Clinical characterization of Italian suicide attempters with bipolar disorder.

IntroductionBipolar disorder (BD) is a chronic, highly disabling condition associated with psychiatric/medical comorbidity and substantive morbidity, mortality, and suicide risks. In prior reports, varying parameters have been associated with suicide risk. OBJECTIVES: To evaluate sociodemographic and clinical variables characterizing Italian individuals with BD with versus without prior suicide attempt (PSA). METHODS: A sample of 362 Italian patients categorized as BD according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM IV-TR) was assessed and divided in 2 subgroups: with and without PSA. Sociodemographic and clinical variables were compared between prior attempters and non-attempters using corrected multivariate analysis of variance (MANOVA). RESULTS: More than one-fourth of BD patients (26.2%) had a PSA, with approximately one-third (31%) of these having>1 PSA. Depressive polarity at onset, higher number of psychiatric hospitalizations, comorbid alcohol abuse, comorbid eating disorders, and psychiatric poly-comorbidity were significantly more frequent (p<.05) in patients with versus without PSA. Additionally, treatment with lithium, polypharmacotherapy (≥4 current drugs) and previous psychosocial rehabilitation were significantly more often present in patients with versus without PSA. CONCLUSIONS: We found several clinical variables associated with PSA in BD patients. Even though these retrospective findings did not address causality, they could be clinically relevant to better understanding suicidal behavior in BD and adopting proper strategies to prevent suicide in higher risk patients.

Differentiating multiple vs single lifetime suicide attempters with bipolar disorders: A retrospective study.

BACKGROUND: The risk of suicide in Bipolar Disorder (BD) has been estimated up to 20-30 times higher compared with the general population. Previous suicide attempts (SAs) represent a well-established risk factor for further attempts and for death by suicide in patients with psychiatric disorders. However, little is known about the socio-demographic and clinical profile of BD patients with a history of multiple SAs (MSAs). The present study sought to characterize BD patients with MSAs versus single suicide attempt (SSA) within a large Italian sample. METHODS: An original sample of 354 bipolar patients, recruited at the University Clinic and related community services at the Department of Psychiatry, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan (Italy), was screened for the presence of previous SAs (n=95). Socio-demographic and clinical variables were then compared between patients with multiple vs single lifetime suicide attempts. RESULTS: Bipolar patients with MSAs versus SSA had longer bipolar illness duration (26.9±12.6 vs 21.2±12.8years; p=0.05), and more frequently lived alone (38.5% vs 17.2%; p<0.05), had more than one psychiatric comorbidity (39.3% vs 17.5%; p=0.04), and utilized substance ingestion (e.g., overdose) (78.6% vs 47.2%, p=0.009), although the latter was the most common suicide attempt method in both groups. CONCLUSION: Present findings suggest different socio-demographic and clinical characteristics in bipolar patients with MSAs versus SSA. Further investigation is needed to confirm reported data.

Cognitive Performance in Euthymic Patients with Bipolar Disorder vs Healthy Controls: A Neuropsychological Investigation.

OBJECTIVES: Cognitive impairment may affect patients with Bipolar Disorder (BD) beyond the acute episodes, qualifying as a potential endophenotype. However, which cognitive domains are specifically affected in euthymic patients with BD and the potential influence of confounding factors (e.g., age and concomitant pharmacological treatment) are still a matter of debate. The present study was, therefore, conducted to assess cognitive performance across specific domains in euthymic bipolar patients, not older than 50 years (to avoid potential age-related bias) versus healthy controls (HCs). METHODS: A cognitive task battery, including the Wisconsin Card Test, Span Attention Test, Tower of London, Trail Making Test, Verbal Fluency Test, Matrices Scores and N-Back, was administered to 62 subjects (30 bipolar patients and 32 matched HCs) and differences between the groups analyzed. RESULTS: Bipolar patients performed significantly worse than HCs in the Span Forward task, in the expression of Verbal Fluency Test (Category) and in the N-Back task (all p<.05), with marginal differences between BD I and BD II patients. CONCLUSION: The present study pointed out significant differences in terms of cognitive performance between euthymic bipolar patients and HCs, supporting the notion that specific cognitive functions may remain impaired even after the resolution of the acute episodes in subjects suffering from BD. Future studies on larger samples are warranted to confirm the present results and further explore potential differences in cognitive impairment across specific bipolar subtypes.

