Pulse-loading treatment consists in a rapid titration of the pharmacological agent in the first days of treatment. A few studies suggested that this kind of titration with intravenous clomipramine could result in a greater and faster response than with a standard titration in obsessive-compulsive disorder (OCD) resistant patients. The aim of this open-label trial was to investigate the effectiveness and tolerability of a citalopram pulse-loading protocol in severe treatment-resistant OCD patients.

We enrolled 8 severe treatment-resistant OCD patients. Patients were treated with intravenous citalopram starting with 40 mg for 3 days and increasing the dose up to 80 mg from the fourth day. The patients continued the treatment with 80 mg of intravenous citalopram for 18 days (a total of 21 days of intravenous treatment), then they switched to oral treatment (80 mg of oral citalopram).

During the pulse-loading treatment no patients showed significant adverse events. No patients showed clinical significant change of the QTc interval and/or of the sodium levels. Five out of eight patients had a partial or full response at the end-point (4 patients had a full response and 1 patient had a partial response) and two of these had remission. Pulse-loading treatment seemed to induce a faster improvement respect to a standard titration, since the responder patients showed a significant improvement already after 3 weeks. Three out of eight patients did not respond.

Taking into account the very limited sample size, this case series suggests that this treatment approach deserves further controlled studies

Perfectionism and Perseverative negative thinking/PNT are both associatedwith OC symptoms. PNT is a prime candidate when investigating the pathway thatlinks perfectionism to psychopathology.

To investigate if PNT mediates the relationshipbetween perfectionismcognitions and OC symptoms.

464 (72.5%females) students (mean age 22.5±4.5 years) participated in an online surveyincluding the Portuguese validated versions of Maudsley O-C Inventory/MOCI (toassess Doubting and Rumination/DR, Checking and Cleaning), PerseverativeThinking Questionnaire/PTQ-15 (Repetitive Thought/RT, Cognitive interferenceand unproductiveness/CIU), Multidimensional Perfectionism CognitionsInventory/MPCI (Concern over Mistakes/CM, Personal Standards/PS, Pursuit of Perfection/PP). Negative affect/NA was assessed with the Profile of Mood States.

Significantpredictors of MOCI_Total were PP (b=.131),RT (b=.228)and CIU (b=.254)(all p<.01). RT (95%CIBCa=.761-1.482) and CIU (95%CI=.813-1.551) were partial mediators of therelationship between MOCI_Total and PP.

DR waspredicted by CM (b=.107),PP (b=.107),RT (b=.333)and CIU (b=.281)(all p<.01). Both RT and CIU were partial mediators of the relationship betweenperfectionism and DR (all the 95%CI not contained zero).

Checkingwas predicted by PP (b=.120), RT (b=.154) andCIU (b=.267)(all p<.01). RT (95%CI =.027-.056) and CIU (95%CI=.086-.128) were partialmediators of the relationship between Checking and PP.

Cleaning wasonly predicted by PP (b=.174; p=.001).

QPP-15_Totaland IMCP_Total were mediators of the association of MOCI_Total (and itsdimensions DR and Checking) with NA.

Characterized by compulsive rituals and Obsessive thoughts, OCD is a chronic and disabling disorder. Despite converging evidence pointing towards the involvement of dysfunctional cortico-striato-thalamo-cortical circuit in OCD, the neurophysiological pathology of OCD is still not well characterized. Indeed, 40%-60% of patients do not respond adequately to standard treatments.

TMS is a noninvasive therapeutic technique, recently applied to treat and investigate OCD. However, lacking the ability to target the CSTC circuit directly, standard TMS treatment protocols for OCD showed diversified results. The use of special deep TMS (dTMS) coils allows direct stimulation of deeper neuronal pathways relative to those affected by standard TMS coils. Here we evaluated whether dTMS targeting the medial prefrontal and the anterior cingulate cortices may influence symptom severity.

