Mood Spectrum Model: Evidence reconsidered in the light of DSM-5

AIM: to investigate studies conducted with the Mood Spectrum Structured Interviews and Self-Report versions (SCI-MOODS and MOODS-SR). METHODS: We conducted a review of studies published between 1997 and August 2014. The search was performed using Pubmed and PsycINFO databases. Analysis of the papers followed the inclusion and exclusion criteria recommended by the PRISMA Guidelines, namely: (1) articles that presented a combination of at least two terms, "SCI-MOODS" [all fields] or "MOODS-SR" [all fields] or "mood spectrum" [all fields]; (2) manuscript in English; (3) original articles; and (4) prospective or retrospective original studies (analytical or descriptive), experimental or quasi-experimental studies. Exclusion criteria were: (1) other study designs (case reports, case series, and reviews); (2) non-original studies including editorials, book reviews and letters to the editor; and (3) studies not specifically designed and focused on SCI-MOODS or MOODS-SR. RESULTS: The search retrieved 43 papers, including 5 reviews of literature or methodological papers, and 1 case report. After analyzing their titles and abstracts, according to the eligibility criteria, 6 were excluded and 37 were chosen and included. The SCI-MOODS and the MOODS-SR have been tested in published studies involving 52 different samples across 4 countries (Italy, United States, Spain and Japan). The proposed mood spectrum approach has demonstrated its usefulness mainly in 3 different areas: (1) Patients with the so-called "pure" unipolar depression that might manifest hypomanic atypical and/or sub-threshold aspects systematically detectable with the mood questionnaire; (2) Spectrum features not detected by other instruments are clinically relevant, because they might manifest in waves during the lifespan, sometimes together, sometimes alone, sometimes reaching the severity for a full-blown disorder, sometimes interfering with other mental disorders or complicating the course of somatic diseases; and (3) Higher scores on the MOODS-SR factors assessing "psychomotor disturbances", "mixed instability" and "suicidality" delineate subtypes of patients characterized by the more severe forms of mood disorders, the higher risk for psychotic symptoms, and the lower quality of life after the remission of the full-blown-episode. CONCLUSION: The mood spectrum model help researchers and clinicians in the systematic assessment of those areas of psychopathology that are still neglected by the Diagnostic and Statistical Manual of Mental Disorders 5 classification

ELECTROCONVULSIVE THERAPY (ECT) IN BIPOLAR DEPRESSIVE, MIXED, MANIC AND CATATONIC STATES. Could be ECT considered a mood stabilizer?

Objective: We prospectively evaluated the short-term outcome and the predictors of response to electroconvulsive therapy (ECT) in a large sample of patients with a bipolar disorder in different phases of the illness. Method: From January 2006 to May 2011, we performed an analysis using data obtained from 500 of 522 consecutive patients with Bipolar Disorder according to DSM-IV-TR diagnostic criteria, who were treated with ECT at the Department of Psychiatry of the University of Pisa. All patients were evaluated prior to and after the ECT course using the Hamilton Depression Rating Scale-17 (HDRS-17), Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale (BPRS), Clinical Global Improvement Impression (CGI) scale and Bush-Francis Catatonia Rating Scale (BFCRS). The CGI subscale “global improvement”, final HDRS-17 and YMRS total scores were used to identify non-responder, responder, and remitters in depressive and mixed patients. Outcome in catatonic patients was evaluated with CGI-I and BFCRS final scores. Descriptive analysis were conducted in manic patients, due to the small size of the sample. Results: At the end of the ECT course, 94 out of 295 depressed patients (31.86%) were considered non-responders, 103 patients (34.92%) responders, and 98 patients (33.22%) remitters. Among 197 mixed patients, 55 patients (27.9%) were defined non-responders, 82 patients (41.6%) were responders, and 60 patients (30.5%) were remitters. At the end of the ECT course, 21 out of 26 catatonic patients (80.8%) were classified as responders (GCI ≤ 2) and 5 patients (19.2%) were classified as non-responders. As expected, at the end of the ECT trial, the CGI-S, HDRS-17, BPRS and BFCRS (for catatonic group) scores were significantly lower in remitters than in responders and non-responders in all groups. In mixed and depressive patients, the length of current episode and baseline YMRS total mean score were statistically significant predictors of non-response versus remission. In catatonic group, the mean number of previous mood episodes was significantly greater in responders than in non-responders. Conclusions: The main finding of this study is that, in our sample of patients with severe and drug-resistant bipolar disorder, ECT appeared to be an effective and safe treatment for all phases of the illness. We observed high rates of response in bipolar depression, mania and mixed state, approximately two-thirds of the cases, with less than 30% of non-responders. In catatonic patients ECT was effective in more than 80% of the cases. With an appropriate monitoring the treatment was very safe with a very low incidence of adverse events. According to existing literature, our data demonstrates that ECT-induced mania is virtually non-existent and long-term mood destabilization, very unlikely. However, data on ECT in long-term prophylaxis are lacking and randomized controlled trials of continuation and maintenance ECT in BD are not available. Despite these limitations, ECT should be considered a mood-stabilizing treatment, clearly superior to pharmacological treatment considering its efficacy in acute phases and in relapse-recurrence prevention