Lifetime presence of psychotic symptoms in bipolar disorder is associated with less favorable socio-demographic and certain clinical features.

BACKGROUND: The presence of psychotic symptoms in bipolar disorder (BD) is considered a feature of higher severity of illness and, in particular, of manic episodes in bipolar I disorder (BD I). However, the possibility to apply the "with psychotic features" specifier to major depressive episodes in either bipolar II disorder (BD II) or BD I highlights the need for additional research in this area. METHODS: The present study assessed the lifetime presence of psychotic symptoms and related socio-demographic and clinical features in a large sample of BD patients (N=360), with (BDPs, N=207) and without a lifetime history of psychosis (BDNPs, N=153). RESULTS: An overall less favorable socio-demographic profile was observed in BDPs vs BDNPs. In terms of clinical variables, BDPs vs BDNPs had: earlier age at onset (27.7±10.5 vs 30.1±12.3years; p=0.02), higher rates of BD I diagnosis (95.7% vs 45.8%; p<0.001), more elevated (manic/hypomanic/mixed) polarity of first (55.2% vs 24.4%; p<0.001) and most recent episode (69.8% vs 35.6%; p<0.001), more comorbid alcohol/substance use disorder (38.1% vs 21.9%; p=0.002), more lifetime hospitalizations (3.8±6.1 vs 2±3; p=0.002) and involuntary commitments (1±1.9 vs 0.1±0.4; p<0.001), more history of psychosocial rehabilitation (17.9% vs 5.7%; p=0.001), more current antipsychotic use (90.1% vs 70.9%; p<0.001), and lower GAF (62.3±14.2 vs 69.3±12.5; p<0.001), but shorter duration of most recent episode (34.1±45.4 vs 50.3±65.7days; p=0.04), lower rates of comorbid anxiety disorders (23.9% vs 38.2%; p=0.005), and antidepressant use (19.4% vs 56.6%; p<0.001). CONCLUSIONS: The present findings indicate an overall worse profile of socio-demographic and certain clinical characteristics associated with the lifetime presence of psychotic symptoms in bipolar patients.

Italian patients with more recent onset of Major Depressive Disorder have a shorter duration of untreated illness.

BACKGROUND: Previous investigation on the duration of untreated illness (DUI) in patients with Major Depressive Disorder (MDD) revealed a different latency to first antidepressant treatment, with adverse consequences in terms of outcome for individuals with a longer DUI. Recent reports, moreover, documented a reduced DUI, as observed with the passage of time, in patients with different psychiatric disorders. Hence, the present study was aimed to assess DUI and related variables in a sample of Italian patients with MDD as well as to investigate potential differences in subjects with onset before and after 2000. METHODS: An overall sample of 188 patients with MDD was assessed through a specific questionnaire investigating DUI and other variables related to the psychopathological onset and latency to first antidepressant treatment, after dividing them in two different subgroups on the basis of their epoch of onset. RESULTS: The whole sample showed a mean DUI of approximately 4.5 years, with patients with more recent onset showing a significantly shorter latency to treatment compared with the other group (27.1±42.6 vs 75.8±105.2 months, P<.05). Other significant differences emerged between the two subgroups, in terms of rates of onset-related stressful events and benzodiazepine prescription, respectively, higher and lower in patients with more recent onset. CONCLUSIONS: Our findings indicate a significant DUI reduction in MDD patients whose onset occurred after vs before 2000, along with other relevant differences in terms of onset-related correlates and first pharmacotherapy. Further studies with larger samples are warranted to confirm the present findings in Italy and other countries.

Italian Bipolar II vs I patients have better individual functioning, in spite of overall similar illness severity.

