Analyzing Fractal Dimension in Electroconvulsive Therapy: Unraveling Complexity in Structural and Functional Neuroimaging.

BACKGROUND: Numerous studies show that electroconvulsive therapy (ECT) induces hippocampal neuroplasticity, but findings are inconsistent regarding its clinical relevance. This study aims to investigate ECT-induced plasticity of anterior and posterior hippocampi using mathematical complexity measures in neuroimaging, namely Higuchi's fractal dimension (HFD) for fMRI time series and the fractal dimension of cortical morphology (FD-CM). Furthermore, we explore the potential of these complexity measures to predict ECT treatment response. METHODS: Twenty patients with a current depressive episode (16 with major depressive disorder and 4 with bipolar disorder) underwent MRI-scans before and after an ECT-series. Twenty healthy controls matched for age and sex were also scanned twice for comparison purposes. Resting-state fMRI data were processed, and HFD was computed for anterior and posterior hippocampi. Group-by-time effects for HFD in anterior and posterior hippocampi were calculated and correlations between HFD changes and improvement in depression severity were examined. For FD-CM analyses, we preprocessed structural MRI with CAT12's surface-based methods. We explored group-by-time effects for FD-CM and the predictive value of baseline HFD and FD-CM for treatment outcome. RESULTS: Patients exhibited a significant increase in bilateral hippocampal HFD from baseline to follow-up scans. Right anterior hippocampal HFD increase was associated with reductions in depression severity. We found no group differences and group-by-time effects in FD-CM. After applying a whole-brain regression analysis, we found that baseline FD-CM in the left temporal pole predicted reduction of overall depression severity after ECT. Baseline hippocampal HFD did not predict treatment outcome. CONCLUSION: This study suggests that HFD and FD-CM are promising imaging markers to investigate ECT-induced neuroplasticity associated with treatment response.

The Effect of Electroconvulsive Therapy on Specific Catatonia Symptoms and Predictors of Late Response.

INTRODUCTION: Electroconvulsive therapy (ECT) is known to be effective in the treatment of catatonia, reaching response rates of about 80 to 100%. It is indicated in cases of treatment resistance to benzodiazepines and in life-threatening conditions such as malignant catatonia. Beneficial effects on specific symptoms or predictors of response are less clear. The objective of this retrospective study is to examine the ECT effect on specific catatonia symptoms in the acute phase of the illness and to identify predictors of response. METHODS: A retrospective study examined data from 20 patients with catatonia, 18 associated with schizophrenia and 2 with bipolar disorder, who underwent ECT from 2008 to 2021. Ten subjects had more than one ECT-series, resulting in a total of 31 ECT-series. Catatonia symptom severity was assessed with the Bush Francis Catatonia Rating Scale (BFCRS). RESULTS: ECT yielded excellent response. Nineteen of 20 patients and 30 of 31 ECT-series achieved response. The mean number of ECT sessions to response was 4.2. Response to ECT was more pronounced for motor inhibition symptoms such as stupor and mutism, while echophenomena, dyskinesia, stereotypy and perseveration responded less well. A predictor of late response was the presence of grasp reflex. DISCUSSION: The present study corroborates the high and rapid effectiveness of ECT in the treatment of catatonia. Focus on single catatonia signs may help to identify those who are most likely to achieve remission quickly, as well as those who might need longer ECT-series.

White matter integrity and pro-inflammatory cytokines as predictors of antidepressant response in MDD.

Major depressive disorder (MDD) is a multifactorial, serious and heterogeneous mental disorder that can lead to chronic recurrent symptoms, treatment resistance and suicidal behavior. MDD often involves immune dysregulation with high peripheral levels of inflammatory cytokines that might have an influence on the clinical course and treatment response. Moreover, patients with MDD show brain volume changes as well as white matter (WM) alterations that are already existing in the early stage of illness. Mounting evidence suggests that both neuroimaging markers, such as WM integrity and blood markers, such as inflammatory cytokines might serve as predictors of treatment response in MDD. However, the relationship between peripheral inflammation, WM structure and antidepressant response is not yet clearly understood. The aim of the present review is to elucidate the association between inflammation and WM integrity and its impact on the pathophysiology and progression of MDD as well as the role of possible novel biomarkers of treatment response to improve MDD prevention and treatment strategies.

