Emotion Regulation and Mentalization in Patients With Depression and Anxiety.

OBJECTIVE: Theoretical conceptualizations of emotion and affect regulation have a considerable common ground. However, mentalization theory considers the ability to regulate affects as being contingent on the ability to mentalize. The aim of the present study is to examine the association between emotion regulation and mentalization, operationalized as reflective functioning, in a sample of patients with depression and/or anxiety. METHODS: The study used data from the TRAns-diagnostic Cognitive behavioural Therapy versus standard cognitive behavioural therapy (TRACT-RCT) trial. Patients with depression and/or anxiety (N = 291; 64.4% female; Mage = 32.2; SD = 11.0) completed the Emotion Regulation Strategies Questionnaire (ERSQ) and the Reflective Functioning Questionnaire (RFQ-6). Correlation and regression analyses were performed to determine associations of the measures of ERSQ and RFQ-6 in relation to the outcome variables, global well-being (World Health Organization Well-being Index; WHO-5) and social functioning (Work and Social Adjustment Scale; WSAS). RESULTS: Overall, the patients had a reduced level of emotion regulation (MERSQ_Total = 1.77; SD = 0.59). However, only mildly impaired reflective functioning was found (MRFQ-6 = 3.57; SD = 1.26). ERSQ correlated significantly with RFQ-6 (r = -0.31), that is, more frequent use of emotion regulation strategies was associated with less hypomentalization. ERSQ was a stronger predictor of well-being and social function than RFQ-6. CONCLUSION: In patients with anxiety and/or depression, hypomentalization as measured by the RFQ-6 is not a major problem, but emotion regulation is. It seems that these two, theoretically related constructs, do not necessarily co-occur. Alternatively, the RFQ-6 scale might not capture the mentalization construct in a valid way. Emotion regulation strategies are highly related to symptomatology; therefore, they are likely to be an important target for psychotherapy.

Cognitive-Behavioral Therapy Enhancement Strategies.

We review the literature on various strategies to augment cognitive-behavioral therapy (CBT). Although traditional pharmacotherapy has only a small additive effect, research demonstrates that it is possible to select interventions that potentiate known mechanisms of CBT. D-cycloserine appears to potentiate activity at the N-methyl D-ethyl aspartate receptor and thereby facilitates fear extinction. Exercise may increase neural plasticity and thereby increase the efficacy of CBT for depression and anxiety. Noninvasive brain stimulation is thought to target the specific cortical regions needed for CBT response, but results have been mixed. Several other compounds appear promising but await controlled research before their efficacy as an augmentation strategy can be determined.

Cognitive Behavioral Therapy for Anxiety and Depression in Children and Adolescents.

Anxiety and depression are prevalent and impairing psychiatric problems for children and adolescents. In this review, the authors summarize information about their prevalence and impact, the most common assessment methods, the main components of cognitive behavioral therapy (CBT), and research on the effectiveness of CBT for these disorders. Future directions, including improving access to CBT through technology-based approaches and increasing personalization of treatment, are discussed.

Cross-sectional study of psychiatric disorders in patients with chronic musculoskeletal pain and individuals without pain.

BACKGROUND: Musculoskeletal chronic pain is a leading cause of global disability and laboral incapacity. However, there is a lack of population-based studies that investigate the relationship between chronic pain and mental disorders with a control group, particularly among low- and middle-income countries. Chronic pain is a serious public health problem in terms of human suffering, and in terms of socioeconomic implications. Frequent association with different mental disorders increases disability, decreases quality of life, and makes diagnosis and treatment challenging. The present study aimed to evaluate the presence of mental disorders in patients with chronic musculoskeletal pain and compare with a control group without pain. METHODS: We selected 100 patients in a regular follow-up at the Musculoskeletal Pain Outpatient Clinic of the University Hospital and compared them with 100 painless individuals from the control group from June 2016 to June 2018. The instruments used were the Mini International Neuropsychiatric Interview (MINI-PLUS) and a structured questionnaire to collect sociodemographic data. Statistical analysis used t-test, chi-square, Fisher's exact test, Mann-Whitney, Kolmogorov-Smirnov tests, and multiple logistic regression. RESULTS: In the sample evaluated, the majority of patients were women (83%), of brown color (54%), with lower-level education (51%), lower salary range (73%) and high absenteeism rate at work (60,7%). Patients with chronic pain had more psychiatric disorders (88% vs. 48% in the control group; p < 0.001). The most frequent diagnoses were anxiety disorders with panic attacks (44%), generalized anxiety (36%), mixed anxiety and depression disorder (33%), social phobia (30%), agoraphobia (29%), suicide risk (28%), and major depression (27%). CONCLUSION: Positive correlations of mental disorders and chronic musculoskeletal pain have been documented. This suggests that psychiatric components must be taken into account in the management of chronic pain syndromes. The use of Mini Plus as a diagnostic tool for psychiatric disorders can contribute to optimizing the diagnosis and treatment of patients with chronic pain and encourage the creation of policies with strategies and criteria for quick access to Multi-professional Services.

