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Background: Major depressive disorder (MDD) is associated with increased allostatic load (AL; a measure of physiological costs of repeated/chronic stress-responding) and metabolic dysregulation (MetD; a measure of metabolic health and precursor to many medical illnesses). Though AL and MetD are associated with poor somatic health outcomes, little is known regarding their relationship with antidepressant-treatment outcomes. Methods: We determined pre-treatment AL and MetD in 67 healthy controls and 34 unmedicated, medically healthy MDD subjects. Following this, MDD subjects completed 8-weeks of open-label selective serotonin reuptake inhibitor (SSRI) antidepressant treatment and were categorized as 'Responders' (⩾50% improvement in depression severity ratings) or 'Non-responders' (<50% improvement). Logistic and linear regressions were performed to determine if pre-treatment AL or MetD scores predicted SSRI-response. Secondary analyses examined cross-sectional differences between MDD and control groups. Results: Pre-treatment AL and MetD scores significantly predicted continuous antidepressant response (i.e. absolute decreases in depression severity ratings) (p = 0.012 and 0.014, respectively), as well as post-treatment status as a Responder or Non-responder (p = 0.022 and 0.040, respectively), such that higher pre-treatment AL and MetD were associated with poorer SSRI-treatment outcomes. Pre-treatment AL and MetD of Responders were similar to Controls, while those of Non-responders were significantly higher than both Responders (p = 0.025 and 0.033, respectively) and Controls (p = 0.039 and 0.001, respectively). Conclusions: These preliminary findings suggest that indices of metabolic and hypothalamic-pituitary-adrenal-axis dysregulation are associated with poorer SSRI-treatment response. To our knowledge, this is the first study to demonstrate that these markers of medical disease risk also predict poorer antidepressant outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Current pharmacological treatments of post-traumatic stress disorder (PTSD) have limited efficacy. Although the diagnosis is based on psychopathological criteria, it is frequently accompanied by somatic comorbidities and perhaps "accelerated biological aging," suggesting widespread physical concomitants. Such physiological comorbidities may affect core PTSD symptoms but are rarely the focus of therapeutic trials.Methods: To elucidate the potential involvement of metabolism, inflammation, and mitochondrial function in PTSD, we integrate findings and mechanistic models from the DOD-sponsored "Systems Biology of PTSD Study" with previous data on these topics.Results: Data implicate inter-linked dysregulations in metabolism, inflammation, mitochondrial function, and perhaps the gut microbiome in PTSD. Several inadequately tested targets of pharmacological intervention are proposed, including insulin sensitizers, lipid regulators, anti-inflammatories, and mitochondrial biogenesis modulators.Conclusions: Systemic pathologies that are intricately involved in brain functioning and behavior may not only contribute to somatic comorbidities in PTSD, but may represent novel targets for treating core psychiatric symptoms. [ABSTRACT FROM AUTHOR]

Posttraumatic stress disorder (PTSD) is associated with impaired major domains of psychology and behavior. Individuals with PTSD also have increased co-morbidity with several serious medical conditions, including autoimmune diseases, cardiovascular disease, and diabetes, raising the possibility that systemic pathology associated with PTSD might be identified by metabolomic analysis of blood. We sought to identify metabolites that are altered in male combat veterans with PTSD. In this case-control study, we compared metabolomic profiles from age-matched male combat trauma-exposed veterans from the Iraq and Afghanistan conflicts with PTSD (n = 52) and without PTSD (n = 51) (‘Discovery group’). An additional group of 31 PTSD-positive and 31 PTSD-negative male combat-exposed veterans was used for validation of these findings (‘Test group’). Plasma metabolite profiles were measured in all subjects using ultrahigh performance liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry. We identified key differences between PTSD subjects and controls in pathways related to glycolysis and fatty acid uptake and metabolism in the initial ‘Discovery group’, consistent with mitochondrial alterations or dysfunction, which were also confirmed in the ‘Test group’. Other pathways related to urea cycle and amino acid metabolism were different between PTSD subjects and controls in the ‘Discovery’ but not in the smaller ‘Test’ group. These metabolic differences were not explained by comorbid major depression, body mass index, blood glucose, hemoglobin A1c, smoking, or use of analgesics, antidepressants, statins, or anti-inflammatories. These data show replicable, wide-ranging changes in the metabolic profile of combat-exposed males with PTSD, with a suggestion of mitochondrial alterations or dysfunction, that may contribute to the behavioral and somatic phenotypes associated with this disease. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Cannabis use is frequent among depressed patients and may lead to the so-called "amotivational syndrome", which combines symptoms of affective flattening and loss of emotional reactivity (i.e. the socalled "negative" symptomatology). The aim of this study was to investigate the negative symptomatology in depressed patients with concomitant cannabis use disorders (CUDs) in comparison with depressed patients without CUDs. PATIENTS AND METHODS: Fifty-one patients with a diagnosis of Major Depressive Disorder (MDD) and concomitant CUD and fiftyone MDD patients were enrolled in the study. The 21-Item Hamilton Depression Rating Scale (HDRS) and the negative symptoms subscales of the Positive and Negative Syndrome Scale (PANSS) were used to assess depressive and negative symptomatology. RESULTS: Patients with cannabis use disorders presented significantly more severe negative symptoms in comparison with patients without cannabis use (15.18 ± 2.25 vs 13.75 ± 2.44; t100 = 3.25 p = 0.002). DISCUSSION: A deeper knowledge of the "negative" psychopathological profile of MDD patients who use cannabis may lead to novel etiopathogenetic models of MDD and to more appropriate treatment approaches. [ABSTRACT FROM AUTHOR]

