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BackgroundHeterogeneity in cognitive functioning among major depressive disorder (MDD) patients could have been the reason for the small-to-moderate differences reported so far when it is compared to other psychiatric conditions or to healthy controls. Additionally, most of these studies did not take into account clinical and sociodemographic characteristics that could have played a relevant role in cognitive variability. This study aims to identify empirical clusters based on cognitive, clinical and sociodemographic variables in a sample of acute MDD patients.MethodsIn a sample of 174 patients with an acute depressive episode, a two-step clustering analysis was applied considering potentially relevant cognitive, clinical and sociodemographic variables as indicators for grouping.ResultsTreatment resistance was the most important factor for clustering, closely followed by cognitive performance. Three empirical subgroups were obtained: cluster 1 was characterized by a sample of non-resistant patients with preserved cognitive functioning (n = 68, 39%); cluster 2 was formed by treatment-resistant patients with selective cognitive deficits (n = 66, 38%) and cluster 3 consisted of resistant (n = 23, 58%) and non-resistant (n = 17, 42%) acute patients with significant deficits in all neurocognitive domains (n = 40, 23%).ConclusionsThe findings provide evidence upon the existence of cognitive heterogeneity across patients in an acute depressive episode. Therefore, assessing cognition becomes an evident necessity for all patients diagnosed with MDD, and although treatment resistant is associated with greater cognitive dysfunction, non-resistant patients can also show significant cognitive deficits. By targeting not only mood but also cognition, patients are more likely to achieve full recovery and prevent new relapses.

La malaltia mental Depressió Major es caracteritza per forts sentiments de tristesa, apatia i un seguit de dèficits cognitius, com problemes de memòria o lentitud. A més, s'ha vist que la percepció pròpia que poden tenir el pacients sobre aquests dèficits afecta també la seva productivitat laboral i qualitat de vida. Investigadors de Parc Taulí - UAB han analitzat la relació entre aquests dèficits cognitius i la percepció dels pacients juntament amb els factors que hi intervenen. La enfermedad mental Depresión Mayor se caracteriza por fuertes sentimientos de tristeza, apatía y de problemas cognitivos, como fallos en la memoria o lentitud. Además, se ha visto que la percepción propia que puedan tener los pacientes sobre estos problemas afecta también su productividad laboral y calidad de vida. Investigadores de Parc Taulí - UAB han analizado la relación entre estos problemas cognitivos y la percepción de los pacientes junto a los factores que intervienen en esta relación.

Altres ajuts: This work was supported partly by a non-competitive grant from the Health Department of the Generalitat de Catalunya (PREDI-NU project, European Alliance Against Depression, 2016); Fondo Europeo de Desarrollo Regional, Unión Europea, Una manera de hacer Europa, CIBERSAM, Secretaria d'Universitats. Background : Childhood maltreatment increases the risk of suicide attempts in the general population, possibly having similar effects among patients with major depressive disorder (MDD). The few studies that have addressed this association have been restricted to specific populations (e.g. treatment-resistant depression, personality disorders) and have rarely taken sex into account. Objective : To examine the impact of childhood maltreatment on suicide attempts among MDD patients above and beyond other risk factors and potential confounders, while considering potential sex-specific effects. Methods : The study assessed 165 patients with a principal diagnosis of MDD. Neurological alterations, psychiatric comorbidities, and drug abuse were reasons for exclusion. Logistic regressions using the whole sample, and divided by sex, were run to test the association between childhood maltreatment and history of suicide attempts, controlling for symptom severity, comorbidities, and treatment-resistant depression. Results : There was a significant and clinically relevant association between childhood maltreatment and history of suicide attempts in the total sample. Patients with childhood maltreatment were 3.01 times more likely to present a history of suicide attempts than patients without childhood maltreatment. A family history of psychiatric disorders also contributed to the variance of attempted suicide, but its interaction with childhood maltreatment was not statistically significant. When testing the model separately, the effect of childhood maltreatment on suicide attempts remained for females, whereas for males, age of MDD onset and Childhood Trauma Questionnaire minimization-denial scale were predictive variables. Conclusions : Childhood maltreatment is a clear predictor of suicidal behaviour among MDD patients, and this effect remains significant after controlling for potential confounders. Also, the sex of patients emerges as a relevant factor that may model the mechanisms underlying the prediction of suicide attempts. Since suicide is the main cause of premature death among MDD patients, interventions targeting childhood maltreatment should be included in preventive and clinical strategies.

