Iris van Oostrom

Electroconvulsive therapy increases hippocampal and amygdala volume in therapy refractory depression: A longitudinal pilot study

Electroconvulsive therapy (ECT) is the most potent biological therapy in depression. Animal studies suggest that ECT acts via neuroplasticity effects on limbic structures involved in the pathophysiology of depression but in vivo evidence at the human system level is scarce. Therefore, the aim of the present study was to investigate the effect of ECT on hippocampus and amygdala volume in 15 antidepressant-free patients with treatment refractory depression (seven males, range 42-63 years). ECT treatment was successful as indexed by a significant decrease in depressive symptoms (t14=13.6; p<0.001). Analysis of normalized volumetric data before and after ECT treatment revealed a significant volume increase of both hippocampus and amygdala (minimum p<0.005) with no evidence for a change in global brain volume. Though this change in volume cannot be clearly related to treatment effects, ECT is associated with broader neurotrophic effects other than mere adult neurogenesis in the hippocampus, which has been previously suggested as a core mechanism on the basis of animal data.

Sex Modulates the Interactive Effect of the Serotonin Transporter Gene Polymorphism and Childhood Adversity on Hippocampal Volume

The common genetic variation of the serotonin transporter-linked polymorphic region (5-HTTLPR) has been related to depressive symptoms, in particular after stressful life events. Although it has been investigated in the past, results suggesting that the 5-HTTLPR genotype also affects hippocampal volume are often inconsistent and it remains unclear to what extent reduced hippocampal volume is influenced by the effect of stressful life events and 5-HTTLPR genotype. Moreover, sex, which is known to affect the prevalence of depression substantially, has not been taken into account when trying to disentangle the interactive effect of common genetic variation and environmental stressors on the hippocampus. We investigated this potentially relevant three-way interaction using an automatic magnetic resonance imaging (MRI)-based segmentation of the hippocampus in 357 healthy individuals. We determined the 5-HTTLPR genotype as a biallelic locus and childhood adversity (CA) using a standard questionnaire. An interaction for hippocampal volume was found between the factors sex, genotype, and severe CA (p=0.010) as well as an interaction between genotype and severe CA (p=0.007) in men only. Post hoc tests revealed that only male S’-allele carriers with severe CA had smaller hippocampi (p=0.002). Interestingly, there was no main effect of genotype in men, while female S’-allele carriers had smaller hippocampi than L’L’ carriers (p=0.023). Our results indicate that sex modulates the interactive effect of the 5-HTTLPR genotype and CA on hippocampal volume. While the S’-allele is associated with hippocampal volume independent of CA in women, men only have smaller hippocampi if they carry the risk allele and experienced severe CA.

Approach and Avoidance of Emotional Faces in Happy and Sad Mood

Since the introduction of the associative network theory, mood-congruent biases in emotional information processing have been established in individuals in a sad and happy mood. Research has concentrated on memory and attentional biases. According to the network theory, mood-congruent behavioral tendencies would also be predicted. Alternatively, a general avoidance pattern would also be in line with the theory. Since cognitive biases have been assumed to operate strongly in case of social stimuli, mood-induced biases in approach and avoidance behavior towards emotional facial expressions were studied. 306 females were subjected to a highly emotional fragment of a sad or a happy movie, to induce either a sad mood or a happy mood. An Approach-Avoidance Task was implemented, in which single pictures of faces (with angry, sad, happy, or neutral expression) and non-social control pictures were presented. In contrast to our expectations, mood states did not produce differential behavioral biases. Mood-congruent and mood-incongruent behavioral tendencies were, however, present in a subgroup of participants with highest depressive symptomatology scores. This suggests that behavioral approach-avoidance biases are not sensitive to mood state, but more related to depressive characteristics.

The Influence of Mood on the Processing of Syntactic Anomalies: Evidence from P600.

In several domains of psychology it has been shown that mood influences the way in which we process information. So far, little is known about the relation between mood and processes of language comprehension. In the present study we explore, whether, and if so how, mood affects the processing of syntactic anomalies in real time by recording event-related potentials (ERPs). To this aim we compared the P600 effect to subject-verb agreement errors relative to correct sentences while ERPs were recorded and mood was manipulated by presenting happy or sad film clips. The prediction was that if emotional state affects processes of language comprehension this should be reflected by an interaction between mood and P600. The results were as follows: first, the mood induction procedure was effective: participants were happier after watching happy film clips and sadder after watching sad film clips compared to baseline. Second, for P600 a mood by syntactic correctness interaction was obtained for the midline and lateral electrodes. The interaction reflected a broadly distributed P600 effect for the happy mood condition and a strong reduction in P600 effect for the sad mood condition. Correlation analyses confirmed that the observed changes in P600 effect were accompanied by reliable changes in emotional state. The present ERP findings demonstrate that mood interacts with processes of language comprehension. Three possible explanations for the mood by syntactic correctness interaction are discussed; one in terms of syntactic processing, one in terms of heuristic processing, and one in terms of more general factors like attention and/or motivation.

Linking genetic variants of the mineralocorticoid receptor and negative memory bias: Interaction with prior life adversity

Substantial research has been conducted investigating the association between life adversity and genetic vulnerability for depression, but clear mechanistic links are rarely identified and investigation often focused on single genetic variants. Complex phenotypes like depression, however, are likely determined by multiple variants in interaction with environmental factors. As variations in the mineralocorticoid receptor gene (NR3C2) have been related to a higher risk for depression, we investigated whether NR3C2 variance is related to negative memory bias, an established endophenotype for depression, in healthy participants. Furthermore, we explored the influence of life adversity on this association. We used a set-based analysis to simultaneously test all measured variation in NR3C2 for an association with negative memory bias in 483 participants and an interaction with life adversity. To further specify this interaction, we split the sample into low and high live adversity groups and repeated the analyses in both groups separately. NR3C2 variance was associated with negative memory bias, especially in the high life adversity group. Additionally, we identified a functional polymorphism (rs5534) related to negative memory bias and demonstrating a gene×life adversity interaction. Variations in NR3C2 are associated with negative memory bias and this relationship appears to be influenced by life adversity. As negative memory bias is implicated in the susceptibility to depression, our findings provide mechanistic support for the notion that variations in NR3C2 - which could compromise the proper function of this receptor - are a risk factor for the development of mood disorders.

