Stimolazione magnetica transcranica (TMS) combinata con navigazione cerebrale nella depressione bipolare farmaco-resistente : un caso clinico=Transcranial Magnetic Stimulation (TMS) combined with navigated brain stimulation in drug-resistant Bipolar Depression : a case report

Recently, Transcranial Magnetic Stimulation \u2013 a brain stimulation technique that allows electrical stimulation of the brain via magnetic fields induction \u2013 has been combined with Brain Imaging techniques increasing the precision and the reliability of stimulation during treatment. Herein it presented the case of a 52-year-old female suffering from drug-resistant Major Depressive Episode and with a diagnosis of Bipolar Disorder (type I), who was successfully treated with a 3-week treatment of low-frequency Transcranial Magnetic Stimulation (1 Hz, intensity 110% of the motor threshold, stimulation on the right hemisphere) combined with brain navigation via magnetic resonance. At the end of the treatment, patient\u2019s symptoms were markedly improved as supported by the reduced scores on the Hamilton depression rating scale and Clinical Global Impression scale. Patient restarted working. Side-effects, consisting of mild headache and confusion, limited primarily to the first hour after the first daily sessions, disappeared during the second week of treatment. After three months of follow-up, the patient maintains the same level of improvement

Exploring the neuroanatomical bases of psychotic features in bipolar disorder

Although bipolar disorder (BD) is traditionally conceptualised as one diagnostic entity, the heterogeneity of pathophysiological manifestations in BD suggests the need to classify the subtypes of the illness based on neural markers. Specifically, the presence of psychotic symptoms seems to be relevant for the clinical outcome and may have specific neuroanatomical bases. The main objective of the present review was to assess whether the distinction between psychotic BD (PBD) and non-psychotic BD (NPBD) can improve the identification of the neurobiological markers of this complex illness. To this end, we summarised the findings from the magnetic resonance imaging studies that explored the cerebral correlates of psychosis in BD in terms of grey matter volume (GMV). Overall, the results suggest the presence of peculiar GMV differences between PBD and NPBD. Specifically, psychosis in BD seems to be associated with cortical GMV deficits compared with both healthy controls and NPBD, mainly in the frontal region. Conversely, NPBD patients showed GMV deficits in selective regions of the basal ganglia when compared with the other groups. Taken together, this evidence confirms the importance to classify BD based on the psychotic dimension, which may have a specific neurobiological architecture that partially overlaps across multiple psychotic disorders

Il desiderio e l’ossessione del desiderio

<p>Desire is characterized by fluctuations in quality and quantity in most people, but sometimes these changes may result in a psychiatric condition. The spectrum of possible alterations is wide, and it may be  characterized by very different clinical pictures.</p><p>The main role of the neurobiological mechanisms that underlie desire is played by dopamine, a neurotransmitter whose concentration can be modified by use or abuse of several compounds, which may have a therapeutic role, in the case of medicines, or may lead to dysfunctional situations, in the case of substances or alcohol.</p><p>Neuroimaging studies have allowed a better knowledge of brain areas involved in mental illnesses, recording functional changes during the execution of specific tasks. The improvement of these techniques in the near future will improve the choice of the most appropriate treatment for each disease, leading to patient tailored therapies.</p><p>Different approaches to the treatment of disorders associated with an alteration of desire are currently available; often their combination, such as the one between psychophamacological drugs and psychotherapy, can lead to a better therapeutic result and to a reduction, or mitigation, of episodes<span style="text-decoration: line-through;">’</span> of severity and recurrences.</p

The association between the serotonin and dopamine neurotransmitters and personality traits

Evidence from previous studies has reported that complex traits, including psychiatric disorders, are moderately to highly heritable. Moreover, it has also been shown that specific personality traits may increase the risk to develop mental illnesses. Therefore the focus of the research shifted towards the identification of the biological mechanisms underpinning these traits by exploring the effects of a constellation of genetic polymorphisms in healthy subjects. Indeed, studying the effect of genetic variants in normal personality provides a unique means for identifying candidate genes which may increase the risk for psychiatric disorders. In this review, we discuss the impact of two of the most frequently studied genetic polymorphisms on personality in healthy subjects, the 5-HTT polymorphism of the serotonin transporter and the DRD2/DRD4 polymorphisms of the D2/D4 dopamine's receptors. The main aims are: (a) to highlight that the study of candidate genes provides a fruitful ground for the identification of the biological underpinnings of personality without, though, reaching a general consensus about the strength of this relationship; and (b) to outline that the research in personality genetics should be expanded to provide a clearer picture of the heritability of personality traits

Augmentative dopaminergic interventions for treatment-resistant bipolar depression: A focus on dopamine agonists and stimulants

