Childhood trauma and anger in adults with and without depressive and anxiety disorders.

BACKGROUND: Childhood trauma (CT) is associated with severe sequelae, including stress-related mental health disorders that can perpetuate long into adulthood. A key mechanism in this relationship seems to be emotion regulation. We aimed to investigate (1) whether childhood trauma is associated with anger in adulthood, and, if so, (2) to explore which types of childhood trauma predominate in the prediction of anger in a cohort that included participants with and without current affective disorders. METHODS: In the Netherlands Study of Depression and Anxiety (NESDA), childhood trauma was assessed with a semi-structured Childhood Trauma Interview (CTI) at baseline, and analyzed in relation to anger as measured at a 4-year follow-up with the Spielberger Trait Anger Subscale (STAS), the Anger Attacks Questionnaire, and cluster B personality traits (i.e., borderline, antisocial) of the Personality Disorder Questionnaire 4 (PDQ-4), using analysis of covariance (ANCOVA) and multivariable logistic regression analyses. Post hoc analyses comprised cross-sectional regression analyses, using the Childhood Trauma Questionnaire-Short Form (CTQ-SF) also obtained at a 4-year follow-up. RESULTS: Participants (n = 2271) were on average 42.1 years (SD = 13.1), and 66.2% were female. Childhood trauma showed a dose-response association with all anger constructs. All types of childhood trauma were significantly associated with borderline personality traits, independently of depression and anxiety. Additionally, all types of childhood trauma except for sexual abuse were associated with higher levels of trait anger, and a higher prevalence of anger attacks and antisocial personality traits in adulthood. Cross-sectionally, the effect sizes were larger compared with the analyses with the childhood trauma measured 4 years prior to the anger measures. CONCLUSIONS: Childhood trauma is linked with anger in adulthood, which could be of particular interest in the context of psychopathology. Focus on childhood traumatic experiences and adulthood anger may help to enhance the effectiveness of treatment for patients with depressive and anxiety disorders. Trauma-focused interventions should be implemented when appropriate.

[Neural mechanisms of dissociation: implication for borderline personality disorder]. / Neurale mechanismen van dissociatie: implicaties voor borderline­persoonlijkheidsstoornis.

BACKGROUND: Dissociation is a prevalent symptom in borderline personality disorder (BPD), which can have detrimental effects on everyday functioning and treatment. Until now, little is known about the brain networks implicated in dissociation in BPD. Research on dissociative disorders and posttraumatic stress disorder found alterations in networks implicated in cognitive control and arousal modulation. However, it is unknown whether these alterations are also affected in BPD.
AIM: To provide an overview of the definitions, neurobiological models, and neuroimaging research on dissociation in BPD.
METHOD: Review of the literature.
RESULTS: During dissociation in BPD, there is evidence for an altered recruitment and interplay of brain regions implicated in the regulation of stress responses and emotions, attention, memory, and self-referential processing (amygdala, anterior cingulate cortex, inferior frontal gyrus, medial prefrontal cortex, superior temporal gyrus, and inferior parietal lobule).
CONCLUSION: Dissociation is associated with alterations in brain networks that regulate affect-cognitive processing in BPD. Given the substantial impact of dissociation on treatment and neural processing, dissociative symptoms should be taken into account in future research and treatment of BPD, even if they are not the primary focus.

Childhood maltreatment and eating disorder pathology: a systematic review and dose-response meta-analysis.

BACKGROUND: Meta-analyses have established a high prevalence of childhood maltreatment (CM) in patients with eating disorders (EDs) relative to the general population. Whether the prevalence of CM in EDs is also high relative to that in other mental disorders has not yet been established through meta-analyses nor to what extent CM affects defining features of EDs, such as number of binge/purge episodes or age at onset. Our aim is to provide meta-analyses on the associations between exposure to CM (i.e. emotional, physical and sexual abuse) on the occurrence of all types of EDs and its defining features. METHOD: Systematic review and meta-analyses. Databases were searched until 4 June 2016. RESULTS: CM prevalence was high in each type of ED (total N = 13 059, prevalence rates 21-59%) relative to healthy (N = 15 092, prevalence rates 1-35%) and psychiatric (N = 7736, prevalence rates 5-46%) control groups. ED patients reporting CM were more likely to be diagnosed with a co-morbid psychiatric disorder [odds ratios (ORs) range 1.41-2.46, p < 0.05] and to be suicidal (OR 2.07, p < 0.001) relative to ED subjects who were not exposed to CM. ED subjects exposed to CM also reported an earlier age at ED onset [effect size (Hedges' g) = -0.32, p < 0.05], to suffer a more severe form of the illness (g = 0.29, p < 0.05), and to binge-purge (g = 0.31, p < 0.001) more often compared to ED patients who did not report any CM. CONCLUSION: CM, regardless of type, is associated with the presence of all types of ED and with severity parameters that characterize these illnesses in a dose dependent manner.

