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Serra, Francesca (2018) The assessment of mood disorders: new methodological perspectives for
differential diagnosis.
[Ph.D. thesis]

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Abstract (english)

This dissertation work aims to provide new methodological perspectives in the assessment of mood disorders, with the main task of suggesting effective solutions for the evaluation of major depressive episode (MDE), in order to support the differential diagnosis of different forms of depression.
Mood disorders are the most prevalent of all mental health diagnoses and their incidence has increased in recent decades, becoming one of the most significant public health problem. Many people fail to go to school or university, lose their jobs, lose their partner and friends, and may commit suicide. The course of these disorders as well as their prognosis are closely related to proper diagnosis and well-timed treatment. Despite this, the risk of misdiagnosis is currently high, with serious consequences both for the current episode and for the course of the illness. In particular, the MDE is often classified without specification, also if there are different possible configurations of symptoms that characterize it. Thus, MDE is almost always treated with antidepressant drugs that in some cases (e.g., agitated depression) may increase the symptoms of agitation and the risk of suicide.
The assessment phase plays a crucial role for the proper treatment of the disorder. Physicians after collecting patients information, need to formulate diagnostic hypotheses in a short time to plan effective clinical interventions. The quality of clinical evaluation is crucial for both diagnosis and treatment.
Formal Psychological Assessment (FPA; Spoto, 2011; Spoto, Bottesi, Sanavio & Vidotto) is a methodology able to maximize the benefits of both semi-structured interviews and self-reports, trying to overcome their limitations. Indeed, the FPA methodological approach allows the construction of:
- Tools that are able to provide qualitative information about patient symptoms that goes beyond the numerical score.
- Tools that are able to differentiate patients who obtain the same score, but replied to different items, and therefore have different symptoms configurations.
- Adaptive tools (as semi-structured interviews) that allow investigating and deepening the patients symptoms.
- Rapid administration as self-report questionnaires.
In this three-year project at the University of Padua, the FPA concepts have been applied to achieve different aims.
In a first phase, a methodological analysis of the most used self-report questionnaires of depression was carried out to explore their ability to investigate all the symptoms of the MDE. The research is based on the relationship between items and diagnostic criteria for depression, in line with the FPA methodology. In the second phase, a new self-report questionnaire of 41 items was built on the basis of 23 clinical criteria for MDE from DSM-5 and literature.
In the third phase, the same questionnaire was validated on non-clinical sample of 265 individuals and clinical sample of 38 patients with MDE diagnosed with major depression or bipolar disorder. The questionnaire provided good results both in terms of validity and reliability. However, the strength of this tool stands in its ability to go beyond the numerical score, allowing to differentiate individuals with the same score but with different symptoms and possibly different severity of the episode. This property is assured by the patients clinical state (the fundamental concept of FPA) as the main output of the test, which is the set of items the individual replied affirmatively with the subset of symptoms investigated by those items. In this way, clinical evaluation will not only be related to the level of depression obtained from the score but also to the specific configuration of symptoms manifested by the individual.
In the fourth phase of the research, the computerized algorithm was implemented in the new questionnaire to obtain the adaptive form of the tool. The questionnaire was subdivided into its three sub-scales (affective, somatic and cognitive) corresponding to the three sub factors of the factorial structure. For each sub-scale, through the probability model of the FPA (i.e. the Basic Local Independent Model; BLIM) the false negative, false positives for each item and all the clinical states of the structure were estimated. An interactive procedure was used with maximum likelihood, which provided an estimate of parameters and fit indexes. After being tested on real data, the adaptive form of the tool allows faster and more efficient administration. Indeed, the items to which the individual will respond will depend on previous responses, in a process that mimics the semi-structured interview, avoiding possible logical inferences of the clinician. The new tool called quantitative and qualitative evaluation of Depressive Symptomatology (QuEDS) can be a support for clinicians; in fact, it differentiates the individual's depressive symptoms beyond the score and allows administering only the items related to its symptomatology following the logical flow of question-answer. Thus, two patients who obtain the same score on the test can be treated differently according to their symptoms, since answering the same number of items does not mean responding to the same items. In particular, it is well known that the use of antidepressant drugs is not always recommended in depression. There are mixed depressions, as defined by many authors, because they are characterized by both depressive symptoms and manic symptoms (such as agitation, anguish, irritability, insomnia, mood lability). Two examples of mixed depression are agitated depression and depression with flight of ideas, in which antidepressant drugs not only increase the excitatory component (manic symptoms) worsening the course of the affective episode but, more seriously, increase the risk of suicide. For this reason, understanding all depressive symptoms is crucial in clinical practice.
