Inflammatory Markers May Inform the Effects of Electroconvulsive Therapy on Cognition in Patients with Depression.

INTRODUCTION: The neurobiological mechanisms underlying the acute cognitive effects of electroconvulsive therapy (ECT) remain poorly understood. Prior research has shown that proinflammatory cytokines such as IL-6, TNF-α, IL1-ß, and IL-10 may interfere with cognitive functioning. Interestingly, immunomodulation is one of the proposed modes of action of ECT. This study investigates whether changes of peripheral levels of IL-6, TNF-α, IL1-ß, and IL-10 are related to changes in cognitive functioning following ECT. METHODS: In the week before and 1 week after an acute course of ECT, 62 patients suffering from depression underwent a neuropsychological evaluation to assess their processing speed using the Symbol Digit Substitution Test (SDST), verbal episodic memory using the Hopkins Verbal Learning Test-Revised (HVLT-R), and their retrospective autobiographic memory using the Autobiographical Memory Interview (AMI) with the peripheral inflammatory markers being measured at the same 2 time points. RESULTS: Patients improved drastically following ECT, while their main performance on both the HVLT-R and AMI declined and their SDST scores remained stable. The levels of IL-6 and IL1-ß had both decreased, where the decrease in IL-6 was related to the decrease in HVLT-R scores. Higher baseline IL-10 levels were associated with a more limited decrease of the HVLT-R scores. CONCLUSION: Our findings tentatively suggest that the effects of ECT on verbal episodic memory may be related to the treatment's immunomodulatory properties, most notably due to decreased IL-6 levels. Moreover, baseline IL-10 appears to be a potential biomarker to predict the effects of ECT on verbal episodic memory. Whilst compelling, the results of this study should be interpreted with caution as, due to its exploratory nature, no correction for multiple comparisons was made. Further, a replication in larger cohorts is warranted.

Inflammation, Hippocampal Volume, and Therapeutic Outcome following Electroconvulsive Therapy in Depressive Patients: A Pilot Study.

INTRODUCTION: Electroconvulsive therapy (ECT) influences the concentration of peripheral inflammatory markers, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In which way this immune effect contributes to the impact of ECT on the central nervous system in depression remains unknown. OBJECTIVE: The aim of this study was to examine whether the hippocampal volumetric increase in depressed patients treated with ECT is related to changes in peripheral IL-6 and TNF-α levels. METHODS: IL-6 and TNF-α plasma levels were measured in 62 patients 1 week before and after an acute course of ECT. Hippocampal volumes were analyzed in a magnetic resonance imaging (MRI) subsample of 13 patients at the same time points. RESULTS: A significant decrease in IL-6 levels was observed in the total sample and a significant increase in hippocampal volume in the MRI subsample. The reduction of peripheral IL-6 correlated with an increase in total hippocampal volume. A more limited decrease of TNF-α correlated with a more limited increase of both the total and left hippocampus volumes. CONCLUSION: This pilot study is the first to highlight the link between peripheral immune changes and hippocampal volume increase following ECT. Further research is required to conclude whether ECT indeed exerts its central effect on the brain via changes of peripheral inflammatory markers.

Imbalance between abstract and concrete repetitive thinking modes in schizophrenia.

OBJECTIVE: Repetitive thoughts can be divided in two modes: abstract/analytic (decontextualized and dysfunctional) and concrete/experiential (problem-focused and adaptive). They constitute a transdiagnostic process involved in many psychopathological states but have received little attention in schizophrenia, as earlier studies only indexed increased ruminations (related to dysfunctional repetitive thoughts) without jointly exploring both modes. This study explored the two repetitive thinking modes, beyond ruminations, to determine their imbalance in schizophrenia. METHODS: Thirty stabilized patients with schizophrenia and 30 matched controls completed the Repetitive Response Scale and the Mini Cambridge-Exeter Repetitive Thought Scale, both measuring repetitive thinking modes. Complementary measures related to schizophrenic symptomatology, depression and anxiety were also conducted. RESULTS: Compared to controls, patients with schizophrenia presented an imbalance between repetitive thinking modes, with increased abstract/analytic and reduced concrete/experiential thoughts, even after controlling for comorbidities. Schizophrenia is associated with stronger dysfunctional repetitive thoughts (i.e. abstract thinking) and impaired ability to efficiently use repetitive thinking for current problem-solving (i.e. concrete thinking). CONCLUSION: This imbalance confirms the double-faced nature of repetitive thinking modes, whose influence on schizophrenia's symptomatology should be further investigated. The present results also claim for evaluating these processes in clinical settings and for rehabilitating the balance between opposite repetitive thinking modes.

Movement, mood and cognition: Preliminary insights into the therapeutic effects of electroconvulsive therapy for depression through a resting-state connectivity analysis.