Chronic depression is associated with a pronounced decrease in serum brain-derived neurotrophic factor over time.

One of the leading neurobiological hypotheses on depression states that decreased expression of brain-derived neurotrophic factor (BDNF) contributes to depression. This is supported by consistent findings of low serum BDNF levels in depressed patients compared with non-depressed controls. Whereas it has been generally assumed that this is a state characteristic of depression, strong inferences about state or trait effects require a longitudinal study design. To investigate the longitudinal association between serum BDNF and depression, we measured serum BDNF, (current and past) depression status, use of antidepressants, and all potential covariates at baseline and after 2 years in 1751 individuals, consisting of patients with an incident (n=153), remitted (n=420) and persistent depression (n=310) and non-depressed controls (n=868). We analyzed change/differences in serum BDNF across these four groups with analyses of covariance adjusted for covariates and baseline BDNF value, together with the effects of starting and stopping antidepressant treatment. Our analyses revealed a significant difference for the depression course groups (P=0.007). Compared with non-depressed controls, persistently depressed and remitted patients had a steeper decrease of BDNF levels over time (-1.33 (P=0.001) and -0.97 ng ml(-1) (P=0.011), respectively), whereas BDNF reductions in patients with incident depression were similar to those in healthy controls. Initiation or discontinuation of antidepressants was not associated with BDNF change (P=0.72). These findings suggest that BDNF not only contributes to depression, but that depression in turn may also contribute to low BDNF.

Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (N=9484).

Meta-analyses, published in 2008-2010, have confirmed abnormally low serum brain-derived neurotrophic factor (BDNF) concentrations in depressed patients and normalization of this by antidepressant treatment. These findings are believed to reflect peripheral manifestations of the neurotrophin hypothesis, which states that depression is secondary to an altered expression of BDNF in the brain. Since the publication of these meta-analyses, the field has seen a huge increase in studies on these topics. This motivated us to update the evidence on the aforementioned associations and, in addition, to compile the data on serum BDNF concentrations in relation to the symptom severity of depression. Using a manifold of data as compared with earlier meta-analyses, we find low serum BDNF concentrations in 2384 antidepressant-free depressed patients relative to 2982 healthy controls and to 1249 antidepressant-treated depressed patients (Cohen's d=-0.71 and -0.56, P-values <0.0000001). When publication bias is accounted for, these effect-sizes become substantially smaller (d=-0.47 and -0.34, respectively, P-values<0.0001). We detect between-study heterogeneity in outcomes for which only year of publication and sample size are significant moderators, with more recent papers and larger samples sizes in general being associated with smaller between-group differences. Finally, the aggregated data negate consistent associations between serum BDNF concentrations and the symptom severity of depression. Our findings corroborate the claim that altered serum BDNF concentrations are peripheral manifestations of depression. However, here we highlight that the evidence for this claim is slimmer as was initially thought and amidst a lot of noise.

The bidirectional impact of perceived and enacted support on mood in bipolar outpatients: A two-year prospective study.

Bipolar disorder (BD) is a chronic illness, and a great need has been expressed to elucidate factors affecting the course of the disease. Social support is one of the psychosocial factors that is assumed to play an important role in the course of BD, but it is largely unknown whether the depressive and/or manic symptoms also affect the patients' support system. Further, the perception of one's social support appears to have stronger effects on disease outcomes than one's enacted or received support, but whether this also applies to BD has not been investigated. The objective of this study is to examine temporal, bidirectional associations between mood states (depression and mania) and both enacted and perceived support in BD patients. The current study was conducted among 173 BD I and II outpatients, with overall light to mild mood symptoms. Severity of mood symptoms and social support (enacted as well as perceived) were assessed every 3months, for 2years (1146 data points). Multilevel regression analyses (linear mixed-models) showed that lower perceived support during 3months was associated with subsequent higher levels of depressive, but not of manic symptoms in the following 3months. Vice versa, depressive symptoms during 3months were associated with less perceived support in the following 3months. Further, manic symptoms during 3months were associated with less enacted support in the subsequent 3 months. The current study suggests that perceived, but not enacted, support is consistently related to depressive symptoms in a bidirectional way, while mania is specifically associated with a subsequent loss of enacted support. Clinical implications of the current findings are discussed.

