Sara Pozzoli

Augmentative repetitive navigated transcranial magnetic stimulation (rTMS) in drug-resistant bipolar depression

OBJECTIVES The efficacy of transcranial magnetic stimulation (TMS) has been poorly investigated in bipolar depression. The present study aimed to assess the efficacy of low-frequency repetitive TMS (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) combined with brain navigation in a sample of bipolar depressed subjects. METHODS Eleven subjects with bipolar I or bipolar II disorder and major depressive episode who did not respond to previous pharmacological treatment were treated with three weeks of open-label rTMS at 1 Hz, 110% of motor threshold, 300 stimuli/day. RESULTS All subjects completed the trial showing a statistically significant improvement on the 21-item Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale, and Clinical Global Impression severity of illness scale (ANOVAs with repeated measures: F = 22.36, p < 0.0001; F = 12.66, p < 0.0001; and F = 10.41, p < 0.0001, respectively). In addition, stimulation response, defined as an endpoint HAM-D score reduction of > or =50% compared to baseline, was achieved by 6 out of 11 subjects, 4 of whom were considered remitters (HAM-D endpoint score < or = 8). Partial response (endpoint HAM-D score reduction between 25% and 50%) was achieved by 3/11 patients. No manic/hypomanic activation was detected during the treatment according to Young Mania Rating Scale scores (ANOVAs with repeated measures: F = 0.62, p = 0.61). Side effects were slight and were limited to the first days of treatment. CONCLUSIONS Augmentative low-frequency rTMS of the right DLPFC combined with brain navigation was effective and well tolerated in a small sample of drug-resistant bipolar depressive patients, even though the lack of a sham controlled group limits confidence in the results.

Cytokine Polymorphisms in the Pathophysiology of Mood Disorders

INTRODUCTION An increasing amount of data suggests that dysregulation of the immune system, including the cytokine network, is associated with the etiology and pathophysiology of mood disorders. Genes encoding cytokines are highly polymorphic and single nucleotide polymorphisms, associated with increased or reduced cytokine production, have been described. The aim of this study was to define the genetic immunologic scenario associated with major depressive disorder (MDD) and bipolar disorder. METHODS Eighty-four Italian outpatients affected by bipolar disorder type I, bipolar disorder type II, or MDD, and 363 healthy controls were enrolled into the study. We analyzed allele and genotype distribution of -308 (G/A) tumor necrosis factor-a (TNF-a), +874 (T/A) interferon-g (IFN-g), -174 (G/C) interleukin (IL)-6, and -1082 (G/A) IL-10 promoter polymorphisms by Polymerase Chain Reaction Sequence Specific Primers technique. RESULTS We observed different genotype and allele distributions of TNF-a, IFN-g, and IL-10 polymorphisms in the three groups of patients analyzed. In particular, bipolar II patients were characterized by an absence of adenine (A) high producer allele of TNF-a (P<.001) and a lower percentage of TT high producer genotype of IFN-g (P<.001); bipolar I individuals showed reduced percentage of AA low producer genotype of IL-10 (P<.001). Both bipolar I and bipolar II patients not carrying guanine (G) high producer IL-6 allele showed a lower mean age at onset (P=.048). CONCLUSION These data support the existence of a genetic profile related to pro-inflammatory cytokines in patients affected by mood disorders. The differences observed across the three clinical phenotypes suggest the presence of different pathogenetic mechanisms involved in the susceptibility of phenotypically different mood disorders.

Role of immunological factors in the pathophysiology and diagnosis of bipolar disorder: Comparison with schizophrenia

Several lines of evidence point to the key role of neurobiological mechanisms and shared genetic background in schizophrenia and bipolar disorder. For both disorders, neurodevelopmental and neurodegenerative processes have been postulated to be relevant for the pathogenesis as well as dysregulation of immuno‐inflammatory pathways. Inflammation is a complex biological response to harmful stimuli and it is mediated by cytokines cascades, cellular immune responses, oxidative factors and hormone regulation. Cytokines, in particular, are supposed to play a critical role in infectious and inflammatory processes, mediating the cross‐talk between the brain and the immune system; they also possibly contribute to the development of the central nervous system. From this perspective, even though mixed results have been reported, it seems that both schizophrenia and bipolar disorder are associated with an imbalance in inflammatory cytokines; in fact, some of these could represent biological markers of illness and could be possible targets for pharmacological treatments. In light of these considerations, the purpose of the present paper was to provide a comprehensive and critical review of the existing literature about immunological abnormalities in bipolar disorder with particular attention to the similarities and differences with schizophrenia.

