Hyperstable regulation of vigilance in patients with major depressive disorder

Abstract

Objectives. This study tested the hypothesis that patients with depression show less and later declines into lower EEG vigilance stages (different global functional brain states) under resting conditions than healthy controls, as proposed by the vigilance theory of affective disorders. Methods. Thirty patients with Major Depressive Disorder (19 female; mean age: 37.2 years, SD: 12.6) without psychotropic medication and 30 carefully age- and sex-matched controls (19 female; mean age: 37.3 years, SD: 12.8) without past or present mental disorders underwent a 15-min resting EEG. EEG-vigilance regulation was determined with a computer-based vigilance classification algorithm (VIGALL, Vigilance Algorithm Leipzig), allowing a classification of vigilance stages A (with substages A1, A2 and A3), B (with substages B1 and B2/3) and C. Results. Depressive patients spent significantly more time in the highest EEG vigilance substage A1, and less time in substages A2, A3 and B2/3 than controls. In depressive patients, a significantly longer latency until the occurrence of substages A2, A3 and B2/3 was observed. No significant group differences in the percentage of B1 segments or the latency until occurrence of B1 were found. Conclusions. The results confirm the hypothesis that patients with depression show less (and later) declines into lower EEG vigilance stages under resting conditions than healthy controls, and support the vigilance theory of affective disorders linking a hyperstable vigilance regulation to depression.     

EEG-vigilance regulation during the resting state in obsessive–compulsive disorder

ObjectiveObsessive compulsive disorder (OCD) has been associated with disturbed sleep-wake cycles and cortical hypermetabolism. However, it still remains unclear whether OCD is associated with a dysregulation of vigilance (i.e. “brain arousal”). VIGALL (Vigilance Algorithm Leipzig) is an EEG-based tool to assess vigilance dynamics. Aim of this study is to test the hypothesis that during resting state less declines to lower vigilance stages are found in unmedicated patients with OCD (n = 30) compared to healthy controls (HCs, n = 30).MethodsFifteen minutes of resting EEG were recorded; preceding sleep duration, nicotine/caffeine consumption and severity of OCD and depressive symptoms were assessed.ResultsSignificant differences of EEG-vigilance were found for the factor “group” (OCD vs. HC), factor “time” and interaction “group × time” in a repeated measures ANOVA with increased EEG-vigilance in OCD patients. OCD patients showed significantly fewer transitions between EEG-vigilance stages.ConclusionsIn line with findings of disturbed sleep regulation, OCD is associated with altered EEG-vigilance regulation with a failure of declining toward low vigilance stages during rest.SignificanceThese results encourage the use of EEG-vigilance regulation for determining subgroups for e.g. studying treatment response and suggest awareness for possible vigilance effects in neuroimaging studies of OCD.     

Increased delta power and discrepancies in objective and subjective sleep measurements in borderline personality disorder

BACKGROUND: Previous studies have shown depression-like sleep abnormalities in borderline personality disorder (BPD). However, findings in BPD are not unequivocal for REM dysregulation, as well as for a decrement of slow wave sleep and sleep continuity disturbances. Earlier findings in sleep EEG abnormalities in BPD may have been confounded by concomitant depressive symptoms. METHODS: Twenty unmedicated female BPD patients without current comorbid major depression and 20 sex- and age-matched control subjects entered the study. Conventional polysomnographic parameters and for the first time sleep EEG spectral power analysis was performed on two sleep laboratory nights. Subjective sleep parameters were collected by sleep questionnaires in order to assess the relationship between objective and subjective sleep measurements. RESULTS: BPD patients showed a tendency for shortened REM latency and significantly decreased NonREM sleep (stage 2). Spectral EEG analysis showed increased delta power in total NREM sleep as well as in REM sleep in BPD patients. Subjective ratings documented drastically impaired sleep quality in BPD patients for the two weeks before the study and during the two laboratory nights. CONCLUSION: Not-depressed BPD patients only showed tendencies for depression-like REM sleep abnormalities. Surprisingly, BPD patients displayed higher levels of delta power in the sleep EEG in NREM sleep than healthy control subjects. There was a marked discrepancy between objective and subjective sleep measurements, which indicates an altered perception of sleep in BPD. The underlying psychological and neurobiological mechanisms of these alterations are still unclear and need to be clarified in future studies including interventions on a pharmacological and cognitive-behavioral level.     

