How emotional abilities modulate the influence of early life stress on hippocampal functioning

Early life stress (ELS) is known to have considerable influence on brain development, mental health and affective functioning. Previous investigations have shown that alexithymia, a prevalent personality trait associated with difficulties experiencing and verbalizing emotions, is particularly related to ELS. The aim of the present study was to investigate how neural correlates of emotional experiences in alexithymia are altered in the presence and absence of ELS. Therefore, 50 healthy individuals with different levels of alexithymia were matched regarding ELS and investigated with respect to neural correlates of audio-visually induced emotional experiences via functional magnetic resonance imaging. The main finding was that ELS modulated hippocampal responses to pleasant (>neutral) stimuli in high-alexithymic individuals, whereas there was no such modulation in low-alexithymic individuals matched for ELS. Behavioral and psychophysiological results followed a similar pattern. When considered independent of ELS, alexithymia was associated with decreased responses in insula (pleasant > neutral) and temporal pole (unpleasant > neutral). Our results show that the influence of ELS on emotional brain responses seems to be modulated by an individual’s degree of alexithymia. Potentially, protective and adverse effects of emotional abilities on brain responses to emotional experiences are discussed.     

Heterogeneity in brain reactivity to pleasant and food cues: evidence of sign-tracking in humans

Aberrant brain reward responses to food-related cues are an implied characteristic of human obesity; yet, findings are inconsistent. To explain these inconsistencies, we aimed to uncover endophenotypes associated with heterogeneity in attributing incentive salience to food cues in the context of other emotionally salient cues; a phenomenon described as sign- vs goal tracking in preclinical models. Data from 64 lean and 88 obese adults who were 35.5 ± 9.4 years old and predominantly women (79%) were analyzed. Participants viewed food-related, pleasant, neutral and unpleasant images while recording electroencephalograph. Late positive potentials were used to assess incentive salience attributed to the visual stimuli. Eating and affective traits were also assessed. Findings demonstrated that obese individuals, in general, do not demonstrate aberrant brain reward responses to food-related cues. As hypothesized, latent profile analysis of the late positive potential uncovered two distinct groups. ‘Sign-trackers’ showed greater responses to food-related cues (P < 0.001) but lower responses to pleasant stimuli (P < 0.001) compared with ‘goal-trackers’. There were proportionally more obese than lean ‘sign-trackers’ (P = 0.03). Obese ‘sign-trackers’ reported significantly higher levels of emotional eating and food craving (P < 0.001). By examining the heterogeneity in brain reactivity to various emotional stimuli, this translational study highlights the need to consider important neurobehavioral endophenotypes of obesity.     

Cognitive and physiological dissociations in response to emotional pictures in patients with anorexia

Recent studies suggest that patients with anorexia may express dissociated cognitive and physiological reactivities to emotional stimuli. The present research aimed to compare subjective and autonomic responses to pleasant, unpleasant and neutral scenes during a categorization task and an activation rating task in anorexic (AN), alexithymic (AL), depressed (DEP) and control participants (CONT). The participants first categorized pictures according to their emotional valence, followed by a rating of their activation level, concomitant with the recording of skin conductance responses (SCRs). Main findings showed that the AN patients presented major difficulty in categorizing pictures, particularly neutral ones. Contrary to the AL participants, this difficulty did not induce significant increases of SCR amplitude in the AN patients. In the second task, the AN patients rated the intensity of activation of unpleasant pictures higher than the AL participants and that of pleasant ones higher than the AL and CONT participants. In addition, no significant linear correlation was observed between the intensity of activation ratings and SCR amplitude in the AN, AL or DEP participants contrarily to what was observed for control participants. This lack of relation suggests a non-specific disconnection between physiological and cognitive self-reported responses to emotional stimuli. Our results highlight a specific form of emotional processing in the AN patients distinct from that observed in alexithymia or depression and characterized by a dissociation between cognitive and physiological responses. This kind of disconnection could be associated with emotional regulation processes and may benefit the AN patients by lowering the psychological stress response.     

