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Background: C-reactive protein (CRP) is a general marker of peripheral inflammation and has been shown to be a good marker of neuroinflammation. CRP has been found to be elevated in patients with mood disorders (especially unipolar disorders (UD) and in schizophrenia (SZ)) but also to be lowered by antidepressants., Objective: The objectives were (i) to determine the prevalence of major depression, antidepressant prescription and remission under antidepressant in a stabilized population of SZ and UD patients consulting in a daily hospital, and (ii) to determine if CRP was a marker of major depression and remission under antidepressant in these SZ and UD populations., Methods: Abnormal CRP was defined by a CRP blood level ≥ 3 mg/L. Depressive symptoms were assessed by the Calgary Depression Rating Scale score. The clinicians were blinded of the CRP status of the patient., Results: 411 patients were included (272 SZ and 139 UD). 171 (41.6%) were diagnosed with current major depression (74 (27.2%) for SZ and 97 (69.8%) for UD). 86 SZ (31.6%) and 119 UD (85.6%) were treated by antidepressant. Only 28/74 (37.8%) of the SZ subjects with major depression were administered antidepressants vs. 87/97 (89.7%) for UD. The non-remission rate under antidepressant was 28/86(32.6%) for SZ and 87/119 (73.1%) for UD. Overall, 105 (40.1%) of SZ and 39 (28.1%) of UD patients were found to have abnormal CRP blood levels. Abnormal CRP levels were significantly associated with increased MDD and more strongly with increased rates of non-remission under antidepressants in SZ patients, independently of age, gender, psychotic symptomatology, functioning, tobacco smoking and metabolic syndrome. This result was not replicated in UD patients, which suggests that CRP may be a specific marker of major depression and remission under antidepressant in SZ patients., Conclusion: The development of biomarkers in psychiatry may orientate specific etiologic therapies in patients with mental disorders. The present findings suggest that major depression is frequent in SZ patients and that increased CRP levels are associated with non-remission under antidepressants in this population. Anti-inflammatory strategies may be particularly useful in this specific population., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: The relation between C-Reactive Protein (CRP), depression and antidepressant consumption has been well explored in major depressive disorders but not in schizophrenia, which has a high rate of depression comorbidity. The objectives of this study were: (i) to determine the prevalence of abnormal CRP levels, depression and antidepressant consumption in a multicenter community-dwelling sample of subjects with schizophrenia (ii) to determine the association between abnormal CRP levels, depression and antidepressant consumption in schizophrenia., Method: 219 stable patients with schizophrenia (mean age=31.6 years, 75.3% male gender) were systematically included in the multicentre network of FondaMental Expert Center for schizophrenia (FACE-SZ) and assessed with a dedicated electronic medical record including the Structured Clinical Interview for DSM-IV Axis I Disorders and Calgary Depression Scale for depression. High sensitivity CRP (hs-CRP) was measured with an assay using nephelometry (Dade Behring). Abnormal CRP level was defined by levels >3mg/L. Current medication was recorded., Results: Overall, 63 subjects (28.8%) were found to have abnormal CRP levels, 43 (20.1%) received a diagnosis of comorbid current depression, and 51 (31.9%) had ongoing antidepressant treatment. In univariate analysis, abnormal CRP levels were found to be significantly associated with body mass index (BMI) (p<0.0001), hypertriglyceridemia (p=0.0015), high waist circumference (p<0.0001), metabolic syndrome (p=0.0011), abdominal obesity (p<0.0001) and with antidepressant consumption (p=0.01), while depression, psychotic symptomatology, age of onset, illness duration, sociodemographic characteristics, current tobacco or cannabis status, hypertension or high fasting glucose were not (all p>0.05). In a multivariate model, abnormal CRP was associated with antidepressant consumption independently of other confounding variables (adjusted Odds Ratio=2.8, 95% confidence interval 1.22-6.62). Metabolic syndrome was also independently associated with abnormal CRP (adjusted Odds Ratio=2.6, 95% confidence interval 1.01-6.71)., Conclusion: Abnormal CRP levels in schizophrenia were found to be associated with antidepressant consumption, but not with depression. The potential mechanisms were discussed. Antidepressant consumption should be systematically recorded in future studies exploring inflammation in schizophrenia. Future clinical trials of interventions directed at lowering the level of CRP and other inflammatory markers are discussed., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Epidemiological studies of major depressive episodes (MDE) highlighted the frequent association of symptoms or signs of mania or hypomania with depressive syndrome. Beyond the strict definition of DSM-IV, epidemiological recognition of a subset of MDE characterized by the presence of symptoms or signs of the opposite polarity is clinically important because it is associated with pejorative prognosis and therapeutic response compared to the subgroup of "typical MDE". The development of DSM-5 took into account the epidemiological data. DSM-5 opted for a more dimensional perspective in implementing the concept of "mixed features" from an "episode" to a "specification" of mood disorder. As outlined in the DSM-5: "Mixed features associated with a major depressive episode have been found to be a significant risk factor for the development of bipolar I and II disorder. As a result, it is clinically useful to note the presence of this specifier for treatment planning and monitoring of response to therapeutic". However, the mixed features are sometimes difficult to identify, and neurophysiological biomarkers would be useful to make a more specific diagnosis. Two neurophysiological models make it possible to better understand MDE with mixed features : i) the emotional regulation model that highlights a tendency to hyper-reactive and unstable emotion response, and ii) the vigilance regulation model that highlights, through EEG recording, a tendency to unstable vigilance. Further research is required to better understand relationships between these two models. These models provide the opportunity of a neurophysiological framework to better understand the mixed features associated with MDE and to identify potential neurophysiological biomarkers to guide therapeutic strategies., (Copyright © 2013 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.)