Distinct and shared patterns of brain plasticity during electroconvulsive therapy and treatment as usual in depression: an observational multimodal MRI-study.

Electroconvulsive therapy (ECT) is a highly effective treatment for depression. Previous studies point to ECT-induced volume increase in the hippocampi and amygdalae, and to increase in cortical thickness. However, it is unclear if these neuroplastic changes are associated with treatment response. This observational study aimed to address this research question by comparing neuroplasticity between patients with depression receiving ECT and patients with depression that respond to treatment as usual (TAU-responders). Twenty ECT-patients (16 major depressive disorder (MDD), 4 depressed bipolar disorder), 20 TAU-responders (20 MDD) and 20 healthy controls (HC) were scanned twice with multimodal magnetic resonance imaging (structure: MP2RAGE; perfusion: arterial spin labeling). ECT-patients were scanned before and after an ECT-index series (ECT-group). TAU-responders were scanned during a depressive episode and following remission or treatment response. Volumes and cerebral blood flow (CBF) of the hippocampi and amygdalae, and global mean cortical thickness were compared between groups. There was a significant group × time interaction for hippocampal and amygdalar volumes, CBF in the hippocampi and global mean cortical thickness. Hippocampal and amygdalar enlargements and CBF increase in the hippocampi were observed in the ECT-group but neither in TAU-responders nor in HC. Increase in global mean cortical thickness was observed in the ECT-group and in TAU-responders but not in HC. The co-occurrence of increase in global mean cortical thickness in both TAU-responders and in ECT-patients may point to a shared mechanism of antidepressant response. This was not the case for subcortical volume and CBF increase.

Electroconvulsive therapy induces remodeling of hippocampal co-activation with the default mode network in patients with depression.

INTRODUCTION: Electroconvulsive therapy (ECT) is a highly efficient treatment for depression. Previous studies repeatedly reported an ECT-induced volume increase in the hippocampi. We assume that this also affects extended hippocampal networks. This study aims to investigate the structural and functional interplay between hippocampi, hippocampal pathways and core regions of the default mode network (DMN). Twenty patients with a current depressive episode receiving ECT-treatment and twenty age and sex matched healthy controls (HC) were included in the study. ECT-patients underwent multimodal magnetic resonance imaging (MRI)-scans (diffusion weighted imaging, resting state functional MRI) before and after an ECT-index series. HC were also scanned twice in a similar between-scan time-interval. Parahippocampal cingulum (PHC) and uncinate fasciculus (UF) were reconstructed for each participant using manual tractography. Fractional anisotropy (FA) was averaged across tracts. Furthermore, we investigated seed-based functional connectivity (FC) from bilateral hippocampi and from the PCC, a core region of the DMN. At baseline, FA in PHC and UF did not differ between groups. There was no baseline group difference of hippocampal-FC. PCC-FC was decreased in ECT-patients. ECT induced a decrease in FA in the left PHC in the ECT group. No longitudinal changes of FA were found in the UF. Furthermore, there was a decrease in hippocampal-PCC-FC, an increase in hippocampal-supplementary motor area-FC, and an increase in PCC-FC in the ECT-group, reversing group differences at baseline. Our findings suggest that ECT induces structural and functional remodeling of a hippocampal-DMN. Those changes may contribute to ECT-induced clinical response in patients with depression.

Reduced corticolimbic habituation to negative stimuli characterizes bipolar depressed suicide attempters.