BackgroundFunctional decline among patients with mental illness is not unique to individuals with psychotic disorders. Despite this, research on early predictors of functional outcome mainly focused on individuals thought to have an ‘at risk mental state’ (ARMS) for psychosis. There is evidence suggesting that certain early vulnerability markers, such as neurological soft signs (NSS), may explain variability in functional outcomes independent of the level of psychosis risk and the traditional diagnostic classification.MethodStructural equation modeling was applied to baseline data from a prospective longitudinal study of 138 young individuals in treatment with secondary services for non-psychotic disorders. We evaluated theoretically based models of pathways to functional outcome starting from NSS. The intervening variables were established according to previous evidence and drawn from two general categories: cognition (neuro- and social-) and negative symptoms (expressive and experiential).ResultsA final trimmed model was a single path running from NSS to neurocognition to experiential negative symptoms to outcome. It could not be improved by adding or dropping connections that would change the single path to multiple paths. The indirect effect from NSS to outcome was significant. The validity of the model was independent of the ARMS status and the psychiatric diagnosis.ConclusionsOur results provide evidence for a single pathway model in which the starting and intervening variables represent modifiable trans-diagnostic therapeutic targets to improve functional trajectories in young individuals with a recent-onset psychiatric diagnosis and different levels of psychosis risk. [ABSTRACT FROM PUBLISHER]

OBJECTIVE: Cannabis use is frequent among depressed patients and may lead to the so-called "amotivational syndrome", which combines symptoms of affective flattening and loss of emotional reactivity (i.e. the socalled "negative" symptomatology). The aim of this study was to investigate the negative symptomatology in depressed patients with concomitant cannabis use disorders (CUDs) in comparison with depressed patients without CUDs. PATIENTS AND METHODS: Fifty-one patients with a diagnosis of Major Depressive Disorder (MDD) and concomitant CUD and fiftyone MDD patients were enrolled in the study. The 21-Item Hamilton Depression Rating Scale (HDRS) and the negative symptoms subscales of the Positive and Negative Syndrome Scale (PANSS) were used to assess depressive and negative symptomatology. RESULTS: Patients with cannabis use disorders presented significantly more severe negative symptoms in comparison with patients without cannabis use (15.18 ± 2.25 vs 13.75 ± 2.44; t100 = 3.25 p = 0.002). DISCUSSION: A deeper knowledge of the "negative" psychopathological profile of MDD patients who use cannabis may lead to novel etiopathogenetic models of MDD and to more appropriate treatment approaches. [ABSTRACT FROM AUTHOR]

