Clinical and psychopathological correlates of duration of untreated illness (DUI) in affective spectrum disorders.

Affective disorders represent psychopathological entities lying on a continuum, characterized by high prevalence and functional impairment. A delay in treatment initiation might increase the burden associated with affective spectrum disorders. The present study was aimed at analyzing the correlates of a long duration of untreated illness (DUI) in these conditions. We recruited subjects diagnosed with affective disorders, both in- and outpatients, and collected information concerning socio-demographic, clinical, and psychopathological characteristics. Long DUI was defined according to previous research criteria as >2 years for Bipolar Disorders or >1 year for Depressive Disorders. Bivariate analyses were performed to compare subjects with a long and short DUI (p<0.05). A logistic regression was operated to evaluate the correlates of long DUI. In the present sample (n=135), 34.1% (n=46) subjects showed a long DUI. This subgroup presented with more physical comorbidities (p=0.003), higher body mass index (BMI) (p<0.001), more frequent anxiety onset (p=0.018), younger onset age (p=0.042), and more severe depressive symptoms (Hamilton Depression Rating Scale item 1-depressed mood (p=0.032) and item 2-guilt feelings (p=0.018)). At the logistic regression, higher severity of depressed mood (OR 1.568), higher BMI (OR 1.264), and younger age at onset (OR 0.935) were associated with long DUI. The present study confirmed a possible role of DUI as a construct underpinning higher clinical severity in affective spectrum disorders, possibly linked to worse illness course and unfavorable outcomes. Intervention strategies targeting physical comorbidities and depressive symptoms severity may decrease disease burden in subjects with a long DUI.

Sex Differences in Bipolar Disorders: Impact on Psychopathological Features and Treatment Response.

Introduction: Sex differences were demonstrated in bipolar disorders (BD) concerning epidemiological, clinical, and psychopathological characteristics, but consensus is lacking. Moreover, data concerning the influence of sex on treatment response in BD is contrasting. The present cross-sectional study aimed to analyze sex differences in a population of BD subjects, with specific focus on psychopathological features and treatment response. Materials and Methods: Subjects diagnosed with BD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th version (DSM-5) were recruited. Socio-demographic and clinical characteristics were collected. The Hamilton Rating Scale for Depression, the Mania Rating Scale (MRS), the brief version of the Temperament Evaluation of Memphis, Pisa and San Diego-Münster version (briefTEMPS-M), and the Barratt Impulsiveness Scale-11 items (BIS-11) were used for psychopathological assessment. Treatment response was appraised with the Alda Scale. We performed bivariate analyses to compare socio-demographic, clinical, and psychopathological characteristics between men and women (p < 0.05). A logistic regression was run to analyze features that were significantly associated with female sex. Results: Among the recruited 219 BD subjects, 119 (54.3%) were females. Women had a lower scholarity (p = 0.015) and were less frequently employed (p = 0.001). As for psychopathological features, a higher MRS total score (p < 0.001) was detected among women, as well as higher BIS-11 total score (p = 0.040), and briefTEMPS-M score for anxious temperament (p = 0.006). Men showed higher prevalence of DSM-5 mixed features (p = 0.025), particularly during a depressive episode (p = 0.014). Women reported longer duration of untreated illness (DUI) (p < 0.001). There were no sex differences in the Alda Scale total score when considering the whole sample, but this was significantly higher among men (p = 0.030) when evaluating subjects treated with anticonvulsants. At the logistic regression, female sex was positively associated with longer DUI (p < 0.001; OR 1.106, 95% CI 1.050-1.165) and higher MRS total score (p < 0.001; OR 1.085, 95% CI 1.044-1.128) and negatively associated with employment (p = 0.003; OR 0.359, 95% CI 0.185-0.698) and DSM-5 mixed features (p = 0.006; OR 0.391, 95% CI 0.200-0.762). Conclusions: The clinical presentation of BD may differ depending on sex. The severity of BD should not be neglected among women, who may also display worse treatment response to anticonvulsants.

Does Post-Traumatic Spectrum Comorbidity Influence Symptom Severity in Bipolar Disorders? A Cross-Sectional Study in a Real-World Setting.