Suicide attempts in Bipolar Disorder are characterized by high levels of lethality and impulsivity. Reduced rates of amygdala and cortico-limbic habituation can identify a fMRI phenotype of suicidality in the disorder related to internal over-arousing states. Hence, we investigated if reduced amygdala and whole-brain habituation may differentiate bipolar suicide attempters (SA, n = 17) from non-suicide attempters (nSA, n = 57), and healthy controls (HC, n = 32). Habituation was assessed during a fMRI task including facial expressions of anger and fear and a control condition. Associations with suicidality and current depressive symptomatology were assessed, including machine learning procedure to estimate the potentiality of habituation as biomarker for suicidality. SA showed lower habituation compared to HC and nSA in several cortico-limbic areas, including amygdalae, cingulate and parietal cortex, insula, hippocampus, para-hippocampus, cerebellar vermis, thalamus, and striatum, while nSA displayed intermediate rates between SA and HC. Lower habituation rates in the amygdalae were also associated with higher depressive and suicidal current symptomatology. Machine learning on whole-brain and amygdala habituation differentiated SA vs. nSA with 94% and 69% of accuracy, respectively. Reduced habituation in cortico-limbic system can identify a candidate biomarker for attempting suicide, helping in detecting at-risk bipolar patients, and in developing new therapeutic interventions.

Link between structural connectivity of the medial forebrain bundle, functional connectivity of the ventral tegmental area, and anhedonia in unipolar depression.

The ventral tegmental area (VTA), nucleus accumbens (NAcc), and prefrontal cortex (PFC) are essential for experiencing pleasure and initiating motivated behaviour. The VTA, NAcc, and PFC are connected through the medial forebrain bundle (MFB). In humans, two branches have been described: an infero-medial branch (imMFB) and a supero-lateral branch (slMFB). This study aimed to explore the associations between structural connectivity of the MFB, functional connectivity (FC) of the VTA, anhedonia, and depression severity in patients with depression. Fifty-six patients with unipolar depression and 22 healthy controls matched for age, sex, and handedness were recruited at the University Hospital of Psychiatry and Psychotherapy in Bern, Switzerland. Diffusion-weighted imaging and resting-state functional magnetic resonance imaging scans were acquired. Using manual tractography, the imMFB and slMFB were reconstructed bilaterally for each participant. Seed-based resting-state FC was computed from the VTA to the PFC. Hedonic tone was assessed using the Fawcett-Clark Pleasure Scale. We identified reduced tract volume and reduced number of tracts in the left slMFB. There was an increase in FC between the VTA and right medial PFC in patients with depression. Depression severity was associated with reduced tract volume and fewer tracts in the left slMFB. Reduced hedonic tone was associated with reduced tract volume. Conversely, reduced hedonic tone was associated with increased FC between the VTA and the PFC. In conclusion, our results suggest reduced structural connectivity of the slMFB in patients with depression. Increases in FC between the VTA and PFC may be associated with anhedonia or compensatory hyperactivity.

Associations between anterior cingulate thickness, cingulum bundle microstructure, melancholia and depression severity in unipolar depression.

BACKGROUND: Structural and functional alterations of the anterior cingulate cortex (ACC) have been related to emotional, cognitive and behavioral domains of major depressive disorder. In this study, we investigate cortical thickness of rostral and caudal ACC. In addition, we explore white matter microstructure of the cingulum bundle (CB), a white matter pathway connecting multiple segments of the ACC. We hypothesized reduced cortical thickness and reduced white matter microstructure of the CB in MDD, in particular in the melancholic subtype. In addition, we expect an association between depression severity and CB microstructure. METHODS: Fifty-four patients with a current depressive episode and 22 healthy controls matched for age, gender and handedness underwent structural and diffusion-weighted MRI-scans. Cortical thickness of rostral and caudal ACC were computed. The CB was reconstructed bilaterally using manual tractography. Cortical thickness and fractional anisotropy (FA) of bilateral CB were compared first between all patients and healthy controls and second between healthy controls, melancholic and non-melancholic patients. Correlations between FA and depression severity were calculated. RESULTS: We found no group differences in rostral and caudal ACC cortical thickness or in FA of the CB comparing all patients with healthy controls. Melancholic patients had reduced cortical thickness of bilateral caudal ACC compared to non-melancholic patients and compared to healthy controls. Across all patients, depression severity was associated with reduced FA in bilateral CB. LIMITATIONS: Impact of medication CONCLUSIONS: Cortical thickness of the caudal ACC is associated with the melancholic syndrome. CB microstructure may represent a marker of depression severity.

Psychopharmacological treatment is not associated with reduced suicide ideation and reattempts in an observational follow-up study of suicide attempters.