Introduction Bipolar disorders (BDs) comprise different variants of chronic, comorbid, and disabling conditions, with relevant suicide and suicide attempt rates. The hypothesis that BD types I (BDI) and II (BDII) represent more and less severe forms of illness, respectively, has been increasingly questioned over recent years, justifying additional investigation to better characterize related sociodemographic and clinical profiles. METHODS: A sample of 217 outpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)-described BD (141 BDI, 76 BDII), without a current syndromal mood episode, was recruited, and sociodemographic and clinical characteristics of BDI and II patients were compared. RESULTS: BDII patients had significantly more favorable sociodemographics, in relation to occupational stability, cohabitation, and marital status. However, BDII compared with BDI patients had significantly longer duration of untreated illness, more frequent lifetime anxiety disorders comorbidity, longer most recent episode duration, higher rate of depressive first/most recent episode, and more current antidepressant use. In contrast, BDI compared with BDII patients had significantly more severe illness in terms of earlier age at onset; higher rate of elevated first/most recent episode, lifetime hospitalizations, and involuntary commitments; lower Global Assessment of Functioning score; and more current antipsychotic use. BDI and II patients had similar duration of illness, psychiatric family history, lifetime number of suicide attempts, current subthreshold symptoms, history of stressful life events, and overall psychiatric/medical comorbidity. CONCLUSION: BDII compared with BDI patients had more favorable sociodemographic features, but a mixture of specific unfavorable illness characteristics, confirming that BDII is not just a milder form of BD and requires further investigation in the field.

Onset polarity in bipolar disorder: A strong association between first depressive episode and suicide attempts.

BACKGROUND: The role of onset polarity (OP) in patients with bipolar disorder (BD) has been increasingly investigated over the last few years, for its clinical, prognostic, and therapeutic implications. The present study sought to assess whether OP was associated with specific correlates, in particular with a differential suicidal risk in BD patients. METHODS: A sample of 362 recovered BD patients was dichotomized by OP: depressed (DO) or elevated onset (EO: hypomanic/manic/mixed). Socio-demographic and clinical variables were compared between the subgroups. Additionally, binary logistic regression was performed to assess features associated with OP. RESULTS: DO compared with EO patients had older current age and were more often female, but less often single and unemployed. Clinically, DO versus EO had a more than doubled rate of suicide attempts, as well as significantly higher rates of BD II diagnosis, lifetime stressful events, current psychotropics and antidepressants use, longer duration of the most recent episode (more often depressive), but lower rates of psychosis and involuntary commitments. LIMITATIONS: Retrospective design limiting the accurate assessment of total number of prior episodes of each polarity. CONCLUSIONS: Our results support the influence of OP on BD course and outcome. Moreover, in light of the relationship between DO and a higher rate of suicide attempts, further investigation may help clinicians in identifying patients at higher risk of suicide attempts.

Which factors influence onset and latency to treatment in generalized anxiety disorder, panic disorder, and obsessive-compulsive disorder?

Anxiety disorders are common, comorbid, and disabling conditions, often underdiagnosed and under-treated, typically with an early onset, chronic course, and prolonged duration of untreated illness. The present study aimed to explore the influence of sociodemographic and clinical factors in relation to onset and latency to treatment in patients with generalized anxiety disorder (GAD), panic disorder (PD), and obsessive-compulsive disorder (OCD). A total of 157 patients with a Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Text Revision (DSM-IV-TR) diagnosis of PD (n=49), GAD (n=68), and OCD (n=40) were recruited, and epidemiological and clinical variables were collected through a specific questionnaire. Statistical analyses were carried out to compare variables across diagnostic groups. PD, GAD, and OCD patients showed a duration of untreated illness of 53.9±81.5, 77.47±95.76, and 90.6±112.1 months, respectively. Significant differences between groups were found with respect to age, age of first diagnosis, age of first treatment, family history of psychiatric illness, onset-related stressful events, benzodiazepine prescription as first treatment, antidepressant prescription as first treatment, and help-seeking (self-initiated vs. initiated by others). Patients with GAD, PD, and OCD showed significant differences in factors influencing onset and latency to treatment, which may, in turn, affect condition-related outcome and overall prognosis. Further studies with larger samples are warranted in the field.

