Neuroplasticita' nei disturbi dell'umore

INTRODUZIONE: Studi di neuroanatomia, osservazioni condotte sul cervello post-mortem e ricerche di neuroimaging in vivo suggeriscono che la compromissione della neuroplasticità a livello di specifiche reti neuronali può essere coinvolta nella patogenesi dei disturbi dell’umore. In particolare, studi recenti hanno sottolineato il ruolo di un fattore neurotrofico denominato Brain Derived Neurotrophic Factor (BDNF), la cui deplezione è associata a riduzione della neurogenesi e del volume di importanti aree cerebrali tra cui l’ippocampo, la corteccia e l’amigdala. Altre ricerche hanno riscontrato concentrazioni ridotte di BDNF nel sangue di pazienti depressi e un successivo incremento a seguito di trattamento con farmaci antidepressivi o con l’elettroconvulsione. In questa ottica, i disturbi dell’umore, da sempre interpretati come un disordine della neurotrasmissione, trovano un loro substrato anatomico e neurobiologico. SCOPO DELLA TESI: Il presente studio si propone di indagare la relazione fra i livelli plasmatici di BDNF in pazienti depressi e le caratteristiche cliniche del disturbo al fine di ricercare le dimensioni psicopatologiche più rappresentative del core neurobiologico della depressione. MATERIALI E METODI: Sono stati reclutati 36 pazienti affetti da Depressione Maggiore in accordo con i criteri del DSM-IV-TR afferenti alla Clinica Psichiatrica dell’Università di Pisa. Le valutazioni cliniche sono state effettuate con la Mini International Neuropsychiatric Interview (MINI), la Hamilton Rating Scale for Depression (HAM-D) e la Clinical Global Impressions (CGI). L’analisi dei livelli di BDNF è stata effettuata tramite un apposito kit ELISA. RISULTATI: E’ stata evidenziata una correlazione negativa significativa fra la gravità della malattia, valutata per mezzo del punteggio totale HAM-D, ed il livello plasmatico di BDNF. Lo stesso si è verificato con i punteggi dei fattori “rallentamento psicomotorio” e “disturbi cognitivi” della HAM-D. A livello comparativo, i pazienti più gravi sulla base della CGI presentavano livelli di BDNF significativamente più bassi rispetto ai meno gravi. Anche i pazienti con episodi ricorrenti di depressione presentavano livelli di BDNF significativamente più bassi rispetto a quelli con episodio singolo. Infine, i pazienti con la presenza di sintomi dissociativi e quelli con maggiore compromissione del pattern ipnico presentavano livelli di BDNF significativamente più bassi. CONCLUSIONI: L’esistenza di un legame fra bassi livelli di BDNF e la gravità, la ricorrenza ed alcuni dei sintomi più caratteristici della depressione quali i disturbi del sonno ed i deficit a livello psicomotorio e cognitivo sembrerebbe confermare l’ipotesi neurotrofica dei disturbi dell’umore e aprire interessanti prospettive nell’impiego del BDNF plasmatico come biomarker utile nello studio della patologia depressiva

Comparing re‐hospitalisation rates in a real‐world naturalistic 24‐month follow‐up of psychotic patients with different treatment strategies: Oral versus LAI antipsychotics

AIM & BACKGROUND Non-adherence to antipsychotic treatment is a major issue in the management of severe psychiatric disorders, because it is usually related to future relapses and re-hospitalisations. Long-Acting-Injection (LAI) antipsychotics can be useful to increase treatment adherence in these patients. The aim of the present study was to compare the re-hospitalisation rates of psychotic patients discharged from a psychiatric ward and then, divided into three groups upon the treatment received: LAI antipsychotic, oral antipsychotic at home or oral antipsychotic administered daily by psychiatric nurse staff as patients lived in a long-term care facility. METHODS Data on all inpatients consecutively admitted to the Psychiatric Unit of the Nuovo Ospedale Apuano (Massa, Italy), between January 2017 and December 2018, were obtained by the registration record system. Information about eventual re-hospitalisations of these patients, occurred within a 24-month timeframe since discharge, were collected from the same database. RESULTS In a Kaplan-Meyer analysis, patients treated with LAI antipsychotics showed significantly lower re-hospitalisation rates in the first 24 months after discharge than those treated with oral ones. CONCLUSIONS This study highlights the impact of LAI antipsychotics in preventing re-hospitalisation in severe psychotic patients at high risk in a naturalistic setting. The benefits appear relevant also with respect to a controlled long-term oral antipsychotic treatment, however, further studies are needed to develop more tailored intervention strategies in such complex psychiatric population