The Effects of Patient Preference on Clinical Outcome, Satisfaction and Adherence Within the Treatment of Anxiety and Depression: A Meta-Analysis.

BACKGROUND: Taking patient preference into consideration has received increased attention in the last decades. We conducted a meta-analysis to estimate the effects of patient preference on clinical outcome, satisfaction and adherence regarding treatment of depression and anxiety. METHODS: Pubmed, Embase, PsycINFO and Scopus were searched for (cluster) randomized controlled trials. Twenty-six randomized controlled clinical trials were included, comprising 3670 participants, examining the effect of patient preference regarding treatment of anxiety and depression on clinical outcome, satisfaction and/or adherence. RESULTS: No effect of patient preference was found on clinical outcome [d = 0.06, 95% CI = (-0.03, 0.15), p = 0.16, n = 23 studies]. A small effect of patient preference was found on treatment satisfaction [d = 0.33, 95% CI = (0.08, 0.59), p = 0.01, n = 6 studies] and on treatment adherence [OR = 1.55, 95% CI = (1.28, 1.87), p < 0.001, n = 22 studies]. LIMITATIONS: Patient preference is a heterogeneous concept, future studies should strive to equalize operationalization of preference. Subgroup analyses within this study should be interpreted with caution because the amount of studies per analysed subgroup was generally low. Most studies included in this meta-analysis focused on patients with depression. The small number of studies (n = 6) on satisfaction, prevents us from drawing firm conclusions. CONCLUSIONS: While this meta-analysis did not find a positive effect of considering patient preference on clinical outcome, it was associated with slightly better treatment satisfaction and adherence. Accommodating preference of patients with anxiety and depression can improve treatment. TRIAL REGISTRATION: PROSPERO: CRD42020172556.

Association of CYP2D6 and CYP2C19 metabolizer status with switching and discontinuing antidepressant drugs: an exploratory study.

BACKGROUND: Tailoring antidepressant drugs (AD) to patients' genetic drug-metabolism profile is promising. However, literature regarding associations of ADs' treatment effect and/or side effects with drug metabolizing genes CYP2D6 and CYP2C19 has yielded inconsistent results. Therefore, our aim was to longitudinally investigate associations between CYP2D6 (poor, intermediate, and normal) and CYP2C19 (poor, intermediate, normal, and ultrarapid) metabolizer-status, and switching/discontinuing of ADs. Next, we investigated whether the number of perceived side effects differed between metabolizer statuses. METHODS: Data came from the multi-site naturalistic longitudinal cohort Netherlands Study of Depression and Anxiety (NESDA). We selected depression- and/or anxiety patients, who used AD at some point in the course of the 9 years follow-up period (n = 928). Medication use was followed to assess patterns of AD switching/discontinuation over time. CYP2D6 and CYP2C19 alleles were derived using genome-wide data of the NESDA samples and haplotype data from the PharmGKB database. Logistic regression analyses were conducted to investigate the association of metabolizer status with switching/discontinuing ADs. Mann-Whitney U-tests were conducted to compare the number of patient-perceived side effects between metabolizer statuses. RESULTS: No significant associations were observed of CYP metabolizer status with switching/discontinuing ADs, nor with the number of perceived side effects. CONCLUSIONS: We found no evidence for associations between CYP metabolizer statuses and switching/discontinuing AD, nor with side effects of ADs, suggesting that metabolizer status only plays a limited role in switching/discontinuing ADs. Additional studies with larger numbers of PM and UM patients are needed to further determine the potential added value of pharmacogenetics to guide pharmacotherapy.

Concentrated transdiagnostic and cross-disciplinary micro-choice based group treatment for patients with depression and with anxiety leads to lasting improvements after 12 months: a pilot study.