Objectives: Bipolar depression is the most difficult-to-treat phase of bipolar disorder, in relation to its significant disruption of every-day life functioning and high suicidality risk. Despite the availability of several treatment options, the management of bipolar depression is still particularly challenging, with limited approved therapies. Mood stabilizers and second-generation antipsychotics may not be as effective in ameliorating depressive compared to mood elevation symptoms, and entail substantial somatic tolerability limitations. In contrast, antidepressants are widely used off-label in bipolar depression (perhaps in part due to their better somatic tolerability), but such use is controversial, as they may be associated with a higher risk of manic/hypomanic switch and rapid cycling. Among pharmacological augmentation strategies, compounds with pro-dopaminergic activity such as stimulants and stimulant-like agents (e.g., methylphenidate, modafinil and armodafinil) and dopamine agonists (e.g., pramipexole and ropinirole), have shown potential antidepressant effects, even though their use in clinical practice is still limited by the paucity of systematic evidence of efficacy and safety. The present review sought to summarize available evidence about such augmentative dopaminergic interventions for treatment-resistant bipolar depression, considering results of recent randomized controlled trials, as well as open studies, systematic reviews and guidelines indications. Methods: A systematic review of the literature was conducted. We first identified articles published in English and focused on the use of stimulants and dopamine agonists in bipolar disorder, using the keywords 'stimulant', 'psychostimulant', 'amphetamine', 'methylphenidate', 'modafinil', 'armodafinil', 'pramipexole', 'ropinirole', 'dopamine agonists', variably combined with 'bipolar disorder', 'bipolar depression', 'major depression' and 'treatmentresistant depression'. A second search was conducted about safety and tolerability, combining the keywords 'stimulant', 'psychostimulant', 'methylphenidate', 'modafinil', 'armodafinil', 'pramipexole', 'ropinirole', 'dopamine agonists' with 'tolerability', 'safety', 'side-effects', 'adverse events', 'discontinuation', 'drop out', 'mania', 'suicide', 'cycle acceleration'. Additionally, reference lists of retrieved articles and proceeding of recent scientific meetings were manually searched for relevant publications. Results: 21 reports met the inclusion criteria and were herein reviewed in detail. 11 reports described of pramipexole in adult bipolar depression, including 2 double-blind RCTs targeting depressive symptoms, 1 double-blind RCT targeting cognitive dysfunction, and 8 open reports, and one report on the use of ropinirole in bipolar depression was identified. 10 reports focused on the use of adjunctive stimulant-like agents and stimulants, including 1 double-blind armodafinil RCTs, and 1 double-blind modafinil RCT targeting depressive symptoms, 4 open uncontrolled modafinil studies, and 4 open uncontrolled methylphenidate studies. With respect to the use of stimulants in adult bipolar depression, although systematic evidence is quite limited, available data seems to support their use in at least some bipolar depressed patients, especially when they show significant drowsiness or fatigue. In contrast, the use of the stimulant-like agents modafinil and armodafinil seems to be more robust, supported by 2 RCTs as well as 4 open reports. Conclusions: Taken as a whole, findings from reviewed studies seem to suggest that pro-dopaminergic compounds agonists, such as pramipexole and stimulant-like agents, deserve consideration as potential adjunct therapeutic agents in adult bipolar depression, at least in specific subgroups of patients, although caution for supporting their use is still recommended. Future research and clinical trials on larger samples and greater follow-up periods are encouraged to extend available evidence and better clarify the potential role of these medications in bipolar depression. Copyright \ua9 2013 by Pacini Editore S.p.A

Escitalopram tolerability as mono- versus augmentative therapy in patients with affective disorders : a naturalistic study

BACKGROUND: Escitalopram is a selective serotonin reuptake inhibitor, widely used in the treatment of affective disorders. The purpose of this study was to examine its safety and tolerability, as mono- versus augmentative therapy, in a group of patients with affective disorders. MATERIALS AND METHODS: The sample consisted of 131 patients suffering from different affective disorders, including major depressive disorder, bipolar disorder, and generalized anxiety disorder, who received escitalopram for at least 4 weeks. Data were analyzed on the basis of mono- versus augmentative therapy, as well as age, gender, mean daily dosage, and patterns of combination therapy. RESULTS: Sixty-seven (51.1%) patients were treated with monotherapy (mean dose of 11.76 mg/day) and 64 (48.9%) with augmentative escitalopram (mean dose of 12.81 mg/day). The mean duration of escitalopram treatment was 14 months. The most frequently combined compounds were: other antidepressants (36.5%), mood stabilizers (33.4%), and atypical antipsychotics (30.1%). Side effects were reported in 5.3% of the total sample and the most common were insomnia (2.3%), nausea (2.3%), and dizziness (0.8%). No significant difference, in terms of tolerability, in mono- versus augmentative therapy groups was found. In addition, neither age nor gender was significantly correlated with a greater presence of side effects. Finally, no significant correlation between dosage and side effects was observed. CONCLUSION: Over a 14-month observation period, escitalopram, either as monotherapy or an augmentative treatment, was found to be well tolerated in a large sample of patients with affective disorders, with an overall low rate of side effects

Are obstetrical complications really involved in the etiology and course of schizophrenia and mood disorders?