Obesity and overeating are among the most prevalent health concerns worldwide and individuals are increasingly using performance and image-enhancing drugs (PIEDs) as an easy and fast way to control their weight. Among these, herbal weight-loss products (HWLPs) often attract users due to their health claims, assumed safety, easy availability, affordable price, extensive marketing, and the perceived lack of need for professional oversight. Reports suggest that certain HWLPs may lead to onset or exacerbation of psychiatric disturbances. Here we review the available evidence on psychiatric adverse effects of HWLPs due to their intrinsic toxicity and potential for interaction with psychiatric medications. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Alternative methods of alcohol consumption have recently emerged among adolescents and young adults, including the alcohol "eyeballing", which consist in the direct pouring of alcoholic substances on the ocular surface epithelium. In a context of drug and behavioural addictions change, "eyeballing" can be seen as one of the latest and potentially highly risky new trends. We aimed to analyze the existing medical literature as well as online material on this emerging trend of alcohol misuse. MATERIALS AND METHODS: Literature on alcohol eyeballing was searched in PsychInfo and Pubmed databases. Results were integrated with a multilingual qualitative assessment of the database provided by The Global Public Health Intelligence Network (GPHIN) and of a range of websites, drug fora and other online resources between March 2013 and July 2013. RESULTS: Alcohol eyeballing is common among adolescents and young adults; substances with high alcohol content, typically vodka, are used for this practice across the EU and internationally. The need for a rapid/intense effect of alcohol, competitiveness, novelty seeking and avoidance of "alcoholic fetor" are the most frequently reported motivations of "eyeballers". Local effects of alcohol eyeballing include pain, burning, blurred vision, conjunctive injection, corneal ulcers or scarring, permanent vision damage and eventually blindness. CONCLUSIONS: Alcohol eyeballing represents a phenomenon with potential permanent adverse consequences, deserving the attention of families and healthcare providers. Health and other professionals should be informed about this alerting trend of misuse. Larger observational studies are warranted to estimate the prevalence, characterize the effects, and identify adequate forms of interventions for this emerging phenomenon. [ABSTRACT FROM AUTHOR]

Purpose : To study if prolonged in vitro exposure to 1800 MHz radiofrequency (RF) could exert an effect on human peripheral blood mononuclear cells (PBMC) from young and elderly donors by affecting apoptosis, mitochondrial membrane potential and heat shock protein (HSP) 70 levels. Materials and methods : Endpoints were analysed in the presence or absence of the apoptosis-inducing agent 2-deoxy-D-ribose. Three different signal modulations typical of the Global System for Mobile communication (GSM) system were applied. The modulations are widely used in mobile telephony (GSM Basic, discontinuous transmission [DTX] and Talk) at specific absorption rates of 1.4 and 2.0 W kg -1 . Results : In all conditions and for all endpoints tested, there was no significant difference between RF- and sham-exposed cells. Conclusion : 1800 MHz RF could not induce apoptosis by itself or affect the apoptotic phenomenon when induced by an apoptotic agent. Moreover, RF did not modify the mitochondrial functionality and the expression of HSP 70. [ABSTRACT FROM AUTHOR]

Francesco Saverio Bersani, Amedeo Minichino, Francesco Fattapposta, Laura Bernabei, Francesco Spagnoli, Daniela Mannarelli, Marta Francesconi, Caterina Pauletti, Alessandra Corrado, Lucilla Vergnani, Ines Taddei, Massimo Biondi, Roberto Delle Chiaie Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy Introduction: Neurocognitive impairments have been observed in patients with bipolar disorder (BD) even during the euthymic phase of the disease, potentially representing trait-associated rather than state-associated characteristics of the disorder. In the present study, we used transcranial direct current stimulation (tDCS) applied to cerebellar and prefrontal cortices to improve the neurophysiological performances of patients with euthymic BD.Methods: Twenty-five outpatients with BD underwent open-label prefrontocerebellar tDCS for 3 consecutive weeks. Neurophysiological performances were assessed through the examination of the P3b and P3a subcomponents of P300 event-related potential at baseline and after stimulation.Results: Compared to baseline, P3b component after tDCS showed significantly higher amplitude and shorter latency (latency: Fz P=0.02, Cz P=0.03, and Pz P=0.04; amplitude: Fz P=0.24, Cz P=0.02, and Pz P=0.35).Conclusion: In our sample of patients with euthymic BD, concomitant prefrontoexcitatory and cerebellar-inhibitory modulations led to improved brain information processing stream. This improvement may at least partially result from neuroplastic modulation of prefrontocerebellar circuitry activity. Keywords: mood disorders, tDCS, cerebellum, P300, dorsolateral prefrontal cortex, event-related potentials