BACKGROUND: The present cross-sectional study investigates the relationship between post-traumatic spectrum comorbidity and the severity of symptoms in subjects diagnosed with Bipolar Disorders (BD). SUBJECTS AND METHODS: In- and outpatients diagnosed with BD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) were consecutively recruited. Sociodemographic and clinical data were collected. Psychopathology was evaluated by means of the Hamilton Rating Scale for Depression (HAM-D), the Young Mania Rating Scale (YMRS), and the Positive and Negative Syndrome Scale (PANSS). Sociodemographic, clinical and psychopathological characteristics of BD subjects with and without sub-threshold PTSD were compared by means of bivariate analyses (p<0.05). RESULTS: BD subjects with post-traumatic spectrum comorbidity (n=24.49%) presented a significantly higher number of hospitalizations when compared to those who did not present the co-occurrence of the two conditions (2.67±2.3 versus 1.65±2.32, p=0.039). As for treatment features, subjects with subthreshold PTSD were more frequently prescribed benzodiazepines at the moment of evaluation or in the past (n=18, 100% versus n=22.55%, p=0.032). When assessing differences in terms of psychopathological characteristics, subjects with subthreshold PTSD showed higher HAM-D total score (16.22±9.06 versus 10.22±7.23, p=0.032) and higher PANSS negative symptom scale score (16.06±6.92 versus 11.41±4.68, p=0.017). CONCLUSIONS: Findings from the present study suggest that subthreshold PTSD may underpin higher symptom severity and worse outcomes when occurring as a comorbid condition in BD.

Comorbidities, Depression Severity, and Circadian Rhythms Disturbances as Clinical Correlates of Duration of Untreated Illness in Affective Disorders.

Background and Objectives: Affective disorders, namely bipolar (BDs) and depressive disorders (DDs) are characterized by high prevalence and functional impairment. From a dimensional point of view, BDs and DDs can be considered as psychopathological entities lying on a continuum. A delay in treatment initiation might increase the burden associated with affective disorders. The aim of this study is to analyze the correlates of a long duration of untreated illness (DUI) in these conditions. Materials and Methods: Subjects with BDs and DDs, both in- and outpatients, were recruited. Long DUI was defined according to previous research criteria as >2 years for BDs or >1 year for DDs. Socio-demographic, clinical and psychopathological characteristics of the recruited subjects were collected. Bivariate analyses were performed to compare subjects with a long and short DUI (p < 0.05). Results: In our sample (n = 61), 34.4% of subjects presented a long DUI. A long DUI was significantly associated with longer overall illness duration (p = 0.022) and a higher rate of psychiatric (p = 0.048) and physical comorbidities (p = 0.023). As for psychopathological features, depressive symptoms were more severe in the long DUI subgroup, as demonstrated by a higher score at the Clinical Global Impression-severity of depression (p = 0.012) item and at the anxiety/depression factor of the Positive and Negative Syndrome Scale (p = 0.041). Furthermore, subjects with a long DUI displayed more severe disruption of circadian rhythms, as evaluated by the Biological Rhythms Interview for Assessment in Neuropsychiatry total (p = 0.044) and social domain (p = 0.005) scores and by the Hamilton Depression Rating Scale diurnal variation items (18a: p = 0.029, 18b: p = 0.047). Conclusions: A long DUI may underpin higher clinical severity, as well as worse illness course and unfavorable prognosis in affective disorders. Intervention strategies targeting comorbidities, depressive symptoms and circadian rhythms may decrease disease burden in subjects with a long DUI.

The Influence of the Urban Environment on Mental Health during the COVID-19 Pandemic: Focus on Air Pollution and Migration-A Narrative Review.

The coronavirus disease 2019 (COVID-19) pandemic caused a crisis worldwide, due to both its public health impact and socio-economic consequences. Mental health was consistently affected by the pandemic, with the emergence of newly diagnosed psychiatric disorders and the exacerbation of pre-existing ones. Urban areas were particularly affected by the virus spread. In this review, we analyze how the urban environment may influence mental health during the COVID-19 pandemic, considering two factors that profoundly characterize urbanization: air pollution and migration. Air pollution serves as a possibly risk factor for higher viral spread and infection severity in the context of urban areas and it has also been demonstrated to play a role in the development of serious mental illnesses and their relapses. The urban environment also represents a complex social context where minorities such as migrants may live in poor hygienic conditions and lack access to adequate mental health care. A global rethinking of the urban environment is thus required to reduce the impact of these factors on mental health. This should include actions aimed at reducing air pollution and combating climate change, promoting at the same time a more inclusive society in a sustainable development perspective.

Dysphoria as a psychiatric syndrome: a preliminary study for a new transnosographic dimensional approach.