40 patients were treated with either dTMS or a sham coil for five weeks in a double-blind controlled study. The patients were divided into groups receiving either high (20Hz) or low (1Hz) stimulation frequencies, and were simultaneously administrated with symptom provocation. EEG measurements were taken at baseline and at the end of treatment.

The active 20Hz dTMS group improved significantly in YBOCS score compared to the 1Hz and placebo groups (28% vs. 6% reduction), {t (93) = -2.29 (p=0.0243)}. Moreover, follow-up assessments revealed 3 months stability in improvements as measured by YBOCS scores. EEG evoked responses measured over the ACC correlated with clinical response.

High frequency dTMS treatment, targeting the medial prefrontal and the anterior cingulate cortices is a promising therapeutic intervention in OCD.

In a previous meta-analysis investigating pharmacological treatment options in obsessive-compulsive disorder (OCD) we determined a significant efficacy for the augmentation of serotonin reuptake inhibitors (SRIs) with antipsychotic drugs. Because new relevant double-blind, randomized, placebo-controlled trials (DB-RCTs) evaluating new antipsychotics were conducted, we updated our meta-analysis.

We included all DB-RCTs that compared augmentation of SRIs with antipsychotics to placebo augmentation in SRI-resistant OCD. Meta-analytic outcomes were treatment response defined by 35% reduction in Yale–Brown Obsessive–Compulsive Scale (Y-BOCS) total score and mean changes in Y-BOCS total score. Effect sizes were standardized mean differences (SMD) and risk ratios (RR).

Fourteen DB-RCTs (n=467) investigating quetiapine (N=5, n=178), risperidone (N=3, n=72), aripiprazole (N=2, n=79),olanzapine (N=2, n=70), haloperidol (N=1, n=34), and paliperidone (N=1, n=34) were incorporated. The pooled antipsychotic augmentation group was significantly superior to the placebo group in terms of response rates (N=14,n=467; RR=1.98, 95% CI: 1.23 to 3.19;p=0.005) and mean change in Y-BOCS total score (N=14, n=465, SMD=-0.6, 95% CI: -0.97 to -0.23; p=0.002). Concerning the individual antipsychotics, aripiprazole and risperidone significantly outperformed placebo in terms of both responder rates and mean Y-BOCS change. Olanzapine, paliperidone, and quetiapine were not significantly different from the control group. There was no significant heterogeneity and no evidence for publication bias.

Aripiprazole and risperidone augmentation of SRIs canbe regarded as evidence-based treatment options in treatment-resistant OCD and showed superiority over olanzapine, paliperidone, and quetiapine. About one third of all SRI-resistant OCD subjects responded to augmentation with antipsychotic drugs.

To examine the gene expression in rat’s brain, treated by non-ionizing electromagnetic radiation from 900MHz-GSM mobile phone.

As studies supported electromagnetic radiation may cause membrane leakage due to loss of calcium. Membrane leakage of lysosomes release. Damage to DNA is a fundamental mechanism for developing tumors and cancer when DNA damage exceeds the rate of DNA repair. DNA damage in brain cells can affect neurological functions.

We investigated whether an exposure of GSM-900 MHz irradiation from the Mobile Phone (3hours/day up to 28 days) could lead to the modulation of gene expression pattern in the rat brain. All rats were habitualised for one week prior to start the experiment in well designed circular mobile phone exposure (CCPE) cage. In the cage, mobile phone was placed in the center and rats were allowed to move around the device within 10 cm. radius. After 28 days, mRNA from the brain of control, sham and GSM-900 MHz exposed rats were isolated and subjected to qRT-PCR array analysis. Gene expression was measured and expressed in fold change. The qRT-PCR was performed by using Sybr green chemistry on ABI 7900HT platform.

There was no significant change in expressions of genes involved in DNA damage and repair pathways such as chromatin assembly (CHAF1A), DNA damage checkpoints (Chk1), DNA synthesis (POLD1), post-transcriptional processes (RBM4), translation synthesis (POLI) and stress signaling (Hsp90) as compared with controls.

Mobile phone’s acute exposure does not support for genes expression involved in DNA damage and repair pathways.