Amygdala and anterior cingulate resting-state functional connectivity in borderline personality disorder patients with a history of interpersonal trauma.

BACKGROUND: Studies in borderline personality disorder (BPD) have consistently revealed abnormalities in fronto-limbic brain regions during emotional, somatosensory and cognitive challenges. Here we investigated changes in resting-state functional connectivity (RSFC) of three fronto-limbic core regions of specific importance to BPD. METHOD: Functional magnetic resonance imaging data were acquired in 20 unmedicated female BPD patients and 17 healthy controls (HC, matched for age, sex and education) during rest. The amygdala, and the dorsal and ventral anterior cingulate cortex (ACC) were defined as seeds to investigate RSFC patterns of a medial temporal lobe network, the salience network and default mode network. The Dissociation Experience Scale (DES), a measure of trait dissociation, was additionally used as a predictor of RSFC with these seed regions. RESULTS: Compared with HC, BPD patients showed a trend towards increased RSFC between the amygdala and the insula, orbitofrontal cortex and putamen. Compared with controls, patients furthermore exhibited diminished negative RSFC between the dorsal ACC and posterior cingulate cortex, a core region of the default mode network, and regions of the dorsomedial prefrontal cortex. Last, increased negative RSFC between the ventral ACC and medial occipital regions was observed in BPD patients. DES scores were correlated with amygdala connectivity with the dorsolateral prefrontal cortex and fusiform gyrus. CONCLUSIONS: Our findings suggest alterations in resting-state networks associated with processing of negative emotions, encoding of salient events, and self-referential processing in individuals with BPD compared with HC. These results shed more light on the role of abnormal brain connectivity in BPD.

Resting-state functional connectivity in adults with childhood emotional maltreatment.

BACKGROUND: Childhood emotional maltreatment (CEM) has been associated with disturbances in emotional and behavioral functioning, and with changes in regional brain morphology. However, whether CEM has any effect on the intrinsic organization of the brain is not known. In this study, we investigated the effects of CEM on resting-state functional connectivity (RSFC) using seeds in the limbic network, the default-mode network (DMN) and the salience network, and the left dorsomedial prefrontal cortex (dmPFC). Method Using 3-T magnetic resonance imaging (MRI), resting-state functional MRI (RS-fMRI) scans were obtained. We defined seeds in the bilateral amygdala, the dorsal anterior cingulate cortex (dACC), the posterior cingulate cortex (PCC) and the left dmPFC, and used these to examine whether individuals reporting CEM (n=44) differed from individuals reporting no CEM (n=44) in RSFC with other brain regions. The two groups were matched for age, gender, handedness and the presence of psychopathology. RESULTS: CEM was associated with decreased RSFC between the right amygdala and the bilateral precuneus and a cluster extending from the left insula to the hippocampus and putamen. In addition, CEM was associated with decreased RSFC between the dACC and the precuneus and also frontal regions of the brain. CONCLUSIONS: We found that CEM has a profound effect on RSFC in the limbic network and the salience network. Regions that show aberrant connectivity are related to episodic memory encoding, retrieval and self-processing operations.

Eye movement desensitization and processing for adolescents with major depressive disorder: study protocol for a multi-site randomized controlled trial.

