight in bipolar disorder: associations with cognitive and emotional processing and illness characteristics

van der Werf‐Eldering MJ, van der Meer L, Burger H, Holthausen EAE, Nolen WA, Aleman A. Insight in bipolar disorder: associations with cognitive and emotional processing and illness characteristics.
Bipolar Disord 2011: 13: 343–354. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objective: To investigate the multifactorial relationship between illness insight, cognitive and emotional processes, and illness characteristics in bipolar disorder patients. Methods: Data from 85 euthymic or mildly to moderately depressed bipolar disorder patients were evaluated. Insight was measured using the Mood Disorder Insight Scale (total score and subscale scores: awareness of illness, symptom attribution, and need for treatment). Cognitive and emotional functioning was measured in four domains (processing speed, memory, executive functioning, and emotional learning) in addition to premorbid IQ. Illness characteristics were assessed using the Mini‐International Neuropsychiatric Interview, the Questionnaire for Bipolar Disorder, and the Inventory of Depressive Symptomatology‐self rating scale. Regression analyses were performed for the whole sample. Post‐hoc, interactions with lifetime psychotic features (LPF) were statistically tested and if significant, analyses were repeated for patients with (n = 36) and without (n = 49) LPF separately. Results: In the whole group, better insight was associated with lower processing speed, better memory performance, increased emotional learning, higher level of depressive symptoms, and longer duration of illness. Patients with LPF had worse awareness of illness, but better symptom attribution than patients without LPF. No group differences for need for treatment and overall insight were found. Finally, processing speed significantly predicted subscores for symptom attribution in patients with LPF only. Conclusions: Cognitive functioning as well as impairments in emotional learning and psychotic features independently contributes to impaired insight in bipolar disorder. Processing speed seems to be a key variable in the prediction of insight in patients with LPF and not in patients without LPF.     

Emotional hyperreactivity as a core dimension of manic and mixed states

Despite its obvious importance in mood disorders, characterization of emotional reactivity has been neglected in bipolar disorders. Concerning manic states and the current classification, the main criterion is the presence of an elevated or expansive mood. In contrast to this characteristic and often prolonged mood state, emotional reactivity refers to a brief evoked response to salient emotional stimuli. The goal of this study was to assess the intensity of emotional responses triggered by viewing slides in bipolar patients with manic or mixed states. Our hypothesis was that all emotional responses are exacerbated, whatever the valence of the stimuli. We compared 33 patients with manic or mixed states with 33 matched euthymic patients and 33 healthy control subjects. Arousal and attribution of valence were assessed while subjects viewed slides taken from the International Affective Picture System (positive, neutral and negative slides). Patients with manic or mixed states reported a higher arousal when viewing all types of slides in comparison with the other groups. Concerning attribution of valence, patients with manic or mixed states assessed neutral slides as more pleasant. When bipolar patients with manic and mixed states are placed in front of positive, neutral and negative slides, the slides trigger a higher intensity of emotions, whatever the valence of the emotional stimuli. These results strengthen the importance of emotional hyperreactivity as a core dimension in manic and mixed states in bipolar disorder.     

Understanding emotion and emotional scarring in recurrent depression

BackgroundA single-item assessment of sad mood after remission from MDD is predictive of relapse, yet the mechanisms that play a role in depressive relapse remain poorly understood.MethodsIn 283 patients, remitted from recurrent depression (DSM-IV-TR criteria; HAM-D₁₇ score ≤10), we examined emotional scarring, that is, whether the number of previous depressive episodes was associated with higher levels of sad mood as assessed with a 1-item Visual Analogue Mood Scale (VAMS). We then fitted a cross-sectional multivariate regression model to predict sad mood levels, including the Dysfunctional Attitude Scale Version-A, cognitive reactivity (Leiden Index of Depression Sensitivity), Ruminative Response Scale, and Everyday Problem Checklist.ResultsPatients with greater numbers of prior episodes experienced higher levels of sad mood after remission. In multivariate regression, intensity of daily stress and dysfunctional beliefs were associated with the VAMS (Adj. R² = .091) although not over and above depressive symptomatology (Adj. R² = .114). Cognitive reactivity was not associated with sadness.ConclusionsOur finding that patients with more previous MDEs reported higher levels of sad mood while remitted could be indicative of emotional scarring. Dysfunctional beliefs and intensity of daily stress were associated with sad mood but not over and above residual symptoms. Thus, illness related characteristics especially are associated with sad mood after remission. More negative affect after remission could result in lower stress tolerance or more stress intensity could result in negative affect. Future studies should examine premorbid sadness in a longitudinal cohort, and should study the exact pathway from stress, affect, and cognition to relapse.     