The MCP-1 gene (SCYA2) and mood disorders: preliminary results of a case-control association study.

The aim of this case-control study was to investigate the potential role of the A-2518G polymorphism of the gene of monocyte chemoattractant protein 1 (MCP-1, a cytokine playing an important role in innate immunity) in conferring susceptibility to mood disorders. The sample studied included 96 outpatients with DSM-IV-TR diagnosis of major depressive disorder, bipolar disorder I (BD I) or BD II and 161 matched healthy controls. All subjects were genotyped for the A-2518G polymorphism of the MCP-1 gene. Genotypic and allelic associations were explored between patients and controls and across the different diagnostic groups (χ2 tests). No genotypic (χ2 = 8.215, d.f. = 6, p = 0.223) or allelic (χ2 = 5.058, d.f. = 3, p = 0.168) association for the A-2518G polymorphism of SCYA2 was found considering cases and controls. Nevertheless, important correlations were observed when patients were divided into diagnostic subgroups. A significantly higher frequency of the AA genotype (χ2 = 7.233, d.f. = 2, p = 0.027) and of the A allele (χ2 = 4.730, d.f. = 1, p = 0.030) was observed in subjects with BD. In addition, independently from diagnosis, a higher number of lifetime suicide attempts was found in subjects with the AA genotype of the A-2518G polymorphism of the MCP-1 gene (F = 3.802, p = 0.026). The present preliminary results, though limited by the relatively small sample, suggest a possible role of the SCYA2 in conferring susceptibility to BD and, if confirmed, may represent a biological discriminative influence between mood disorder subtypes.

Who is who: Italian norms for visual recognition and identification of celebrities

Age-, education- and sex-adjusted norms are provided for two new neuropsychological tests, namely (i) Face Recognition (guess of familiarity) and (ii) Person Identification (biographical contextualisation). Sixty-three pictures of celebrities and 63 of unknown people were selected following two interwoven criteria1: the realm of their celebrity (i. e., entertainment, culture and politics) and the period of celebrity acquisition (i. e., pre-war, post-war and contemporary). Both media- and education-dependent knowledge of celebrity were considered. Ninety-eight unpaid healthy participants aged between 50 and 93 years and with at least 8 years of formal education took part in this study. Reference is made to serial models of familiar face/persons processing. Recognition is held to tackle the activity of Personal Identity Nodes (PINs) and identification of the Exemplar Semantics Archives. Given the seriality of the reference model, the Identification Test is embedded in the Recognition test. This entailed that only previously recognised faces were employed to achieve norms for identification.

Cost of disorders of the brain in Italy

The aim of this study was to estimate the cost of “brain” disorders in Italy. Country-specific prevalence and health-economic data on addiction, affective, anxiety and psychotic disorders, tumours, dementia, epilepsy, migraine/other headaches, multiple sclerosis, Parkinson’s disease, stroke and head trauma were reviewed. Direct medical/non-medical and indirect costs were computed. Population-based samples and national or regional registries were used. The Italian population expected with a brain disorder was 12.4 million in 2004. The highest cost per case was for tumours and multiple sclerosis; the lowest was for anxiety disorders and migraine. Dementia (€8.6 billion), psychotic and affective disorders (€18.7 billion), migraine (€3.5 billion) and stroke (€3.4 billion) represented the highest total costs. Direct medical costs were predominant for psychiatric and neurosurgical disorders, direct non-medical costs for dementia, and indirect costs for neurological disorders. The total cost of brain disorders in Italy was €40.8 billion, 3% of the gross national product, and €706 per Italian citizen/year. This figure is however likely to be underestimated as it is based on retrospective methodology and samples of brain disorders, and does not include intangible costs.SommarioObbiettiviStimare il costo delle “malattie del cervello” in Italia.DisegnoDati epidemiologici ed economici specifici della nostra popolazione sono stati raccolti dalla letteratura per dipendenza da droga ed alcol, disturbi affettivi, psicotici e ansia, tumori cerebrali, demenza, epilessia, emicrania/altre cefalee, sclerosi multipla, M. Parkinson, ictus e traumi cranici. I costi diretti medici/non medici e quegli indiretti sono stati calcolati.SettingCampioni di popolazione e registri nazionali o regionali.Metodi e RisultatiLe stime indicano che 12.4 milioni di Italiani erano affetti da una di queste patologie nel 2004. I costi più elevati per paziente sono stati ricavati per tumori cerebrali e sclerosi multipla, i più bassi per il disturbo d’ansia e l’emicrania. Demenza (8.6 miliardi), disturbo psicotico/affettivo (18.7 miliardi), emicrania (3.5 miliardi) ed ictus cerebrale (3.4 miliardi) rappresentano i costi totali più elevati. I costi diretti medici sono predominanti per le patologie psichiatriche e neurochirurgiche, i costi diretti non medici per la demenza, ed i costi indiretti per altre malattie neurologiche.ConclusioniIl costo totale delle “malattie del cervello” in Italia è di 40.8 miliardi, il 3% del prodotto nazionale lordo, e 706 per cittadino Italiano/anno. Questo valore è tuttavia sicuramente sottostimato, in relazione all’utilizzo di una metodologia retrospettiva, di un piccolo campione di queste patologie, e non include i costi intangibili.