Introducció El trastorn depressiu major (TDM), caracteritzat per sentiments de tristesa i/o apatia, malestar físic i dèficits cognitius, presenta un 50% de recaigudes i un 20% de cronificació. Les teories etiològiques més integradores postulen que les alteracions de matèria gris i els dèficits cognitius facilitarien la recurrència/cronifiació del episodi. No obstant, les àrees afectades són inconsistents entre els estudis, complicant la millora dels tractaments. A més, les estratègies terapèutiques per als pacients resistents als tractaments (DRT) són escasos, afetcant generalment la cognició, i dificultant una complerta recuperació. Així, es requereixen noves vies d'estudi centrades en la prevenció de la recurrència/cronificació dels pacients a través de la detecció de variables predictores individuals que optimitzin les opcions terapèutiques. Objectius E1: Investigar l'afectació de matèria gris cerebral en diferents estadis de la malaltia depressiva i determinar l'efecte de les carcateristiques clíniques en el seu volum. E2: Determinar els canvis metabòlics cerebrals que ocorren al aturar l'estimulació cerebral profunda (ECP) del cortex cingulat anterior subgenual (CASg) en pacients amb DRT. E3: Evaluar les funcions cognitives en pacients amb DRT abans i després de l'ECP del còrtex CASg). E4: Examinar el potencial predictiu de les dades cliniques i de neuroimatge estructural en el curs del TDM. Mètodes Es compara el volum de matèria gris (VMG) entre pacients amb TDM en diferents estadis de la malaltia amb controls sans a través de la tècnia de morfometria basada en el voxel (E1). Els pacients ressonats es contacten als 5 anys i es divideixen en 4 grups segons l'evolució clínica que han tingut. Es fa un anàlisi de regressió amb les dades cliniques i de neuroimatge basals com a variables predictores del curs observat (E3). Finalment s'administra una bateria neuropicològica abans i després de l'ECP del CAsg en pacients amb DRT, agafant com a grup control pacients amb un primer episodi (E2). A més, se'ls realitza una tomografia per emissió de positrons després d'un període d'estabilitat clínica amb el neuroestimulador on versus off. Resultats Els pacients amb DRT exhibien menor VMG frontotemporal. El VMG en l'insula dreta i el cortex prefrontal medial dret correlaciona negativament amb la duració de la malaltia (E1). En el tercer estudi s'observà que el VMG explicava un 20% més de variància que les dades clíniques soles a l'hora de predir el curs clínic dels pacients, essent el gir cingulat anterior l'àrea amb més poder predictiu. Aquesta àrea, a més, mostra un descens en la seva activitat metabòlica quan s'apaga el neuroestimulador en pacients amb DRT que havien respòs clinicament (E2). Per últim, l'ECP no empitjora cap funció cognitiva en aquests pacients i l'evaluació neuropsicològica mostra una millora mnèsica posterior a l'intervenció (E3). Conclusions Els pacients amb DRT tenen menors VMG frontotemporolimbics, els quals estan associats amb la durada de malaltia, suggerint efectes nocius del trastorn depressiu per se en la matèria gris. A més, el VMG tindria un valor afegit a la informació purament clínica a l'hora de predir la resposta clínica dels pacients a llarg termini. La part dorsal del còrtex cingulat anterior dret es relaciona amb la resposta al tractament. Finalment, l'estudi neuropsicològic dóna suport a la seguretat cognitiva de ECP del CASg, contribuïnt en la seva implantació com a alternativa terapèutica pels pacients amb DRT. Limitacions El seguiment de primers episodis respondria millor si les reduccions de VMG són resultat de la depressió o si ja estaven presents d'un inici, incidint en el curs del trastorn. Quant a l'estudi longitudinal, la diferència en l'estadi del TDM basal podria ser un factor confusor. En l'estudi neuropsicològic i metabòlic dels pacients intervinguts caldria tenir en compte el reduït tamany de la mostra., Introduction Major depressive disorder (MDD) is characterized by feelings of sadness and/or apathy, physical