Self-reference modulates the processing of emotional stimuli in the absence of explicit self-referential appraisal instructions

Self-referential evaluation of emotional stimuli has been shown to modify the way emotional stimuli are processed. This study aimed at a new approach by investigating whether self-reference alters emotion processing in the absence of explicit self-referential appraisal instructions. Event-related potentials were measured while subjects spontaneously viewed a series of emotional and neutral nouns. Nouns were preceded either by personal pronouns (‘my’) indicating self-reference or a definite article (‘the’) without self-reference. The early posterior negativity, a brain potential reflecting rapid attention capture by emotional stimuli was enhanced for unpleasant and pleasant nouns relative to neutral nouns irrespective of whether nouns were preceded by personal pronouns or articles. Later brain potentials such as the late positive potential were enhanced for unpleasant nouns only when preceded by personal pronouns. Unpleasant nouns were better remembered than pleasant or neutral nouns when paired with a personal pronoun. Correlation analysis showed that this bias in favor of self-related unpleasant concepts can be explained by participants’ depression scores. Our results demonstrate that self-reference acts as a first processing filter for emotional material to receive higher order processing after an initial rapid attention capture by emotional content has been completed. Mood-congruent processing may contribute to this effect.     

Association of depressive disorders,depression characteristics and antidepressant medication with inflammation

Growing evidence suggests that immune dysregulation may be involved in depressive disorders, but the exact nature of this association is still unknown and may be restricted to specific subgroups. This study examines the association between depressive disorders, depression characteristics and antidepressant medication with inflammation in a large cohort of controls and depressed persons, taking possible sex differences and important confounding factors into account. Persons (18–65 years) with a current (N=1132) or remitted (N=789) depressive disorder according to DSM-IV criteria and healthy controls (N=494) were selected from the Netherlands Study of Depression and Anxiety. Assessments included clinical characteristics (severity, duration and age of onset), use of antidepressant medication and inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)). After adjustment for sociodemographics, currently depressed men, but not women, had higher levels of CRP (1.33 versus 0.92 mg l⁻¹, P<0.001, Cohen''s d=0.32) and IL-6 (0.88 versus 0.72 pg ml⁻¹, P=0.01, Cohen''s d=0.23) than non-depressed peers. Associations reduced after considering lifestyle and disease indicators — especially body mass index — but remained significant for CRP. After full adjustment, highest inflammation levels were found in depressed men with an older age of depression onset (CRP, TNF-α). Furthermore, inflammation was increased in men using serotonin–norepinephrine reuptake inhibitors (CRP, IL-6) and in men and women using tri- or tetracyclic antidepressants (CRP), but decreased among men using selective serotonin reuptake inhibitors (IL-6). In conclusion, elevated inflammation was confirmed in depressed men, especially those with a late-onset depression. Specific antidepressants may differ in their effects on inflammation.     

Variety in emotional life: within-category typicality of emotional experiences is associated with neural activity in large-scale brain networks

The tremendous variability within categories of human emotional experience receives little empirical attention. We hypothesized that atypical instances of emotion categories (e.g. pleasant fear of thrill-seeking) would be processed less efficiently than typical instances of emotion categories (e.g. unpleasant fear of violent threat) in large-scale brain networks. During a novel fMRI paradigm, participants immersed themselves in scenarios designed to induce atypical and typical experiences of fear, sadness or happiness (scenario immersion), and then focused on and rated the pleasant or unpleasant feeling that emerged (valence focus) in most trials. As predicted, reliably greater activity in the ‘default mode’ network (including medial prefrontal cortex and posterior cingulate) was observed for atypical (vs typical) emotional experiences during scenario immersion, suggesting atypical instances require greater conceptual processing to situate the socio-emotional experience. During valence focus, reliably greater activity was observed for atypical (vs typical) emotional experiences in the ‘salience’ network (including anterior insula and anterior cingulate), suggesting atypical instances place greater demands on integrating shifting body signals with the sensory and social context. Consistent with emerging psychological construction approaches to emotion, these findings demonstrate that is it important to study the variability within common categories of emotional experience.     