Presence and correlates of autistic traits among patients with social anxiety disorder

IntroductionDue to their similar behavioral presentation, it can sometimes be challenging to distinguish between a social anxiety disorder (SAD) and the social avoidance that is frequently described in autism spectrum disorder (ASD). Moreover, a growing body of evidences is reporting that a significant proportion of subjects with ASD also meet the requirements for SAD and, vice versa, subjects with SAD tend to exhibit a higher prevalence of autistic traits.AimIn this framework, the current study aims to evaluate prevalence and correlates of autistic traits in a sample of adult subjects diagnosed with SAD and healthy controls (HC), also evaluating which autism spectrum dimensions may statistically predict higher SAD symptoms.Methods56 subjects with a clinical diagnosis of SAD and 56 gender and age matched HC were recruited from the Psychiatric Clinic of the University of Pisa. Subjects were assessed with the SCID-5, the Social Anxiety Spectrum – Short Version (SHY- SV) and the Adult Autism Subthreshold Spectrum (AdAS Spectrum).ResultsSAD group scored significantly higher in all AdAS Spectrum and SHY-SV domains and total score compared to the HC group with no significant gender difference. SHY-SV total and domain scores, were strongly and positively and strongly correlated with all AdAS Spectrum domains and total score. AdAS Spectrum total score and Childhood/Adolescence, Non-Verbal Communication, Empathy and Restricted interests and Rumination domain scores score were significant predictors of higher SHY-SV score.ConclusionOur results confirm the link between SAD and autistic traits also in adult population, describing not only high levels of autistic traits in SAD adults, but also significant correlations between many core features of the two disorders and a predictive role of autistic traits on higher SAD symptoms

Adult Autism Subthreshold Spectrum (AdAS Spectrum): validation of a questionnaire investigating subthreshold autism spectrum

Increasing epidemiological and genetic studies have raised the issue of a clinical and etiological continuity between Autism Spectrum Disorder (ASD) and autistic traits in non-clinical populations. In this perspective, still disregarded by the DSM-5, autistic traits are conceptualized as both cardinal and associated features of ASD, continuously distributed in the general population and used to characterize the so-called Broad Autism Phenotype (BAP), frequently found among relatives of people with autism. A growing body of works have also documented higher rates of mental disorders in relatives of autistic patients with respect to healthy control subjects, suggesting that autistic traits in different domains of functioning, including subclinical and atypical features, could play a significant role in raising the risk for mental disorders as well as for suicidality. At the same time, some studies have also hypothesized that a psychiatric comorbidity may happen to mask ASD, especially in subjects with normal intelligence and moderate ASD symptoms. Recent literature, in fact, has highlighted a possible link between ASD and Eating Disorders (EDs) with some authors even suggesting that autistic traits may manifest as Anorexia Nervosa in females. In line with these studies, the presence of subclinical and often undetected forms of ASD among patients seeking for treatment for other mental disorders could be of potentially clinical significance needing an appropriate diagnosis and treatment. Consistently, increasing literature suggests the usefulness of dimensional approaches to autism. In the framework of the so-called Spectrum Project, an Italian–American collaboration research project (www.spectrumproject.org), a spectrum approach has been proposed that encompasses not only clinical features associated with the DSM mental disorders, but also isolated and atypical symptoms, as well as subthreshold symptom clusters, personality traits and behavioral manifestations that may precede, follow or be manifested in concurrence with DSM mental disorders. The present study aimed to determine the psychometric properties of the Adult Autism Subthreshold Spectrum (AdAS Spectrum), a new questionnaire specifically tailored to assess subthreshold forms of Autism Spectrum Disorder (ASD), that includes 160 items, coded in a dichotomously (yes/no), organized into seven domains. The data were collected between Maj 2015 and April 2016 at 7 Italian University Departments of Psychiatry, coordinated by the University of Pisa: Brescia, Catania, Florence, Naples, Pavia and Siena. A total sample of 405 subjects were enrolled, in particular: 102 adults endorsing at least one DSM-5 symptom criterion for ASD (ASDc), 143 adults diagnosed with Feeding and Eating Disorders (FED) and 160 subjects with no current or lifetime mental disorders (CTL). All subjects were also administered the Structured Clinical Interview for DSM-5 Axis-I disorders (SCID-5), the Autism Quotient (AQ), the Ritvo Autism and Asperger Diagnostic Scale 14-item version (RAADS-14). The AdAS Spectrum demonstrated excellent overall internal consistency (Kuder–Richardson’s coefficient=.964), as well as for five out of seven AdAS Spectrum domains (>.90), and sound test-retest reliability (Intraclass Correlation Coefficient=.976). The total and domain AdAS Spectrum scores showed a moderate to strong (>.50) positive correlation with one another and with the AQ and the RAADS-14 total scores. ASDc subjects reported significantly higher AdAS Spectrum total scores than both FED (p<.001) and CTL (p<.001), and reported significantly higher scores on the Childhood/adolescence, Verbal communication and Restricted interests and rumination domains (all p<.001) of the AdAS Spectrum, compared to FED, while on all the domains compared to CTL. These latter also displayed significantly lower total and domain scores than FED (all p<.001). Two Receiver Operating Characteristic (ROC) analyses found the best cut-off scores to identify either subjects endorsing only one DSM-5 ASD symptom criterion or those endorsing two of them. The two cut-off values assuring an excellent balance between sensitivity and specificity were 45 (sensitivity = 0.706, specificity = 0.769) and 60 (sensitivity = 0.971, specificity = 0.887), respectively. In conclusion, we found excellent internal consistency and test-retest reliability, strong convergent validity with alternative dimensional measures of autism. As expected, the questionnaire performed differently among the three diagnostic groups explored

