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Recurrence in major depressive disorder (MDD) is common, but neurobiological models capturing vulnerability for recurrences are scarce. Disturbances in multiple resting-state networks have been linked to MDD, but most approaches focus on stable (vs. dynamic) network characteristics. We investigated how the brain's dynamical repertoire changes after patients transition from remission to recurrence of a new depressive episode. Sixty two drug-free, MDD-patients with ≥2 episodes underwent a baseline resting-state fMRI scan when in remission. Over 30-months follow-up, 11 patients with a recurrence and 17 matched-remitted MDD-patients without a recurrence underwent a second fMRI scan. Recurrent patterns of functional connectivity were characterized by applying Leading Eigenvector Dynamics Analysis (LEiDA). Differences between baseline and follow-up were identified for the 11 non-remitted patients, while data from the 17 matched-remitted patients was used as a validation dataset. After the transition into a depressive state, basal ganglia-anterior cingulate cortex (ACC) and visuo-attentional networks were detected significantly more often, whereas default mode network activity was found to have a longer duration. Additionally, the fMRI signal in the basal ganglia-ACC areas underlying the reward network, were significantly less synchronized with the rest of the brain after recurrence (compared to a state of remission). No significant changes were observed in the matched-remitted patients who were scanned twice while in remission. These findings characterize changes that may be associated with the transition from remission to recurrence and provide initial evidence of altered dynamical exploration of the brain's repertoire of functional networks when a recurrent depressive episode occurs.
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Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Depressão , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Recompensa , Mapeamento EncefálicoRESUMO
In line with the Research Domain Criteria (RDoC) , we set out to investigate the brain basis of psychopathology within a transdiagnostic, dimensional framework. We performed an integrative structural-functional linked independent component analysis to study the relationship between brain measures and a broad set of biobehavioral measures in a sample (n = 295) with both mentally healthy participants and patients with diverse non-psychotic psychiatric disorders (i.e. mood, anxiety, addiction, and neurodevelopmental disorders). To get a more complete understanding of the underlying brain mechanisms, we used gray and white matter measures for brain structure and both resting-state and stress scans for brain function. The results emphasize the importance of the executive control network (ECN) during the functional scans for the understanding of transdiagnostic symptom dimensions. The connectivity between the ECN and the frontoparietal network in the aftermath of stress was correlated with symptom dimensions across both the cognitive and negative valence domains, and also with various other health-related biological and behavioral measures. Finally, we identified a multimodal component that was specifically associated with the diagnosis of autism spectrum disorder (ASD). The involvement of the default mode network, precentral gyrus, and thalamus across the different modalities of this component may reflect the broad functional domains that may be affected in ASD, like theory of mind, motor problems, and sensitivity to sensory stimuli, respectively. Taken together, the findings from our extensive, exploratory analyses emphasize the importance of a dimensional and more integrative approach for getting a better understanding of the brain basis of psychopathology.
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Transtorno do Espectro Autista , Transtornos Mentais , Humanos , Encéfalo/diagnóstico por imagem , Psicopatologia , Transtornos de Ansiedade , Imageamento por Ressonância Magnética/métodosRESUMO
Cognitive theories of depression hold that negative contextual triggers (e.g., stressful events) induce more negative and less positive mood, in turn instigating negatively biased memories. However, context-related variability in mood and emotional memory has received insufficient attention, while the dynamic interaction between these factors plays a crucial role in the kindling of new depressive episodes. Experience Sampling Method (ESM) for repeated, daily life measures of context, mood, and autobiographic emotional memory was used in 46 currently depressed, 90 remitted-depressed, and 55 never-depressed individuals. Currently depressed individuals showed strongest negative processing style and never-depressed most positive, with remitted-depressed patients scoring intermediate. The moderated mediation model indicated that context appraisal had a direct effect on the appraisal of the recalled event (i.e., our operationalization of emotional memory), which was mediated by positive (but hardly by negative) mood and was independent of depression status. This mediation strength was relatively similar to the strength of the direct effect of context on memory. Results are in line with cognitive theories of depression. Especially context seems important for emotional memory. The association between context, mood, and memory, however, may be independent of depression status. Yet, the "level" of mood, context, and event appraisal does depend on depression status. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Depressão , Memória Episódica , Humanos , Depressão/psicologia , Emoções , Afeto , Rememoração MentalRESUMO