Genome-wide association studies in non-anxiety individuals identified novel risk loci for depression

BackgroundDepression is a debilitating mental disorder that often coexists with anxiety. The genetic mechanisms of depression and anxiety have considerable overlap, and studying depression in non-anxiety samples could help to discover novel gene. We assess the genetic variation of depression in non-anxiety samples, using genome-wide association studies (GWAS) and linkage disequilibrium score regression (LDSC).MethodsThe GWAS of depression score and self-reported depression were conducted using the UK Biobank samples, comprising 99,178 non-anxiety participants with anxiety score <5 and 86,503 non-anxiety participants without self-reported anxiety, respectively. Replication analysis was then performed using two large-scale GWAS summary data of depression from Psychiatric Genomics Consortium (PGC). LDSC was finally used to evaluate genetic correlations with 855 health-related traits based on the primary GWAS.ResultsTwo genome-wide significant loci for non-anxiety depression were identified: rs139702470 (p = 1.54 × 10⁻⁸, OR = 0.29) locate in PIEZO2, and rs6046722 (p = 2.52 × 10⁻⁸, OR = 1.09) locate in CFAP61. These associated genes were replicated in two GWAS of depression from PGC, such as rs1040582 (p_{replication GWAS1} = 0.02, p_{replication GWAS2} = 2.71 × 10⁻³) in CFAP61, and rs11661122 (p_{replication GWAS1} = 8.16 × 10⁻³, p_{replication GWAS2} = 8.08 × 10⁻³) in PIEZO2. LDSC identified 19 traits genetically associated with non-anxiety depression (p < 0.001), such as marital separation/divorce (rg = 0.45, SE = 0.15).ConclusionsOur findings provide novel clues for understanding of the complex genetic architecture of depression.     

Trace of depression: Network structure of depressive symptoms in different clinical conditions

BackgroundPsychopathological network model has received attention recently in the traditional debate about the continuity of depression. However, there is little evidence for comparing the network structure of depressive symptoms in several depressive states at different clinical stages. Through this study of a broad sample of patients with nonclinical to clinical depression, we examined differences in the network structure of depressive symptoms.MethodsFour groups of participants, including cohorts of clinical depression (current depression, n = 294; remitted depression, n = 118) and nonclinical depression (subthreshold depression, N = 184; healthy control, n = 257), responded to Beck Depression Inventory-II (BDI-II). After adjusting for age and sex, the residual scores of the 21 BDI-II items were input into a regularized partial correlation network for each group. Then, the estimated edge strengths/densities and node characteristics were compared.ResultsCurrent depression has a discontinuous structure with a stronger and denser network of symptoms compared with nonclinical groups. Interestingly, remitted depression had improved to the level in healthy controls; however, it retained the same network structure as current depression, which indicates a trace of depression.ConclusionsWe found the traces of depression that remained even after the symptoms disappeared. This study might provide a novel framework for elucidating the development and formation of depression.     

Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder

Fear conditioning is an established model for investigating posttraumatic stress disorder (PTSD). However, symptom triggers may vaguely resemble the initial traumatic event, differing on a variety of sensory and affective dimensions. We extended the fear-conditioning model to assess generalization of conditioned fear on fear processing neurocircuitry in PTSD. Military veterans (n=67) consisting of PTSD (n=32) and trauma-exposed comparison (n=35) groups underwent functional magnetic resonance imaging during fear conditioning to a low fear-expressing face while a neutral face was explicitly unreinforced. Stimuli that varied along a neutral-to-fearful continuum were presented before conditioning to assess baseline responses, and after conditioning to assess experience-dependent changes in neural activity. Compared with trauma-exposed controls, PTSD patients exhibited greater post-study memory distortion of the fear-conditioned stimulus toward the stimulus expressing the highest fear intensity. PTSD patients exhibited biased neural activation toward high-intensity stimuli in fusiform gyrus (P<0.02), insula (P<0.001), primary visual cortex (P<0.05), locus coeruleus (P<0.04), thalamus (P<0.01), and at the trend level in inferior frontal gyrus (P=0.07). All regions except fusiform were moderated by childhood trauma. Amygdala–calcarine (P=0.01) and amygdala–thalamus (P=0.06) functional connectivity selectively increased in PTSD patients for high-intensity stimuli after conditioning. In contrast, amygdala–ventromedial prefrontal cortex (P=0.04) connectivity selectively increased in trauma-exposed controls compared with PTSD patients for low-intensity stimuli after conditioning, representing safety learning. In summary, fear generalization in PTSD is biased toward stimuli with higher emotional intensity than the original conditioned-fear stimulus. Functional brain differences provide a putative neurobiological model for fear generalization whereby PTSD symptoms are triggered by threat cues that merely resemble the index trauma.     