BACKGROUND: Major depressive disorder (MDD) is one of the most common mental disorders in adolescence carrying a serious risk of adverse development later in life. Extant treatments are limited in effectiveness and have high drop-out and relapse rates. A body of literature has been published on the association between distressing/ traumatic experiences and development and maintenance of MDD, but the effectiveness of a trauma-focused treatment approach for MDD has hardly been studied. This study aims to determine the effectiveness of eye movement desensitization and reprocessing (EMDR) therapy as stand-alone intervention in adolescents diagnosed with MDD. METHODS: This study will be a randomized controlled trial with two conditions: (1) EMDR treatment (6 sessions) and (2) waiting list condition (WL: 6 weeks, followed by EMDR treatment). First, participants receive a baseline measure after which they will be randomized. Participants will be assessed post-intervention after which the WL participants will also receive six EMDR sessions. Follow-up assessments will be conducted at 3 and 6 months follow-up. STUDY POPULATION: In total, 64 adolescents (aged 12-18) diagnosed with a major depressive disorder (DSM-5) and identified memories of at least one distressing or traumatic event related to the depressive symptomatology will be included. Main study parameters/endpoints: Primary outcome variables will be the percentage of patients meeting criteria for MDD classification, and level of depressive symptoms. Secondary outcome measures include symptoms of PTSD, anxiety, and general social-emotional problems. At baseline, family functioning and having experienced emotional abuse or neglect will be assessed to explore whether these factors predict post-treatment outcome. DISCUSSION: With the present study, we aim to investigate whether EMDR as a trauma-focussed brief intervention may be effective for adolescents with a primary diagnosis of MDD. EMDR has been proven an effective treatment for traumatic memories in other disorders. It is hypothesized that traumatic memories play a role in the onset and maintenance of depressive disorders. Particularly in adolescence, early treatment of these traumatic memories is warranted to prevent a more chronic or recurrent course of the disorder. TRIAL REGISTRATION: International Clinical Trial Registry Platform (ICTRP): NL9008 (30-10-2020).

Influence of emotional distraction on working memory performance in borderline personality disorder.

BACKGROUND: Emotion dysregulation, characterized by heightened emotional arousal and increased emotional sensitivity, is a core feature of borderline personality disorder (BPD). Although current theories emphasize the disruptive potential of negative emotions on cognitive functioning in BPD, behavioral and neurobiological data on this relationship are still lacking. METHOD: Using functional magnetic resonance imaging (fMRI), neural activity was investigated in 22 unmedicated BPD patients and 22 healthy participants (matched for age, education and intelligence) performing an adapted Sternberg working memory task, while being distracted by emotional (negatively arousing) and neutral pictures from the International Affective Picture System (IAPS). RESULTS: Emotional distraction was associated with significantly higher activation in the amygdala and decreased activation in the dorsolateral prefrontal cortex (DLPFC), extending findings of previous studies in healthy individuals. Patients with BPD showed significantly longer reaction times (RTs) along with significantly higher activation in the amygdala and insula during emotional distraction compared to healthy participants, suggesting that they were more distracted by emotional pictures during the working memory task. Moreover, in the group of BPD patients, a significant negative correlation was found between activation in limbic brain regions and self-reports of current dissociative states. CONCLUSIONS: Our findings suggest hyper-responsiveness to emotionally distracting pictures in BPD patients that negatively affects working memory performance. This stresses the importance of emotion dysregulation in the context of cognitive functioning. Moreover, our findings suggest that dissociative states have a dampening effect on neural reactivity during emotional challenge in BPD.

Treatment effects on insular and anterior cingulate cortex activation during classic and emotional Stroop interference in child abuse-related complex post-traumatic stress disorder.

BACKGROUND: Functional neuroimaging studies have shown increased Stroop interference coupled with altered anterior cingulate cortex (ACC) and insula activation in post-traumatic stress disorder (PTSD). These brain areas are associated with error detection and emotional arousal. There is some evidence that treatment can normalize these activation patterns. METHOD: At baseline, we compared classic and emotional Stroop performance and blood oxygenation level-dependent responses (functional magnetic resonance imaging) of 29 child abuse-related complex PTSD patients with 22 non-trauma-exposed healthy controls. In 16 of these patients, we studied treatment effects of psycho-educational and cognitive behavioural stabilizing group treatment (experimental treatment; EXP) added to treatment as usual (TAU) versus TAU only, and correlations with clinical improvement. RESULTS: At baseline, complex PTSD patients showed a trend for increased left anterior insula and dorsal ACC activation in the classic Stroop task. Only EXP patients showed decreased dorsal ACC and left anterior insula activation after treatment. In the emotional Stroop contrasts, clinical improvement was associated with decreased dorsal ACC activation and decreased left anterior insula activation. CONCLUSIONS: We found further evidence that successful treatment in child abuse-related complex PTSD is associated with functional changes in the ACC and insula, which may be due to improved selective attention and lower emotional arousal, indicating greater cognitive control over PTSD symptoms.