Repetitive negative thinking (RNT) captures an important transdiagnostic factor that predisposes to a maladaptive stress response and contributes to diverse psychiatric disorders. Although RNT can best be seen as a continuous symptom dimension that cuts across boundaries from health to various psychiatric disorders, the neural mechanisms underlying RNT have almost exclusively been studied in health and stress-related disorders, such as depression and anxiety disorders. We set out to study RNT from a large-scale brain network perspective in a diverse population consisting of healthy subjects and patients with a broader range of psychiatric disorders. We studied 46 healthy subjects along with 153 patients with a stress-related and/or neurodevelopmental disorder. We focused on three networks, that are associated with RNT and diverse psychiatric disorders: the salience network, default mode network (DMN) and frontoparietal network (FPN). We investigated the relationship of RNT with both network connectivity strength at rest and with the stress-induced changes in connectivity. Across our whole sample, the level of RNT was positively associated with the connectivity strength of the left FPN at rest, but negatively associated with stress-induced changes in DMN connectivity. These findings may reflect an upregulation of the FPN in an attempt to divert attention away from RNT, while the DMN result may reflect a less flexible adaptation to stress, related to RNT. Additionally, we discuss how our findings fit into the non-invasive neurostimulation literature. Taken together, our results provide initial insight in the neural mechanisms of RNT across the spectrum from health to diverse psychiatric disorders.
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BACKGROUND: Electroconvulsive therapy (ECT) is a potent option for treatment-resistant major depressive disorder (MDD). Cognitive models of depression posit that negative cognitions and underlying all-or-nothing negative schemas contribute to and perpetuate depressed mood. This study investigates whether ECT can modify negative schemas, potentially via memory reactivation, and whether such changes are related to MDD symptom improvement. METHOD: Seventy-two patients were randomized to either an emotional memory reactivation electroconvulsive therapy (EMR-ECT) or control memory reactivation electroconvulsive therapy (CMR-ECT) intervention prior to ECT-sessions in a randomized controlled trail. Emotional memories associated with patients' depression were reactivated before ECT-sessions. At baseline and after the ECT-course, negative schemas and depression severity were assessed using the Dysfunctional Attitude Scale (DAS) and Hamilton Depression Rating Scale HDRS. Mediation analyses were used to examine whether the effects of ECT on HDRS-scores were mediated by changes in DAS-scores or vice versa. RESULTS: Post-ECT DAS-scores were significantly lower compared to baseline. Post-ECT, the mean HDRS-score of the whole sample (15.10 ± 8.65 [SD]; n = 59) was lower compared to baseline (24.83 ± 5.91 [SD]). Multiple regression analysis showed no significant influence of memory reactivation on schema improvement. Path analysis showed that depression improvement was mediated by improvement of negative cognitive schemas. CONCLUSION: ECT is associated with improvement of negative schemas, which appears to mediate the improvement of depressive symptoms. An emotional memory intervention aimed to modify negative schemas showed no additional effect.
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Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Eletroconvulsoterapia , Cognição , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Resistente a Tratamento/terapia , Humanos , Escalas de Graduação Psiquiátrica , Resultado do TratamentoRESUMO
Self-referent negative memory bias is a known risk factor for depression, but recent evidence suggests its function as a transdiagnostic cognitive depressotypic marker. The amygdala's sensitivity for negative information is considered a neurobiological depressotypic marker. However, their relationship remains unknown. We transdiagnostically investigated the association between the amygdala's sensitivity, self-referent negative memory bias and its two components: negative endorsement bias and negative recall bias. Patients (n= 125) with (multimorbid) stress-related and neurodevelopmental psychiatric disorders and healthy controls (n= 78) performed an fMRI task to assess the amygdala's sensitivity for negative information and a task outside the scanner for the biases. Linear regression models assessed their associations. The left amygdala's sensitivity for negative information was significantly positively associated with negative recall bias in patients, but not controls. There were no significant associations with self-referent negative memory bias or negative endorsement bias or between the two depressotypic markers. Thus, the left amygdala's sensitivity for negative information may be considered a neural marker of negative memory bias across psychiatric diagnoses. Further research on the interactons with known determinants such as genetic predisposition is required to fully understand the relationship between the amygdala's sensitivity for negative information and these biases.
