Shared reduction of oscillatory natural frequencies in bipolar disorder, major depressive disorder and schizophrenia.

INTRODUCTION: Recent studies have demonstrated that cortical brain areas tend to oscillate at a specific natural frequency when directly perturbed by transcranial magnetic stimulation (TMS). Fast electroencephalographic (EEG) oscillations, which typically originate from frontal regions, have been reported to be markedly reduced in schizophrenia. METHODS: Here we employed TMS/EEG to assess the natural frequency of the premotor area in a sample of 48 age-matched participants (12 each in major depression disorder (MDD)), bipolar disorder (BPD), schizophrenia (SCZ) and healthy controls. Event related spectral perturbations (ERSP) were obtained for each study participant using wavelet decomposition. RESULTS: TMS resulted in a significant activation of the beta/gamma band response (21-50 Hz) to frontal cortical perturbation in healthy control subjects. By contrast, the main frequencies of frontal EEG responses to TMS were significantly reduced in patients with BPD, MDD and SCZ (11-27 Hz) relative to healthy subjects. CONCLUSIONS: Patients with bipolar disorder, major depression and schizophrenia showed a significantly lower natural frequency of frontal cortico-thalamocortical circuits compared to healthy controls. These results suggest a common neurobiological mechanism of corticothalamic impairment. The most likely candidates include dysfunction of GABAergic circuits. LIMITATIONS: Further studies are needed to consider other biological markers, gene variants, and their interaction with clinical variables.

Changes of cortical excitability as markers of antidepressant response in bipolar depression: preliminary data obtained by combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG).

BACKGROUND: It is still unclear which biological changes are needed to recover from a major depressive episode. Current perspectives focus on cortical synaptic neuroplasticity. Measures of cortical responses evoked by transcranial magnetic stimulation (TMS) change with sleep homeostasic pressure in humans and approximate measures of synaptic strength in animal models. Using repeated total sleep deprivation as a model of antidepressant treatment, we aimed to correlate recovery from depression with these measures of cortical excitability. METHODS: We recorded electroencephalographic responses to TMS in the prefrontal cortex of 21 depressed inpatients with bipolar disorder treated with repeated sleep deprivation combined with light therapy. We performed seven TMS/electroencephalography sessions during one week and calculated three measures of cortical excitability. RESULTS: Cortical excitability progressively increased during the antidepressant treatment and as a function of time awake. Higher values differentiated responders from non-responders at baseline and during and after treatment on all measures. CONCLUSIONS: Changes in measures of cortical excitability parallel and predict antidepressant response to combined sleep deprivation and light therapy. Data suggest that promoting cortical plasticity in bipolar depression could be a major effect of successful antidepressant treatments, and that patients not responding could suffer a persistent impairment in their neuroplasticity mechanisms.

Neuropsychological deficits in bipolar depression persist after successful antidepressant treatment.

BACKGROUND: Bipolar disorder is a common disabling illness with a lifetime morbid risk of approximately 4%. Neuropsychological deficits constitute enduring trait-like features in bipolar disorder, are associated with each phase of the illness and persist also in euthymia. Total sleep deprivation (TSD) has been shown to cause rapid and sustained antidepressant effects in bipolar depression and to revert the biased self description and speed of information processing present in these patients. The aim of the study was to assess neuropsychological performances first in a sample of bipolar patients during a depressive episode compared to healthy controls and secondly to investigate if TSD treatment would change cognitive performances. METHODS: One-hundred bipolar patients and 100 healthy controls were evaluated through the Brief Assessment of Cognition in Schizophrenia, 42 patients were assessed before and after TSD treatment. RESULTS: Bipolar patients obtained significantly lower domain scores across the entire battery compared to healthy subjects. Cognitive deficits persisted in each function despite a clinical improvement of depressive symptomatology. LIMITATIONS: Limitations of the study include issues such as generalizability, possible undetected past comorbidities, population stratification and ongoing medication. CONCLUSIONS: This is the first study of the effect of TSD treatment on cognitive performance. TSD treatment improved clinical symptoms but not cognitive deficits however bipolar patients did not experience the well known worsening of performance observed in healthy controls after sleep loss.