Painful Life Events in Psychiatric Disorders: A Quantitative and Qualitative Analysis.

We reported in a previous study the painful events experienced in the past in subjects with schizophrenia or major depression, in comparison to controls, and related them to the experimental pain sensitivity, anxiety, and the diagnosis. We present here the detailed analysis of these past painful events, with the aim of determining whether schizophrenic, depressive and control groups are qualitatively (type of painful events experienced, emotional or sensory components associated with pain) and quantitatively (duration, severity, and intensity) comparable concerning their past painful experiences. The questionnaire used relies on memory and feelings and will provide an indication about the way pain is experienced and memorized in daily life. The reported history of pain was not the same in the three groups. Depressed subjects differed from the others by the number of reported painful events. Painful events of everyday life, such as trauma without fracture and wounds, were the most highly reported painful events for all groups. Surprisingly, the daily pain events are associated to affective component of pain perception. Other kinds of event were differently reported between the groups. Experience of pain appears to be memorized and reported differently depending on the psychiatric disorder and type of event. The characteristics of each individual, their previous experience, contribute to the expression of psychiatric disorders, including in the field of pain. Past pain experience should be taken into account when attending someone for pain.

Past Pain Experience and Experimentally induced Pain Perception.

Many intercurrent factors may be involved in the modulation of the pain message and its expression, such as the previous experience of pain built along the life. In this study, we aimed to determine whether susceptibility to experimentally induced pain is differentially influenced by the individual previous painful experience in subjects with schizophrenia (SC) major depression (MD), and controls (C). METHODS: The SC (30), MD (32) and C (30) groups participated in experimental pain tests (application of pressure and induction of ischemia) after a semi-structured interview to make an inventory of the previous painful experiences, and the evaluation of anxiety either with autonomic (heart rate, blood pressure) or psychological (Hospital Anxiety Depression scale HAD) measures, and catastrophism. RESULTS: The reported pain intensities, severities, duration, of the previous pain events, and the number of previous painful events were equivalent in the three groups, except for the number of painful events experimented before the last six months which was lower in the MD group. Experimental pain sensitivity was influenced by the diagnosis, the HAD scores or the number and intensities of previous lived painful events. CONCLUSION: The lack of a past experience of pain was comparable for the different groups, suggesting that psychiatric disorders do not affect the experience of pain associated with daily life or past events. For each subject, the reported previous experience of pain influences the present feeling of pain.

BDNF CpG methylation and serum levels covary during alcohol withdrawal in patients with alcohol use disorder: A pilot study.

OBJECTIVES: Brain-derived neurotrophic factor (BDNF) levels vary in various conditions including alcohol use disorder (AUD). We aimed to identify drivers of these variations. METHODS: Twelve patients with AUD were assessed at hospitalisation for alcohol withdrawal and four months later. We looked for associations between the change in serum BDNF levels and (1) length of abstinence, (2) anxiety (Hamilton Anxiety Scale) and depression (Beck-Depression Inventory), (3) one functional BDNF genotype (rs6265) and (4) methylation levels of 12 CpG sites within the BDNF gene (located in exons I, IV and IX). RESULTS: While abstinence remained, serum BDNF level increased. This increase correlated with the variation of methylation levels of the BDNF gene, and more specifically of exon I. We found no significant effect of length of abstinence, rs6265, depression or anxiety on serum BDNF level. CONCLUSIONS: Epigenetic regulation of the BDNF gene may be involved in variations of BDNF blood level associated with alcohol abstinence.

Distinct Predictors of Clinical Response after Repetitive Transcranial Magnetic Stimulation between Bipolar and Unipolar Disorders.

Background: Repetitive transcranial magnetic stimulation (rTMS) has been shown to be therapeutically effective for patients suffering from drug-resistant depression. The distinction between bipolar and unipolar disorders would be of great interests to better adapt their respective treatments. Methods: We aimed to identify the factors predicting clinical improvement at one month (M1) after the start of rTMS treatment for each diagnosis, which was preceded by a comparison of the patients' clinical conditions. We used the data collected and the method employed in a previous publication on 291 patients. Results: Although the bipolar group had fewer responders, these patients seemed to better maintain their post-rTMS improvement on anxiety and perception of the severity of their illness than those in the unipolar group. For the bipolar group, young age coupled with low number of medications and high fatigue was shown to be the best combination for predicting improvement at M1. The duration of current depressive episode, which was previously demonstrated for whole group, combined with being attached was shown to favor clinical improvement among the patients in unipolar group. Conclusion: We were able to define a combination of specific factors related to each diagnosis for predicting the patients' clinical response. This could be extremely useful to predict the efficacy of rTMS during routine clinical practice in neuromodulation services.