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Tonsila do Cerebelo , Transtornos Mentais , Tonsila do Cerebelo/diagnóstico por imagem , Viés , Cognição , Humanos , Transtornos Mentais/diagnóstico por imagem , Rememoração MentalRESUMO
Tricyclic antidepressants (TCAs) are frequently prescribed in case of non-response to first-line antidepressants in Major Depressive Disorder (MDD). Treatment of MDD often entails a trial-and-error process of finding a suitable antidepressant and its appropriate dose. Nowadays, a shift is seen towards a more personalized treatment strategy in MDD to increase treatment efficacy. One of these strategies involves the use of biomarkers for the prediction of antidepressant treatment response. We aimed to summarize biomarkers for prediction of TCA specific (i.e. per agent, not for the TCA as a drug class) treatment response in unipolar nonpsychotic MDD. We performed a systematic search in PubMed and MEDLINE. After full-text screening, 36 papers were included. Seven genetic biomarkers were identified for nortriptyline treatment response. For desipramine, we identified two biomarkers; one genetic and one nongenetic. Three nongenetic biomarkers were identified for imipramine. None of these biomarkers were replicated. Quality assessment demonstrated that biomarker studies vary in endpoint definitions and frequently lack power calculations. None of the biomarkers can be confirmed as a predictor for TCA treatment response. Despite the necessity for TCA treatment optimization, biomarker studies reporting drug-specific results for TCAs are limited and adequate replication studies are lacking. Moreover, biomarker studies generally use small sample sizes. To move forward, larger cohorts, pooled data or biomarkers combined with other clinical characteristics should be used to improve predictive power.
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Antidepressivos Tricíclicos , Transtorno Depressivo Maior , Antidepressivos/uso terapêutico , Antidepressivos Tricíclicos/uso terapêutico , Biomarcadores , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Nortriptilina/uso terapêuticoRESUMO
INTRODUCTION: Each year almost 800.000 people die from suicide, of which up to 87% are affected by major depressive disorder (MDD). Despite the strong association between suicidality and MDD, it remains unknown if suicidal symptoms during remission put remitted recurrent MDD patients (rrMDD) at risk for recurrence. METHODS: At baseline we compared sociodemographic characteristics and suicidal symptoms in un-medicated rrMDD participants to matched never-depressed controls. We used the HDRS17 and IDS-SR30 to assess suicidal symptoms and depressive symptomatology. Next, we studied the longitudinal association between baseline suicidal symptoms and time to recurrence(s) in rrMDD during a 2.5-year follow-up period using cox regression analyses. Further, we studied with longitudinal data whether suicidal symptoms and depressive symptomatology were cross-sectionally associated using mixed model analysis. RESULTS: At baseline, rrMDD participants (N = 73) had higher self-reported suicidal symptoms than matched never-depressed controls (N = 45) (χ2 = 12.09 p < .002). Self-reported suicidal symptoms were almost four times higher (27.9% versus 6.9%) compared to clinician-rated suicidal symptoms in rrMDD at baseline. Self-reported baseline suicidal symptoms, but not clinician-rated symptoms, predicted earlier MDD-recurrence during follow-up, independent of other residual depressive symptoms (χ2 = 7.26, p < .026). Higher suicidal symptoms were longitudinally related to higher depressive symptoms (HDRS17; F = 49.87, p < .001), IDS-SR30; (F = 22.36, p < .001). CONCLUSION: This study showed that self-reported - but not clinician-rated - suicidal symptoms persist during remission in rrMDD and predict recurrence, independent from residual symptoms. We recommend to monitor both suicidal and depressive symptomatology during remission in rrMDD, preferably also including self-reported questionnaires apart from clinician-rated. It would be beneficial for future research to assess suicidality using questionnaires primarily designed for measuring suicidal ideation.