The last part of this project was carried out in England, in collaboration with the University of Cardiff and Worcester, in particular with the Bipolar Disorder Research Network (BDRN). The BDRN data used in this research include 3750 mood disorders patients divided into three subgroups: Major Depressive Disorder (MDD), Bipolar Disorder Type I (BD-I) and Bipolar Disorder Type II (BD-II). The 29.3% of the whole sample had suffered from an episode of agitated depression (AD), particularly AD was more related to bipolar disorder, especially BD-II. Moreover, patients with agitated depression had higher comorbidities with panic disorder and substance abuse, made greater use of psychiatric drugs, and suffer of more mixed states in lifetime. Agitated depression was related to lifetime suicide attempts and suicidal ideation during the affective episode. These results confirm and strengthen the indications of several other studies on smaller clinical samples. The recognition and differential diagnosis of mixed depression is essential to avoid improper treatment with dangerous consequences.
The construction of tools to support clinicians task providing the patient symptom configuration with more clinical information can become a strength in clinical practice.
The tool presented in this work represents a step in this direction; however, to allow differential diagnosis of each MDE, this step needs to be combined to the experience and awareness of the clinician in the field of mood disorders, and especially to the development of further insights in the methodological context. Indeed, as the data demonstrate, the recognition of mixed depression is a difficult task both from a clinical and from a methodological point of view in relation to the construction of suitable and exhaustive instruments. The fundamental issue that remains unclear concerns the ability to investigate the symptoms of manic component that are underestimated by the patient itself (such as racing crowed thought, mood lability etc.) during depression phase.
The first three Chapters form the theoretical framework, and the starting point for the researches. In the first Chapter, mood disorders are described: prevalence, genetic component, diagnostic classification (major depression, dysthymia, bipolar disorder I, bipolar disorder II, cyclotymic disorder, and rapid-cycle disorder); Also depression is described, followed by mixed depression and the differential diagnosis. Finally, the pharmacological treatment and the etiopathogenetic theories of depression are briefly explained. The second Chapter describes the assessment, therefore the tools most used by the clinician with their strengths and weaknesses; The CBA 2.0 (Cognitive Behavioral Assessment) and Adaptive Assessment are also described. The third Chapter is devoted to the explanation of FPA starting from the mathematical theories to the implementation of the method in the clinical context. Chapters 4, 5, 6, 7 describe the four main researches carried out in this PhD project. To conclude, Chapter 8 will present the final discussion.

Abstract (italian)

Il presente lavoro di tesi si propone di offrire nuove prospettive metodologiche nell'assessment dei disturbi dell'umore, con l'obiettivo principale di suggerire alternative efficaci alla valutazione dell'episodio depressivo maggiore, nell'ottica di sostenere la diagnosi differenziale di diverse forme di depressione.
I disturbi dell'umore sono il più frequente disturbo mentale e la loro incidenza è aumentata negli ultimi decenni, diventando uno dei più significativi problemi sociosanitari. Perdita del lavoro, divorzio, difficoltà  nel crescere i figli e abuso di sostanze sono solo alcuni dei gravi rischi associati ai disturbi dell'umore. Il suicidio è la più tragica delle conseguenze. Il decorso di questi disturbi così come la loro prognosi sono strettamente legati alla corretta diagnosi e al tempestivo trattamento. Purtroppo, attualmente è molto alto il rischio di diagnosi non corretta, con gravi ripercussioni sul trattamento e quindi sul decorso della malattia. In particolare l'episodio depressivo maggiore viene troppo spesso classificato in un solo modo e senza specificazioni, nonostante le possibili diverse configurazioni di sintomi che lo caratterizzano. Come tale esso viene trattato con farmaci antidepressivi, che in alcuni casi (ad esempio la depressione agitata) possono non solo aumentare i sintomi di agitazione, ma anche aumentare il rischio di suicidio.
La fase di assessment riveste un ruolo cruciale in vista di un trattamento adeguato del disturbo. I medici dopo aver raccolto il maggior numero possibile di informazioni sul paziente, devono formulare ipotesi diagnostiche in breve tempo per pianificare interventi clinici efficaci. La qualità  della valutazione clinica è fondamentale sia per la diagnosi che per il trattamento.
Il Formal Psychological Assessment (FPA; Spoto, 2011; Spoto, Bottesi, Sanavio & Vidotto, 2013) si configura come una metodologia che unisce i vantaggi delle interviste semi-strutturate e dei self-report, cercando di superare i loro limiti. Infatti l'approccio metodologico dell'FPA permette la costruzione di strumenti:
- In grado di restituire delle informazioni qualitative, relative ai sintomi del paziente, che vanno oltre lo score numerico.