MECHANISM OF ACTION OF ELECTROCONVULSIVE THERAPY (ECT): A NEUROIMMUNOCHEMICAL APPROACH

Background: Electroconvulsive therapy (ECT) is one of the most effective and fast acting therapeutic options for treatment-resistant psychiatric diseases, in particular mood disorders. Mood disorders are highly heterogeneous, disabling and severe mental illness, at still unknown etiology, which have been associated with a multifaceted pathogenesis, encompassing genetic, epigenetic and metabolic vulnerabilities together psychosocial/lifestyle factors. Among the various biological patterns thought to be involved in the physiopathology of dysthymia, major depression, cyclothymia, bipolar I, II, mixed states and related disorders, alterations in the neuroendocrine and immune systems have been also evidenced. Additionally, an increasing number of studies have highlighted the relevance of impaired mechanisms of defense against reactive oxygen species (ROS) in the progression and severity of BD. Oxidative stress and redox states are indeed part of the metabolic and chemical networks of the immune/inflammation response. Despite such evidences, few studies have examined, by now, the impact of ECT on specific neuroendocrine, immune and oxidative stress paths in patients undergoing this therapy. It has been reported that ECT-induced epileptic seizures stimulate the intra-cerebral release of cytokines, including the cytokine network associated with the pathophysiology of affective disorders. It is therefore challenging to consider that the therapeutic efficacy of ECT may reside on the degree of activation of the immune/inflammatory system and that patients, under depressive, hypomanic, manic or mixed states, may change their specific profile of biochemical/immunological markers by ECT. ECT would thus act on complex biochemical cascades, formed by several neurotransmitters, neuro-hormones, neurotrophic factors and metabolic substrates, playing a significant therapeutic role. Hypothesis: Beside possible neurotransmitter and neurotrophin variations, mood disorder patients would also present significant changes of peripheral cytokine and oxidative stress profiles, before and after ECT; it might be thus possible to identify specific redox chemical and immune features related to the response/Non-response to this treatment. Such a result could also considerably help to detect peripheral molecular correlates of immunochemical dysregulation, refractory symptoms and ECT therapeutic benefits or adverse effects in mood disorders. Aims: The foremost aims of this study were: 1) to explore the degree of expression/activity of peripheral immune and oxidative stress markers during the course of ECT in bipolar patients; 2) to possibly evidence differences of these biochemical parameters among Remitter and Non-Remitter patients, assessed by means of suitable examinations and psychometric questionnaires, administered to recruited patients before, during and after ECT. Methods: From 2016 to 2018, we recruited and investigated 17 consecutive patients with a BD diagnosis accordingly to DSM-V diagnostic criteria, all treated by ECT at the Psychiatry section of the Department of Clinical and Experimental Medicine of the University of Pisa. All patients were examined during three main phases of ECT course, following this schedule: 1) at T0, by both psychometric and biochemical evaluations, before the first application; 2) at T1, by biochemical evaluations carried out 3 hours after the first application; 3) at T2, at the end of the treatment, by both psychometric and biochemical examinations. A forth biochemical assessment was carried out also at T3, 3 hours after