Serum levels of brain-derived neurotrophic factor in major depressive disorder: state-trait issues, clinical features and pharmacological treatment.

Recent evidence supports 'the neurotrophin hypothesis of depression' in its prediction that brain-derived neurotrophic factor (BDNF) is involved in depression. However, some key questions remain unanswered, including whether abnormalities in BDNF persist beyond the clinical state of depression, whether BDNF levels are related to the clinical features of depression and whether distinct antidepressants affect BDNF levels equally. We addressed these questions and investigated serum BDNF levels in 962 depressed patients, 700 fully remitted persons (≥6 months) and 382 healthy controls. We found serum BDNF levels to be low in antidepressant-free depressed patients relative to controls (P=0.007) and to depressed patients who were treated with an antidepressant (P=0.001). BDNF levels of fully remitted persons (whether unmedicated or treated with an antidepressant) were comparable to those of controls. Analyzing the sample of antidepressant-free depressed patients showed that BDNF levels were unrelated to the core clinical features of depression such as its severity or first versus a recurrent episode. The antidepressant associated upregulation of serum BDNF in depressed patients was confined to selective serotonin reuptake inhibitors (SSRIs) (P=0.003) and St John's wort (P=0.03). Our results suggest that low serum levels of BDNF are a state abnormality that is evident during depression and normalizes during remission. Increases in serum levels of BDNF during antidepressant treatment appear to be confined to some antidepressants and do not parallel clinical characteristics, such as the severity of depressive symptoms.

Salivary immune markers are not associated with self-reported childhood maltreatment or psychopathology in adults.

BACKGROUND: Psychological stress has repeatedly been found to be associated with pro-inflammatory markers in blood, and neuro-inflammation may play a role in the development of psychopathology after early life stress. Salivary immune testing is a novel method to non-invasively assess immune functioning. We examined a large range of salivary immune markers in relation to self-reported childhood maltreatment and psychopathology in an adult sample. METHODS: Participants (N = 118, 51% female, mean age = 46.6 yrs, range 22-64) were drawn from a cross-sectional three-generation study, and supplied 2 ml of saliva via passive drool. They reported on childhood maltreatment experiences and on psychopathological symptoms in the last 6 months. Hair cortisol was additionally assessed in a subsample (n = 68). Levels of IL1ß, IL6, IL8, IFNγ, TNFα, tIgE, sIgA, FLCƛ, and FLCƙ were assessed. RESULTS: Linear mixed model analyses showed that several salivary immune markers were associated with age (sIgA and IgE), BMI (sIgA, IL1ß, and IL6), sex (FLCs and IgE), and bad health (IL6, IL8, TNFα). No associations with (anti-inflammatory) medication use or oral health problems were found. Notably, no associations between the immune markers and self-reported childhood maltreatment, psychopathology, or hair cortisol were found. CONCLUSIONS: Salivary immune measures were found to be sensitive to individual differences in age, sex, health and BMI. However. in the current sample there was no indication of inflammation in relation to chronic psychological stress. Larger studies, including participants with higher stress levels, are needed to further examine associations between salivary immune markers and psychological stress.

Positive and negative life events and personality traits in predicting course of depression and anxiety.

OBJECTIVE: To examine the prognostic value of personality dimensions and negative and positive life events for diagnostic and symptom course trajectories in depressive and anxiety disorder. METHOD: A total of 1209 subjects (18-65 years) with depressive and/or anxiety disorder were recruited in primary and specialized mental health care. Personality dimensions at baseline were assessed with the NEO-FFI and incidence and date of life events retrospectively with a structured interview at 2-year follow-up. DSM-IV-based diagnostic interviews as well as life chart assessments allowed course assessment at both the diagnostic and symptom trajectory level over 2 years. RESULTS: Life events were significantly related to diagnostic and symptom course trajectories of depression and anxiety also after correcting for sociodemographic and clinical characteristics. Only negative life events prospectively predicted longer time to remission of depressive disorder. Prospective associations of neuroticism and extraversion with prognosis of anxiety and depression were greatly reduced after correcting for baseline severity and duration of index disorder. Personality traits did not moderate the effect of life events on 2-year course indicators. CONCLUSIONS: Negative life events have an independent effect on diagnostic and symptom course trajectories of depression and to a lesser extent anxiety unconfounded by sociodemographic, clinical, and personality characteristics.