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Transtorno Depressivo Maior , Suicídio , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Autorrelato , Ideação Suicida , Inquéritos e QuestionáriosRESUMO
Patients with attention-deficit/hyperactivity disorder (ADHD) often develop early onset substance use disorder (SUD) and show poor treatment outcomes. Both disorders show similar reward-processing alterations, but it is unclear whether these are associated with familial vulnerability to SUD. Our aim was to investigate effects of family history of SUD (FH) on reward processing in individuals with and without ADHD, without substance misuse. Behavioural and functional magnetic resonance imaging (fMRI) data from a modified monetary incentive delay task were compared between participants with and without FH (FH positive [FH+]: n = 76 and FH negative [FH-]: n = 69; 76 with ADHD, aged 16.74 ± 3.14, 82 males), while accounting for continuous ADHD scores. The main analysis showed distinct positive association between ADHD scores and reaction times during neutral versus reward condition. ADHD scores were also positively associated with anticipatory responses of dorsolateral prefrontal cortex, independent of FH. There were no main FH effects on brain activation. Yet, FH+ participants showed distinct neural alterations in ventrolateral prefrontal cortex (VLPFC), dependent on ADHD. This was driven by positive association between ADHD scores and VLPFC activation during reward outcome, only in FH+. Sensitivity analysis with stricter SUD index showed hyperactivation of anterior cingulate cortex for FH+, independent of ADHD, during reward anticipation. There were no FH or ADHD effects on activation of ventral striatum in any analysis. Findings suggest both FH and ADHD effects in circuits of reward and attention/memory during reward processing. Future studies should examine whether these relate to early substance use initiation in ADHD and explore the need for adjusted SUD prevention strategies.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Motivação , Recompensa , Transtornos Relacionados ao Uso de Substâncias/diagnóstico por imagemRESUMO
(1) Background: Current evidence-based treatments for alcohol use disorder (AUD) are moderately effective. Studies testing repetitive transcranial magnetic stimulation (rTMS) in AUD commonly apply a limited number of rTMS sessions with different rTMS settings, showing inconsistent effects on craving for alcohol. This study tested the efficacy of a robust rTMS protocol on craving and alcohol use. (2) Methods: In a single-blind randomized controlled trial in recently detoxified patients with AUD, ten days of high-frequency rTMS over the right dorsolateral prefrontal cortex on top of treatment as usual (n = 14) was compared with sham rTMS (n = 16). Outcome measures were alcohol craving and use over a follow-up period of one year. Analysis was performed by means of repeated measures multivariate analysis of variance. (3) Results: The results showed a main group-by-time interaction effect on craving (Wilks' Λ = 0.348, F (12, 17) = 2.654, p = 0.032) and an effect of group on alcohol use (Wilk's Λ = 0.44, F (6, 23) = 4.9, p = 0.002), with lower alcohol craving and use in the group with active rTMS compared to the control group. Differences in craving between groups were most prominent three months after treatment. At 12 months follow-up, there was no effect of rTMS on craving or abstinence. (4) Conclusions: This small-scale randomized controlled trial showed the efficacy of high-frequency rTMS over the right dlPFC diminished alcohol craving and use in recently detoxified patients with AUD during the first months after detoxification. These findings suggest that rTMS might be an effective add-on in treating patients with AUD and warrant replication in future large-scale studies.
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ABSTRACTWith an annual incidence of about 1.5 million new infections, HIV is an ongoing public health concern. Sexual transmission risk behavior (STRB) is a main driver of the HIV epidemic in most Western countries, particularly among specific populations such as men who have sex with men (MSM). This quasi-experimental pilot study examined the effectiveness of a ten-session group intervention, aiming to reduce STRB among a high-risk subpopulation of MSM living with HIV. Self-reported STRB, impulsivity, mental health symptoms, and functional impairment were compared between the intervention group (n = 12) and a control group (n = 16). At baseline, participants in the intervention group had higher levels of STRB, impulsivity, mental health problems, and functional impairment, compared to the control group. A significant time-by-group interaction effect revealed that after the intervention, STRB, impulsivity, and functional impairment reduced in the intervention group to levels comparable to the control group. These findings suggest that a targeted behavioral intervention might be an effective strategy to reduce persistent STRB and related factors in MSM living with HIV. Future studies should confirm these findings in larger samples, using randomized designs.