BACKGROUND: A concentrated transdiagnostic and micro choice-based group treatment for patients with depression and anxiety has previously shown to yield significant reduction in symptoms and increased level of functioning from pre to 3-month follow-up. In the present study, we report the results after 12 months follow-up. METHODS: This was a non-randomized clinical intervention pilot study, conducted in line with a published protocol. Sixty-seven consecutively referred patients, aged 19-47 (mean age 32.5, SD = 8.0) were included and completed treatment. All had a severity of their problems that entitled them to care in the specialist public mental health care. Self-reported age at onset of symptoms was 17.6 (SD = 7.9) years. Mean number of prior treatment courses was 3.5 (SD = 3.3; range 0-20). The main objective was to assess the treatment effectiveness by questionnaires measuring relevant symptoms at pre-treatment, 7 days-, 3 months-, 6 months- and at 12-months follow-up. RESULTS: Validated measures of functional impairment (WSAS), depression (PHQ9), anxiety (GAD7), worry (PSWQ), fatigue (CFQ), insomnia (BIS) and illness perception (BIPQ) improved significantly (p < .0005) from before treatment to 12 months follow-up, yielding mostly large to extremely large effect sizes (0.89-3.68), whereas some moderate (0.60-0.76). After 12 months, 74% report an overall improvement in problems related to anxiety and depression. Utilization of specialist, public and private mental health care was reported as nonexistent or had decreased for 70% of the patients at 12-month follow up. CONCLUSIONS: The concentrated, micro-choice based group treatment approach yielded a highly clinically significant reduction in a wide range of symptoms already one week after treatment, and the positive results persisted at 12-month follow-up. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05234281, first posted date 10/02/2022.

Predicting CBT modality, treatment participation, and reliable improvements for individuals with anxiety and depression in a specialized mental health centre: a retrospective population-based cohort study.

BACKGROUND: Cognitive Behaviour Therapy (CBT) is one of the most successful therapeutic approaches for treating anxiety and depression. Clinical trials show that for some clients, internet-based CBT (eCBT) is as effective as other CBT delivery modes. However, the fidelity of these effects may be weakened in real-world settings where clients and providers have the freedom to choose a CBT delivery mode and switch treatments at any time. The purpose of this study is to measure the CBT attendance rate and identify client-level characteristics associated with delivery mode selection and having reliable and clinically significant improvement (RCSI) of treatment in each delivery mode in a real-world CBT outpatient program. METHODS: This is a retrospective cohort analysis of electronic medical records collected between May 1, 2019, and March 31, 2022, at Ontario Shores Centre for Mental Health Sciences. Regression models were used to investigate the impact of individual client characteristics on participation and achieving RCSI of different CBT delivery modes. RESULTS: Our data show a high attendance rate for two and more CBT sessions across all modalities (98% of electronic, 94% of group, 100% of individual, and 99% of mixed CBT). Individuals were more likely to enter mixed and group CBT modality if they were younger, reported being employed, and reported higher depression severity at the baseline. Among the four modalities of CBT delivery, group CBT clients were least likely to have RCSI. Of those who started sessions, clients were significantly more likely to experience RCSI on the Patient Health Questionnaire (PHQ)-9 and the Generalized Anxiety Disorder (GAD)-7 if they were employed, reported more severe symptoms at baseline, and were living in the most deprived neighborhoods. CONCLUSIONS: This study will contribute to the body of knowledge about the implementation and treatment planning of different CBT delivery modes in real-world settings. With the changing clinical environment, it is possible to advocate for the adoption of the eCBT intervention to improve therapy practices and achieve better treatment success. The findings can help guide future CBT program planning based on client socio-demographic characteristics, allowing the optimal therapy type to be targeted to the right client at the right time.

Causal relationship between resting-state networks and depression: a bidirectional two-sample mendelian randomization study.

BACKGROUND: Cerebral resting-state networks were suggested to be strongly associated with depressive disorders. However, the causal relationship between cerebral networks and depressive disorders remains controversial. In this study, we aimed to investigate the effect of resting-state networks on depressive disorders using a bidirectional Mendelian randomization (MR) design. METHODS: Updated summary-level genome-wide association study (GWAS) data correlated with resting-state networks were obtained from a meta-analysis of European-descent GWAS from the Complex Trait Genetics Lab. Depression-related GWAS data were obtained from the FinnGen study involving participants with European ancestry. Resting-state functional magnetic resonance imaging and multiband diffusion imaging of the brain were performed to measure functional and structural connectivity in seven well-known networks. Inverse-variance weighting was used as the primary estimate, whereas the MR-Pleiotropy RESidual Sum and Outliers (PRESSO), MR-Egger, and weighted median were used to detect heterogeneity, sensitivity, and pleiotropy. RESULTS: In total, 20,928 functional and 20,573 structural connectivity data as well as depression-related GWAS data from 48,847 patients and 225,483 controls were analyzed. Evidence for a causal effect of the structural limbic network on depressive disorders was found in the inverse variance-weighted limbic network (odds ratio, [Formula: see text]; 95% confidence interval, [Formula: see text]; [Formula: see text]), whereas the causal effect of depressive disorders on SC LN was not found(OR=1.0025; CI,1.0005-1.0046; P=0.012). No significant associations between functional connectivity of the resting-state networks and depressive disorders were found in this MR study. CONCLUSIONS: These results suggest that genetically determined structural connectivity of the limbic network has a causal effect on depressive disorders and may play a critical role in its neuropathology.