Mixed states are complex manifestations of bipolar disorders. Pathophysiology of mixed states remains unclear. Several models have been proposed to understand the mechanisms underlying these mood states. These models describe mixed state either as a combinaison of depression and mania, as well as a transition between mania and depression, or mixed state as a severe type of depression or mania. Pathophysiological hypotheses involve temperaments or some personality disorders, psychiatric comorbidities as well as substance use disorders, or thyroid dysfunction. However, the formal demonstration of any specific genetic vulnerability to mixed state has not yet been provided., (Copyright © 2013 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.)

Background: The efficiency of repetitive transcranial magnetic stimulation (rTMS) in the treatment of psychiatric disorders is robust for major depressive episode (MDE) while results are encouraging for schizophrenia. However, rTMS protocols need to be optimized. Basic researches in TMS led to the concept of "state dependency TMS". This concept suggests that the neural circuits' activation states, before and during the stimulation, influence the pulse effect. Indeed, TMS effect must be seen, not simply as a stimulus, but also as the result of an interaction between a stimulus and a level of brain activity. Those data suggest that rTMS efficiency could be increased in psychiatric disorders by triggering patients' neurocognitive activities during stimulation. Thus "interactive rTMS protocols" have been submitted., Objectives: This article provides a review and a classification of different interactive protocols implemented in the treatment of MDE and schizophrenia. Protocols' interactions with cognitive activities and brain electrical activities will be discussed., Literature Findings: Interactive rTMS protocols that manipulate cognitive activities have been developed for MDE treatments. They aim at regulating emotional states of depressed patients during the stimulation. The patients perform emotional tasks in order to activate cortical networks involving the left dorsolateral prefrontal cortex (DLPFC) into a state that may be more sensitive to the rTMS pulse effect. Simultaneous cognitive behavioral therapy ("CBT rTMS") and cognitive-emotional reactivation ("affective rTMS") have thus been tested during left DLPFC rTMS in MDE. Interactive rTMS protocols that manipulate brain electrical activities have been developed for MDE and schizophrenia treatments. Two categories of protocols should be identified. In the first set, personalized brain activity has been analyzed to determine the parameters of stimulation (i.e. frequency of stimulation) matching the patient ("personalized rTMS"). Personalized rTMS protocols can be made "online" or "offline" depending on whether the EEG activity is measured during or prior to rTMS. Online protocol is called "contingent rTMS": it consists in stimulating the brain only when a specific EEG pattern involving the intensity of alpha rhythm is recorded and recognized. Offline protocol is called "alpha rTMS", and relies on ascertaining frequency of stimulation in accordance with personalized alpha peak frequency prior to rTMS. In the second set, electrical brain activity is modulated before or during rTMS in order to stimulate the DLPFC in optimal conditions. Brain activity modulation may be obtained by transcranial direct current stimulation ("tDCS rTMS") or EEG-biofeedack ("EEG-biofeedback rTMS")., Conclusion: Interactive rTMS studies have various limitations, notably their exploratory character on a small sample of patients. Furthermore, their theoretical neurocognitive framework justification remains unclear. Nonetheless, interactive rTMS protocols allow us to consider a new field of rTMS, where cognitive and cerebral activities would no longer be considered as simple neural noise, leading to a kind of "first person rTMS", and certainly to innovative therapy in psychiatry., (Copyright © 2013 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

A literature search on the pharmacological treatment of acute bipolar mixed episodes in current guidelines shows that only seven of them address the acute management of mixed episodes as a separate condition, whereas the vast majority of these guidelines include the treatment of mixed episodes in the chapter of mania. As a general rule, most guidelines advise to stop antidepressant treatment and mention the superiority of valproate over lithium. Specific recommendations for the treatment of "mixed states" can be found in two guidelines, while specific recommendations for that of "mixed mania" are present in five of them. Recommendations for the treatment of "mixed depression" exist in only three guidelines. If some consensus may be found for the treatment of "mixed states" as a whole, recommendations for the treatment of "mixed mania" appear to be variable, whereas those for the treatment of "mixed depression" seem to be limited., (Copyright © 2013 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.)