Determinants of Blood Brain-Derived Neurotrophic Factor Blood Levels in Patients with Alcohol Use Disorder.

BACKGROUND: Blood brain-derived neurotrophic factor (BDNF) levels are influenced by both addiction and mood disorders, as well as somatic conditions, gender, and genetic polymorphisms, leading to widely varying results. Depressive symptoms and episodes are frequently observed in patients with alcohol use disorder, and vary widely over time, making it a challenge to determine which aspects are specifically involved in variations of serum BDNF levels in this population. METHODS: We assessed 227 patients with alcohol dependence involved in a detoxification program, at baseline and after a follow-up of 6 months, for the Alcohol Use Disorders Identification Test score, the length of alcohol dependence, and the number of past detoxification programs. The Beck Depression Inventory and information on current tobacco and alcohol use, suicidal ideation, body mass index, age, gender, and psychotropic treatments were also collected. Serum BDNF (ELISA) and 2 genetic polymorphisms of the BDNF gene (Val33Met and rs962369) were analyzed. RESULTS: The presence of the Met allele, 2 markers of the history of alcohol dependence (gamma glutamyl transferase and the number of past treatments in detoxification programs), and the presence of a depressive episode (but not depressive score) were significantly associated with the 2 blood levels of BDNF at baseline and after 6 months. After controlling for baseline BDNF levels, the presence of the Met allele and an ongoing depressive episode were the only variables associated with changes in BNDF levels after 6 months. CONCLUSIONS: Low serum BDNF levels are associated with characteristics related to alcohol consumption and mood disorders, and variants of the BDNF gene in alcohol use disorder patients. The factors that most strongly influenced changes in serum BDNF levels following treatment in an alcohol detoxification program were variants of the BDNF gene and ongoing depression.

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.

Snapshot of the supports of communication used by patients at a French psychiatric hospital: a digital or social division?

BACKGROUND: The role of information and communications technology is becoming increasingly prevalent in daily life and in the organization of medical care: are some people being left out? AIMS: To evaluate access to and the uses of communication resources by psychiatric patients, focusing on the means of communication (e.g. mobile phones and computers), access and frequency of internet use. METHODS: A questionnaire was distributed, over a period of 1 week, to inpatients or day hospitalised patients aged over 12 years in all care units. RESULTS: Access to and the uses of modern communication resources were lower than in the general population. Among places and means of internet consultation, the personal computer was most often cited, but only by 34%, and the use of mobile phones is still not widespread. Finally, day hospitalised subjects, the elderly, or subjects being treated in the psychosis care sector use internet and technology the least. CONCLUSIONS: Some differences exist between this population with mental illness and the general population on the use of new communication technologies. The possibility of integrating these techniques in individualized psychiatric care requires prior equipment and/or updates.

A prospective hospital study of alcohol use disorders, comorbid psychiatric conditions and withdrawal prognosis.

BACKGROUND: The objective of this study was to describe the profile and alcoholic status of a population with alcohol use disorders (AUD) requesting help from a psychiatric hospital to stop drinking, as well as their clinical outcome and care consumption over the 2 years following the request. METHODS: The visits were conducted at baseline (M0) and at 6, 12, 18 and 24 months (M6, M12, M18, M24). Demographic, clinical and psychometric data [Beck Depression Inventory (BDI), AUDIT questionnaire, Global Assessment of Functioning (GAF) scale], and information regarding the use of psychiatric care and therapeutics were collected. RESULTS: The 330 subjects included were mostly male, aged 45.2 ± 10.2 years with an employment rate of 55.4 %, living alone (69.1 %), with a psychiatric comorbidity (60.9 %), especially depressive, and with few somatic complications. Their global functioning was poor (GAF score 49.14 ± 15.6), and less than 10 % were addicted to another substance. The abstinence rate at 24 months was 41.4 %, but only 23 % (20) abstained continuously between M0 and M24, and 66.7 % (58) intermittently. The likelihood of abstinence at M24 was greater for females aged over 60 years. The BDI score decreased significantly between M0 and M24. In all, 56.2 % of the participants were re-hospitalized after weaning, but were not integrated in long-term medical care. CONCLUSIONS: Abstinence after alcohol withdrawal fluctuated over time indicating the need for long-term support. The treatment of AUD should not target total, continuous abstinence. Prognostic profiles combining socio-demographic, clinical and biological indicators must be established.