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Infecções por HIV , Minorias Sexuais e de Gênero , Infecções por HIV/epidemiologia , Homossexualidade Masculina/psicologia , Humanos , Masculino , Projetos Piloto , Assunção de Riscos , Comportamento Sexual/psicologiaRESUMO
OBJECTIVES: Depression and ADHD often co-occur and are both characterized by altered attentional processing. Differences and overlap in the profile of attention to emotional information may help explain the co-occurence. We examined negative attention bias in ADHD as neurocognitive marker for comorbid depression. METHODS: Patients with depression (n = 63), ADHD (n = 43), ADHD and depression (n = 25), and non-psychiatric controls (n = 68) were compared on attention allocation toward emotional faces. The following eye-tracking indices were used: gaze duration, number of revisits, and location and duration of first fixation. RESULTS: Controls revisited the happy faces more than the other facial expressions. Both the depression and the comorbid group showed significantly less revisits of the happy faces compared to the ADHD and the control group. Interestingly, after controlling for depressive symptoms, the groups no longer differed on the number of revisits. CONCLUSION: ADHD patients show a relative positive attention bias, while negative attention bias in ADHD likely indicates (sub)clinical comorbid depression.
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Transtorno do Deficit de Atenção com Hiperatividade , Viés de Atenção , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Depressão/epidemiologia , Depressão/psicologia , Tecnologia de Rastreamento Ocular , Expressão Facial , HumanosRESUMO
INTRODUCTION: Substance use disorders (SUDs) among physicians affect their health, quality of life, but potentially also their quality of care. Despite the availability of effective specific Physician Health Programs (PHPs), physicians with SUD often experience barriers when seeking professional help. Therefore, we studied barriers and facilitators when seeking help for SUD among physicians from a multiple perspective approach. METHODS: A qualitative design was adopted for 2 sub-studies. First, answers of 2 open-ended questions (about anticipated barriers and facilitators) of an existing questionnaire were analyzed. This questionnaire was filled out by 1,685 general physicians (response rate = 47%). The answers of these open-ended questions were coded inductively. Second, 21 semi-structured interviews (about experienced barriers and facilitators) were performed with physician SUD-patients, significant others, and PHP employees. Themes identified in the first sub-study were used to deductively code the interview transcripts. Results were reported in accordance with the Consolidated Criteria for Reporting Qualitative Research guidelines. RESULTS: Barriers were found at the level of the individual physician (negative feelings and lack of disease awareness), whereas facilitators were found at the level of social relationships (confrontation with SUD and social support) and health services (supportive approach, good accessibility, and positive image of services). The interviews emphasized the importance of nonjudgmental confrontation by social relationships in the process of seeking help for SUD. CONCLUSION: Physicians with SUD face barriers when seeking help for SUD mostly at the level of the individual physician. Health services and people around physicians with SUD could facilitate the help-seeking process by offering confidential and nonpunitive support. Future studies should explore whether the barriers and facilitators identified in this study also hold for other mental health issues.
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Médicos , Transtornos Relacionados ao Uso de Substâncias , Humanos , Pesquisa Qualitativa , Qualidade de Vida , Apoio Social , Transtornos Relacionados ao Uso de Substâncias/terapiaRESUMO
BACKGROUND: Classic theories posit that depression is driven by a negative learning bias. Most studies supporting this proposition used small and selected samples, excluding patients with comorbidities. However, comorbidity between psychiatric disorders occurs in up to 70% of the population. Therefore, the generalizability of the negative bias hypothesis to a naturalistic psychiatric sample as well as the specificity of the bias to depression, remain unclear. In the present study, we tested the negative learning bias hypothesis in a large naturalistic sample of psychiatric patients, including depression, anxiety, addiction, attention-deficit/hyperactivity disorder, and/or autism. First, we assessed whether the negative bias hypothesis of depression generalized to a heterogeneous (and hence more naturalistic) depression sample compared with controls. Second, we assessed whether negative bias extends to other psychiatric disorders. Third, we adopted a dimensional approach, by using symptom severity as a way to assess associations across the sample. METHODS: We administered a probabilistic reversal learning task to 217 patients and 81 healthy controls. According to the negative bias hypothesis, participants with depression should exhibit enhanced learning and flexibility based on punishment v. reward. We combined analyses of traditional measures with more sensitive computational modeling. RESULTS: In contrast to previous findings, this sample of depressed patients with psychiatric comorbidities did not show a negative learning bias. CONCLUSIONS: These results speak against the generalizability of the negative learning bias hypothesis to depressed patients with comorbidities. This study highlights the importance of investigating unselected samples of psychiatric patients, which represent the vast majority of the psychiatric population.