Prognostic significance of social network, social support and loneliness for course of major depressive disorder in adulthood and old age.

AIMS: Poor recovery from depressive disorder has been shown to be related to low perceived social support and loneliness, but not to social network size or frequency of social interactions. Some studies suggest that the significance of social relationships for depression course may be greater in younger than in older patients, and may differ between men and women. None of the studies examined to what extent the different aspects of social relationships have unique or overlapping predictive values for depression course. It is the aim of the present study to examine the differential predictive values of social network characteristics, social support and loneliness for the course of depressive disorder, and to test whether these predictive associations are modified by gender or age. METHODS: Two naturalistic cohort studies with the same design and overlapping instruments were combined to obtain a study sample of 1474 patients with a major depressive disorder, of whom 1181 (80.1%) could be studied over a 2-year period. Social relational variables were assessed at baseline. Two aspects of depression course were studied: remission at 2-year follow-up and change in depression severity over the follow-up period. By means of logistic regression and random coefficient analysis, the individual and combined predictive values of the different social relational variables for depression course were studied, controlling for potential confounders and checking for effect modification by age (below 60 v. 60 years or older) and gender. RESULTS: Multiple aspects of the social network, social support and loneliness were related to depression course, independent of potential confounders - including depression severity - but when combined, their predictive values were found to overlap to a large extent. Only the social network characteristic of living in a larger household, the social support characteristic of few negative experiences with the support from a partner or close friend, and limited feelings of loneliness proved to have unique predictive value for a favourable course of depression. Little evidence was found for effect modification by gender or age. CONCLUSIONS: If depressed persons experience difficulties in their social relationships, this may impede their recovery. Special attention for interpersonal problems, social isolation and feelings of loneliness seems warranted in depression treatment and relapse prevention. It will be of great interest to test whether social relational interventions can contribute to better recovery and relapse prevention of depressive disorder.

Does oxytocin lead to emotional interference during a working memory paradigm?

BACKGROUND: Oxytocin administration may increase attention to emotional information. We hypothesized that this augmented emotional processing might in turn lead to interference on concurrent cognitive tasks. To test this hypothesis, we examined whether oxytocin administration would lead to heightened emotional interference during a working memory paradigm. Additionally, moderating effects of childhood maltreatment were explored. METHODS: Seventy-eight healthy males received 24 IU of intranasal oxytocin or placebo in a randomized placebo-controlled double-blind between-subjects study. A working memory task was performed during which neutral, positive, and negative distractors were presented. RESULTS: The main outcome observed was that oxytocin did not enhance interference by emotional information during the working memory task. There was a non-significant trend for oxytocin to slow down performance irrespective of distractor valence, while accuracy was unaffected. Exploratory analyses showed that childhood maltreatment was related to lower overall accuracy, but in the placebo condition only. However, the maltreated group sample size was very small precluding any conclusions on its moderating effect. CONCLUSIONS: Despite oxytocin's previously proposed role in enhanced emotional processing, no proof was found that this would lead to reduced performance on a concurrent cognitive task. The routes by which oxytocin exerts its effects on cognitive and social-emotional processes remain to be fully elucidated.

A Network Approach to Bipolar Symptomatology in Patients with Different Course Types.

OBJECTIVE: The longitudinal mood course is highly variable among patients with bipolar disorder(BD). One of the strongest predictors of the future disease course is the past disease course, implying that the vulnerability for developing a specific pattern of symptoms is rather consistent over time. We therefore investigated whether BD patients with different longitudinal course types have symptom correlation networks with typical characteristics. To this end we used network analysis, a rather novel approach in the field of psychiatry. METHOD: Based on two-year monthly life charts, 125 patients with complete 2 year data were categorized into three groups: i.e., a minimally impaired (n = 47), a predominantly depressed (n = 42) and a cycling course (n = 36). Associations between symptoms were defined as the groupwise Spearman's rank correlation coefficient between each pair of items of the Young Mania Rating Scale (YMRS) and the Quick Inventory of Depressive Symptomatology (QIDS). Weighted symptom networks and centrality measures were compared among the three groups. RESULTS: The weighted networks significantly differed among the three groups, with manic and depressed symptoms being most strongly interconnected in the cycling group. The symptoms with top centrality that were most interconnected also differed among the course group; central symptoms in the stable group were elevated mood and increased speech, in the depressed group loss of self-esteem and psychomotor slowness, and in the cycling group concentration loss and suicidality. CONCLUSION: Symptom networks based on the timepoints with most severe symptoms of bipolar patients with different longitudinal course types are significantly different. The clinical interpretation of this finding and its implications are discussed.