Prediction of treatment resistance in obsessive compulsive disorder patients based on EEG complexity as a biomarker

ObjectiveThis study aimed to identify an Electroencephalography (EEG) complexity biomarker that could predict treatment resistance in Obsessive compulsive disorder (OCD) patients. Additionally, the statistical differences between EEG complexity values in treatment-resistant and treatment-responsive patients were determined. Moreover, the existence of correlations between EEG complexity and Yale-Brown Obsessive Compulsive Scale (YBOCS) score were evaluated.MethodsEEG data for 29 treatment-resistant and 28 treatment-responsive OCD patients were retrospectively evaluated. Approximate entropy (ApEn) method was used to extract the EEG complexity from both whole EEG data and filtered EEG data, according to 4 common frequency bands, namely delta, theta, alpha, and beta. The random forests method was used to classify ApEn complexity.ResultsApEn complexity extracted from beta band EEG segments discriminated treatment-responsive and treatment-resistant OCD patients with an accuracy of 89.66% (sensitivity: 89.44%; specificity: 90.64%). Beta band EEG complexity was lower in the treatment-resistant patients and the severity of OCD, as measured by YBOCS score, was inversely correlated with complexity values.ConclusionsThe results indicate that, EEG complexity could be considered a biomarker for predicting treatment response in OCD patients.SignificanceThe prediction of treatment response in OCD patients might help clinicians devise and administer individualized treatment plans.     

Event-related potentials in patients with obsessive-compulsive disorder

Twenty-three unmedicated patients with obsessive-compulsive disorder (OCD) were compared with 12 unmedicated patients with social phobia (SP) and 18 age-matched normal controls (C) using a two-tone auditory oddball event-related potentials (ERP) paradigm. The OCD group showed significantly shorter P300 latencies and shorter N200 latencies for target stimuli than the SP and the C groups. The OCD patients also tended to have greater N200 negativity compared with normal controls. However, there were no significant relationships between these ERP abnormalities in OCD patients and the type or severity of their OCD symptoms. In the mean ERP waveforms, increased N200 negativity for target stimuli, as well as the provocation in the later part of N200 for non-target stimuli, were more commonly observed in the OCD and the SP groups compared with the C group. These results raise the possibility that the shorter N200 and P300 latencies in OCD patients may be an OCD-specific phenomenon that is more closely related to the biological basis for OCD, rather than the characteristics of their OCD symptoms. On the other hand, increased negativity in the N200 region, even for non-target stimuli, may represent the common abnormalities among anxiety disorders.     

Cerebral processing of social rejection in patients with borderline personality disorder

An intense fear of abandonment or rejection is a central feature of social relationships for individuals with borderline personality disorder (BPD). A total of 20 unmedicated BPD patients and 20 healthy participants (HC, matched for age and education) played a virtual ball-tossing game including the three conditions: exclusion, inclusion and a control condition with predefined game rules, whereas cerebral activity was assessed using functional magnetic resonance imaging. Subjective experiences of exclusion were assessed after each blocked condition. Both groups felt similarly excluded during the exclusion condition; however, BPD subjects felt more excluded than HC during the inclusion and control conditions. In all three conditions, BPD patients showed a stronger engagement of the dorsal anterior cingulate and medial prefrontal cortex. For HC, activation in several cerebral regions such as the insula and the precuneus differed depending on the interaction situation, whereas for BPD subjects activation in these regions was not modulated by experimental conditions. Subjects with BPD differed from HC in both their subjective reactions to and their neural processing of social interaction situations. Our data suggest that individuals with BPD have difficulty in discriminating between social situations, and tend to hypermentalize during social encounters that are not determined by the intentions of others.     