Should mood reactivity be included in the DSM-IV atypical features specifier?

Background The definition of atypical depression is still an unsolved issue. DSM-IV atypical features specifier criteria always require mood reactivity, but why mood reactivity should be included is unclear. The study aim was to test whether mood reactivity should be included in DSM-IV atypical features specifier. Methods Consecutively, 164 unipolar and 241 «soft» bipolar II major depressive episode (MDE) outpatients were interviewed with the Structured Clinical Interview for DSM-IV. The DSM-IV criteria for atypical features specifier were strictly followed. Associations were tested by univariate logistic regression. Results MDE with atypical features was present in 41.4 % of patients. Bipolar II disorder was significantly more common in patients with atypical features. MDE with atypical features was significantly associated with bipolar II, female gender, lower age of onset, more axis I comorbidity, fewer psychotic features, and more depressive mixed states. In the whole sample, mood reactivity was significantly associated with all the atypical symptoms, apart from leaden paralysis, and all the other atypical symptoms were significantly associated with each other. In the bipolar II sub-sample, mood reactivity was associated with many, but not all, atypical symptoms, while in the unipolar sub-sample it was associated with no atypical symptom. Atypical symptoms were significantly more common in mood reactive than in non-mood reactive patients, apart from leaden paralysis. Bipolar II disorder and mood reactivity were strongly associated. Conclusions Results may support the inclusion of mood reactivity in the DSM-IV atypical features specifier for bipolar II disorder, but not for unipolar depression.     

Summer mood in winter depressives: validation of a structured interview

Two structured interviews, the Hypomania Interview Guide (Including Hyperthymia), for Seasonal Affective Disorder (HIGH-SAD) and its successor, the Hypomania Interview Guide (Including Hyperthymia), Retrospective Assessment Version (HIGH-R), were validated for the assessment of nondepressed spring/summer mood states in patients with DSM-III-R or DSM-IV diagnoses of Recurrent Bipolar disorder (I, II or NOS) or Recurrent Major Depressive Disorder (MDD; unipolar), both with Seasonal Pattern, and in normal control subjects (HIGH-SAD only). The instruments retrospectively rate the frequency and severity of DSM diagnostic criterion features as well as several non-DSM features. Both instruments had high internal consistency. Normal controls had lower total scores than unipolar patients, who had lower scores than bipolar patients. Total score classified 85-91% of patients with seasonal affective disorder (SAD) into the correct unipolar or bipolar group. For boundary mood cases, small subsets of features provided better classification accuracy. Based on total score, MDD patients were divided into three subgroups: euthymes (normal mood), hyperthymes (slightly elevated mood), and high-hyperthymes (scores overlapping with hypomania). With the exception of sharpened thinking, DSM items dominated patient classifications. Distinct clusters of "positive" (pleasant, agreeable) or "negative" (impairing) features described the mood states. The HIGH-R and HIGH-SAD are useful for discriminating and classifying hypomania and mania in bipolar patients, and euthymia and hyperthymia in unipolar patients.     

The Internal State Scale: replication of its discriminating abilities in a multisite, public sector sample

Objective: The Internal State Scale (ISS) is a self-report instrument that has been validated for discriminating mood states in patients with bipolar disorder. This study a) extends investigation to a multisite public sector sample and b) tests a revised scoring algorithm that formally identifies patients in mixed states.