BACKGROUND: Electroconvulsive therapy (ECT) is a highly effective treatment for depression but how it achieves its clinical effects remains unclear. METHODS: We set out to study the brain's response to ECT from a large-scale brain-network perspective. Using a voxelwise analysis, we looked at resting-state functional connectivity before and after a course of ECT at the whole-brain and the between- and within-network levels in 17 patients with a depressive episode. Using a group-independent component analysis approach, we focused on four networks known to be affected in depression: the salience network (SN), the default mode network (DMN), the cognitive executive network (CEN), and a subcortical network (SCN). Our clinical measures included mood, cognition, and psychomotor symptoms. RESULTS: We found ECT to have increased the connectivity of the left CEN with the left angular gyrus and left middle frontal gyrus as well as its within-network connectivity. Both the right CEN and the SCN showed increased connectivity with the precuneus and the anterior DMN with the left amygdala. Finally, improvement of psychomotor retardation was positively correlated with an increase of within-posterior DMN connectivity. LIMITATIONS: The limitations of our study include its small sample size and the lack of a control dataset to confirm our findings. CONCLUSION: Our voxelwise data demonstrate that ECT induces a significant increase of connectivity across the whole brain and at the within-network level. Furthermore, we provide the first evidence on the association between an increase of within-posterior DMN connectivity and an improvement of psychomotor retardation, a core symptom of depression.

Improvement of psychomotor retardation after electroconvulsive therapy is related to decreased IL-6 levels.

BACKGROUND: Prior studies suggest that IL-6 may be involved in the pathophysiology of psychomotor symptoms in depression. Electroconvulsive therapy (ECT), as yet the most effective biological treatment of severe depression, is known to improve psychomotor functioning, while recent studies have shown a decrease in the elevated IL-6 levels of depressed patients following ECT. OBJECTIVES: This study investigates whether the improvement in psychomotor functions in patients with depression after ECT is related to changes in IL-6 levels. METHODS: Peripheral IL-6 was quantified and the severity of psychomotor agitation and retardation determined using the CORE assessment of psychomotor symptoms in 62 patients with a (unipolar or bipolar) depressive episode within one week before and within one week after their course of ECT. RESULTS: IL-6 levels had decreased significantly following ECT and both psychomotor retardation and agitation had improved. The decrease in IL-6 levels was related to the improvement of psychomotor retardation, with post-hoc analysis revealing that higher baseline IL-6 levels positively correlated with higher psychomotor retardation scores. CONCLUSION: With this study, we provide the first evidence that the improvement of psychomotor retardation after ECT for depression is related to the immunomodulatory properties of the treatment, most specifically the decrease in IL-6 levels.

The basal ganglia: A central hub for the psychomotor effects of electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) is the most effective biological treatment for depression. Aside the well-known therapeutic effect on mood symptoms, it has also a unique positive impact on psychomotor agitation and retardation, which are core symptoms of depression. The neurobiology behind these effects, however, remains unclear. The basal ganglia are proposed to be important regions in the pathogenesis of psychomotor symptoms in depression. Since ECT can trigger neuroplasticity in these subcortical nuclei, we speculate that ECT-induced volumetric changes of the basal ganglia will positively influence psychomotor symptoms. METHODS: Psychomotor symptoms were analyzed in 17 patients with severe depression before and after an acute ECT course using a CORE assessment of the retardation, agitation, and non-interaction domains. The volumes of the caudate, putamen, pallidum, and accumbens regions were determined using magnetic resonance imaging one week before and after ECT. RESULTS: Psychomotor functions had improved significantly after ECT and significant volume increases were found for the accumbens region, the putamen, and pallidum. The volume increase of the nucleus accumbens correlated with an improvement of psychomotor retardation, while the volume increase of the pallidum correlated negatively with an improvement of the agitation subscore. CONCLUSION: Our findings support the notion of an association between the impact of ECT on depression-related psychomotor symptoms and volume increases of the accumbens region and pallidum, pointing to the importance of the basal ganglia in the therapeutic effect of ECT on psychomotor functioning.

Facial decoding in schizophrenia is underpinned by basic visual processing impairments.

Schizophrenia is associated with a strong deficit in the decoding of emotional facial expression (EFE). Nevertheless, it is still unclear whether this deficit is specific for emotions or due to a more general impairment for any type of facial processing. This study was designed to clarify this issue. Thirty patients suffering from schizophrenia and 30 matched healthy controls performed several tasks evaluating the recognition of both changeable (i.e. eyes orientation and emotions) and stable (i.e. gender, age) facial characteristics. Accuracy and reaction times were recorded. Schizophrenic patients presented a performance deficit (accuracy and reaction times) in the perception of both changeable and stable aspects of faces, without any specific deficit for emotional decoding. Our results demonstrate a generalized face recognition deficit in schizophrenic patients, probably caused by a perceptual deficit in basic visual processing. It seems that the deficit in the decoding of emotional facial expression (EFE) is not a specific deficit of emotion processing, but is at least partly related to a generalized perceptual deficit in lower-level perceptual processing, occurring before the stage of emotion processing, and underlying more complex cognitive dysfunctions. These findings should encourage future investigations to explore the neurophysiologic background of these generalized perceptual deficits, and stimulate a clinical approach focusing on more basic visual processing.