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Depressão , Reversão de Aprendizagem , Transtornos de Ansiedade/epidemiologia , Depressão/epidemiologia , Humanos , Punição , RecompensaRESUMO
Patients with attention-deficit/hyperactivity disorder (ADHD) are often diagnosed with comorbid substance misuse (SM), which is associated with poor treatment efficacy. Although literature indicates similar inhibitory control deficits in both conditions, it is unclear whether SM in ADHD exaggerates pre-existing deficits, with additive or distinct impairments in patients. Our aim was to examine SM effects on inhibitory control in ADHD. Behavioural and functional magnetic resonance imaging (fMRI) data from a stop-signal task were compared across ADHD patients with and without SM (ADHD + SM and ADHD-only, respectively) and controls (n = 33/group; 79 males, mean age 18.02 ± 2.45). To limit substance use disorder (SUD) trait effects, groups were matched for parental SUD. Overall, we found worse performance for ADHD-only and/or ADHD + SM compared with controls but no difference between the ADHD groups. Moreover, the ADHD groups showed decreased frontostriatal and frontoparietal activity during successful and failed stop trials. There were no differences between the ADHD groups in superior frontal nodes, but there was more decreased activation in temporal/parietal nodes in ADHD-only compared with ADHD + SM. During go-trials, ADHD + SM showed decreased activation in inferior frontal nodes compared with ADHD-only and controls. Findings during response inhibition showed deficits in inhibition and attentional processes for ADHD patients with and without SM. Despite no evidence for SM effects during response inhibition, results during go-trials suggest distinct effects on nodes that are associated with several executive functions. Future studies should investigate whether distinct deficits in ADHD + SM relate to poor treatment results and can direct development of distinct ADHD treatment strategies for these patients.
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Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Inibição Psicológica , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Adolescente , Adulto , Atenção , Encéfalo/fisiopatologia , Mapeamento Encefálico , Função Executiva , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Países Baixos , Testes Neuropsicológicos , Adulto JovemRESUMO
BACKGROUND: Traditionally tricyclic antidepressants (TCAs) have an important place in treatment of major depressive disorder (MDD). Today, often other antidepressant medications are considered as first step in the pharmacological treatment of MDD, mainly because they are associated with less adverse effects, whereby the position of TCAs appears unclear. In this study we aimed to examine the current practice of TCAs in treatment of unipolar MDD. METHODS: A mixed methods approach was applied. First, a selection of leading international and national guidelines was reviewed. Second, actual TCA prescription was examined by analyzing health records of 75 MDD patients treated with the TCAs nortriptyline, clomipramine or imipramine in different centers in the Netherlands. Third, promotors and barriers influencing the choice for TCAs and dosing strategies were explored using semi-structured interviews with 24 Dutch psychiatrists. RESULTS: Clinical practice guidelines were sometimes indirective and inconsistent with each other. Health records revealed that most patients (71%) attained therapeutic plasma concentrations within two months of TCA use. Patients who achieved therapeutic plasma concentrations reached them on average after 19.6 days (SD 10.9). Both health records and interviews indicated that therapeutic nortriptyline concentrations were attained faster compared to other TCAs. Various factors were identified influencing the choice for TCAs and dosing by psychiatrists. CONCLUSIONS: Guideline recommendations and clinical practice regarding TCA prescription for MDD vary. To increase consistency in clinical practice we recommend development of an up-to-date guideline integrating selection and dosing of TCAs, including the roles of therapeutic drug monitoring and pharmacogenetics. Such a guideline is currently lacking and would contribute to optimal TCA treatment, whereby efficacy and tolerability may be increased.