Methods: Eighty-six patients with bipolar disorder from four Veterans Affairs medical centers were assessed in a cross-sectional design. Physician-conducted semi-structured interviews used DSM-IV criteria to identify subjects as meeting criteria for euthymia, mania or hypomania, depression, or mixed state (mania or hypomania plus depression). A revised ISS scoring algorithm independently assigned mood state. Mean subscale scores were analyzed across groups. Receiver-operating characteristic (ROC) curve analysis was conducted to determine optimal algorithm structure.

Results: Analysis of mean scores for the ISS subscales replicated original results for Activation, Well-Being, and Perceived Conflict, but indicated differences from the original results for the Depression Index. The ROC curve analysis identified optimal cut-off scores for the revised algorithm. The overall kappa score indicated moderate agreement between ISS and physician ratings of mood state, including mixed states.

Limitations: The study used a sample consisting primarily of male veterans. Mood state was assigned by experts using expert clinician diagnosis, not structured interviews.

Conclusion: The performance of the ISS in this multisite, public sector sample was similar to the performance in the initial research clinic sample. This finding confirms the validity of the ISS as a discriminator of mood states in bipolar disorder. The development of a revised scoring algorithm makes feasible formal identification of mixed episodes with the ISS.     

Amygdala hyperreactivity in borderline personality disorder: implications for emotional dysregulation.

BACKGROUND: Disturbed interpersonal relations and emotional dysregulation are fundamental aspects of borderline personality disorder (BPD). The amygdala plays important roles in modulating vigilance and generating negative emotional states and is often abnormally reactive in disorders of mood and emotion. The aim of this study was to assess amygdala reactivity in BPD patients relative to normal control subjects. We hypothesized that amygdala hyperreactivity contributes to hypervigilance, emotional dysregulation, and disturbed interpersonal relations in BPD. METHODS: Using functional magnetic resonance imaging, we examined neural responses to 20-sec blocks of neutral, happy, sad, and fearful facial expression (or a fixation point) in 15 BPD and 15 normal control subjects. The DSM IV-diagnosed BPD patients and the normal control subjects were assessed by a clinical research team in a medical school psychiatry department. RESULTS: Borderline patients showed significantly greater left amygdala activation to the facial expressions of emotion (vs. a fixation point) compared with normal control subjects. Post-scan debriefing revealed that some borderline patients had difficulty disambiguating neutral faces or found them threatening. CONCLUSIONS: Pictures of human emotional expressions elicit robust differences in amygdala activation levels in borderline patients, compared with normal control subjects, and can be used as probes to study the neuropathophysiologic basis of borderline personality disorder.     

Role of depressive symptoms in early adolescents' online emotional responding to a peer evaluation challenge

Background: Problems regulating emotions effectively (emotion dysregulation) are implicated in many psychological problems. Depression in particular has been increasingly conceptualized as a disorder of emotion regulation. Methods: This study examines the linkage between children's depressive symptoms and the activation and regulation of positive and negative affect in response to an manipulated peer evaluation outcome. Participants (N=142) aged 10–13 played a computer contest (“Survivor”) and were randomized to either a negative (i.e., receiving the lowest “likeability” score from a group of peer judges), a positive (i.e., highest score), or a neutral peer evaluation outcome. Positive and negative affect were assessed at baseline, immediately post‐feedback, and after a 5 min post‐feedback waiting period. Results: No linkage was observed between depressive symptoms and emotional activation in response to either success or failure feedback. Consistent with expectations, we observed a negative linkage between depressive symptoms and children's up‐regulation of positive affect subsequent to receiving negative peer feedback. No such linkage was observed for the maintenance of mood improvement over time. Conclusions: Results suggest that depressive symptoms in children are not linked with deficits or excesses in the overall magnitude of emotional reactivity. However, it appears that elevated depressive symptoms interfere with the ability to swiftly transition out of negative affective states. Depression and Anxiety, 2009. © 2008 Wiley‐Liss, Inc.