Amedeo Minichino, Francesco Saverio Bersani, Laura Bernabei, Francesco Spagnoli, Lucilla Vergnani, Alessandra Corrado, Ines Taddei, Massimo Biondi, Roberto Delle Chiaie Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy Objective: The aim of the study was to improve neuropsychological functioning of euthymic patients with bipolar disorder (BD) using transcranial direct current stimulation (tDCS) applied to cerebellar and prefrontal cortices.Methods: Twenty-five BD outpatients underwent prefrontal (anodal) and cerebellar (cathodal) tDCS for 3 consecutive weeks. All participants were assessed through the Rey Complex Figure Test delay and copy and the Neurological Examination Scale at baseline and after therapy with tDCS.Results: After tDCS treatment, patients showed significant improvements in visuospatial memory tasks. Patients with worse baseline cognitive performances also showed a significant improvement in executive functioning tasks. Neurological Examination Scale total score and motor coordination subscale significantly improved.Conclusion: Prefrontal-excitatory and cerebellar-inhibitory stimulations in euthymic BD patients may lead to better neurocognitive performances. This improvement could result from the modulation of prefronto–thalamic–cerebellar circuit activity pattern, which can be disrupted in BD. Keywords: cerebellum, dorsolateral prefrontal cortex, neuropsychology, cognition

The concepts of "accelerated biological ageing" and "premature biological senescence" have been receiving increasing attention in relation to psychiatric diseases, with clinical, epidemiological and molecular observations suggesting that psychopathological processes can have significant relationships with aging-related phenomena. The deficit accumulation model postulates that the individual's biological age and functional status is related to the amount of health deficits accumulated over time and that one's biological age can be estimated by summarizing health deficits in a single continuous variable, the so-called "frailty index" (FI). In this presentation it will be discussed the possibility that the FI, which condenses information arising from multidimensional evaluations, represents a potential clinically-useful macroscopic indicator of biological age which can add relevant information to the measurements currently implemented in the study of accelerated biological age in psychiatric diseases. [ABSTRACT FROM AUTHOR]

Giuseppe Bersani,1 Elisa Polli,1 Giuseppe Valeriani,1 Daiana Zullo,1 Claudia Melcore,1 Enrico Capra,2 Adele Quartini,1 Pietropaolo Marino,1 Amedeo Minichino,2 Laura Bernabei,2 Maddalena Robiony,1 Francesco Saverio Bersani,1,2 Damien Liberati1 1Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy; 2Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy Introduction: It has recently been highlighted that patients affected by schizophrenia (SCZ) and those affected by bipolar disorder (BD) undergo gradual chronic worsening of cognitive and social functioning. The objective of the current study was to evaluate and compare (using the Facial Action Coding System [FACS]) the way by which patients with the two disorders experience and display emotions in relation to specific emotional stimuli. Materials and methods: Forty-five individuals participated in the study: 15 SCZ patients, 15 BD patients, and 15 healthy controls. All participants watched emotion-eliciting video clips while their facial activity was videotaped. The congruent/incongruent feeling of emotions and the facial expression in reaction to emotions were evaluated. Results: SCZ and BD patients presented similar incongruent emotive feelings and facial expressions (significantly worse than healthy participants); SCZ patients expressed the emotion of disgust significantly less appropriately than BD patients. Discussion: BD and SCZ patients seem to present a similar relevant impairment in both experiencing and displaying emotions; this impairment may be seen as a behavioral indicator of the deficit of social cognition present in both the disorders. As the disgust emotion is mainly elaborated in the insular cortex, the incongruent expression of disgust of SCZ patients can be interpreted as a further evidence of a functional deficit of the insular cortex in this disease. Specific remediation training could be used to improve emotion and social cognition in SCZ and BD patients. Keywords: schizophrenia, bipolar disorder, facial expression, FACS, social cognition

Massimo Salviati, Francesco Saverio Bersani, Francesco Macrì, Marta Fojanesi, Amedeo Minichino, Mariana Gallo, Francesco De Michele, Roberto Delle Chiaie, Massimo BiondiDepartment of Neurology and Psychiatry, Sapienza University of Rome, Rome, ItalyAbstract: Delusional misidentification syndromes are a group of delusional phenomena in which patients misidentify familiar persons, objects, or themselves, believing that they have been replaced or transformed. In 25%–40% of cases, misidentification syndromes have been reported in association with organic illness. We report an acute episode of Capgras-like delusion lasting 8 days, focused on the idea that people were robots with human bodies, in association with an acute urinary infection. To our knowledge, this is the first case report associating urinary tract infection with Capgras-like syndrome. Awareness of the prevalence of delusional misidentification syndromes associated with acute medical illness should promote diligence on the part of clinicians in recognizing this disorder.Keywords: delusional misidentification, Capgras syndrome, urinary tract infection, psychosis