Quality of Life, Depression, and Anxiety in Patients with Uveal Melanoma: A Review

The aim is to summarize current knowledge on both QoL and depressive/anxious symptoms in patients with UM, including studies on the effect on QoL and psychological status of genetic testing related to the risk of metastatic disease. A review from the last 25 years by using the databases "PsycInfo," "Medline," and "Science Direct" was performed. As a total result, eighteen papers were retrieved. Eight studies (44.4%) used a prospective design methodology: two were retrospective observations (11.1%), three were cross-sectional observational studies (16.6%), and three (16.6%) were naturalistic follow-up studies. One trial was conducted with a case-control design (5.5%), and one was a methodological paper (5.5%). The number of subjects included in the studies ranged widely, between 7 and 842 (mean: 152.1 ± 201.3), for a total of 2587 patients, 1306 males (50.5%) and 1281 females (49.5%). The mean age of subject enrolled was 61.3 ± 4.1 years. Twenty-six different scales, questionnaires, or interviews were utilized. No significant differences in QoL between radiotherapy and enucleation emerged. Genetic testing did not significantly affect QoL or psychological status

Life events (Loss and traumatic) and emotional responses to them in acute catastrophe survivors and long-lasting heroin use disorder patients never exposed to catastrophic events

Background. Symptoms of PTSD denote alterations in several neurobiological systems, including the opioid system. In a previous study on methadone-treated heroin use disorder (HUD) patients, we demonstrated strong correlations between the severity and progression of HUD and the subsequently greater severity of PTSD spectrum symptoms, so suggesting a unitary perspective. Methods. A comparative cross-sectional study was carried out to evaluate post-traumatic spectrum reactivity to loss and traumatic events in three groups: acute catastrophic event survivors experiencing (N=77) and the same number not experiencing PTSD (N=77), and a third group, of long-lasting HUD subjects who had never been exposed to catastrophic events (N=77). Results. To obtain an index of the magnitude of emotional response to losses and traumatic events, we conducted a preliminary ROC analysis on the TALS-SR total scores observed in our L’Aquila 2009 earthquake database, after having classified subjects as PTSD and No-PTSD (according to the SCID-questionnaire). That analysis determined the cut-off value required to ensure the best balance between sensitivity and specificity. The percentage of subjects who were over the threshold in the HUD group proved to be very similar to that observed in the PTSD earthquake survivors group [51 (66.2%) vs 56 (72.7%), Chi-square=0.49, p=.484], whereas it turned out to be significantly higher than that observed in the No-PTSD earthquake survivors group [51 (66.2%) vs 11 (14.3%), Chisquare= 41.07, p<.001]. Furthermore, the discriminant analysis utilizing TALS-SR domain scores as predictive variables failed to discriminate between the HUD group and the PTSD earthquake group, whereas it appears to clearly differentiate the No-PTSD earthquake group from the other two. Conclusions. This study, besides providing evidence of similarities in the type of reaction shown to loss and to traumatic events between HUD patients and earthquake survivors with PTSD, also supports the probable implication of the opioid system in the aetio(patho)logy of PTSD