Aberrant ventral striatal responses during incentive processing in unmedicated patients with obsessive-compulsive disorder

Jung WH, Kang D‐H, Han JY, Jang JH, Gu B‐M, Choi J‐S, Jung MH, Choi C‐H, Kwon JS. Aberrant ventral striatal responses during incentive processing in unmedicated patients with obsessive–compulsive disorder. Objective: Obsessive–compulsive disorder (OCD) is characterized by the dysfunction of control and reward mechanisms. However, only few neuroimaging studies of OCD have examined the reward processing. We examined the neural responses during incentive processing in OCD. Method: Twenty unmedicated patients with OCD and 20 age‐, sex‐, and IQ‐matched healthy controls underwent functional magnetic resonance imaging while performing a modified monetary incentive delay task. Results: Compared with controls, patients with OCD showed increased ventral striatal activation in the no‐loss minus loss outcome contrast and a significant positive correlation between the ventral striatal activation and compulsion symptom severity. In addition, patients with OCD showed increased activations in the frontostriatal regions in the gain minus no‐gain outcomes contrast. During loss anticipation, patients with OCD showed less activations in the lateral prefrontal and inferior parietal cortices. However, during gain anticipation, patients with OCD and healthy controls did not differ in the ventral striatal activation. Conclusion: These findings provide neural evidence for altered incentive processing in unmedicated patients with OCD, suggesting an elevated sensitivity to negatively affect stimuli as well as dysfunction of the ventral striatum.     

EEG-vigilance and response to stimulants in paediatric patients with attention deficit/hyperactivity disorder

ObjectiveIn a pilot study it was investigated whether assessment of EEG-vigilance is useful for the prediction of treatment outcome in ADHD patients.MethodsResting EEG recordings of 49 unmedicated ADHD patients and 49 age-matched controls were analyzed. Vigilance level was determined for 1-s segments with a computer-based algorithm, distinguishing six stages from higher vigilance stages A1, A2 and A3 with dominant alpha activity to lower stages B1 and B2/3 with low amplitude non-alpha and increasing theta and delta activity and further onto stage C characterizing sleep onset. Treatment outcome was measured as changes in continuous performance test (CPT) results from baseline after at least 4 weeks of medication.ResultsADHD patients spend less time in higher A1-stages (ADHD = 66%, controls = 81%) and showed more switching between vigilance stages (ADHD = 26.02%, controls = 19.09%), indicating a more unstable vigilance regulation. Patients with less stable vigilance showed a worse pre-treatment CPT performance but achieved a better post-treatment result compared to patients with more stable vigilance regulation. These differences did not reach statistical significance.ConclusionsSigns of vigilance instability where found in ADHD patients compared to controls. Those patients with a higher degree of vigilance instability seemed to benefit more from stimulant medication.SignificanceThis is the first investigation of EEG-vigilance in ADHD-patients. Results are limited by a short recording time but the results strongly suggest further investigation of the vigilance regulation in ADHD patients.     

Altered EEG lagged coherence during rest in obsessive–compulsive disorder

Objective

Functional magnetic resonance imaging (fMRI) studies found alterations of functional connectivity in obsessive compulsive disorder (OCD). However, there is little knowledge about region of interest (ROI) based electroencephalogram (EEG) connectivity, i.e. lagged non-linear and linear coherence in OCD. Goal of this study was to compare these EEG measures during rest and at different vigilance stages between patients and healthy controls (HC).

Methods

A 15 min resting-state EEG was recorded in 30 unmedicated patients and 30 matched HC. Intracortical lagged non-linear coherence of the main EEG-frequency bands within a set of frontal ROIs and within the default mode network (DMN) were computed and compared using intracortical exact low resolution electromagnetic tomography (eLORETA) software.

Results

Lagged non-linear but not linear coherence was significantly decreased for patients in comparison to HC for the beta 2 frequency between frontal brain areas but not within the DMN. When analysing separate EEG-vigilance stages, only high vigilance stages yielded decreased frontal phase synchronisation at beta and theta frequencies.

Conclusions

The results underline an altered neuronal communication within frontal brain areas during rest in OCD.

Significance

These findings encourage further research on connectivity measures as possible biomarkers for physiological homogeneous subgroups.     