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.

Brain-derived neurotrophic factor serum levels in alcohol-dependent subjects 6 months after alcohol withdrawal.

BACKGROUND: Diagnosing alcohol dependence is based on clinical signs and on the measured levels of biological markers of alcohol consumption. However, these markers are neither sufficiently sensitive and nor specific enough to definitively determine alcohol dependence. The neuroadaptive changes associated with alcohol dependence involve markers such as brain-derived neurotrophic factor (BDNF), which regulate neuronal plasticity. Serum levels of BDNF have been reported to decrease during alcohol dependence and may be restored to normal soon after alcohol is withdrawn. However, the long-term relationship between serum BDNF levels and abstinence status is unknown. METHODS: We investigated serum BDNF levels in 101 abstinent and relapsing alcohol-dependent subjects at the moment of hospitalization for alcohol withdrawal (M0) and 6 months later (M6) and compared them to the serum BDNF levels of 41 nondependent subjects. The BDNF levels of the alcohol-dependent subjects were compared to their serum gamma glutamyl transferase (GGT) levels, mean corpuscular volume (MCV) values, and their score on the Beck Depression Inventory (BDI) questionnaire. RESULTS: Forty-four percent of the alcohol-dependent participants remained abstinent during the 6 months following alcohol detoxification. Serum BDNF levels of the abstinent group at M6 were significantly higher than those of the original group of alcohol-dependent subjects at M0 (p = 0.034). Only the abstinent group had higher BDNF levels than the control group (p < 0.001). Serum BDNF levels increased to a greater extent in the abstinent group than in the nonabstinent group (p = 0.016). No correlations were found between serum BDNF levels and GGT level, MCV value, or BDI score. CONCLUSIONS: Our data confirm that serum BDNF levels do not correlate with either chronic alcohol consumption or peripheral toxicity but may be linked to neuronal aspects of alcohol consumption and dependence. The increased serum levels of BDNF may reflect the concomitant activation of BDNF synthesis that accompanies the neuronal remodeling triggered by alcohol withdrawal and suggests that BDNF synthesis may have a role in the long-term maintenance of abstinence. Monitoring the serum BDNF levels of alcoholics undergoing treatment could help to characterize alcohol dependence profiles and predict relapse.

Evolution of BDNF serum levels during the first six months after alcohol withdrawal.

OBJECTIVES: Brain-Derived Neurotrophic Factor (BDNF) has been associated with alcohol dependence and appear to vary after withdrawal, although the link with the withdrawal outcome on the long term is unknown. We aimed to assess the evolution of BDNF levels during the six months following withdrawal and determine the association with the status of alcohol consumption. METHODS: Serum BDNF levels of alcohol-dependent patients (n = 248) and biological and clinical parameters were determined at the time of alcohol cessation (D0), 14 days (D14), 28 days (D28), and 2, 4, and 6 months after (M2, M4, M6). RESULTS: Abstinence decreased during follow-up and was 31.9% after six months. BDNF levels increased by 14 days after withdrawal and remained elevated throughout the six-month period, independently of alcohol consumption. Serum BDNF levels evolved over time (p < 0.0001), with a correlation between BDNF and GGT levels. The prescription of baclofen at the time of withdrawal was associated with higher serum BDNF levels throughout the follow-up and that of anti-inflammatory drugs with lower BDNF levels. CONCLUSIONS: A link between BDNF levels, liver function, and the inflammatory state in the context of alcohol abuse and not only with alcohol dependence itself is proposed.

Serum inflammatory molecules and markers of neuronal damage in alcohol-dependent subjects after withdrawal.