the last application, in order to possible appraise a different reactivity of immune/oxidative stress patterns at the end of ECT applications. To constantly monitor patients, psychiatric and physical examinations were always performed for the duration of the study. Psychometric questionnaires carried out prior to (T0) and after (T3) the ECT course, consisted into: the Hamilton Depression Rating Scale-17 (HAM-D), Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale (BPRS) and Clinical Global Improvement Impression (CGI) scale. The CGI subscale “global improvement”, final HAM-D and YMRS total scores were used to identify Remitter and Non-Remitter groups . Biochemical investigations, performed after blood samplings carried out at the 4 scheduled times, T0, T1, T2 and T3, were: 1)-the plasma levels of the immune/inflammatory cytokines IL-6, IL-8 and TNFα; 2)-the plasma levels/ activity of the antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD), total thiols (R-SH), the ferric reducing ability of plasma (FRAP), uric acid as well as an index of oxidative damage, the advanced oxidation plasma protein products (AOPP). Results: At the end of therapy, about the 53% of ECT-treated BD patients was found to remit. Concerning biochemical investigation, we observed that, globally, in 17 subjects, 3 hours after ECT (T1), the activity of SOD in plasma increased nearly attaining the statistical significance, while FRAP was found significantly decreased; when analyzing Remitters and Non-Remitters separately, the nearly significant increased SOD reported in all patients at T1, after the first ECT application, was due to a greater enzyme activity in Remitters, while the global T1 FRAP reduction was due to the significant decrease of plasma ferric reducing power in Non-Remitters only. We also reported that Non-Remitters had a significantly reduced CAT activity both at T1 and in the long term, at the end of ECT course (T2), and a higher percent of responce in uric acid and IL 8 after the last ECT (T3 vs. T2). Also, Non-Remitters tended to concomitantly have, at T2, higher plasma FRAP, SOD,IL6 and lower CAT, Thiols in respect to baseline (T0) values as well as in respect to Remitters. No significant effect on the plasma level of AOPP was observed at any scheduled time in all patients, indicating that no relevant protein damage, due to ROS was reported during ECT sessions. Limitations: The study, at the present stage, had a small sample size; moreover the patient group was heterogeneous, consisting of treatment resistant bipolar patients in different phases of illness and with different pharmacological regimes. Conclusions: According to literature, we showed that ECT is an effective and safe treatment able to heal drug-resistant bipolar patients with very severe clinical presentation and risk of suicide, in all phases of the illness. Preliminary results suggest that ECT can induce changes of the antioxidant system: an increased ROS scavenging activity at T1 seems to be an index of favorable response. The diminuition of antioxidant defense system would be conversely linked to reduced benefits deriving from this therapy. The recruitment of a larger cohort of patients is needed to confirm and pursue this useful investigation of peripheral biomarkers of ECT response. This will permit to perform more robust statistical tests as multivariate regression or principal component analyses and to possibly define peculiar immunochemical changes related to the clinical response

The Role of Electroconvulsive Therapy (ECT) in Bipolar Disorder: Effectiveness in 522 Patients with Bipolar Depression, Mixed-state, Mania and Catatonic Features