disturbances and cognitive impairment. After the first episode, 50% of patients relapse and up to 20% become chronic. Current etiological theories postulate that structural alterations and cognitive impairments would ease recurrence and chronicity. However, the brain areas implied are inconsistent throughout studies, hindering the characterization of MDD pathophysiological models and slowing the finding of new treatments. In addition, therapeutic strategies for patients with treatment resistant depression (TRD) are scarce and generally have a negative impact on cognition, preventing them from a complete recovery. Thus, new studies determining individual variables predicting clinical trajectories such as chronicity are needed. Objectives: E1: To investigate structural brain abnormalities at different stages of the illness and to determine the effect of clinical characteristics on brain GMV. E2: To determine the cerebral metabolism changes during a switch-off of electrical stimulation in implanted patients with TRD who had achieved clinical improvement. E3: To evaluate cognitive function of TRD patients before and after DBS of the SCG. E4: To examine the prognostic potential of clinical and sMRI data in the long-term clinical outcomes of MDD. Methods Voxel-based morphometry (VBM) was used to compare 66 MDD patients at different illness stages with 32 healthy controls. GMV were also correlated with patients clinical characteristics (E1). 66 MDD patients were contacted at 5 years after MRI scan and split in 4 groups depending on their clinical trajectories during that time (n=49). Regression analysis with clinical and neuroimaging data as predictive variables and clinical outcomes as dependent variable was carried out (E4). Finally, a neuropsychological battery was administered before and after DBS of subgenual cingulate gyrus (SCG) in TRD patients, with a control group of first episode patients (E3). In addition, clinically stable TRD patients underwent a positron emission tomography (PET) analysis comparing active versus inactive DBS (E2). Results VBM showed a significant group effect in right superior frontal gyrus, left medial frontal gyrus and left cingulate gyrus. Patients whose condition was treatment resistant/chronic exhibited the smallest volumes in frontotemporal areas. Longer illness duration was negatively correlated with decreases in right medial frontal cortex and left insula (E1). Third study showed that GMV explained a 20% more of variance when joined to clinical characteristics predicting long-term clinical outcomes. Anterior cingulate gyrus was the area adding more value to the prediction. In addition, such cingulate area showed a metabolic decrease in TRD patients who were clinically stable when the stimulation was stopped. Finally, neuropsychological assessment of TRD patients show no impairment of cognitive functioning after DBS, but a memory improvement (E2). Conclusions Frontotemporolimbic areas were smaller in the patients with severe depression and were associated with duration of illness, but not with medication patterns, suggesting negative effects of long-lasting MDD on grey matter. In addition, GMV may demonstrated an added value to clinical information of depressive patients in terms of predicting their long-term clinical outcome (E4). Right dorsal anterior cingulate gyrus seems to be closely related to treatment response (E2). Finally, neuropsychological performance of patients after DBS (E3) supported the cognitive safety of this new technique adding a valuable information for its future implementation as a therapeutic alternative for TRD patients. Limitations A longitudinal study would be more appropriate to ascertain whether volume reductions in chronic patients are a result of enduring MDD effects or the cause of a more severe disorder. Regarding the longitudinal study (E4), differences in illness stage at baseline could lead to confusion. The results of second and third study should be interpreted cautiously given the small sample size.