Psychological stress is associated with accelerated cellular aging and increased risk for aging-related diseases, but the underlying molecular mechanisms are unclear.

We examined the effect of stress on a DNA methylation age predictor that was shown to correlate strongly with chronological age across human tissues (Horvath 2013). Genome-wide DNA methylation was measured in peripheral blood using the 450K Illumina array in three independent cohorts: the Grady Trauma Project/GTP (N=366); a panic disorder case/control sample recruited at the Max Planck Institute of Psychiatry/MPI-P (N=318); and the Conte Center for the Psychobiology of Early-Life Trauma/Conte (N=42). Age acceleration was calculated by subtracting chronological age from age predicted by DNA methylation. Psychiatric symptomatology and stressors were assessed using standard questionnaires.

DNA methylation age strongly correlated with chronological age in all samples (r=0.9, p=2.5x10^-133). Cumulative lifetime stress but not childhood or current stress predicted age acceleration in GTP (p=0.012) and MPI-P (p=0.021). Moreover, epigenetic age acceleration predicted depression (GTP: p=0.002; Conte: p=0.014) and panic disorder (p=0.007). In secondary analyses, we examined the effect of lifetime stress on individual CpGs of the DNA methylation age predictor. After correcting for multiple comparisons, we identified in both GTP and MPI-P a stress-regulated CpG near MCAM, a gene implicated in aging-related diseases, including cardiovascular disease and cancers.

Cumulative lifetime stress, but not childhood or current stress, and psychiatric phenotypes are associated with accelerated epigenetic aging. Our findings may explain the accelerated cellular aging and increased disease risk associated with chronic stress and psychiatric disorders.

Chronic pain is one of the most common symptoms in the general population and it can lead to worsened quality of life, reduced productivity, significant economic loss and higher comorbidity of physical and mental disorders. Particularly when the underlying causes are not identified its treatment becomes a serious challenge.

To review the current existing evidence base regarding the rTMS therapeutic role on chronic unexplained symptoms of pain.

A literature review, based on a PubMed research, takes stock of the studies that have investigated this subject in the latest years.

Despite only a small amount of research available, findings from some case series and randomized sham-controlled rTMS study on fibromyalgia provide a growing body of evidence indicating that high frequency rTMS has promising analgesic efficacy on chronic unexplained pain, particularly when targeted at the left prefrontal and the left motor cortex. Overall, the actual mechanisms of rTMS's analgesic effects on these symptoms are unknown, but may include endogenous opioid releases and the functional improvement in certain brain regions such as the prefrontal cortex, the anterior cingulate cortex and the primary sensory cortex.

In the future, rTMS may become an important therapeutic option for the treatment of unexplained chronic pain. Until then, further consistent clinical experience is needed. The optimization of the rTMS parameters and the specific mechanisms involved also demand additional research.

chronic pain (CP) is seen currently as a multidetermined phenomenon that involves an interaction of physical, social, cultural, and psychological factors. This conception makes clear how important it is for scientific research. Therefore, it is so importante to provide an integrated view of meanings attributed to life experiences for patients with CP, going beyond the fragmented reflections on body, mind, and social dimension.

to discuss the meanings brought to emotional experiences reported by CP patients.

Clinical-Qualitative, a particularization of generic qualitative methods from the Humanities. The sample of participants was intentional and closed by the criterion of information saturation with 17 patients. The technique of semi-directed interview with open-ended questions in depth was used followed by transcription of the interviews. Qualitative Content Analysis has included both: free-floating rereading to unveil cores of meanings from interviewees' discourse and categorization in topics for discussion.

an accurate analysis has made emerge four categories. 1) The Mystery: portraits the difficult understanding and description from where the pain is and how it is. 2) The Chronicity: it takes account the awareness that there is no cure for their pain. 3) The Limitations: it represents the losses experienced in everyday, emotional and social life caused by the CP. 4) The Metaphors: it shows representations of this entity that causes so many problems on patient's lives.