- In grado di differenziare pazienti che ottengono lo stesso punteggio al test, ma che hanno risposto a item diversi, e che hanno quindi configurazioni diverse di sintomi.
- Adattivi (come le interviste semi-strutturate) che permettono di indagare le aree sintomatologiche del paziente e di approfondirle.
- Di rapida somministrazione come i questionari self-report.
Nel progetto svolto in questi tre anni all'Università di Padova, sono stati utilizzati i concetti dell'FPA in diverse fasi.
In una prima fase è stata svolta un'analisi metodologica dei questionari self-report più utilizzati nel campo della depressione per esplorare la loro capacità di indagare tutti i sintomi dell'episodio depressivo maggiore. La ricerca si è basata sulle relazioni tra gli item e i criteri diagnostici per la depressione, in linea con la metodologia dell'FPA.
Nella seconda fase, è stato costruito un nuovo questionario di 41 item sulla base di 23 criteri clinici per l'episodio depressivo maggiore, ricavati dal DSM-5, e dalla diffusa letteratura sulla depressione.
Nella terza fase il questionario è stato validato su una popolazione non clinica di 265 individui e su una popolazione clinica di 38 pazienti con episodio depressivo maggiore diagnosticati con depressione maggiore o disturbo bipolare. Il questionario ha mostrato buoni risultati sia per i diversi criteri di validità  che per l'affidabilità. Tuttavia, la peculiarità  di questo strumento sta nella sua capacità  di andare oltre lo score numerico, permettendo di differenziare individui con lo stesso punteggio al test ma che presentano diverse sintomatologie. Questa proprietà è garantita dallo stato clinico del paziente (concetto fondamentale dell'FPA), come principale output del test, ossia dall'insieme di item a cui l'individuo ha risposto affermativamente con il sotto-insieme di sintomi indagati da quegli item. In questo modo la valutazione clinica non sarà  solo legata al livello di depressione ottenuto dallo score, ma dalla configurazione specifica di sintomi manifestati da una precisa persona.
Nella quarta fase della ricerca, è stato implementato l'algoritmo computerizzato per il nuovo questionario, in modo da ottenere la forma adattiva dello strumento. Per raggiungere quest'ultimo step, il questionario è stato suddiviso nelle sue tre sotto-scale (affettiva, somatica e cognitiva) corrispondenti ai tre
sotto-fattori della struttura fattoriale. Per ogni sotto-scala, attraverso il Basic Local Independent Model (BLIM), modello probabilistico dell'FPA, sono stati stimati i parametri relativi alle probabilità di falso positivo, falso negativo per ogni item e di tutti gli stati clinici della struttura. E' stata utilizzata una procedura interattiva per massima verosimiglianza, che ha fornito una stima dei parametri e degli indici di fit. Una volta testato sui dati reali, la forma adattiva dello strumento permette una somministrazione più rapida ed efficiente. Infatti, gli item a cui l'individuo dovrà  rispondere dipenderanno dalle risposte precedentemente date, in un processo che imita l'intervista semi-strutturata, evitando possibili inferenze logiche del clinico. Il nuovo strumento per l'assessment della depressione chiamato QuEDS (Quantitative and Qualitative Evaluation of Depressive Symptomatology) rappresenta quindi un supporto per lo psichiatra o lo psicoterapeuta, in quanto offre la possibilità di distinguere i sintomi depressivi di ogni individuo al di là dello score ottenuto al test, e permette di somministrare solo gli item legati alla sua sintomatologia seguendo il flusso logico di domanda-risposta. Dunque due pazienti che ottengono lo stesso punteggio al test, indice dello stesso potenziale livello di depressione, potranno essere trattati comunque in accordo con i loro sintomi; infatti aver risposto allo stesso numero di item non significa aver risposto agli stessi item. In particolare è noto che l'uso di farmaci antidepressivi non è sempre consigliato nella depressione. Esistono infatti le depressioni miste, così definite da moltissimi autori, perchè caratterizzate sia da sintomi depressivi che da sintomi maniacali (come agitazione, angoscia, irritabilità, insonnia, labilità  emotiva). Due esempi di depressione mista sono la depressione agitata e la depressione con fuga delle idee, in cui i farmaci antidepressivi non solo aumentano la componente eccitatoria (quindi i sintomi maniacali) peggiorando il decorso della malattia ma, problema ancora più grave aumentano il rischio di suicidio. Per questo motivo capire tutta la sintomatologia depressiva risulta fondamentale nella pratica clinica. L'ultima parte del progetto di questi tre anni, è stata svolta in Inghilterra, in collaborazione con le Università di Cardiff e Worcester, in particolare con Il Bipolar Disorder Research Network (BDRN). I dati del BDRN utilizzati in questa ricerca comprendono 3750 pazienti con disturbi dell'umore divisi nei tre sotto-gruppi: Disturbo Depressivo Maggiore (MDD), Disturbo Bipolare di tipo I (BD-I) e Disturbo Bipolare di tipo II (BD-II); nel 29,3% dell'intero campione era presente un episodio di depressione agitata, in particolare la depressione agitata era più presente nel disturbo bipolare, soprattutto BD-II.