Increased diurnal salivary cortisol in women with borderline personality disorder

Borderline personality disorder (BPD) is characterized by a pervasive pattern of instability in affect regulation, impulse control, interpersonal relationships, and self-image. In previous studies, we have used portable mini-computers to assess the severity of recurrent states of aversive emotional distress and dissociation during ambulatory conditions. Here, we used this approach for the assessment of the hypothalamic–pituitary–adrenal (HPA) axis in patients with BPD. We studied 23 unmedicated female patients with BPD and 24 matched healthy controls. Salivary cortisol was collected from all participants during ambulatory conditions in response to reminders provided by portable mini-computers on 3 consecutive days every 2 h for 14 h after awakening. In addition, cortisol in response to awakening was determined in four 15 min intervals on days 1 and 2. After the last collection of cortisol on the second day, 0.5 mg dexamethasone was administered in order to achieve cortisol suppression on day 3 (low-dose dexamethasone suppression test, DST). Patients with BPD displayed significantly higher salivary cortisol levels than healthy controls as demonstrated by higher total cortisol in response to awakening and higher total daily cortisol levels. There were significantly more non-suppressors of cortisol in the low-dose DST in the patient group when compared to the control group. The ambulatory assessment of saliva cortisol is a suitable approach to study basic parameters of the HPA-axis in patients with BPD. Increased adrenal activity and lowered feedback sensitivity of the HPA-axis may characterise BPD. Further studies have to reveal reasons of heightened adrenal activity in these patients.     

Obsessive-compulsive disorder comorbid with borderline personality disorder: A long-term case study

Abstract Three case reports of patients with borderline personality disorder (BPD) and obsessive-compulsive disorder (OCD) for more than 10 years are used to illustrate the relationship between OCD and borderline pathology. The recognizable features of the obsessive-compulsive symptoms in these reports are: (i) pervasiveness, the symptomatic overlap of obsessive-compulsive symptoms; (ii) poor insight and resistance; and (iii) obsessive control evident in personal relationships. These features are manifestations of OCD psychopathology as well as of a personality disorder. The symptoms with these features are located hypothetically towards the severe end of the symptomatic spectrum of OCD. The comorbidity is not a simple relationship, and the symptomatology of the comorbid patient is derived from OCD pathology linked with the personality disorder rather than from independent BPD pathology.     

Altered cAMP-dependent protein kinase A in platelets of patients with obsessive-compulsive disorder

OBJECTIVE: The purpose of this study was to assess cAMP-dependent protein kinase A in patients with obsessive-compulsive disorder (OCD). METHOD: The levels and the activity of protein kinase A were evaluated in whole platelets obtained from 12 unmedicated patients with OCD and 15 healthy comparison subjects. RESULTS: The immunolabeling of protein kinase A regulatory subunits type I and II were significantly greater but that of the catalytic subunit significantly lower in patients with OCD than in healthy subjects. The cAMP-stimulated activity in patients with OCD was significantly lower than that in healthy subjects. CONCLUSIONS: These data suggest a possible role of protein kinase A in the pathophysiology of OCD.     

Reduced functional connectivity within the limbic cortico‐striato‐thalamo‐cortical loop in unmedicated adults with obsessive‐compulsive disorder

Cortico‐striato‐thalamo‐cortical (CSTC) loops project from the cortex to the striatum, then from the striatum to the thalamus via the globus pallidus, and finally from the thalamus back to the cortex again. These loops have been implicated in Obsessive‐Compulsive Disorder (OCD) with particular focus on the limbic CSTC loop, which encompasses the orbitofrontal and anterior cingulate cortices, as well as the ventral striatum. Resting state functional‐connectivity MRI (rs‐fcMRI) studies, which examine temporal correlations in neural activity across brain regions at rest, have examined CSTC loop connectivity in patients with OCD and suggest hyperconnectivity within these loops in medicated adults with OCD. We used rs‐fcMRI to examine functional connectivity within CSTC loops in unmedicated adults with OCD (n = 23) versus healthy controls (HCs) (n = 20). Contrary to prior rs‐fcMRI studies in OCD patients on medications that report hyperconnectivity in the limbic CSTC loop, we found that compared with HCs, unmedicated OCD participants had reduced connectivity within the limbic CSTC loop. Exploratory analyses revealed that reduced connectivity within the limbic CSTC loop correlated with OCD symptom severity in the OCD group. Our finding of limbic loop hypoconnectivity in unmedicted OCD patients highlights the potential confounding effects of antidepressants on connectivity measures and the value of future examinations of the effects of pharmacological and/or behavioral treatments on limbic CSTC loop connectivity. Hum Brain Mapp 35:2852–2860, 2014. © 2013 Wiley Periodicals, Inc .     

Posttraumatic stress disorder and fMRI activation patterns of traumatic memory in patients with borderline personality disorder.