Brain-Derived Neurotrophic Factor and Antidepressive Effect of Electroconvulsive Therapy: Systematic Review and Meta-Analyses of the Preclinical and Clinical Literature.

Emerging data suggest that Electro-Convulsive Treatment (ECT) may reduce depressive symptoms by increasing the expression of Brain-Derived Neurotrophic Factor (BDNF). Yet, conflicting findings have been reported. For this reason we performed a systematic review and meta-analysis of the preclinical and clinical literature on the association between ECT treatment (ECS in animals) and changes in BDNF concentrations and their effect on behavior. In addition, regional brain expression of BDNF in mouse and human brains were compared using Allen Brain Atlas. ECS, over sham, increased BDNF mRNA and protein in animal brain (effect size [Hedge's g]: 0.38-0.54; 258 effect-size estimates, N = 4,284) but not in serum (g = 0.06, 95% CI = -0.05-0.17). In humans, plasma but not serum BDNF increased following ECT (g = 0.72 vs. g = 0.14; 23 effect sizes, n = 281). The gradient of the BDNF increment in animal brains corresponded to the gradient of the BDNF gene expression according to the Allen brain atlas. Effect-size estimates were larger following more ECT sessions in animals (r = 0.37, P < .0001) and in humans (r = 0.55; P = 0.05). There were some indications that the increase in BDNF expression was associated with behavioral changes in rodents, but not in humans. We conclude that ECS in rodents and ECT in humans increase BDNF concentrations but this is not consistently associated with changes in behavior.

Are the neural substrates of memory the final common pathway in posttraumatic stress disorder (PTSD)?

A model for the posttraumatic stress disorder (PTSD) as a disorder of memory is presented drawing both on psychological and neurobiological data. Evidence on intrusive memories and deficits in declarative memory function in PTSD-patients is reviewed in relation to three brain areas that are involved in memory functioning and the stress response: the hippocampus, amygdala, and the prefrontal cortex. Neurobiological studies have shown that the noradrenergic stress-system is involved in enhanced encoding of emotional memories, sensitization, and fear conditioning, by way of its effects on the amygdala. Chronic stress also affects the hippocampus, a brain area involved in declarative memories, suggesting that hippocampal dysfunction may partly account for the deficits in declarative memory in PTSD-patients. Deficits in the medial prefrontal cortex, a structure that normally inhibits the amygdala, may further enhance the effects of the amygdala, thereby increasing the frequency and intensity of the traumatic memories. Thus, by way of its influence on these brain structures, exposure to severe stress may simultaneously result in strong emotional reactions and in difficulties to recall the emotional event. This model is also relevant for understanding the distinction between declarative and non-declarative memory-functions in processing trauma-related information in PTSD. Implications of our model are reviewed.

Stressful life events in bipolar I and II disorder: cause or consequence of mood symptoms?

BACKGROUND: Life events are assumed to be triggers for new mood episodes in bipolar disorder (BD). However whether life events may also be a result of previous mood episodes is rather unclear. METHOD: 173 bipolar outpatients (BD I and II) were assessed every three months for two years. Life events were assessed by Paykel׳s self-report questionnaire. Both monthly functional impairment due to manic or depressive symptomatology and mood symptoms were assessed. RESULTS: Negative life events were significantly associated with both subsequent severity of mania and depressive symptoms and functional impairment, whereas positive life events only preceded functional impairment due to manic symptoms and mania severity. These associations were significantly stronger in BD I patients compared to BD II patients. For the opposite temporal direction (life events as a result of mood/functional impairment), we found that mania symptoms preceded the occurrence of positive life events and depressive symptoms preceded negative life events. LIMITATIONS: The use of a self-report questionnaire for the assessment of life events makes it difficult to determine whether life events are cause or consequence of mood symptoms. Second, the results can only be generalized to relatively stable bipolar outpatients, as the number of severely depressed as well as severely manic patients was low. CONCLUSIONS: Life events appear to precede the occurrence of mood symptoms and functional impairment, and this association is stronger in BD I patients. Mood symptoms also precede the occurrence of life event, but no differences were found between BD I and II patients.