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.

Access and latency to first antipsychotic treatment in Italian patients with schizophrenia and other schizophrenic spectrum disorders across different epochs.

BACKGROUND: The duration of untreated illness (DUI) is a measure to express the latency to first psychopharmacological treatment: it differs among psychiatric disorders, being influenced by several illness-intrinsic and environmental factors. The present study aimed to assess differences in DUI and related variables in patients with schizophrenia (SKZ) versus other schizophrenic spectrum disorders (SSDs) across different epochs. METHODS: 101 SKZ or SSD patients were assessed with respect to DUI and related variables through clinical interview and questionnaire. RESULTS: Patients with SKZ showed earlier ages of onset, first diagnosis and first antipsychotic treatment compared with patients with other SSDs (F = 11.02, p < 0.001; F = 12.68, p < 0.001; F = 13.74, p < 0.001, respectively) who showed an earlier access to benzodiazepines than SKZ patients (F = 6.547; p < 0.05). Dividing the total sample by the epoch of onset (before 1978; between 1978-2000; after 2000) showed a significantly later age of onset in patients with onset within the two most recent epochs (F = 7.46; p < 0.001) and a reduced DUI across epochs (from 144 to 41 to 20 months, on average; F = 11.78, p < 0.001). CONCLUSION: Schizophrenic patients showed earlier onset and longer DUI compared with patients with other SSDs. Data on the total sample showed a later age of onset and a reduced DUI across epochs.

Reduced duration of untreated illness over time in patients with schizophrenia spectrum, mood and anxiety disorders.

AIMS: Psychiatric disorders represent highly impairing conditions, often underdiagnosed and undertreated, with a conspicuous duration of untreated illness (DUI). Given that social and cultural factors influence the DUI and assuming that progress in diagnosis and treatment determines a reduced latency to pharmacotherapy, we assessed and compared DUI and related variables in a large sample of psychiatric patients (n = 562) whose onset occurred within three different a priori-defined epochs. METHODS: Two temporal cut-offs were established - the year 1978, when Law 180 (redefining standards for mental care) was introduced in Italy, and the year 2000 - in order to divide patients into three subgroups: onset before 1978, onset 1978-2000 and onset after 2000. RESULTS: A significant difference in terms of age at onset, age at first diagnosis and age at first treatment was observed in patients with onset 1978-2000 and in those with onset after 2000. In addition, a significant reduction of the DUI was found across epochs (onset before 1978: 192.25 ± 184.52 months; onset 1978-2000: 77.00 ± 96.63 months; and onset after 2000: 19.00 ± 31.67 months; P < 0.001). Furthermore, the proportion of patients with onset-related stressful events, use of benzodiazepines and neurological referral was found to be significantly different between the three epochs (χ(2) = 23.4, P < 0.001; χ(2) = 9.92, P = 0.007; χ(2) = 16.50, P = 0.011). CONCLUSIONS: Present data indicate a progressive, statistically significant reduction of latency to treatment and other related changes across subsequent epochs of onset in patients with different psychiatric disorders. Future studies will assess specific changes within homogeneous diagnostic subgroups.

Altered prefrontal cortex activity during working memory task in Bipolar Disorder: A functional Magnetic Resonance Imaging study in euthymic bipolar I and II patients.