:the mystery, the chronicity and the limitations from the pain seems to improve its meaning. This is expressed through the metaphors that reflects the suffering experienced.

The prescription of opioid medications to treat chronic non cancer pain (CNCP) has increased substantially in the past years.1 To ensure adequate treatment outcomes and reduce the risks linked with the chronic use of opioids, French recommendations were developed.2–4 This study evaluated physicians adherence to these recommendations.

A questionnaire was mailed to a random sample of 150 general practitioners (GPs) practicing in one of the following French regions: Alsace, Bourgogne, Champagne-Ardenne, Franche-Comté and Lorraine. Outcome measures were adherence of physicians to current guidelines.

Forty-six responses were received. Respondents' mean age was 51.0 years and 72% were men. Seventy percent of GPs used pain scales to assess patient's pain intensity and up to 90% suggested to patients non-pharmacological approaches. Despite these good practices, only 25% of GPs assessed the risk of opiate addiction and numerous GPs prescribed opiates in non-recommended indications, including: migraine pain (82%), pure psychogenic pain (30%), fibromyalgic pain (72%) etc. In addition, 74% considered having received none or insufficient pain management education in medical school.

The present study identified that most physicians do not adhere with all French pain guidelines that has implications for patient care and the health care system. Thus, this study suggests a need for guidelines more practical to physicians and further education of physicians in the appropriate use of opioids to treat CNCP.

Over the past years, opioid analgesics use to treat chronic non-cancer pain (CNCP) has greatly increased.1Despite the existence of pain guidelines2,3,4 a majority of physicians still consider non chronic pain management as a challenge.5This study evaluate the current prescription practices of step 2 (S2A) and 3 (S3A) analgesics in northeast France.

An observational and retrospective study was conducted in a random sample of 1,000 patients using a large general health insurance reimbursement database in order to evaluate: 1) most commonly prescribed analgesics; 2) the socio-demographic data of pain patients and physicians; and 3) the adherence of physicians to French guidelines, including: i) initiate analgesic treatment with the lowest dosage, ii) do not prescribe S3A to opioid naïve patient and iii) do not associate S2A with S3A.

Almost 70% percent of the patients were women aged older than 60 years. Eighty-three percent were exclusively treated with S2A, 6% exclusively received S3A and 11% received opioid S2A with S3A. Tramadol, codeine and fentanyl transdermal were the most prescribed drugs. Fifty-one percent of patients did not start the treatment at the lowest dosage and nearly 15% of the patients receiving S3A were opioid-naïve.

This study highlights that there is still a vast domain to improve clinical practice of physicians in order to shift to best practices in the field of prescription of opioids to treat CNCP.

The concept of indicated prevention has proliferated in psychiatry. Accumulating evidence suggests that it may indeed be possible to prevent or delay the onset of a First Episode of Psychosis (FEP) though adequate interventions in individuals deemed at Clinical High Risk (CHR) for such an event. However, a challenge undermining these efforts is the relatively poor predictive accuracy of clinical assessments used in practice for CHR individuals. to improve prediction by combining different types of assessments.

To improve prediction of clinical course of disease by combining biological and clinical types of assessment.

To present a probabilistic prediction model containing clinical and biological data for the transition to first episode psychosis.

Using data from published studies, and employing predictive models based on the odds ratio form of Bayes’ rule, we simulated scenarios where clinical interview, neurocognitive testing, structural magnetic resonance imaging (MRI) and electrophysiology are part of the initial assessment process of a CHR individual (Extended Diagnostic Approach).

Our findings indicate that for most at-risk patients, at least three types of assessments are necessary to arrive at a clinically meaningful differentiation into high- intermediate-, and low-risk groups. In particular, patients with equivocal results in the initial assessments require additional diagnostic testing to produce an accurate risk profile forming part of the comprehensive initial assessment.

The findings may inform future research into reliable identification and personalized therapeutic targeting of CHR patients, to prevent transition to full-blown psychosis and to inform decision in intervention.