BACKGROUND: Disorders of mental health are major risk factors for suicidal behavior and require adequate treatment. However, the effect of psychotropic medication on suicidal behavior is unclear. METHODS: The 120 participants in a randomized clinical trial of a brief therapy for suicide attempters (Attempted Suicide Short Intervention Program, ASSIP) reported on repeated suicide attempts, suicidal ideation, depression, and medication in the treatment as usual (TAU), at baseline, 6, 12, 18, and 24 months follow-up. The RCT had no influence on medication prescribed. Drugs prescribed were categorized as any psychotropic, antidepressants plus lithium, and antipsychotics. To assess the effect of long-term medication we identified participants with periods of continuous use of psychotropics and antidepressants plus lithium over twelve months or more, and medication-free participants for the same drug categories during the same time period. RESULTS: Reattempts and suicide ideation decreased in all drug categories. When comparing participants on medication fulfilling the definition of long-term use with participants without medication, reattempts and suicidal ideation were higher in the psychotropics and the antidepressants/lithium groups. These drug categories were associated with higher depression scores in comparison to no-medication. The survival analysis revealed a higher risk of reattempts in the long-term antidepressants/lithium group in comparison to no-medication. Treatment with the brief psychological therapy ASSIP, added to medication, was associated with a lower risk of reattempts. LIMITATIONS: The study relied on the patients' reports on treatment as usual in a randomized controlled clinical trial. Blood levels of the psychotropic compounds were not assessed. CONCLUSIONS: In this observational study of the TAU condition in a clinical trial of a brief psychological therapy for patients who had recently attempted suicide, psychotropic drug use over twelve months or more was not associated with reduced suicide ideation and reattempts. Depression scores suggest that patients on psychotropic medication had more psychiatric pathology. This may be a confounding factor for the effect of medication on suicidal behavior.

Vagus Nerve as Modulator of the Brain-Gut Axis in Psychiatric and Inflammatory Disorders.

The vagus nerve represents the main component of the parasympathetic nervous system, which oversees a vast array of crucial bodily functions, including control of mood, immune response, digestion, and heart rate. It establishes one of the connections between the brain and the gastrointestinal tract and sends information about the state of the inner organs to the brain via afferent fibers. In this review article, we discuss various functions of the vagus nerve which make it an attractive target in treating psychiatric and gastrointestinal disorders. There is preliminary evidence that vagus nerve stimulation is a promising add-on treatment for treatment-refractory depression, posttraumatic stress disorder, and inflammatory bowel disease. Treatments that target the vagus nerve increase the vagal tone and inhibit cytokine production. Both are important mechanism of resiliency. The stimulation of vagal afferent fibers in the gut influences monoaminergic brain systems in the brain stem that play crucial roles in major psychiatric conditions, such as mood and anxiety disorders. In line, there is preliminary evidence for gut bacteria to have beneficial effect on mood and anxiety, partly by affecting the activity of the vagus nerve. Since, the vagal tone is correlated with capacity to regulate stress responses and can be influenced by breathing, its increase through meditation and yoga likely contribute to resilience and the mitigation of mood and anxiety symptoms.

Early maladaptive schemas in adult patients with attention deficit hyperactivity disorder.

The main purpose of this study was to examine whether adult patients with attention deficit hyperactivity disorder (ADHD) demonstrate sets of dysfunctional cognitive beliefs and behavioural tendencies according to Jeffrey Young's schema-focused therapy model. Sets of dysfunctional beliefs (maladaptive schemas) were assessed with the Young Schema Questionnaire (YSQ-S2) in 78 adult ADHD patients and 80 control subjects. Patients with ADHD scored significantly higher than the control group on almost all maladaptive schemas. The 'Failure', 'Defectiveness/Shame', 'Subjugation' and 'Emotional Deprivation' schemas were most pronounced in adult ADHD patients, while only 'Vulnerability to Harm or Illness' did not differ between the two groups. The schemas which were most pronounced in adult patients with ADHD correspond well with their learning histories and core symptoms. By demonstrating the existence of early maladaptive schemas in adults suffering from ADHD, this study suggests that schema theory may usefully be applied to adult ADHD therapy.