Giuseppe Bersani,1 Francesco Saverio Bersani,1,2 Giuseppe Valeriani,1 Maddalena Robiony,1 Annalisa Anastasia,1 Chiara Colletti,1,3 Damien Liberati,1 Enrico Capra,2 Adele Quartini,1 Elisa Polli11Department of Medical-Surgical Sciences and Biotechnologies, 2Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, 3Department of Neuroscience and Behaviour, Section of Psychiatry, Federico II University of Naples, Naples, ItalyBackground: Research shows that impairment in the expression and recognition of emotion exists in multiple psychiatric disorders. The objective of the current study was to evaluate the way that patients with schizophrenia and those with obsessive-compulsive disorder experience and display emotions in relation to specific emotional stimuli using the Facial Action Coding System (FACS).Methods: Thirty individuals participated in the study, comprising 10 patients with schizophrenia, 10 with obsessive-compulsive disorder, and 10 healthy controls. All participants underwent clinical sessions to evaluate their symptoms and watched emotion-eliciting video clips while facial activity was videotaped. Congruent/incongruent feeling of emotions and facial expression in reaction to emotions were evaluated.Results: Patients with schizophrenia and obsessive-compulsive disorder presented similarly incongruent emotive feelings and facial expressions (significantly worse than healthy participants). Correlations between the severity of psychopathological condition (in particular the severity of affective flattening) and impairment in recognition and expression of emotions were found.Discussion: Patients with obsessive-compulsive disorder and schizophrenia seem to present a similarly relevant impairment in both experiencing and displaying of emotions; this impairment may be seen as a chronic consequence of the same neurodevelopmental origin of the two diseases. Mimic expression could be seen as a behavioral indicator of affective flattening. The FACS could be used as an objective way to evaluate clinical evolution in patients.Keywords: schizophrenia, obsessive-compulsive disorder, facial expression, Facial Action Coding System

Amedeo Minichino¹, Francesco Saverio Bersani¹, Enrico Capra¹, Rossella Pannese¹, Celeste Bonanno², Massimo Salviati¹, Roberto Delle Chiaie¹, Massimo Biondi¹¹Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, ²Aldo Moro University of Bari, Bari, ItalyBackground: Biological treatments are considered as additional options for the treatment of resistant unipolar depression. Controversial data exist about the efficacy and tolerability of three of the most used somatic treatments: electroconvulsive therapy (ECT), transcranial magnetic stimulation (rTMS), and deep transcranial magnetic stimulation (deepTMS). The aim of this review is to investigate and compare the efficacy and tolerability of these three techniques in drug-free patients with pharmacoresistant unipolar depression.Methods: Three independent reviewers extracted data and assessed the quality of methodological reporting of selected studies. The first outcome was the clinical response to the three different techniques defined as a percentage improvement of Hamilton Depression Rating Scale (HDRS). The second outcome was the evaluation of their neuropsychological effects. The third outcome was the evaluation of the number of remitted patients; remission was defined as an absolute HDRS-24 score of ≤11 or as an absolute HDRS-17 score of ≤8. Tolerability was the fourth outcome; it was evaluated by examining the number of dropped-out patients.Results: The comparative evaluation of HDRS percentage variations shows ECT as the most effective method after 4 weeks of therapy; on the other hand, a better efficacy is obtainable by deepTMS after 2 weeks of therapy. DeepTMS is the technique that gives the best improvement of cognitive performances. The percentage of remitted patients obtained with ECT treatment is the same obtained in the deepTMS group. Both techniques have a remitted patients percentage two times larger than the rTMS. DeepTMS shows a tolerability, measured by the number of dropped-out patients, worse than ECT.Conclusion: Our investigation confirms the great therapeutic power of ECT. DeepTMS seems to be the only therapy that provides a substantial improvement of both depressive symptoms and cognitive performances; nevertheless it is characterized by a poor tolerability. rTMS seems to provide a better tolerability for patients, but its therapeutic efficacy is lower. Considering the small therapeutic efficacy of deepTMS in the last 2 weeks of treatment, it could be reasonable to shorten the standard period of deepTMS treatment from 4 to 2 weeks, expecting a reduction of dropped-out patients and thus optimizing the treatment outcome.Keywords: deep transcranial magnetic stimulation, transcranial magnetic stimulation, electroconvulsive therapy, pharmacoresistant unipolar depression