BACKGROUND: Working memory (WM) deficits are among the most frequently impaired cognitive domains in patients with Bipolar Disorder (BD), being considered promising cognitive endophenotype of the disorder. However, the related neurobiological correlates still deserve further investigation. The present study was aimed to explore whether dorsolateral prefrontal cortex (DLPFC) activity during WM processing was abnormal in euthymic bipolar patients and may represent a potential trait-related phenotype associated with the disorder. METHODS: Using 3 Tesla functional Magnetic Resonance Imaging (3T fMRI), we studied 28 euthymic bipolar patients (15 BDI and 13 BDII), and 27 healthy controls (HCs), matched for a series of socio-demographic variables, while performing the N-back task for WM assessment. RESULTS: We found that euthymic bipolar patients showed increased right middle frontal gyrus engagement compared with HCs (FWE-corrected p = 1 × 10(-3)), regardless of WM load, and in spite of similar WM behavioral performance between groups. In particular, BDI patients had greater BOLD signal change compared to HCs (post-hoc Tukey HSD, p = 1 × 10(-3)), while BDII patients expressed an intermediate pattern of activation between BDI patients and HCs. No other significant effects were detected in the corrected whole-brain analysis. LIMITATIONS: Sample size, cross-sectional assessment and potential influence of some clinical variables. CONCLUSIONS: Results provide direct evidence of a primary physiological abnormality in DLPFC function in BDI and II, even in the absence of behavioral differences with HCs. Such exaggerated fMRI response suggests inefficient WM processing in prefrontal circuitry, and further studies are warranted to investigate whether the dysfunction is related to the genetic risk for the disorder.

Misdiagnosis, duration of untreated illness (DUI) and outcome in bipolar patients with psychotic symptoms: A naturalistic study.

BACKGROUND: A number of data show the negative role of duration of untreated illness (DUI) on outcome in mood disorders, but no investigation has been carried out about the impact of this variable in bipolar disorder (BD) with psychotic symptoms. Clinical experience shows that many bipolar patients with psychotic symptoms receive other diagnoses and often are chronically treated with first generation antipsychotics, with the effect to reduce duration of untreated psychosis/untreated episode with psychotic symptoms (DUP), but not DUI. Purpose of the study was to define the rate of misdiagnosis and the impact of DUP/DUI on outcome of bipolar patients with psychotic symptoms. METHOD: Clinical information (DUP, DUI, first received diagnosis) about bipolar outpatients with psychotic symptoms (N=240) were extrapolated through a retrospective review of the clinical charts, Lombardy database and, if necessary, through clinical interviews with patients and their relatives. Outcome measures included psychiatric and substance abuse comorbidity, occupational status, Global Assessment of Functioning (GAF), number of hospitalizations and of suicidal attempts, number of depressive/manic recurrences. Patients were divided in two groups according to the DUP (1 year) and DUI (8 years) median, and the groups were compared through analyses of variance (ANOVAs) for continuous variables or χ(2) tests for dichotomous ones. Multivariate analysis of variance (MANOVA) with duration of illness as covariate was then performed to eliminate the effect of this variable. Finally, binary logistic regressions were performed considering age at onset, DUI, DUP as independent variables and outcome variables as dependent ones (presence of hospitalizations/suicidal attempts, GAF scores<50, occupational status). RESULTS: Most of patients (61.5%) received a first diagnosis different from BD with the most frequent DSM-diagnosis being delusional disorder (17.9%). Patients with longer DUP were not different in outcome measures with respect to patients with shorter DUP. Patients with a DUI >8 years presented higher number of hospitalizations (F=6.04, p=0.015), higher number of manic recurrences (F=5.25, p=0.023), higher number of depressive recurrences (F=7.13, p=0.008) and lower GAF scores (F=17.74, p<0.001). Statistical significance persisted for number of hospitalizations (p<0.001) and GAF scores (p=0.003) after MANOVA. Finally binary logistic regression showed that a longer DUI was predictive of GAF scores<50 (F=17.74, p<0.001). DISCUSSION: More than half of bipolar patients with psychotic symptoms receive a different diagnosis at first contact with psychiatric services. DUI (but not DUP) is a predictor of outcome in bipolar patients with psychotic symptoms. This indicates that an early diagnosis and proper treatment with a mood stabilizer (or an atypical antipsychotic with mood stabilizing effects) may improve long-term outcome of these patients. In the light of the naturalistic design of the present paper, these results have to be considered as preliminary and have to be confirmed by prospective controlled studies.