Oxidative stress has been implicated in the pathogenesis of major psychiatric disorders, as the brain has comparatively greater vulnerability to oxidative damage

We are the first to study the relationship between oxidative stress (by measuring plasma F2-isoprostane, as a marker of lipid peroxidation, and glutathione peroxidase, as an antioxidant enzyme) and autoimmunity (as indicated by serum antineuronal antibodies).

We studied these markers in a group of 44 Egyptian autistic children and 44 healthy matched-children.

Our results showed that oxidative stress was found in 88.64% of autistic children. Oxidative stress, resulting from elevated plasma F2-isoprostane and/or reduced glutathione peroxidase, had significant risk for antineuronal positivity, which was found in 54.5% of autistic children, (odds ratio: 12.38 and 6.43, respectively, confidence interval: 1.37–112.10 and 1.21–34.19, respectively).

the strong association between oxidative stress and autoimmunity in autistic children may indicate the possible role of oxidative stress, through induction of autoimmunity, in some autistic patients. Therefore, studies considering the role of antioxidants and immunotherapy in amelioration of autistic manifestations are recommended.

Seasonal Affective Disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occur during autumn or winter and remit in spring. Second-generation antidepressants (SGAs) are established interventions to treat acute episodes of SAD. However, little is known about the efficacy and potential harms of these interventions for preventing SAD.

To assess the efficacy and safety of SGAs to prevent SAD and improve patient–centered outcomes in adults with a history of SAD.

We searched the Cochrane Depression, Anxiety and Neuorosis Review Group's specialised register, EMBASE, MEDLINE, PsycINFO and the Cochrane Central Register of Controlled Trials. In addition, we searched pharmaceutical industry trials registers via the Internet to identify unpublished trial data. We also conducted grey literature searches and handsearches of pertinent reference lists. Two authors reviewed the evidence, abstracted data, and assessed risk of bias. We pooled data for meta-analysis when participant groups were similar and the studies assessed the same treatments with the same comparator.

We did not find eligible studies for most comparisons. We included three RCTs comparing bupropion XL with placebo. Statistically significantly fewer patients treated with bupropion experienced the onset of a major depressive episode during winter months. The overall risk of adverse events was similar between treatment groups. However, bupropionn-treated patients had significantly higher risk for headache, insomnia, and nausea.

The evidence base on SGA treatment to prevent SAD is limited. Future studies are needed to provide a sufficient evidence base for clinical decisionmaking.

The basic symptom criterion 'cognitive disturbances” (COGDIS) and ultra-high risk (UHR) criteria are commonly used for the prediction of psychosis.

However, their predictive value has been assessed so far only by survival analyses using one-time baseline ratings and time-to-conversion. Thereby, potentially risk status-informative fluctuations in risk criteria ratings over time remained unaccounted for.

Therefore we studied if and how the predictive value of COGDIS and the main UHR criterion attenuated psychotic symptoms (APS) and their combination might be influenced by their presence across different assessment times.

In a naturalistic 24-month study, 146 patients at risk for 'cognitive-perceptive basic symptoms” were repeatedly examined (monthly assessments until month 6, thereafter 3-monthly) for COGDIS and APS with the Schizophrenia Proneness Instrument, Adult version, and the Structured Interview of Prodromal Syndromes. Joint latent class analysis was applied to identify different patterns of risk criteria over time and to detect the degree of their association with risk for conversion to psychosis.

The final model included 4 classes: no risk criteria, exclusively BS, exclusively APS and the combination of COGDIS and APS. Class-specific trajectories and survival functions were associated with an increased risk for the conversion to psychosis from a mild to an intense degree, demonstrating a superior performance of the combination of BS and APS.

This result reinforces earlier results of a clearly superior psychosis-predictive value of this combination at baseline and shows that its stability over time. Thus, APS and COGDIS should be repeatedly monitored.

Childhood adversity (CA) is associated with poor mental health outcomes including psychotic symptoms.

However, the mechanisms linking CA to the development of psychosis are still poorly understood – in both their nature and the specificity of links for psychosis development. Possible links (mediators) are an excessive use of external attributions, dysfunctional coping patterns, and depressive symptoms that were associated with CA in healthy subjects but have not been studied in patients at-risk for psychosis.