OBJECTIVES: Our aim is to describe changes in serum concentration for the pro-inflammatory factors TNF-α, IFN-γ, IL-1ß, IL-8, IL-6, IL-10, IL-12 and MCP-1, for the satiety factor leptin and for factors associated with neuronal changes, neuron-specific enolase (NSE) and glial activation S100-beta protein (S100-ß), and explore their association with abstinence in alcohol-dependent subjects after withdrawal. METHODS: Serum sampling and clinical assessments from 115 alcohol-dependent subjects admitted to a psychiatric hospital for alcohol were repeated during the first 48 h of withdrawal (M0) and 1, 2, 4 and 6 months (M1, M2, M4 and M6) thereafter. Serum factors were determined with Luminex technology or by ELISA. RESULTS: The levels of TNF-α, IL-1ß, IL-8, IL-6, IL-12, MCP-1, and leptin decreased after withdrawal and remained low until M6, regardless of alcohol consumption. IFN-γ levels remained constant and IL-10 levels changed only slightly. NSE levels were not modified, whereas serum S100-ß concentration increased significantly on M1 and then plateaued, regardless of abstinence status at 6 months. CONCLUSIONS: Alcohol-dependent subjects present an inflammatory condition that is not dependent on alcohol consumption. An understanding of the changes in concentration of the various proteins considered here would provide insight into the physiology of withdrawal or dependence.

Experimental pain sensitivity in subjects with major depression: Many pain complaints without hypersensitivity.

OBJECTIVE: Patients with major depression frequently complain of pain, but conflicting data exist concerning their changes in pain sensitivity. This study aimed at comparing the sensitivity to moderate controlled pain between subjects presenting a major depressive episode (isolated and recurrent depressive episodes or a bipolar disorder), controls, and subjects with schizophrenia from a previous study. METHOD: Pain sensitivity was assessed obtaining the visual analog scale (VAS) rating for the application of a 160 kPa pre-fixed pressure (fpVAS), the pressure corresponding to a VAS score of 3, and the time required to achieve a VAS score of 3 during ischemia induction. The effects of depression intensity, alexithymia, current and past general pain, and of six weeks of antidepressant treatment on fpVAS were investigated. RESULTS: The results did not differ significantly between the depressed groups and the controls, without any effect of depression intensity. Presence of long-lasting pain and current pain felt on the day of testing correlated with fpVAS. The subjects of the depressed group were less sensitive than subjects with schizophrenia. FpVAS was significantly lower before and after antidepressant treatment in the subjects presenting clinical improvement. CONCLUSIONS: No difference in experimental pain sensitivity and expression between major depressive episode subjects and controls, in opposite to pain complaints, is to be detected. The changes in the sensation of pain routinely attributed to subjects presenting depression may result from changes in a differential processing of pain signals, not in relation with the depression intensity, or the kind of depressive disorder.

rTMS for pharmacoresistant major depression in the clinical setting of a psychiatric hospital: effectiveness and effects of age.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method of brain stimulation used in the treatment of drug-resistant major depressive disorder (MDD). It has been suggested that the efficacy of rTMS decreases with the age of the patient, but the data are contradictory. Here, we analyze in our clinical setting the efficacy of a 3-week rTMS treatment in drug-resistant MDD during a 3 month period and the potential influence of age on this efficacy. METHODS: Stimulation consisted of 15 sessions of rTMS over the dorsolateral prefrontal cortex. Clinical evaluations included the Hamilton Depression Rating Scale (HDRS), and the Beck Depression Inventory (BDI) at baseline, after 3 weeks of treatment, and 1 month and 3 months after the last session. RESULTS: Data from 93 patients issued from the 178 patients active file were analyzed. The antidepressant effect observed in the two age groups (<65 and ≥65) did not differ at the end of the treatment and 3 months later, with a comparable number of responders (50% decrease in HDRS score from baseline) (53.3% for age <65 versus 46.7% for age ≥65, p=0.51). The treatment had a significant effect over time. We found no evidence of the age affecting outcome at 3 months after the last session. LIMITATIONS: Previous antidepressant treatments, and therapeutic drug use modifications after rTMS treatment, degree of pharmaco-resistance or duration of current episode are not reported. CONCLUSION: RTMS of the DFPLC is effective as an add-on treatment for cases of pharmacologically refractory major depression, independent of the patient age.

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.