Exploring the Relationship Between Movement Disorders and Physical Activity in Patients With Schizophrenia: An Actigraphy Study

Low physical activity (PA) and sedentary behavior (SB) are major contributors to mental health burden and increased somatic comorbidity and mortality in people with schizophrenia and related psychoses. Movement disorders are highly prevalent in schizophrenia populations and are related to impaired functioning and poor clinical outcome. However, the relationship between movement disorders and PA and SB has remained largely unexplored. Therefore, we aimed to examine the relationship between movement disorders (akathisia, dyskinesia, dystonia, and parkinsonism) and PA and SB in 216 patients with schizophrenia and related psychoses. Actigraphy, the St. Hans Rating Scale for extrapyramidal syndromes, and psychopathological ratings (PANSS-r) were applied. Data were analyzed using multiple linear regression, adjusting for sex, age, negative symptoms, and defined daily dose of prescribed antipsychotics. Parkinsonism was significantly associated with decreased PA (β = −0.21, P < .01) and increased SB (β = 0.26, P < .001). For dystonia, only the relationship with SB was significant (β = 0.15, P < .05). Akathisia was associated with more PA (β = 0.14, P < .05) and less SB (β = −0.15, P < .05). For dyskinesia, the relationships were non-significant. In a prediction model, akathisia, dystonia, parkinsonism and age significantly predicted PA (F(5,209) = 16.6, P < .001, R²_Adjusted = 0.27) and SB (F(4,210) = 13.4, P < .001, R²_Adjusted = 0.19). These findings suggest that movement disorders, in particular parkinsonism, are associated with reduced PA and increased SB in patients with psychotic disorders. Future studies should take movement disorders into account when examining PA and SB, to establish the clinical value of movement disorders in activating people with psychotic disorders to improve their mental and somatic health.     

Social-specific impairment of negative emotion perception in alexithymia

Alexithymia has been characterized as an impaired ability of emotion processing and regulation. The definition of alexithymia does not include a social component. However, there is some evidence that social cognition may be compromised in individuals with alexithymia. Hence, emotional impairments associated with alexithymia may extend to socially relevant information. Here, we recorded electrophysiological responses of individuals meeting the clinically relevant cutoff for alexithymia (ALEX; n = 24) and individuals without alexithymia (NonALEX; n = 23) while they viewed affective scenes that varied on the dimensions of sociality and emotional valence during a rapid serial visual presentation task. We found that ALEX exhibited lower accuracy and larger N2 than NonALEX in the perception of social negative scenes. Source reconstruction revealed that the group difference in N2 was localized at the dorsal anterior cingulate cortex. Irrespective of emotional valence, ALEX showed stronger alpha power than NonALEX in social but not non-social conditions. Our findings support the hypothesis of social processing being selectively affected by alexithymia, especially for stimuli with negative valence. Electrophysiological evidence suggests altered deployment of attentional resources in the perception of social-specific emotional information in alexithymia. This work sheds light on the neuropsychopathology of alexithymia and alexithymia-related disorders.     

De la non-expression à la surexpression des émotions ou comment l’expérience émotionnelle repose la question des liens entre sexe, alexithymie et répression

Objectives

Alexithymia, considered as a disorder of affect regulation, is well known for its consequences on the vulnerability to negative emotions, but nevertheless it raises the question of the repressive dimension according to Myers’ (1995) and Newton and Contrada’s (1994) researches. If, under certain conditions, alexithymia refers to this dimension we should observed traces of this repressive behaviour on emotional distress. We thus studied the influence of alexithymia scores on trait anxiety, state anxiety and depression, and this relatively to the gender of the participants.