Factors characterizing access and latency to first pharmacological treatment in Italian patients with schizophrenia, mood, and anxiety spectrum disorders.

Latency to first pharmacological treatment [duration of untreated illness (DUI)] in psychiatric disorders can be measured in years, with differences across diagnostic areas and relevant consequences in terms of socio-occupational functioning and outcome. Within the psychopathological onset of a specific disorder, many factors influence access and latency to first pharmacotherapy and the present study aimed to investigate such factors, through an ad-hoc developed questionnaire, in a sample of 538 patients with diagnoses of schizophrenia-spectrum disorder (SZ), mood disorder (MD), and anxiety disorder (AD). Patients with SZs showed earlier ages at onset, first diagnosis and treatment, as well as shorter DUI compared with other patients (43.17 months vs. 58.64 and 80.43 months in MD and AD; F=3.813, P=0.02). Patients with MD and AD reported more frequently onset-related stressful events, benzodiazepines as first treatment, and autonomous help seeking compared with patients with SZs. In terms of first therapist, psychiatrist referral accounted for 43.6% of the cases, progressively decreasing from SZ to MD and AD (57.6, 41.8, and 38.3%, respectively). The opposite phenomenon was observed for nonpsychiatrist clinician referrals, whereas psychologist referrals remained constant. The present findings confirm the presence of a relevant DUI in a large sample of Italian patients with different psychiatric disorders (5 years, on average), pointing out specific differences, in terms of treatment access and latency, between psychotic and affective patients. Such aspects are relevant for detection of at-risk patients and implement early intervention programs.

Wake-promoting pharmacotherapy for psychiatric disorders.

Medications promoting wakefulness are currently used in psychopharmacology in different contexts and with different objectives. In particular, they may be used for the treatment of syndromes that primarily show significant impairment in alertness/wakefulness (e.g., excessive sleepiness and other sleep disorders) as well as for the symptomatic treatment of different neuropsychiatric disorders that, in turn, are not exclusively characterized by sleep-wake disturbances (like mood disorders, for instance). In addition, several psychotropic compounds, including some antipsychotics, mood stabilizers, antidepressants, and anxiolytics have well-established sedating side effects that may go beyond the therapeutic target and require the symptomatic use of wake-promoting agents. Even though such a clinical scenario reflects millions of individuals affected (alterations of wakefulness have a prevalence rate of 20-43% in the general population), relatively few pharmacotherapies are available, mainly including compounds with psychostimulating effects, such as methylphenidate, modafinil, and armodafinil and some amphetaminic agents. In light of their side effects and potential for abuse, such compounds have received FDA approval only for a limited number of psychiatric disorders. Nonetheless, their clinical application has recently become more widespread, including attention deficit hyperactivity disorder, narcolepsy, treatment-resistant depression, bipolar disorder, shift work sleep disorder, schizophrenia, and addictions. Wake-promoting agents have different mechanisms of action, peculiar clinical strengths and specific limitations, with novel drugs in the field under extensive investigation. The present review is aimed to provide an updated overview of the aforementioned compounds as well as investigational drugs in the field, in terms of mechanism of action, indications and use in clinical practice.

Neuroimaging procedures and related acquisitions in bipolar disorder: state of the art.

Bipolar disorder (BD) is a chronic and disabling mood disorder, with significant suicide rates among psychiatric disorders. Although the pathophysiological bases of BD have not been fully elucidated yet, over the last two decades, neuroimaging research has documented specific neuroanatomic and functional abnormalities in bipolar patients. The present review was aimed to provide an updated and comprehensive overview about currently available evidence on main structural and functional alterations documented in BD by neuroimaging procedures, through a Medline research. Among the structural alterations, the most consistent ones seem to be at the level of frontal, temporal and insular cortices, amygdala and basal ganglia, having been ventriculomegaly reported as well. Magnetic resonance spectroscopy findings showed, in turn, biochemical alterations in several neurotransmitter systems. Functional neuroimaging data are quite heterogeneous with positron emission tomography and single photon emission computed tomography studies showing phase-specific abnormalities of blood flow and glucose metabolism, as well as modifications of serotonin transporter density and binding. Functional magnetic resonance imaging data documented impaired neural networks involved in emotional regulation, including anterior limbic, ventral and dorsal prefrontal regions. Taken as a whole, neuroimaging data are strongly advancing the understanding of the neural bases of BD as described in the present review.