BACKGROUND: Early traumatization and additional posttraumatic stress disorder are frequent in patients with borderline personality disorder (BPD). The purpose of this study was to investigate neural correlates of traumatic memory in BPD with and without posttraumatic stress disorder (PTSD) using functional magnetic resonance imaging (fMRI). METHODS: We studied 12 traumatized female patients BPD, 6 of them with and 6 without PTSD. According to an autobiographical interview key words (cues) were defined for traumatic and for negative but nontraumatic episodes. In a block-designed fMRI task patients recalled these episodes. Contrasts between trauma condition and nontrauma condition were analyzed. RESULTS: Analyses for all subjects revealed activation of orbitofrontal cortex areas in both hemispheres, anterior temporal lobes, and occipital areas. In the subgroup without PTSD, activation of orbitofrontal cortex on both sides and Broca's area predominated. In the subgroup with additional PTSD, we observed right more than left activation of anterior temporal lobes, mesiotemporal areas, amygdala, posterior cingulate gyrus, occipital areas, and cerebellum. CONCLUSIONS: Dependent on absence or presence of additional PTSD different neural networks seem to be involved in the traumatic memory of patients with BPD.     

Decreased limbic and increased fronto‐parietal connectivity in unmedicated patients with obsessive‐compulsive disorder

Obsessive‐compulsive disorder (OCD) is characterized by recurrent intrusive thoughts and ritualized, repetitive behaviors, or mental acts. Convergent experimental evidence from neuroimaging and neuropsychological studies supports an orbitofronto‐striato‐thalamo‐cortical dysfunction in OCD. Moreover, an over excitability of the amygdala and over monitoring of thoughts and actions involving the anterior cingulate, frontal and parietal cortex has been proposed as aspects of pathophysiology in OCD. We chose a data driven, graph theoretical approach to investigate brain network organization in 17 unmedicated OCD patients and 19 controls using resting‐state fMRI. OCD patients showed a decreased connectivity of the limbic network to several other brain networks: the basal ganglia network, the default mode network, and the executive/attention network. The connectivity within the limbic network was also found to be decreased in OCD patients compared to healthy controls. Furthermore, we found a stronger connectivity of brain regions within the executive/attention network in OCD patients. This effect was positively correlated with disease severity. The decreased connectivity of limbic regions (amygdala, hippocampus) may be related to several neurocognitive deficits observed in OCD patients involving implicit learning, emotion processing and expectation, and processing of reward and punishment. Limbic disconnection from fronto‐parietal regions relevant for (re)‐appraisal may explain why intrusive thoughts become and/or remain threatening to patients but not to healthy subjects. Hyperconnectivity within the executive/attention network might be related to OCD symptoms such as excessive monitoring of thoughts and behavior as a dysfunctional strategy to cope with threat and uncertainty. Hum Brain Mapp 35:5617–5632, 2014. © 2014 Wiley Periodicals, Inc.     

fMRI of neuronal activation with symptom provocation in unmedicated patients with obsessive compulsive disorder

BACKGROUND: Previous studies suggest that a neural circuit involving over-activation of cortical, paralimbic, limbic, and striatal structures may underlie OCD symptomatology, but results may have been limited by medication use in those studies. To address this, we examined the effects of symptom induction on fMRI neural activation in medication-free patients with OCD. METHODS: Seven outpatients with OCD were exposed to individually tailored provocative and innocuous stimuli during fMRI scans. Self-ratings of OCD symptoms were performed prior to each scan and after exposure to stimuli. Images were analyzed as composite data sets and individually. RESULTS: Stimulus presentation was associated with significant increases in OCD self-ratings. Significant activation was demonstrated in several regions of the frontal cortex (orbitofrontal, superior frontal, and the dorsolateral prefrontal); the anterior, medial and lateral temporal cortex; and the right anterior cingulate. Right superior frontal activation inversely correlated with baseline compulsion symptomatology and left orbitofrontal cortical activation was inversely associated with changes in OCD self-ratings following provocative stimuli. CONCLUSIONS: These results in unmedicated patients are consistent with those from previous studies with medicated patients and suggest that OCD symptomatology is mediated by multiple brain regions including the anterior cingulate as well as frontal and temporal brain regions.     

Subcortical functioning in obsessive-compulsive disorder: an exploratory EEG coherence study.