Therefore, pathways models from CA to depressiveness were generated based on literature and examined separately in two samples by structural equation modeling: 137 patients at-risk for psychosis and 228 help-seeking controls.

Mediators between CA (Trauma and Distress Scale) and depressiveness (BDI II) were attribution style, self-efficacy (Competence and Control Beliefs Questionnaire) and coping strategies (Stress-Coping-Questionnaire).

Both final models showed 3 pathways running from CA to external attributions and low-self-efficacy, from these beliefs to maladaptive coping strategies and from there to depressiveness (CFI>0.9, RMSEA<0.1). In addition, the at-risk group displayed an alternative effect of CA on maladaptive coping.

Our findings suggest that CA generally increases the risk for mental health problems by the development of dysfunctional attributions and low self-efficacy that lead to maladaptive coping strategies and heightened levels of depressiveness with an additional effect of CA on maladaptive coping in at-risk patients. Thus, integrated interventions targeting these factors may enhance resilience and, thereby, prevent both the persistence of distressing symptoms and their progression to mental disorders, including psychosis.

Involvement of the nervous system by SLE is considered a challenge in their diagnosis and treatment due to the uncertainty regarding the pathogenic mechanisms and paucity of data to support therapeutic strategies.

The involvement of Antibody production especially Anti Ribosomal P protein with the presence on CNS manifestations of SLE due to the disease process is debatable.

To assess the correlation between the Neuropsychiatric manifestation of SLE and the presence of the anti Ribosomal P protein antibody.

The study was conducted on 30 SLE patients Diagnosed according to the American College of Rheumatology criteria and 10 control subjects of matching age and sex.

All subjects undergone full history, clinical and neurological examination. Laboratory tests of ANA, anti ds-DNA, antiribosomal P protein antibody and ESR were done. Hamilton Depression score and MMSE were also done for all subjects.

Depression and headaches were the most common presenting symptoms.

Antiribosomal P protein Antibody has shown a statistical significant relation with neuropsychiatric involvement especially CNS manifestations. It also showed a statistically significant positive correlation with the Hamilton Depression score. However it was not affected neither by age nor disease duration.

Antiribosomal P protein antibody is correlated to the presence of central nervous system manifestations of SLE.

Limbic encephalitis is an inflammatory disorder, commonly characterized by psychiatric features and cognitive impairment. It used to be considered a rare disease, usually paraneoplastic, with poor prognosis. Recent findings of membrane-surface directed antibodies, including anti-VGKC (Voltage-Gated Potassium Channels) antibodies, showed a substantial proportion of cases with no association with any malignancy and better prognosis.

A 56-year-old woman was admitted to the psychiatric ward in Nov/2007, with an acute onset of psychomotor retardation and agitation periods, apathy and nihilistic symptoms. She improved very slowly with lorazepam, clomipramine and quetiapine.

In Jun/2014, she was admitted again to the psychiatric ward with acute onset of intense headache, confusion, insomnia, agitation and prejudice ideas. There was a clinical deterioration with mnesic deficits, catatonic stupor, autonomic dysfunction and seizures. Complementary exams revealed: ESR>120mm; hyponatraemia; acelular CSF with slightly elevated protein; EEG with slow base activity; Brain MRI with diffuse cortical atrophy and multiples subcortical hyperintensities of frontoparietal regions on FLAIR and T2 sequences; and positive anti-VGKC antibodies. Initially there was a poor transitory improvement with high-dose steroids and intravenous immunoglobulins. After 5 months, she did plasmapheresis with relevant clinical improvement.

About 80% of anti-VGKC encephalitis patients have clinical improvement following prompt treatment. In this case, there was not as good improvement as initially expected probably because of the prolonged duration of disease prior to effective treatment. Given the good prognostic outcome with prompt initiation of immunotherapy, early recognition and diagnosis of this rare neuropsychiatric syndrome is crucial.