Augmentative transcranial direct current stimulation (tDCS) in poor responder depressed patients: a follow-up study.

OBJECTIVES: Transcranial direct current stimulation (tDCS) is a non-invasive neurostimulation technique that has received increasing interest in the area of mood disorders over the last several years. While acute, double-blind, sham-controlled studies have already reported positive findings in terms of efficacy and safety for tDCS, follow-up data are lacking. This need prompted the present follow-up study, which assesses post-acute effects of tDCS (no maintenance stimulation was performed), in the mid-term, in a sample of major depressives. METHODS: After completing an acute, open trial of tDCS, 23 outpatients with either major depressive disorder or bipolar disorder entered a naturalistic follow-up (T1) with clinical evaluations at one week (T2), 1 month (T3), and 3 months (T4). A quantitative analysis of Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS) total scores, through repeated measures analysis of variance (ANOVA) (T1-T4) and paired t-test for comparing specific time points (T1-T2, T2-T3, and T3-T4), was performed. In addition, a qualitative analysis on the basis of treatment response and remission (HAM-D) was performed. RESULTS: Even though a progressive reduction of follow-up completers was observed from T2 to T4 (95.6% at T2, 65.2% at T3, and 47.8% at T4), the antidepressant effects of acute tDCS persisted over 3 months in almost half of the sample. Of note, no post-acute side effects emerged during the follow-up observation. The most frequent causes of drop-out from this study included major modifications in therapeutic regimen (30%) and poor adherence to follow-up visits (17%). CONCLUSIONS: In this mid-term, open, follow-up study, tDCS showed mixed results. Further controlled studies are urgently needed to assess its effects beyond the acute phase.

Augmentative asenapine in a recurrent manic catatonic patient with partial response to clozapine.

Catatonia is a severe but treatable neuropsychiatric syndrome known since the middle of the nineteenth century. It has been considered for a long time as a subtype of schizophrenia, even though this association occurs only in 10% of cases. In contrast, it is frequently observed in bipolar patients. First-line treatment consists of benzodiazepines, while in case of resistance electroconvulsive therapy (ECT) and clozapine have shown positive results. In addition, recent studies reported the efficacy of some atypical antipsychotics. The present case shows the clinical response to augmentative asenapine in a catatonic manic patient with a partial response to clozapine.

Assessing working memory via N-back task in euthymic bipolar I disorder patients: a review of functional magnetic resonance imaging studies.

Bipolar disorder (BD) is a chronic and highly disabling mood disorder, associated with the highest suicide rate among psychiatric disorders. Even though neurobiological bases of BD have still to be further elucidated, recent neuroimaging studies provided compelling evidence about functional correlates of cognitive deficits in BD patients, with working memory (WM) impairment being one of the most commonly reported findings. Such dysfunctions are likely to persist beyond acute phases of the illness, so they qualify as endophenotypic markers for the disorder. This review sought to synthesize, through a MEDLINE search up to December 2012, published functional magnetic resonance imaging (fMRI) studies on WM networks, conducted through N-back task in euthymic BD I patients and including a control comparison group. Eight studies meeting the search criteria were identified. Despite heterogeneity across findings, particularly in relation to task performance (i.e. accuracy and reaction time), most studies reported a loss of connectivity in BD patients' prefrontal networks, traditionally involved in WM, as well as patterns of abnormal activation in the dorso/ventrolateral prefrontal cortex, other prefrontal areas and the parietal and temporal cortex. These findings suggest the involvement of intact secondary systems in order to overcome lack of integrity across WM circuits in BD patients. Further investigation in the field is warranted.

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.