BACKGROUND: We currently define dysphoria as a complex and disorganized emotional state with proteiform phenomenology, characterized by a multitude of symptoms. Among them prevail irritability, discontent, interpersonal resentment and surrender. Dysphoria, in line with the most recent Interpersonal Dysphoria Model, could represent a "psychopathological organizer" of the Borderline Personality Disorder. We would like to extend this theoretical concept to other psychiatric disorders in order to consider dysphoria as a possible psychopathological nucleus, a syndrome on its own. This syndromic vision may open up the possibility of new paths both in the differential diagnosis and in the therapeutic approach to the various disorders. AIMS: The goal of this paper is to understand if the dimensional spectrum that composes dysphoria differs from the different psychiatric disorders. Specifically, we would like to assess if the phenomenological expression of dysphoria differs in patients with Borderline Personality Disorder (BPD), Mixed State Bipolar Disorder (BDM) and Major Depressive Disorder (MDD) through an observational comparative study. SUBJECTS AND METHODS: In this study, 30 adult patients, males and females between the ages of 18 and 65, were enrolled from the Psychiatric Service of the Santa Maria della Misericordia Hospital in Perugia (PG), Italy, from January 1st to June 30th, 2018. The aim was to form 3 groups each one composed of 10 individuals affected respectively with Borderline Personality Disorder (BPD), with Bipolar Disorder, Mixed State (BPM) and Major Depression Disorder (MDD). After a preliminary assessment to exclude organic and psychiatric comorbidity, we administered them the Neapen Dysphoria Scale - Italian Version (NDS-I), a specific dimensional test for dysphoria. Starting from the dataset, with the aid of the statistical program SPSS 20, we have obtained graphs showing the comparison between disorders groups selected and NDS-I total score and subscales (irritability, discontent, interpersonal resentment, surrender). Finally, a comparison was made, taking two groups at a time, between the means of single groups for total scores and for single subscales considered into the NDS-I test. We made it using the Mann-Whitney U test, a nonparametric test with 2 independent samples, by setting a significance level α=0.05. CONCLUSIONS: This study, through a transnosographic-dimensional approach, allowed us to explore dysphoria and its expressions in different psychopathological groups, despite analyzing a small sample. Differences between means of values obtained through NDS-I subscales were statistically significant in patients with BPD, BDM and MDD (p<0.05). Among the latter, the group of BPD patients has greater pervasiveness and severity of dysphoria symptoms.

Consultation-Liaison Psychiatry-from theory to clinical practice: an observational study in a general hospital.

BACKGROUND: To investigate significant association between various clinical and extra-clinical factors brought out the activities of Consultation-Liaison Service. METHODS: Data from all psychiatric consultations for patients admitted to the Perugia General Hospital and carried out over a 1-year period (from July the 1st 2009 to June the 30th 2010) were collected by a structured clinical report including: socio-demographic features, features of referrals, features of back-referrals. T-test, Mann-Whitney U-test, χ(2)-test and Fischer's were statistically used. RESULTS: 1098 consultations were performed. The consultations carried out the Emergency Unit were excluded from the study. The type and the reasons for the referrals were discussed such as the ICD-10 diagnosis and the liaison interventions too. Significant associations emerged between gender and: social status and occupation (p < 0.05 and p < 0.01 respectively). Clinical sector related with reason for referral (p < 0.01), type of consultation (p < 0.01), liaison investigations (p < 0.01) and long-term treatment plan after hospital discharge (p < 0.01). The ICD-10 psychiatric diagnosis (Schizophrenia, Affective Syndrome and Neurotic-StressSomatoform Syndrome) was associated with social status (p < 0.01), social condition (p < 0.01), consultation type (p < 0.01), advice (p < 0.01) and reason for consultation (p < 0.01). CONCLUSIONS: The need for better physical and psychological investigation is confirmed in order to promote not only disease remission but overall wellbeing.

Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: results and lessons of an underpowered randomised clinical trial.

BACKGROUND: As lithium treatment might be effective in reducing the risk of deliberate self-harm (DSH) in adult patients with unipolar affective disorders, we designed a pragmatic randomised trial to assess its efficacy in more than 200 patients with treatment-resistant depression. However, we randomised 56 patients only. The aim of this report is therefore twofold: first, to disseminate the results of this underpowered study which may be incorporated into future meta-analytical reviews; second, to analyse some critical aspects of the study which might explain failure to reach the target sample size. METHODS: We carried out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode were allocated to add lithium to usual care (intervention arm) versus usual care alone (control arm). Suicide completion and acts of DSH during the 12 months of follow-up constituted the composite primary outcome. RESULTS: Of 58 patients screened for inclusion, 29 were allocated to lithium plus usual care and 27 were assigned to usual care without lithium. Six patients in the lithium plus usual care group and seven in the usual care group committed acts of DSH during the follow-up phase. The survival probability did not differ between the two treatment arms (Chi2 = 0.17, p =0.676). With regard to changes in the severity of depressive symptomatology from baseline to endpoint, no significant differences were detected. CONCLUSIONS: The present study failed to achieve the minimum sample size needed to detect a clinically meaningful difference between the two treatment arms. Consequently, the finding that lithium, in addition to usual care, did not exert a positive effect in terms of reduction of DSH after 12 months of follow-up is likely due to the lack of sufficient statistical power to detect a difference, if a difference existed. The dissemination of the results of this underpowered study will inform future meta-analytical reviews on lithium and suicide-related outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550.

