Catherine Donaldson

Neural responses to sad facial expressions in major depression following cognitive behavioral therapy

BACKGROUND Affective facial processing is an important component of interpersonal relationships. The neural substrate has been examined following treatment with antidepressant medication but not with psychological therapies. The present study investigated the neural correlates of implicit processing of sad facial expressions in depression pretreatment and posttreatment with cognitive behavioral therapy (CBT). METHODS The patient group consisted of 16 medication-free subjects (mean age 40 years) with a DSM-IV diagnosis of acute unipolar major depression, and the comparison group were 16 matched healthy volunteers. Subjects participated in a prospective study with functional magnetic resonance imaging (fMRI) at weeks 0 and 16. During the fMRI scans, subjects performed an affect recognition task with facial stimuli morphed to display varying intensities of sadness. Patients received 16 sessions of CBT. Functional magnetic resonance imaging data were analyzed for the mean activation and differential response to variable intensity (load-response) of facial affect processing. RESULTS During an acute depressive episode, patients showed elevated amygdala-hippocampal activity relative to healthy individuals. Baseline dorsal anterior cingulate activity in patients showed a significant relationship with subsequent clinical response. CONCLUSIONS These data provide further support for elevated amygdala activity in depression and suggest that anterior cingulate activity may be a predictor of treatment response to both pharmacotherapy and CBT.

Neural basis of the emotional Stroop interference effect in major depression

BACKGROUND A mood-congruent sensitivity towards negative stimuli has been associated with development and maintenance of major depressive disorder (MDD). The emotional Stroop task assesses interference effects arising from the conflict of emotional expressions consistent with disorder-specific self-schemata and cognitive colour-naming instructions. Functional neuroimaging studies of the emotional Stroop effect advocate a critical involvement of the anterior cingulate cortex (ACC) during these processes. METHOD Subjects were 17 medication-free individuals with unipolar MDD in an acute depressive episode (mean age 39 years), and 17 age-, gender- and IQ-matched healthy volunteers. In an emotional Stroop task, sad and neutral words were presented in various colours, and subjects were required to name the colour of words whilst undergoing functional magnetic resonance imaging (fMRI). Overt verbal responses were acquired with a clustered fMRI acquisition sequence. RESULTS Individuals with depression showed greater increases in response time from neutral to sad words relative to controls. fMRI data showed a significant engagement of left rostral ACC (BA 32) and right precuneus during sad words in patients relative to controls. Additionally, rostral ACC activation was positively correlated with latencies of negative words in MDD patients. Healthy controls did not have any regions of increased activation compared to MDD patients. CONCLUSIONS These findings provide evidence for a behavioural and neural emotional Stroop effect in MDD and highlight the importance of the ACC during monitoring of conflicting cognitive processes and mood-congruent processing in depression.

What happens to patients with treatment-resistant depression? A systematic review of medium to long term outcome studies

BACKGROUND Treatment-resistant depression (TRD) is relatively common and accounts for a large proportion of the overall burden caused by depression. We conducted a systematic review of outcome studies of TRD in order to summarise findings on the longer term outcome of TRD and make recommendations. METHODS Studies were identified through MEDLINE (1960--June Week 1 2008), EMBASE (1974--June Week 1 2008) and PsycINFO (1967--June Week 1 2008) searches. We included studies that followed adults with highly probable TRD for a minimum of 6 months. Statistical analyses were conducted on selected outcome variables whenever possible. Methodological heterogeneity of studies prohibited formal meta-analysis. RESULTS We identified nine outcome studies with a total of 1279 participants and follow-up duration of between 1 and 10 years. In the short term, TRD was highly recurrent with as many as 80% of those requiring multiple treatments relapsing within a year of achieving remission. For those with a more protracted illness, the probability of recovery within 10 years was about 40%. TRD was also associated with poorer quality of life and increased mortality. LIMITATIONS Included primary studies were heterogeneous. CONCLUSIONS TRD is associated with poorer clinical outcome, particularly among those who require multiple antidepressant medications. The main limitations of the review arise from the variability in recruitment procedures, definitions and outcome assessments of the original studies. We recommend further follow-up studies of carefully identified samples in order to gain a more detailed understanding of this domain of depression and plan effective interventions.

Rumination, mood and social problem-solving in major depression.

BACKGROUND Ruminating when depressed is thought to lower mood and impair problem-solving, while distraction is thought to alleviate mood and assist problem-solving. The present study investigates each of these proposals using both naturally occurring and experimentally induced rumination and distraction in a sample of patients with major depression. METHOD Thirty-six patients with major depression and 36 control participants were randomly allocated to either a rumination or distraction induction condition. Levels of trait rumination and distraction were measured at baseline, mood and problem-solving were measured before and after the inductions. RESULTS In terms of trait measures, depressed patients with higher levels of trait rumination reported poorer mood and gave less effective problem solutions than those who were less ruminative. Trait distraction was not associated with mood or problem-solving. In terms of induced responses, depressed patients who were made to ruminate experienced a deterioration in their mood and gave poorer problem solutions. For those receiving the distraction induction, mood improved in all patients and problem-solving improved in patients who were not naturally ruminating at a high level. Neither induction had an impact on mood or problem-solving in control participants. CONCLUSIONS Treatment for depression associated with adverse life events may need to target rumination as well as problem-solving deficits if interventions are to be effective. The differential effects of self-applied versus experimentally induced distraction require further investigation. Future research will need to consider that high levels of trait rumination may interfere with the impact of experimental inductions.