We evaluated the effectiveness of Electroconvulsive Therapy (ECT) in the treatment of Bipolar Disorder (BD) in a large sample of bipolar patients with drug resistant depression, mania, mixed state and catatonic features. Method: 522 consecutive patients with DSM-IV-TR BD were evaluated prior to and after the ECT course. Responders and nonresponders were compared in subsamples of depressed and mixed patients. Descriptive analyses were reported for patients with mania and with catatonic features. Results: Of the original sample only 22 patients were excluded for the occurrence of side effects or consent withdrawal. After the ECT course, 344 (68.8%) patients were considered responders (final CGIi score ≤3) and 156 (31.2%) nonresponders. Response rates were respectively 68.1% for BD depression, 72.9% for mixed state, 75% for mania and 80.8% for catatonic features. Length of current episode and global severity of the illness were the only statistically significant predictors of nonresponse. Conclusion: ECT resulted to be an effective and safe treatment for all the phases of severe and drugresistant BD. Positive response was observed in approximately two-thirds of the cases and in 80% of the catatonic patients. The duration of the current episode was the major predictor of nonresponse. The risk of ECT-induced mania is virtually absent and mood destabilization very unlikely. Our results clearly indicate that current algorithms for the treatment of depressive, mixed, manic and catatonic states should be modified and, at least for the most severe patients, ECT should not be considered as a "last resort".</p

Psychopharmacological options for adult patients with anorexia nervosa

The aim of this review was to summarize evidence from research on psychopharmacological options for adult patients with anorexia nervosa (AN). Database searches of MEDLINE and PsycINFO (from January 1966 to January 2014) were performed, and original articles published as full papers, brief reports, case reports, or case series were included. Forty-one papers were screened in detail, and salient characteristics of pharmacological options for AN were summarized for drug classes. The body of evidence for the efficacy of pharmacotherapy in AN was unsatisfactory, the quality of observations was questionable (eg, the majority were not blinded), and sample size was often small. More trials are needed, while considering that nonresponse and nonremission are typical of patients with AN

Catatonia in 26 patients with bipolar disorder: Clinical features and response to electroconvulsive therapy

Objectives: We describe the clinical characteristics and short-term outcomes of a sample of inpatients with bipolar disorder with severe catatonic features resistant to pharmacological treatment. Methods: The study involved 26 catatonic patients, resistant to a trial of benzodiazepines, and then treated with electroconvulsive therapy (ECT). All patients were evaluated prior to and one week following the ECT course using the Bush-Francis Catatonia Rating Scale (BFCRS) and the Clinical Global Impression (CGI). Results: In our sample, women were over-represented (n = 23, 88.5%), the mean (± standard deviation) age was 49.5 ± 12.5 years, the mean age at onset was 28.1 ± 12.8 years, and the mean number of previous mood episodes was 5.3 ± 2.9. The mean duration of catatonic symptoms was 16.7 ± 11.8 (range: 3-50) weeks, and personal history of previous catatonic episodes was present in 10 patients (38.5%). Seventeen (65.4%) patients showed abnormalities at cerebral computerized tomography and/or magnetic resonance imaging and neurological comorbidities were observed in 15.4% of the sample. Stupor, rigidity, staring, negativism, withdrawal, and mutism were observed in more than 90% of patients. At the end of the ECT course, 21 patients (80.8%) were classified as responders. The BFCRS showed the largest percentage of improvement, with an 82% reduction of the initial score. The number of previous mood episodes was significantly lower and the use of anticholinergic and dopamine-agonist medications was significantly more frequent in non-responders than in responders. Conclusions: Our patients with bipolar disorder had predominantly retarded catatonia, frequent previous catatonic episodes, indicating a recurrent course, and high rates of concomitant brain structure alterations. However, ECT was a very effective treatment for catatonia in this patient group that was resistant to benzodiazepines

Electroconvulsive therapy in catatonic patients: Efficacy and predictors of response