BACKGROUND: Given the paucity of quantitative EEG studies using coherence measures to understand the electrophysiological functional integrity of sub-cortical structures in obsessive-compulsive disorder, the current study was carried out. METHODS: We obtained EEG coherence values for 20 adult OCD patients (10 males; 10 females) and 19 appropriately matched healthy controls across delta (0.5-3.5 Hz), theta (4-7.5 Hz), alpha (8-12 Hz), beta1 (12.5-20 Hz) and beta2 (20.5-30 Hz) bands. As coherence between distant brain regions reflects physiological activities at sub-cortical neural networks, we chose EEG channels at four distant brain regions - anterior interhemispheric, posterior interhemispheric, fronto-temporal and fronto-occipital. RESULTS: In comparison to controls we found significant increase of theta band EEG coherence in the fronto-occipital region in OCD patients (P = 0.045) which did not correlate significantly with either medication status or disease severity. CONCLUSION: This EEG coherence study that suggests hyperactivity at subcortical circuitry in OCD patients is in agreement with existing neuro-imaging findings. Furthermore, this finding provides external validity for sub-cortical dysfunction hypothesis of OCD.     

Neurochemical alterations in women with borderline personality disorder and comorbid attention-deficit hyperactivity disorder

Background. Borderline personality disorder (BPD) is associated with structural and functional brain changes. Recent models and findings refer to alterations of glutamate and total N-acetylaspartate (tNAA) in this condition. Methods. Absolute quantities of tNAA, creatine, glutamate, glutamine, myoinositol and total choline were measured using 3 Tesla magnetic resonance spectroscopy of the left anterior cingulate cortex and the left cerebellum in 14 unmedicated women with BPD and comorbid attention-deficit hyperactivity disorder (ADHD) and 18 healthy women. Both groups were matched with respect to age, education and premorbid intelligence. Results. In the anterior cingulate, we found significantly higher tNAA and glutamate concentrations and a trend for lower glutamine levels in women with BPD and comorbid ADHD as compared to healthy women. There were no significant group differences in cerebellar metabolite concentrations. Conclusions. Glutamatergic changes in the anterior cingulate may be associated with BPD and comorbid ADHD. Increased anterior cingulate tNAA may indicate disturbed energy metabolism or impaired frontal maturation.     

Structural changes in the gray matter of unmedicated patients with obsessive-compulsive disorder: a voxel-based morphometric study

The aim of the current study was to use whole brain voxel-based morphometry（VBM）to assess the gray matter（GM）changes in unmedicated patients with obsessive-compulsive disorder（OCD）compared with normal controls.We compared the GM volumes in28 patients with 22 matched healthy controls using a1.5T MRI.Three-dimensional T1-weighted magnetic resonance images were obtained from all participants.VBM was performed to detect GM volume differences between the two groups.We detected increased regional GM volumes in the bilateral middle temporal gyri,bilateral middle occipital gyri,bilateral globus pallidus,right inferior parietal gyrus,left superior parietal gyrus,right parahippocampus,right supramarginal gyrus,right medial superior frontal gyrus,and left inferior frontal opercular cortex in the OCD patients relative to controls（P〈0.001,uncorrected,cluster size〉100 voxels）.No decreased GM volume was found in the OCD group compared with normal controls.Our findings suggest that structural changes in the GM are not limited to fronto-striato-thalamic circuits in the pathogenesis of OCD.Temporo-parietal cortex may also play an important role.     

Sleep EEG of patients with obsessive-compulsive disorder

Summary Twenty-two patients suffering from an obsessive and compulsive disorder (OCD) according to DSM-III-R were investigated by polysomnographic sleep EEG recordings under drug-free conditions and compared to age- and sex-matched healthy controls. Sleep efficiency was significantly lower and wake % SPT was significantly increased in the patient group compared to healthy subjects. Sleep architecture did not differ among the two samples. Especially REM sleep measures, in particular, REM latency did not differ among the groups. No positive correlation was found between sleep variables and rating inventories for obsession and compulsions (Y-BOCS), depression (Hamilton) and anxiety (CAS). A secondary depression did not influence sleep EEG variables. The results of this study contradict the assumption that OCD patients show REM sleep and slow wave sleep abnormalities similar to those shown by patients with primary depression.