The impact of stressful experiences during gestation or early life, leading to increased psychiatric disorders susceptibility, is currently well described in literature, however, few data are available on the association between obstetrical complications and later development of specific diagnoses or clinical features (e.g. psychotic symptoms). Aim of the present paper was to evaluate obstetrical complications frequency in different psychiatric diagnoses and their association with clinical features. Three hundred and eighty-eight patients with a diagnosis of schizophrenia, bipolar disorder or major depressive disorder were compared in terms of clinical presentation according to the presence, type and severity of obstetrical complications. Seventeen percent of the total sample (N=65) had history of at least one obstetrical complication. Patients with a history of at least one obstetrical complication result in an earlier age of onset (F=3.93, p=0.04) and a current higher GAF score (F=6.46, p=0.01). Lewis-Murray scale score was directly correlated with GAF scores (t=2.9, p=0.004) and inversely correlated with age at onset (t=-2.77, p=0.006). Obstetrical complications are frequently registered in patients with schizophrenia or mood disorders. In our sample, they appear to have an anticipatory effect on illness onset, but they seem not to be associated with a specific psychiatric diagnosis

Quetiapine-Induced Hypomania and its Association with Quetiapine/Norquetiapine Plasma Concentrations : A Case Series of Bipolar Type 2 Patients

International guidelines consider quetiapine at medium doses (300-400 mg/day) as valid options for the treatment of bipolar depression for the supposed lower risk of a switch to hypomania/mania than antidepressants. Norquetiapine is an active metabolite with antidepressant action. We describe three cases of induced hypomania in bipolar type 2 subjects who received quetiapine extended-release monotherapy (300 mg/day) for a mild/moderate major depressive episode. Quetiapine and norquetiapine plasma concentrations were measured after 1 week of treatment. Hypomania appeared after 7-10 days of quetiapine extended-release monotherapy and all subjects had a quetiapine/norquetiapine plasma concentration ratio <1. We propose a ratio value <1 as a predictor of risk for a switch to hypomania in bipolar depressed subjects receiving quetiapine extended-release monotherapy. Future research should ascertain the validity of this laboratory parameter to assess the risk of quetiapine-induced hypomania in large samples of bipolar patient

Differential core pharmacotherapy in bipolar I versus bipolar II disorder and European versus American patients not in a syndromal episode

Assess bipolar disorder subtype and treatment location effects on bipolar disorder core pharmacotherapy. Outpatients not in a syndromal episode referred to the University of Milan and Stanford University Bipolar Disorder Clinics were assessed with SCID for the fourth Edition of the Diagnostic and Statistical Manual of Mood Disorders, and the Systematic Treatment Enhancement Program for Bipolar Disorder Affective Disorders Evaluation, respectively. Prevalence and clinical correlates of antidepressant, antipsychotic, and mood stabilizer use, in aggregate and individually, were compared in bipolar I (BDI) versus II (BDII) patients in Milan/Stanford and in Milan versus Stanford patients, stratified by subtype. Milan/Stanford pooled BDI versus BDII patients significantly more often took antipsychotic (69.8 versus 44.8%), mood stabilizers (68.6 versus 57.7%), and valproate (40.1 versus 17.5%), and less often took antidepressants (23.1 versus 55.6%) and lamotrigine (9.9 versus 25.2%). Milan versus Stanford patients (stratified by bipolar disorder subtype) significantly more often took antipsychotic (BDI and BDII), antidepressants (BDII), and valproate (BDII), and less often took lamotrigine (BDI). Research regarding bipolar disorder core pharmacotherapy relationships with bipolar subtype and treatment location is warranted to enhance clinical management

Is recurrent brief depression an expression of mood spectrum disorders in young people? Results of a large community sample

The clinical relevance of Recurrent Brief Depression (RBD) has not received sufficient attention to date and continues to represent a controversial issue. The present study was carried out in a community sample to evaluate the lifetime prevalence of RDB, the degree of comorbidity, as well as possible risk factors. Subjects from a community survey in Sardinia (Italy) were randomly selected from registers of a rural, an urban and a mining area (n = 1040, 461 males, 579 females). Interviews were carried out by physicians using the Italian version of the Composite International Diagnostic Interview Simplified which had been modified for the purpose of this study. Lifetime prevalence of RBD was 7.6%; 5.8% in males, 9% in females. Subjects aged 18 to 24 years presented higher frequencies (13.8%, OR 2.2) than those aged 25 or over. Comorbidity with Major Depression was particularly frequent. RBD was furthermore associated with suicide attempts and substance abuse, thereby constituting an effective health problem. Further epidemiological and clinical studies of RBD are warranted in order to develop specific treatments and prevention strategies