Methodology

We first compared the mean scores of distress of our three groups of subjects (low alexithymia, N = 32; moderate alexithymia, N = 62, high alexithymia, N = 33) with the norms of the general population. Secondly, we studied the consequences of alexithymia intensity on depressive symptoms, trait and state anxiety, with regard to the gender differences. We used 1) the State-Trait Anxiety Inventory (Spielberger) to assess dispositional and acute anxiety, 2) the Center for Epidemiological Scale for Depression (Radloff) to evaluate depressive symptomatology and 3) the Toronto Alexithymia Scale (Bagby) for the alexithymia construct.

Results

In the lower alexithymia group, the total mean scores of depression for men or women (men: 8.06 ± 7.06; women: 8.88 ± 6.84) were significantly lower than those in the general population (men: 12.73 ± 3.02; women: 13.97 ± 3.62). We obtained the same pattern of consequences of a low alexithymia with regard to trait anxiety (men: 32.73 ± 10.20 versus 41.86 ± 9.48; women: 37.17 ± 8.48 versus 45.09 ± 11.11). Finally, there was no difference between the lower alexithymia group mean scores and the general population references, regardless of gender. In addition, in our group of women, the higher the alexithymia mean scores, the more important were the depression (F(2,68) = 21.13, P ≤ 0.000), trait anxiety (F(2,68) = 12.51, P ≤ 0.000) and state anxiety (F(2,68) = 6.72, P ≤ 0.002) mean scores. The male participants did not show a particular vulnerability to the alexithymia intensity, except for trait anxiety in the moderate condition (t(43) = -2.30, P ≤ 0.026).

Conclusion

Our results support the reality of the emotional repression in the condition of lower alexithymia and raise the question of the links between alexithymia and gender. Indeed, emotional experience follows different and surprising ways, inviting us to think about the relevance of a differentiation of the type of alexithymia according to whether one is a man or a woman.     

Emotional self-reference: brain structures involved in the processing of words describing one's own emotions

The present functional magnetic resonance imaging study investigated the role of emotion-related (e.g., amygdala) and self-related brain structures (MPFC in particular) in the processing of emotional words varying in stimulus reference. Healthy subjects (N = 22) were presented with emotional (pleasant or unpleasant) or neutral words in three different conditions: (1) self (e.g., my fear), (2) other (e.g., his fear) and (3) no reference (e.g., the fear). Processing of unpleasant words was associated with increased amygdala and also insula activation across all conditions. Pleasant stimuli were specifically associated with increased activation of amygdala and insula when related to the self (vs. other and no reference). Activity in the MPFC (vMPFC in particular) and anterior cingulate cortex (ACC) was preferentially increased during processing of self-related emotional words (vs. other and no reference). These results demonstrate that amygdala activation in response to emotional stimuli is modulated by stimulus reference and that brain structures implicated in emotional and self-related processing might be important for the subjective experience of one's own emotions.     

Affective startle modulation in clinical depression: preliminary findings.

BACKGROUND: Modulation of the startle reflex by affective foreground stimuli was investigated in a group receiving inpatient treatment for major depressive episodes (n = 14) and an age and gender matched nondepressed group (n = 14). METHODS: Participants viewed 27 pleasant, neutral, and unpleasant pictures chosen from the International Affective Picture System. Acoustic startle probes were presented during picture viewing, and participants also rated the affective qualities of the pictures. RESULTS: While ratings of the pictures were largely similar between the depressed and nondepressed groups, they displayed dissimilar patterns of startle modulation. In the nondepressed group, blinks elicited during unpleasant pictures were significantly larger than during pleasant pictures, whereas the depressed group failed to show this effect. Analyses, which separated the depressed participants into moderate and severe groups based on Beck Depression Inventory scores, revealed that while the moderately depressed group also showed a normal pattern of startle modulation, the severely depressed showed potentiated startles during the pleasant pictures. CONCLUSIONS: These preliminary results suggest that severely depressed patients may respond to some pleasant stimuli as if they are aversive, possibly because such stimuli are seen as signals of frustrative nonreward.     