Expressed emotion and attributions in the carers of patients with Alzheimer's disease: The effect on carer burden.

Burden of care, expressed emotion (EE), causal attributions, and salivary cortisol were assessed in 100 carers of patients with Alzheimers disease. Forty-one carers were rated high EE, which was associated with higher scores of carer distress and strain, and greater reports of noncognitive features in the patient, but not with cortisol levels. High EE carers made more attributions personal to, and controllable by, the patient for negative events. Critical carers made more attributions of the patients behavior that was idiosyncratic. Warmth toward the patient was associated with the opposite of this pattern. Overinvolved carers made attributions of the patients behavior to causes external to the patient and internal to themselves. Cortisol levels were associated with self-reports of strain and distress.

Subregional hippocampal deformations in major depressive disorder

BACKGROUND Hippocampal atrophy is a well reported feature of major depressive disorder, although the evidence has been mixed. The present study sought to examine hippocampal volume and subregional morphology in patients with major depressive disorder, who were all medication-free and in an acute depressive episode of moderate severity. METHODS Structural magnetic resonance imaging scans were acquired in 37 patients (mean age 42 years) and 37 age, gender and IQ-matched healthy individuals. Hippocampal volume and subregional structural differences were measured by manual tracings and identification of homologous surface points to the central core of each hippocampus. RESULTS Both right (P=0.001) and left (P=0.005) hippocampal volumes were reduced in patients relative to healthy controls (n=37 patients and n=37 controls), while only the right hippocampus (P=0.016) showed a reduced volume in a subgroup of first-episode depression patients (n=13) relative to healthy controls. Shape analysis localised the subregional deformations to the subiculum and CA1 subfield extending into the CA2-3 subfields predominantly in the tail regions in the right (P=0.017) and left (P=0.011) hippocampi. LIMITATIONS As all patients were in an acute depressive episode, effects associated with depressive state cannot be distinguished from trait effects. CONCLUSIONS Subregional hippocampal deficits are present early in the course of major depression. The deformations may reflect structural correlates underlying functional memory impairments and distinguish depression from other psychiatric disorders.

Intrusive memories and images in bipolar disorder.

Modifying intrusive memories and images is a powerful intervention in depression and anxiety disorders, but little is known about the presence of these intrusions in bipolar disorder. A semi-structured interview was administered to 29 euthymic patients with bipolar disorder, requiring them to report the intrusive memories and images recalled from their most recent episode of euthymia, depression and hypomania. Euthymia was characterised by intrusive memories of the past, which were less distressing than the memories experienced in depressed states. In addition to intrusive memories, depression was associated with vivid images focussed on death and suicide. Intrusive memories were rare in hypomanic states, which instead were characterised by vivid, enjoyable images of future events. Behaviours and emotions in different bipolar states may be amplified by characteristic intrusive memories and images, suggesting novel opportunities for therapeutic intervention. For example, intrusive images may be particularly important prodromal indicators and hence require greater emphasis in relapse-prevention programmes. Rescripting that incorporates negative elements into overly positive images may also be valuable in minimising the extent of hypomanic episodes.

Reactivity of affect and self-esteem during remission in bipolar affective disorder: An experimental investigation

BACKGROUND Bipolar affective disorder (BPAD) is characterised by a lifelong vulnerability to develop episodes of depressed or elevated mood in response to stressful life events involving achievement or failure. We hypothesised that this latent vulnerability can manifest as reactivity of affect and self-esteem to experimentally induced experiences of success and failure and is shaped by history of childhood adversity. METHODS Twenty-four people with remitted BPAD and twenty-four healthy controls underwent anagram-solving tasks designed to generate experiences of success and failure in two separate sessions. Positive and negative affect and implicit and explicit self-esteem were measured before and after each task. Early adversity was measured by Childhood Trauma Questionnaire. RESULTS People with BPAD showed larger reactivity of affect and explicit self-esteem in response to experimental success and failure than did healthy controls. There were no significant differences in reactivity of implicit self-esteem. History of childhood trauma predicted increased affective reactivity to failure but not to success. LIMITATIONS We used a convenience sample. CONCLUSIONS The present experimental paradigm reveals reactivity of affect and self-esteem as features of BPAD, which are present even during good remission and thus are accessible as targets of interventions aiming at relapse prevention. Differential associations with childhood adversity indicate aetiological heterogeneity, with reactivity to failure influenced by early trauma and reactivity to success driven by other mechanisms.

How disorder-specific are depressive attributions? A comparison of individuals with depression, post-traumatic stress disorder and healthy controls

Depressed individuals tend to assign internal, stable, and global causes to negative events. The present study investigated the specificity of this effect to depression and compared depressive attributional styles of individuals with major depression (MD), post-traumatic stress disorder (PTSD), and healthy controls. We indexed attributional style using the depressive attributions questionnaire in 164 participants. Additionally, we assessed appraisals characteristic of PTSD using the post-traumatic cognitions inventory (PTCI), depressive rumination, trauma history, and depression and PTSD symptom severity. Individuals with MD endorsed a depressive attributional style to a greater extent than both individuals with PTSD, who were not depressed, and healthy controls. Depressive attributional style was associated with the severity of depressive and PTSD symptoms, number and distress of traumatic experiences, frequency of rumination, and post-traumatic cognitions. Depressive attributions and PTCI appraisals independently predicted MD and PTSD symptom severity. They may thus be useful in predicting MD and PTSD, and should be targeted in psychological treatments of these conditions.