Inoltre i pazienti con depressione agitata avevano più comorbidità con disturbo di panico e con abuso di sostanze, facevano maggior uso di psicofarmaci, e soffrivano di maggiori episodi misti durante l'arco di vita. La depressione agitata era correlata ai tentati suicidi durante l'arco di vita e all'ideazione suicidaria durante l'episodio affettivo. Questi risultati confermano e rafforzano le indicazioni di diversi altri studi svolti su campioni clinici meno ampi. Il riconoscimento e la diagnosi differenziale della depressione mista è essenziale per evitare una diagnosi scorretta e un successivo trattamento pericoloso.
La costruzione di strumenti di supporto al medico, che siano in grado di restituire la configurazione di sintomi del paziente e di garantire maggiori informazioni cliniche può diventare un punto di forza nella pratica clinica. Lo strumento presentato in questo lavoro, rappresenta un passo avanti in questa direzione; tuttavia per permettere una diagnosi differenziale dell'episodio depressivo questo primo step ha bisogno di essere accompagnato dall'esperienza e la consapevolezza del clinico nel campo dei disturbi dell'umore, e soprattutto dallo sviluppo di ulteriori approfondimenti nel contesto metodologico. Infatti come i dati dimostrano, riuscire a catturare i sintomi di una depressione mista risulta un'impresa ardua sia dal punto di vista clinico che dal punto di vista metodologico per quanto concerne la costruzione di strumenti adatti ed esaustivi. La questione fondamentale che resta aperta, riguarda la capacità di riuscire ad indagare quei sintomi di componente maniacale che vengono sottostimati dal paziente stesso (come il flusso rapido dei pensieri, la labilità  emotiva ecc.) in fase depressiva.
I primi tre capitoli di questo lavoro formano la cornice teorica, e il punto di partenza per la ricerca. Nel primo capitolo sono infatti descritti nel dettaglio i disturbi dell'umore: la prevalenza, la componente genetica, la classificazione dei vari disturbi (Depressione Maggiore, Distimia, Disturbo Bipolare I, Disturbo Bipolare II, Disturbo Ciclotimico, e disturbo a cicli rapidi); inoltre viene descritta la depressione, e in seguito la depressione mista con particolare attenzione alla diagnosi differenziale. Infine viene brevemente spiegato il trattamento farmacologico e le teorie eziopatogenetiche della depressione.
Nel secondo capitolo viene descritto l'assessment, quindi gli strumenti maggiormente utilizzati con i loro punti di forza e di debolezza; vengono inoltre descritti la batteria CBA 2.0 (Cognitive Behavioural Assessment 2.0), e l'assessment adattivo. Il terzo capitolo è dedicato alla spiegazione dell'FPA a partire dalle teorie matematiche sulle quali si fonda fino alla realizzazione del metodo nel contesto clinico. I capitoli 4, 5, 6, 7 descrivono le quattro ricerche principali di questo progetto di dottorato. Infine nel capitolo 8 sarà presentata la discussione finale dell'intero percorso.

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EPrint type:Ph.D. thesis
Tutor:Vidotto, Giulio
Supervisor:Altoe, Gianmarco
Ph.D. course:Ciclo 30 > Corsi 30 > SCIENZE PSICOLOGICHE
Data di deposito della tesi:11 January 2018
Anno di Pubblicazione:2018
Key Words:Valutazione psicodiagnostica, FPA, validazione strumento, Depressione, stati misti, diagnosi differenziale, tool validation, Assessment, Formal Psychological Assessment, Depression, mixed states, differential diagnosis
Settori scientifico-disciplinari MIUR:Area 11 - Scienze storiche, filosofiche, pedagogiche e psicologiche > M-PSI/03 Psicometria
Struttura di riferimento:Centri > Centro Interdipartimentale di servizi di Psicologia
Dipartimenti > Dipartimento di Psicologia Generale
Codice ID:10616
Depositato il:25 Oct 2018 16:59
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