Heterogeneity and Classification of Recent Onset Psychosis and Depression: A Multimodal Machine Learning Approach

Diagnostic heterogeneity within and across psychotic and affective disorders challenges accurate treatment selection, particularly in the early stages. Delineation of shared and distinct illness features at the phenotypic and brain levels may inform the development of more precise differential diagnostic tools. We aimed to identify prototypes of depression and psychosis to investigate their heterogeneity, with common, comorbid transdiagnostic symptoms. Analyzing clinical/neurocognitive and grey matter volume (GMV) data from the PRONIA database, we generated prototypic models of recent-onset depression (ROD) vs. recent-onset psychosis (ROP) by training support-vector machines to separate patients with ROD from patients with ROP, who were selected for absent comorbid features (pure groups). Then, models were applied to patients with comorbidity, ie, ROP with depressive symptoms (ROP+D) and ROD participants with sub-threshold psychosis-like features (ROD+P), to measure their positions within the affective-psychotic continuum. All models were independently validated in a replication sample. Comorbid patients were positioned between pure groups, with ROP+D patients being more frequently classified as ROD compared to pure ROP patients (clinical/neurocognitive model: χ² = 14.874; P < .001; GMV model: χ² = 4.933; P = .026). ROD+P patient classification did not differ from ROD (clinical/neurocognitive model: χ² = 1.956; P = 0.162; GMV model: χ² = 0.005; P = .943). Clinical/neurocognitive and neuroanatomical models demonstrated separability of prototypic depression from psychosis. The shift of comorbid patients toward the depression prototype, observed at the clinical and biological levels, suggests that psychosis with affective comorbidity aligns more strongly to depressive rather than psychotic disease processes. Future studies should assess how these quantitative measures of comorbidity predict outcomes and individual responses to stratified therapeutic interventions.     

Emotional states and informational brain processing in drug addicts free of drugs: An ERPs study

Objective

To analyze brain event-related responses in heroin-dependent patients under different emotional conditions, in order to determine the influence of specific emotional loading on information processing in drug addicts.

Methods

Fifteen male heroin-dependent patients, matched to 11 male healthy individuals, were exposed to emotion-triggering slides designed to elicit neutral, pleasant or unpleasant emotions, while ERPs were obtained by means of an auditory oddball paradigm. Evoked potential analysis consisted of measuring the amplitude, latency, and topographic distribution (mapped from 19 scalp sites) of the early and late latency component waveforms.

Results

Both groups showed large-amplitude, long-latency, and positive-polarity responses to odd stimuli under all emotional conditions. A within-group comparison between the three emotional conditions showed that the control group had smaller P300 amplitudes under pleasant stimulation; drug addicts showed no differences between all three emotional conditions. Between-group analysis revealed smaller P300 amplitudes in drug addicts than in controls, both for unpleasant and neutral emotional conditions, but this was only significant for some electrode sites. Brain electrical activity mapping at P300 showed that high activation is less spread in the brain areas of drug addicts than in controls for unpleasant and neutral emotional conditions.

Conclusion

Drug addicts have deficits in extracting relevant information from sensory stimuli under different emotional conditions, particularly under unpleasant and neutral stimulation. Decreased P300 in controls under pleasant stimulation is interpreted as a result of an attentional bias mechanism that directs attentional resources to environmental stimuli of positive emotional valence, in contrast to drug addicts where there is no such effect.     

Cognitive behavioral therapy for depression changes medial prefrontal and ventral anterior cingulate cortex activity associated with self-referential processing

Cognitive behavioral therapy (CBT), an effective treatment for depression, targets self-referential processing of emotional stimuli. We examined the effects of CBT on brain functioning during self-referential processing in depressive patients using functional magnetic resonance imaging (fMRI). Depressive patients (n = 23) and healthy participants (n = 15) underwent fMRI scans during a self-referential task using emotional trait words. The depressive patients had fMRI scans before and after completing a total of 12 weekly sessions of group CBT for depression, whereas the healthy participants underwent fMRI scans 12 weeks apart with no intervention. Before undergoing CBT, the depressive patients showed hyperactivity in the medial prefrontal cortex (MPFC) during self-referential processing of negative words. Following CBT, MPFC and ventral anterior cingulate cortex (vACC) activity during self-referential processing among depressive patients was increased for positive stimuli, whereas it was decreased for negative stimuli. Improvements in depressive symptoms were negatively correlated with vACC activity during self-referential processing of negative stimuli. These results suggest that CBT-related improvements in depressive symptoms are associated with changes in MPFC and vACC activation during self-referential processing of emotional stimuli.     