Recent evidence favors the view of catatonia as an autonomous syndrome, frequently associated with mood disorders, but also observed in neurological, neurodevelopmental, physical and toxic conditions. From our systematic literature review, electroconvulsive therapy (ECT) results effective in all forms of catatonia, even after pharmacotherapy with benzodiazepines has failed. Response rate ranges from 80% to 100% and results superior to those of any other therapy in psychiatry. ECT should be considered first-line treatment in patients with malignant catatonia, neuroleptic malignant syndrome, delirious mania or severe catatonic excitement, and in general in all catatonic patients that are refractory or partially responsive to benzodiazepines. Early intervention with ECT is encouraged to avoid undue deterioration of the patient's medical condition. Little is known about the long-term treatment outcomes following administration of ECT for catatonia. The presence of a concomitant chronic neurologic disease or extrapyramidal deficit seems to be related to ECT non-response. On the contrary, the presence of acute, severe and psychotic mood disorder is associated with good response. Severe psychotic features in responders may be related with a prominent GABAergic mediated deficit in orbitofrontal cortex, whereas non-responders may be characterized by a prevalent dopaminergic mediated extrapyramidal deficit. These observations are consistent with the hypothesis that ECT is more effective in "top-down" variant of catatonia, in which the psychomotor syndrome may be sustained by a dysregulation of the orbitofrontal cortex, than in "bottom-up" variant, in which an extrapyramidal dysregulation may be prevalent. Future research should focus on ECT response in different subtype of catatonia and on efficacy of maintenance ECT in long-term prevention of recurrent catatonia. Further research on mechanism of action of ECT in catatonia may also contribute to the development of other brain stimulation techniques

Electroconvulsive therapy in 197 patients with a severe, drug-resistant bipolar mixed state: treatment outcome and predictors of response

Abstract OBJECTIVE: We prospectively evaluated the short-term outcome and the predictors of response to electroconvulsive therapy (ECT) in a large sample of patients with a bipolar mixed state. METHOD: From January 2006 to May 2011, we performed an analysis using data obtained from 197 of 203 consecutive patients with a bipolar mixed state, according to DSM-IV-TR diagnostic criteria, who were treated with ECT at the Department of Psychiatry of the University of Pisa. All patients were evaluated prior to and after the ECT course using the Hamilton Depression Rating Scale-17 (HDRS-17), Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impressions (CGI) scale. The CGI subscale "global improvement" and final HDRS-17 and YMRS total scores were used to identify nonresponder, responder, and remitter groups. RESULTS: At the end of the ECT course, 55 patients (27.9%) were considered nonresponders, 82 responders (41.6%), and 60 remitters (30.5%). As expected, at the end of the ECT trial, the CGI-Severity scale (CGI-S; P < .0001), HDRS-17 (P < .0001), and BPRS (P < .0001) scores were significantly lower in remitters than in responders and nonresponders. Using backward stepwise logistic regression, the length of current episode, lifetime comorbidity of obsessive-compulsive disorder, and baseline YMRS total mean score were statistically significant predictors of nonresponse versus remission (P < .0001). CONCLUSIONS: Less than 30% of the patients included in the study were nonresponders to ECT. Long-lasting mixed episode with excitatory symptoms and lifetime comorbidity of obsessive-compulsive disorder significantly predicted a lack of complete remission

Plankton dynamics across the freshwater, transitional and marine research sites of the LTER-Italy Network. Patterns, fluctuations, drivers

A first synoptic and trans-domain overview of plankton dynamics was conducted across the aquatic sites belonging to the Italian Long-Term Ecological Research Network (LTER-Italy). Based on published studies, checked and complemented with unpublished information, we investigated phytoplankton and zooplankton annual dynamics and long-term changes across domains: from the large subalpine lakes to mountain lakes and artificial lakes, from lagoons to marine coastal ecosystems. This study permitted identifying common and unique environmental drivers and ecological functional processes controlling seasonal and long-term temporal course. The most relevant patterns of plankton seasonal succession were revealed, showing that the driving factors were nutrient availability, stratification regime, and freshwater inflow. Phytoplankton and mesozooplankton displayed a wide interannual variability at most sites. Unidirectional or linear long-term trends were rarely detected but all sites were impacted across the years by at least one, but in many case several major stressor(s): nutrient inputs, meteo-climatic variability at the local and regional scale, and direct human activities at specific sites. Different climatic and anthropic forcings frequently co-occurred, whereby the responses of plankton communities were the result of this environmental complexity. Overall, the LTER investigations are providing an unparalleled framework of knowledge to evaluate changes in the aquatic pelagic systems and management options