BDNF and pro-BDNF in serum and exosomes in major depression: Evolution after antidepressant treatment.

BACKGROUND: The study of clinically related biological indicators in Major Depression (MD) is important. The Brain Derived Neurotrophic Factor (BDNF) appears to play an important role in MD, through its neurotrophic effect, and its levels are significantly decreased. The variation in the serum levels of its precursor proBDNF, which has opposite effects, is not known. Their distribution between serum and exosomes and their evolution during antidepressant treatment is also not known, and may be important in modulating their effects. The aim of this study is to evaluate whether serum and exosome mBDNF and proBDNF levels are altered in patients with MD during antidepressant treatment compared to controls, and their association with clinical improvement and clinical variables. MATERIALS AND METHODS: 42 MD subjects and 40 controls were included. Questionnaires to assess the severity of depression and cognitive impairment and blood samples were collected during the three visits at D0 (inclusion) and 3 and 7 weeks after the start of antidepressant treatment. Assays for mBDNF and proBDNF levels were performed in serum and exosomes by ELISA. RESULTS: MD subjects had decreased serum and exosomal BDNF levels and increased proBDNF levels at D0 compared to controls. BDNF and pro-BDNF vary in an inverse manner in both serum and exosomes during antidepressant treatment. No relationship of BDNF and proBDNF levels to clinical improvement and depression scales was found. CONCLUSION: We demonstrated an evolution of those molecules either in serum or in exosomes after MD treatment. These transport vesicles could have a role in the regulation of BDNF.

Predictors of clinical response after rTMS treatment of patients suffering from drug-resistant depression.

Repeated transcranial magnetic stimulation (rTMS) is a therapeutic brain-stimulation technique that is particularly used for drug-resistant depressive disorders. European recommendations mention the effectiveness of 30 to 64%. The failure rate of treatment is high and clinical improvement is visible only after a certain period of time. It would thus be useful to have indicators that could anticipate the success of treatment and more effectively guide therapeutic choices. We aimed to find predictive indicators of clinical improvement at 1 month after the start of rTMS treatment among the data collected during the care of patients with drug-resistant depression included in the Neuromodulation Unit of the Esquirol Hospital in Limoges since 2007. In total, 290 patients with a pharmaco-resistant depressive episode, according to the Hamilton Depression Rating Scale (HDRS) (score ≥8), before treatment who underwent a complete course of rTMS treatment and did not object to the use of their collected data were included. The clinical response in routine practice, corresponding to a decrease in the HDRS score of at least 50% from inclusion, was determined and complemented by interquartile analysis. A combination of factors predictive of clinical response during care, such as a short duration of the current depressive episode associated with a higher HDRS agitation item value (or a lower perceived sleepiness value) and a higher number of previous rTMS treatments, were identified as being useful in predicting the efficacy of rTMS treatment in routine clinical practice, thus facilitating the therapeutic choice for patients with drug-resistant depression.

Experimental pain hypersensitivity in schizophrenic patients.

OBJECTIVE: Whether schizophrenic patients are hypoalgesic or feel pain in the same manner as unaffected individuals can affect the primary care of schizophrenic patients, which often involves an assessment of pain severity made by a medical provider. This study was developed to explore the pain sensitivity of schizophrenics under conditions similar to those of a medical examination that included investigating for sites of pain. METHODS: We developed 2 experimental models of pain induction using either pressure or ischemia and used them with 35 schizophrenic patients and 35 controls to record: (1) the stimulus intensity required to induce moderate pain; and (2) the pain intensity induced by a predetermined level of pressure. Clinical data were also collected for the schizophrenic group. RESULTS: Schizophrenic patients needed less pressure (P=0.006) and a shorter duration of ischemia (P<0.001) than controls to record moderate pain, and they felt more pain from a fixed pressure stimulus (P<0.001). Pain histories for the previous 6 months and the heart rate variations that occurred during the tests did not differ between the groups. Pain responses were unrelated to the clinical characteristics of the schizophrenic patients, although hallucination production correlated with the pain felt during the fixed pressure test. DISCUSSION: Under these conditions, schizophrenic patients were hypersensitive to pain induction compared with normal individuals. The hypoalgesia typically associated with schizophrenic patients may correspond to fewer than normal reports of pain, rather than to impaired sensations of pain. This should be taken into account during routine medical practice.