Electroconvulsive therapy mediates neuroplasticity of white matter microstructure in major depression

Whether plasticity of white matter (WM) microstructure relates to therapeutic response in major depressive disorder (MDD) remains uncertain. We examined diffusion tensor imaging (DTI) correlates of WM structural connectivity in patients receiving electroconvulsive therapy (ECT), a rapidly acting treatment for severe MDD. Tract-Based Spatial Statistics (TBSS) applied to DTI data (61 directions, 2.5 mm³ voxel size) targeted voxel-level changes in fractional anisotropy (FA), and radial (RD), axial (AD) and mean diffusivity (MD) in major WM pathways in MDD patients (n=20, mean age: 41.15 years, 10.32 s.d.) scanned before ECT, after their second ECT and at transition to maintenance therapy. Comparisons made at baseline with demographically similar controls (n=28, mean age: 39.42 years, 12.20 s.d.) established effects of diagnosis. Controls were imaged twice to estimate scanning-related variance. Patients showed significant increases of FA in dorsal fronto-limbic circuits encompassing the anterior cingulum, forceps minor and left superior longitudinal fasciculus between baseline and transition to maintenance therapy (P<0.05, corrected). Decreases in RD and MD were observed in overlapping regions and the anterior thalamic radiation (P<0.05, corrected). Changes in DTI metrics associated with therapeutic response in tracts showing significant ECT effects differed between patients and controls. All measures remained stable across time in controls. Altered WM microstructure in pathways connecting frontal and limbic areas occur in MDD, are modulated by ECT and relate to therapeutic response. Increased FA together with decreased MD and RD, which trend towards normative values with treatment, suggest increased fiber integrity in dorsal fronto-limbic pathways involved in mood regulation.     

Multimodal brain imaging connectivity analyses of emotional and motivational deficits in depression among women

BackgroundMajor depressive disorder (MDD) is characterized by impaired cortical–subcortical functional connectivity. Apathy adds to functional impairment, but its cerebral basis in MDD remains unknown. Our objective was to describe impairments in functional connectivity during emotional processing in MDD (with varying levels of congruency and attention), and to determine their correlation with apathy.MethodsWe used the Variable Attention Affective Task during functional MRI, followed by diffusion-weighted MRI, to assess 55 right-handed women (30 with MDD and 25 healthy controls) between September 2012 and February 2015. We estimated functional connectivity using generalized psychophysiologic interaction and anatomic connectivity with tract-based spatial statistics. We measured apathy using the Apathy Evaluation Scale.ResultsWe found decreased functional connectivity between the left amygdala and the left anterior cingulate cortex (ACC) during negative stimuli in participants with MDD (t₅₄ = 4.2; p = 0.035, family-wise error [FWE]–corrected). During high-attention stimuli, participants with MDD showed reduced functional connectivity between the right dorsolateral prefrontal cortex (dlPFC) and the right ACC (t₅₄ = 4.06, p_FWE = 0.02), but greater functional connectivity between the right dlPFC and the right amygdala (t₅₄ = 3.35, p = 0.048). Apathy was associated with increased functional connectivity between the right dlPFC and the right ACC during high-attention stimuli (t₂₈ = 5.2, p = 0.01) and increased fractional anisotropy in the right posterior cerebellum, the anterior and posterior cingulum and the bilateral internal capsule (all p_FWE < 0.05).LimitationsLimitations included a moderate sample size, concomitant antidepressant therapy and no directed connectivity.ConclusionWe found that MDD was associated with impairments in cortical–subcortical functional connectivity during negative stimuli that might alter the recruitment of networks engaged in attention. Apathy-related features suggested networks similar to those observed in degenerative disorders, but possible different mechanisms.