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Antidepressivos Tricíclicos , Transtorno Depressivo Maior , Antidepressivos Tricíclicos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Países BaixosRESUMO
BACKGROUND: Alterations in brain structure in attention-deficit/hyperactivity disorder (ADHD) show considerable overlap with those observed in substance use disorder (SUD). These overlapping structural alterations in ADHD and SUD might be explained by family history (FH-trait) effects of SUD, and/or substance misuse (state) effects. Our aim was to investigate effects of 1) current parental SUD (SUD-FH) and 2) recent substance misuse (SM) on brain structure in a cohort of ADHD patients and controls. DESIGN: Cortical thickness and subcortical volumes were measured using structural MRI. We compared ADHD subjects and controls with or without SUD-FH (aim 1) and additionally explored differences between SUD-FH- and SUD-FH + subjects with one versus two parents with SUD. We also compared ADHD groups with and without SM (ADHD + SM and ADHD-only, respectively) and controls (aim 2). FINDINGS: There was no association between SUD-FH and brain structure. Exploratory analysis on SUD-FH showed decreased IFG thickness (p = 0.032) and nucleus accumbens (NAcc) volume (p = 0.017) in subjects with two versus one SUD parent, regardless of ADHD. ADHD + SM showed decreased inferior frontal gyrus (IFG) thickness compared to controls (pars opercularis p = 0.025, pars orbitalis p = 0.010, pars triangularis p = 0.049), while no difference was found between ADHD-only and either ADHD + SM or controls. CONCLUSIONS: Despite negative findings in the primary trait-analysis, exploratory trait-analysis on SUD-FH loading suggested potential SUD trait-effects on IFG thickness and NAcc volume. Substance misuse state effects in ADHD were linked to lower IFG thickness. Future studies should confirm these findings and investigate their clinical relevance, including the functional consequences of decreased IFG thickness.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtorno do Deficit de Atenção com Hiperatividade/genética , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Anamnese , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/genética , Adulto JovemRESUMO
Patients with chronic non-cancer pain (CNCP) often use opioids for long periods of time. This may lead to opioid use disorder (OUD) and psychiatric symptoms: mainly depression and anxiety. The current study investigated the effect of buprenorphine/naloxone (BuNa) rotation on opioid misuse, craving, psychiatric symptoms and pain in patients with CNCP and OUD. Forty-three participants with CNCP and OUD were converted from a full mu-receptor agonist opioid (mean morphine equivalent dose: 328.3 mg) to BuNa, in an inpatient setting. Opioid misuse, craving, co-occurring psychiatric symptoms, and pain perception were determined at baseline and after a two-month follow-up, using the following self-report questionnaires: Current Opioid Misuse Measurement (COMM), Visual Analog Scale (VAS-craving and VAS-pain) and Depression, Anxiety and Stress Scale (DASS), respectively. VAS-craving and VAS-pain were also determined immediately after conversion. A total of 37 participants completed the protocol. The mean COMM decreased from 17.1 to 6.7 (F = 36.5; p < 0.000), the mean VAS-craving decreased from 39.3 to 5.3 (-86.6%; F = 26.5, p < 0.000), the mean DASS decreased from 12.1 to 6.6 (F = 56.3, p < 0.000), and the mean VAS-pain decreased from 51.3 to 37.2 (-27.4%, F = 3.3; p = 0.043). Rotation to BuNa in patients with CNCP and OUD was accompanied by reductions in (i) opioid misuse, (ii) opioid craving, (iii) the severity of co-occurring psychiatric symptoms, and (iv) self-reported pain. BuNa as opioid agonist treatment may therefore be a beneficial strategy in CNCP patients with OUD. The limited sample size and the observational nature of this study underline the need for the replication of the current findings in large-scale, controlled studies.
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OBJECTIVE: Perseverative cognition (PC) is the repeated or long-term activation of the cognitive representation of psychological stressors and is associated with prolonged stress including somatic and mental consequences. Hence, PC might represent a cognitive process linking mental and somatic pathology, but current research on this link is limited by investigating healthy samples, markers of somatic disease, and single disorders. The present study explored the importance of PC for different mental and somatic disorders in psychiatric patients. METHODS: Data from 260 naturalistic psychiatric outpatients were used. Psychiatric diagnoses were based on structured clinical interviews. Somatic diseases were assessed using a well-validated questionnaire and were clustered into (cardio)vascular and immune/endocrine diseases. PC was operationalized using the Perseverative Thinking Questionnaire (PTQ). RESULTS: Multiple regression complemented with relative importance analyses showed that the PTQ total and subscale scores were associated with the presence of mood disorders, addiction, and anxiety. Unexpectedly, no relatively important associations were found between the PTQ and autism spectrum disorder, attention-deficit/hyperactivity disorder, or somatic disease. CONCLUSIONS: Our data complement previous work linking PC to stress-related mental disorders but question its immediate role in neurodevelopmental and somatic disorders. Targeting PC in the treatment of mood disorders and perhaps also in addiction seems promising.