The outcomes of mental health care for depression over time: A meta-regression analysis of response rates in usual care.

BACKGROUND: Over the past decades dozens of randomized trials have shown that psychological treatments are more effective than care-as-usual (CAU). It could be expected that these treatments are implemented in routine care and that the response rates in usual care improve over time. The aim of the current meta-analysis is to examine if response and remission rates in usual care have improved over time. METHODS: We used an existing meta-analytic database of randomized controlled trials examining the effects of psychological treatments of depression and selected CAU control groups from these trials. We only included CAU conditions in primary care, specialized mental health care, perinatal care and general medical care. The response rate (50 % symptom reduction) was the primary outcome. RESULTS: We included 125 CAU control groups (8542 participants). The response rate for all CAU control groups was 0.22 (95 % CI: 0.19; 0.24) with high heterogeneity (I2 = 83; 95 % CI: 80; 85), with somewhat higher rates in primary care (0.27; 95 % CI: 0.23; 0.31). We found hardly any indications that the outcomes have improved over the years. The meta-regression analysis with publication year as predictor in the full dataset resulted in a coefficient of 0.1 (SE = 0.01; p = 0.0.35). A series of sensitivity analyses supported the main findings. Remission rates and pre-post effect sizes also did not significantly improve over time. CONCLUSIONS: Response and remission rates in usual care are low, with the large majority of patients not responding or remitting, and the outcomes have probably not improved over time.

Long-term remission and relapse of anxiety and depression in older adults after Cognitive Behavioural Therapy (CBT): A 10-year follow-up of a randomised controlled trial.

BACKGROUND: This study examined the long-term durability of cognitive behaviour therapy (CBT) for older adults with comorbid anxiety and depression 10 years after treatment, in comparison to an active control group. METHOD: Participants from a randomised controlled trial for older adults with comorbid anxiety and depression (Wuthrich et al., 2016) were re-contacted. Participants had received either group CBT or an active control treatment (Discussion Group). The final sample (N = 54; Aged 70-84, Mage = 76.07, SD = 3.83; 59 % of the eligible original sample) completed a diagnostic interview, cognitive assessment and self-report measures of symptoms and quality of life. RESULTS: CBT was associated with significantly improved long-term (10-year) efficacy for reducing anxiety and depression in older adults compared to the Discussion group. Effects included higher rates of remission (58 % remission of all diagnoses vs 27 %, 88 % of all depressive diagnoses vs 54 %, 63 % of all anxiety diagnoses vs 35 %, 67 % of primary diagnosis vs 42 %), lower rates of relapse (25-31 % vs 50-78 %) and lower rates of chronic treatment-resistance (8 % primary disorder vs 39 %, 21 % any disorder vs 58 %). Participants who showed an acute treatment response at post-treatment were 7-9 times more likely to be in remission after 10 years than those with residual symptoms. LIMITATIONS: Results may not generalise to those who do not complete CBT, and the time trajectory of symptom change is unclear. CONCLUSIONS: Long-term improvements in symptoms are specific to CBT. Results provide compelling evidence for CBT as an effective and durable treatment for late-life anxiety and depression.

Sex-specific associations between circadian-related genes and depression in UK Biobank participants highlight links to glucose metabolism, inflammation and neuroplasticity pathways.

Depressive disorders have increased in global prevalence, making improved management of these disorders a public health priority. Prior research has linked circadian clock genes to depression, either through direct interactions with mood-related pathways in the brain or by modulating the phase of circadian rhythms. Using machine learning and statistical techniques, we explored associations between 157,347 SNP variants from 51 circadian-related genes and depression scores from the patient health questionnaire 9 (PHQ-9) in 99,939 UK Biobank participants. Our results highlight multiple pathways linking the circadian system to mood, including metabolic, monoamine, immune, and stress-related pathways. Notably, genes regulating glucose metabolism and inflammation (GSK3B, LEP, RORA, and NOCT) were prominent factors in females, in addition to DELEC1 and USP46, two genes of unknown function. In contrast, FBXL3 and DRD4 emerged as significant risk factors for male depression. We also found epistatic interactions involving RORA, NFIL3, and ZBTB20 as either risk or protective factors for depression, underscoring the importance of transcription factors (ZBTB20, NFIL3) and hormone receptors (RORA) in depression etiology. Understanding the complex, sex-specific links between circadian genes and mood disorders will facilitate the development of therapeutic interventions and enhance the efficacy of multi-target treatments for depression.