Resilience and depressive disorders.

INTRODUCTION: There is considerable variability in the response of individuals to adverse environmental conditions, while some develop psychiatric illnesses like depression, others seem very capable of dealing with it. It is in this observation that the concepts of vulnerability and resilience are rooted. METHODS: We conducted a review of the literature by inserting in PubMed the keywords resilience, vulnerability and depressive disorders. DISCUSSION AND CONCLUSIONS: Freud formerly used the so-called crystal-principle to describe the concept of vulnerability: according to this, the different psychopathologies would arise depending on the different psychological weaknesses, just like a crystal thrown to the ground shatters along its lines of cleavage intrinsic to it, albeit invisible. The term resilience has been borrowed from physics where it is used to describe the ability of a material to withstand impact without cracking. In psychology, the term resilience refers to a complex and dynamic multidimensional construct, which derives from the interaction of neurobiological, social and personal factors and indicates the ability to adaptively cope with stress and adversity, preserving a normal physical and psychological functioning. Resilience has proven to be a protective factor against the development of psychiatric disorders such as depression. Making a conceptual leap, the concepts of vulnerability and resilience can be related to the psychodynamic classification of depression postulated by Gaetano Benedetti, who distinguished four kinds of depression: the first due to the failure of the ego, the second to the perversion of the superego, the third to the inhibition of the Id and the fourth to the collapse of the ego ideal. It is possible to improve the resilience of depressed subjects through pharmacological and psychotherapeutic interventions.

Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: a protocol for a randomised, independent, pragmatic, multicentre, parallel-group, superiority clinical trial.

BACKGROUND: Data on therapeutic interventions following deliberate self harm (DSH) in patients with treatment-resistant depression (TRD) are very scant and there is no unanimous consensus on the best pharmacological option for these patients. There is some evidence that lithium treatment might be effective in reducing the risk of completed suicide in adult patients with unipolar affective disorders, however no clear cut results have been found so far. The primary aim of the present study is to assess whether adding lithium to standard therapy is an effective treatment strategy to reduce the risk of suicidal behaviour in long term treatment of people with TRD and previous history of DSH. METHODS/DESIGN: We will carry out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode will be allocated to add lithium to current therapy (intervention arm) or not (control arm). Following randomisation, treatment is to be taken daily for 1 year unless some clear reason to stop develops. Suicide completion and acts of DSH during the 12 months of follow-up will constitute the composite primary outcome. To preserve outcome assessor blindness, an independent adjudicating committee, blind to treatment allocation, will anonymously review all outcome events. DISCUSSION: The results of this study should indicate whether lithium treatment is associated with lower risk of completed suicide and DSH in adult patients with treatment resistant unipolar depression, who recently attempted suicide. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550.

Axonal injury within language network in primary progressive aphasia.

Primary progressive aphasia (PPA) is characterized by an isolated progressive impairment of word use and comprehension reflecting the distribution of pathological processes within the left hemisphere. We used proton magnetic resonance spectroscopy (1H-MRS) to study in vivo the integrity of axonal fibers connecting perisylvian language areas in 11 patients with PPA, 11 subjects with Alzheimer's disease, and 22 controls. Brain metabolites (N-acetylaspartate, myoinositol, choline, creatine) were measured bilaterally within a volume of interest located in the central portion of the superior longitudinal fasciculus, a long associative bundle connecting Broca's area with Wernicke's area, and other language regions of the temporal lobe. In the PPA group, there was an asymmetrical N-acetylaspartate to creatine ratio reduction compared with Alzheimer's disease and controls, with greater changes on the left side. The myoinositol to creatine ratio was increased in the PPA group bilaterally compared with controls. The choline to creatine ratio did not differ among the three groups. These results indicate an asymmetrical focal axonal injury within the language network in PPA. The marked difference in the distribution of N-acetylaspartate to creatine between PPA and Alzheimer's disease suggests that proton magnetic resonance spectroscopy may help to differentiate between these two conditions.