Verbal and facial-emotional Stroop tasks reveal specific attentional interferences in sad mood

Mood congruence refers to the tendency of individuals to attend to information more readily when it has the same emotional content as their current mood state. The aim of the present study was to ascertain whether attentional interference occurred for participants in sad mood states for emotionally relevant stimuli (mood‐congruence), and to determine whether this interference occurred for both valenced words and valenced faces. A mood induction procedure was administered to 116 undergraduate females divided into two equal groups for the sad and happy mood condition. This study employed three versions of the Stroop task: color, verbal‐emotional, and a facial‐emotional Stroop. The two mood groups did not differ on the color Stroop. Significant group differences were found on the verbal‐emotional Stroop for sad words with longer latencies for sad‐induced participants. Main findings for the facial‐emotional Stroop were that sad mood is associated with attentional interference for angry‐threatening faces as well as longer latencies for neutral faces. Group differences were not found for positive stimuli. These findings confirm that sad mood is associated with attentional interference for mood‐congruent stimuli in the verbal domain (sad words), but this mood‐congruent effect does not necessarily apply to the visual domain (sad faces). Attentional interference for neutral faces suggests sad mood participants did not necessarily see valence‐free faces. Attentional interference for threatening stimuli is often associated with anxiety; however, the current results show that threat is not an attentional interference observed exclusively in states of anxiety but also in sad mood.

What is the contribution of different cognitive biases and stressful childhood events to the presence and number of previous depressive episodes

Negative cognitive biases as well as stressful childhood events are well-known risk factors for depression. Few studies have compared the association of different types of biases and events with depression. The current study examined whether different cognitive biases and stressful childhood events variables were associated with depression and recurrence. Three types of childhood events were assessed in 83 never-depressed and 337 formerly depressed individuals: trauma within the family, trauma outside the family, and adverse events. Furthermore, after a sad mood induction procedure, participants executed a Dot Probe task (selective attentional bias), an Emotional Stroop task (attentional interference bias) and an incidental learning task (memory bias). The association of these measures with case status and recurrence status (one or multiple past episodes) was examined. Negative memory bias and traumatic childhood events within the family were associated with case status, whereas none of the bias measures or childhood events variables were associated with recurrence status. The results indicate that memory bias as well as the experience of aggression and/or abuse within the family during childhood are independently associated with depression. Biases and stressful childhood events did not offer differentiation between individuals with one or multiple past episodes.

Coherence Between Attentional and Memory Biases in Sad and Formerly Depressed Individuals

Cognitive theories assume a uniform processing bias across different samples, but the empirical support for this claim is rather weak and inconsistent. Therefore, coherence between biases across different cognitive domains in a sample of 133 non-depressed (Study 1) and a sample of 266 formerly depressed individuals (Study 2) was examined. In both studies, individuals were selected after a successful sad mood induction procedure. A Dot Probe task, an Emotional Stroop task and a self-referential Incidental Learning and Free Recall task were administered to all participants. Principle component analyses indicated coherence between attentional and memory bias in non-depressed, while in formerly depressed individuals distinct components for attentional biases and for memory bias were uncovered. The data suggest that in formerly depressed individuals, self-referent processing during encoding may be related to memory bias, whereas in non-depressed individuals memory bias may be related to both attentional bias and self-referent processing.

Can Memory Bias be Modified? The Effects of an Explicit Cued-Recall Training in Two Independent Samples

Cognitive bias modification (CBM) has been found to be effective in modifying information-processing biases and in reducing emotional reactivity to stress. Although modification of attention and interpretation biases has frequently been studied, it is not clear whether memory bias can be manipulated through direct training of emotional recall. In two studies (in undergraduate students and in a community sample), memory bias for emotional verbal stimuli was trained with cued recall of either positive or negative words. We did not find evidence for malleability of memory bias for trained stimuli or induction of emotional reactivity to stress in either study. The training did, however, stimulate training-congruent incorrect recall in the community sample. Although we found no evidence for the direct modification of memory bias, the more global effect obtained with respect to retrieval of emotional information from memory holds promise for CBM-memory studies in clinical samples.

Never-depressed females with a family history of depression demonstrate affective bias

According to cognitive theories of depression, individuals susceptible to depression attend selectively to negative information. The purpose of the study was to examine if such an affective processing bias is present in never-depressed individuals with a family history of major depressive disorder (MDD). Formerly depressed female patients having at least one first-degree relative with a history of MDD (n=23), their never-depressed female siblings (n=21) and never-depressed female controls (n=21) performed a conventional and an emotional Stroop task using negative, positive and neutral words. A significant effect was found of group on negative processing bias; post hoc comparisons indicated that never-depressed siblings showed a larger negative processing bias than never-depressed controls. No significant differences were observed in positive bias or conventional interference between the three groups. Our findings suggest that never-depressed females with a family history of depression, like depressed patients, have more difficulties to inhibit negative material and to direct their attention towards task-specific material. This adds to the existing evidence that affective processing bias is a trait characteristic that contributes to the onset of depression and that could be a useful endophenotype for MDD.