Predictors of recurrence during long-term treatment of bipolar I and II disorders. A 4 year prospective naturalistic study

Background Despite the large number of treatments available for bipolar disorder (BD), more than one half of patients have a recurrence within 2 years, and over 90% experience at least one additional affective episode during their lifetime. Methods The aim of this study was to test the impact of a number of demographic and clinical features on the risk to recurrence in a real- word representative sample of 266 outpatients with BD-I or II treated in a naturalistic setting during a 4-years-follow-up period. Results We found that the number of episodes per year after study entry, compared to the number of episodes per year before study entry,significantly decreased and that about one third of patients had no recurrences during the observation period. The length of follow-up and the number of previous episodes, mainly depressive, predicted the risk of recurrence, while female gender, higher age at intake, and a higher frequency of past mixed episodes predicted a higher frequency of recurrences. Limitations The study had some limitations to consider: i.e. the risk of poor reliability of information on the previous course of illness or the naturalistic treatment during the follow-up. Conclusions Our study suggests that (a) an evidence-based long-term treatment, with regular follow-up visits could improve the course of disease and prognosis; (b) clinicians should carefully consider the presence of a high number of mixed episodes, to provide more targeted treatment strategies; (c) an appropriate use of antidepressants in selected patients did not worsen the course of illness

Lifetime mania is related to post-traumatic stress symptoms in high school students exposed to the 2009 L'Aquila earthquake

Background Bipolar patients seem to be at high risk of trauma exposure and, when exposed, of PTSD. When comorbid, PTSD has shown a negative impact on the course of the bipolar illness. Conversely, a correlation between even manic symptoms and an increased risk for suicide has also been reported in PTSD patients. The aim of this study was to investigate the relationships between lifetime mood spectrum symptoms and PTSD in a sample of earthquake survivors. Methods A total of 475 young adults who survived the L’Aquila 2009 earthquake, 21 months earlier, were assessed by the Moods Spectrum-Self Report (MOODS-SR) and the Trauma and Loss Spectrum Self Report (TALS-SR). Results Significantly higher MOODS-SR and TALS-SR domain scores were found in PTSD survivors compared to those without. The mood depressive (O.R. = 1.17, 95% CI: 1.10–1.25), cognition depressive (O.R. = 1.07, 95% CI: 1.01–1.14) and energy manic (O.R. = 1.13, 95% CI: 1.02–1.25) MOODS-SR domains were significantly associated with an increased likelihood of PTSD. Conclusions Our data corroborate the strong relationship between mood disorder and PTSD highlighting a relationship between lifetime depressive and manic symptoms and PTSD, with a particular impact of the latter on the number of traumatic exposures and maladaptive behaviors

Impact of Mood Spectrum Spirituality and Mysticism Symptoms on Suicidality in Earthquake Survivors with PTSD

The aim of the present study was to explore the correlations between Spirituality/Mysticism/Psychoticism symptoms and suicidality in young adult survivors of the L’Aquila earthquake. The sample included 475 subjects recruited among high school seniors who had experienced the April 6, 2009, earthquake. Assessments included: Trauma and Loss Spectrum–Self Report and Mood Spectrum–Self Report (MOODS-SR). Mysticism/Spirituality dimension and suicidality were evaluated by means of some specific items of the MOOD-SR. The Spirituality/Mysticism/Psychoticism MOODS-SR factor score was significantly higher among subjects with PTSD diagnosis with respect to those without. Similarly, subjects with suicidal ideation, as well as those who committed a suicide attempt, reported significantly higher scores than those without