What do you know about Ho Chi Minh? Italian norms of proper name comprehension.

Ninety-eight healthy participants were examined with a new test of Famous Name Comprehension which, in the framework of a serial model of person processing, sequentially assessed Name Recognition (i.e., the ability to classify items as familiar or unfamiliar) and Person Identification (i.e., the ability to provide biographical knowledge of recognised items). Names were presented in a written format. A perfectly equivalent face version of the test allowed a comparison of familiarity and identification of people from name and from face input. Furthermore, the effect of the “age” of the items, i.e. the time elapsed from the presumed first exposure to the stimulus to the time of testing, was also investigated. Normative data are provided. Education was the only significant variable for recognition, while education, age and gender turned out to be significant for identification. Recognition was significantly better with name than with face input, while on identification names and faces did not differ significantly. “Oldest” items were both recognised and identified significantly worse than recent ones. The results of face-name comparison are interpreted in terms of the different opportunities to be exposed to names and faces, the relevance of visuoperceptual attributes linked to faces and the evidence of shared knowledge from different inputs. The relative advantage of recent celebrities supports the semantic characterisation of knowledge of famous people.

Depression, Dementia, and Pseudodementia

Depression and dementia represent frequent clinical presentations in the elderly population. Both diseases are interlinked. Indeed, depression in the elderly may reflect an increased risk for the later development of dementia. Worldwide, about 47 million people are affected by dementia, which represents about 10% of the general population over 65 years of age. On the other hand, among elderly people, the prevalence of depressive symptoms and major depressive disorder (MDD) is 15% and 1–3%, respectively. Female gender, alcohol and substance or drug abuse, family history, and medical conditions are factors associated with depression in the elderly.

Benzodiazepine ingestion as a way to die by suicide and related safety: the case of an elderly patient

Benzodiazepines (BDZs) are widespread psychotropic compounds, often prescribed as first-line symptomatic option by general practitioners in patients with different psychiatric disorders. Sometimes, however, they contribute to delay the administration of the first appropriate psychopharmacological treatment, thus leading to a longer duration of untreated illness in patients with depressive and anxiety disorders. The well-established pros of BDZs use in clinical practice include efficacy, rapidity of action, versatility, and safety. Among the cons, BDZs can provoke cognitive side-effects, asthenia, and misuse/abuse. Although their overall safety has been traditionally viewed as one of their greatest strengths, BDZs massive ingestion for suicidal purposes may pose, in some cases, serious life-threatening conditions, as described in the present case report. Hence, particular attention needs to be paid in prescribing these compounds to special populations, such as elderly patients. Among these, their prescription should be limited to the short-term and particularly monitored in case of risk factors, as they may be unsafe in case of overdose.

Is trazodone more effective than clomipramine in major depressed outpatients? A single-blind study with intravenous and oral administration

OBJECTIVE Some antidepressants, such as trazodone or clomipramine, can be administered intravenously in patients with major depressive disorder (MDD), with potential benefits compared to the standard oral treatment, but available data about their efficacy are limited. The present study was aimed to compare the effectiveness of trazodone and clomipramine (intravenous [i.v.] followed by oral administration). METHODS Some 42 patients with a diagnosis of MDD according to the DSM-5 were selected and treated with i.v. trazodone or clomipramine according to clinical judgment. The Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Montgomery-Åsberg Depression Rating Scale were administered at baseline, after 2 weeks, and after 6 weeks, as well as after 1 week of intravenous antidepressant administration. Raters were blinded to type of treatment. RESULTS No significant differences were found between treatment groups in terms of effectiveness at endpoint. Borderline statistical significance was found in terms of number of responders in favor of trazodone. In addition, patients treated with trazodone reported fewer total side effects than those treated with clomipramine. CONCLUSION Both i.v. trazodone and clomipramine are rapid and effective options for improving depressive symptoms, although trazodone appears to be tolerated better. Further studies with larger samples and double-blind conditions are warranted to confirm our results.