Cognitive, psychological, and physiological effects of a web-based mindfulness intervention in older adults during the COVID-19 pandemic: an open study.

BACKGROUND: The development of effective strategies to maintain good mental health of older adults is a public health priority. Mindfulness-based interventions have the potential to improve psychological well-being and cognitive functions of older adults, but little is known about the effect of such interventions when delivered through internet. During the COVID-19 pandemic we evaluated short- and long-term cognitive, psychological, and physiological effects of a mindfulness-based intervention (MBI) delivered via web-based videoconference in healthy older adults. METHODS: Fifty older adults participated in an 8-week MBI, which comprised structured 2-h weekly group sessions. A comprehensive evaluation encompassing cognitive (verbal memory, attention and processing speed, executive functions) and psychological assessments (depression and anxiety symptoms, mindfulness, worries, emotion regulation strategies, well-being, interoceptive awareness and sleep) was conducted. Additionally, electroencephalography (EEG) data were recorded before and after the MBI and at the 6-month follow-up (T6). Data were analyzed using an intention-to-treat approach, using linear mixed models adjusted for age. The effect size for time was computed as omega squared. RESULTS: We observed significant improvements from pre-MBI to post-MBI and at the T6 across several measures. These improvements were notable in the areas of verbal memory (California Verbal Learning Test, p ≤ .007), attention and executive functions (Trail Making Test A and BA, p < .050), interoceptive awareness (Multidimensional Assessment of Interoceptive Awareness, p = .0002 for self-regulation and p < .05 for noticing, body listening, and trusting dimensions), and rumination (Heidelberg Form for Emotion Regulation Strategies, p = .018). These changes were associated with low to medium effect size. Moreover, we observed significant changes in EEG patterns, with a decrease in alpha1 (p = .004) and an increase in alpha2 (p < .0001) from pre-MBI to T6. Notably, improvements in TMTBA and rumination were correlated with the decrease in alpha1 (p < .050), while improvements in TMTA were linked to the increase in alpha2 (p = .025). CONCLUSIONS: The results of our study show that a web-based MBI in older adults leads to improvements in cognitive and psychological measures, with associated modulations in specific brain rhythms. While these findings are promising, further controlled studies are required to validate these preliminary results. TRIAL REGISTRATION: The trial has been registered with the United States National Library of Medicine at the National Institutes of Health Registry of Clinical Trials under the code NCT05941143 on July 12, 2023.

Insomnia and somnolence associated with second-generation antidepressants during the treatment of major depression: a meta-analysis.

BACKGROUND: Sleep reduction or enhancement is frequently observed with second-generation antidepressant treatments, and they can be beneficial or harmful depending on the symptom profile of each subject. Nevertheless, relatively little attention has been given so far to rank those effects across compounds. The aim of this meta-analysis is to provide quantitative data about short-term rates of insomnia and somnolence associated with 14 second-generation antidepressants during the treatment of major depression. METHODS: A literature search and a search of unpublished documents were performed. Eligible studies focusing on MD patients treated with second-generation antidepressants were entered in the analysis. Our primary outcome measures were insomnia and somnolence rates induced by antidepressants as compared with those associated with placebo. Sensitivity analyses were carried out as well. RESULTS: Ten second-generation antidepressants showed higher rates of insomnia than placebo. The highest incidence was found for bupropion and desvenlafaxine. Agomelatine was the only antidepressant with a lower likelihood of inducing insomnia than placebo. Eleven antidepressants were associated with higher rates of somnolence than placebo. Fluvoxamine and mirtazapine showed the highest frequency of somnolence. Bupropion induced somnolence to a lower extent than placebo. Sensitivity analyses showed a degree of variation of those findings. DISCUSSION: Antidepressants are associated with different insomnia and somnolence rates, mainly depending on their mechanisms of action. Despite some limitations, we underscore that the treatment-emergent insomnia and/or somnolence are frequent, and they could be used in clinical practice to face the specific needs of each patient.

Genetics of psychotropic medication induced side effects in two independent samples of bipolar patients.

The treatment of bipolar disorder (BD) usually requires combination therapies, with the critical issue of the emergence of adverse drug reactions (ADRs) and the possibility of low treatment adherence. Genetic polymorphisms are hypothesized to modulate the pharmacodynamics of psychotropic drugs, representing potential biological markers of ADRs. This study investigated genes involved in the regulation of neuroplasticity (BDNF, ST8SIA2), second messenger cascades (GSK3B, MAPK1, and CREB1), circadian rhythms (RORA), transcription (SP4, ZNF804A), and monoaminergic system (HTR2A and COMT) in the risk of neurological, psychic, autonomic, and other ADRs. Two independent samples of BD patients naturalistically treated were included (COPE-BD n = 147; STEP-BD n = 659). In the COPE-BD 34 SNPs were genotyped, while in the STEP-BD polymorphisms in the selected genes were extracted from the genome-wide dataset. Each ADRs group was categorized as absent-mild or moderate-severe and logistic regression with appropriate covariates was applied to identify possible risk genotypes/alleles. 58.5 and 93.5 % of patients were treated with mood stabilizers, 44.2 and 50.7 % were treated with antipsychotics, and 69.4 and 46.1 % were treated with antidepressants in the COPE-BD and STEP-BD, respectively. Our findings suggested that ST8SIA2 may be associated with psychic ADRs, as shown in the COPE-BD (rs4777989 p = 0.0017) and STEP-BD (rs56027313, rs13379489 and rs10852173). A cluster of RORA SNPs around rs2083074 showed an effect on psychic ADRs in the STEP-BD. Trends supporting the association between HTR2A and autonomic ADRs were found in both samples. Confirmations are needed particularly for ST8SIA2 and RORA since the few available data regarding their role in relation to psychotropic ADRs.

Disentangling the neural mechanisms involved in Hinduism- and Buddhism-related meditations.

The most diffuse forms of meditation derive from Hinduism and Buddhism spiritual traditions. Different cognitive processes are set in place to reach these meditation states. According to an historical-philological hypothesis (Wynne, 2009) the two forms of meditation could be disentangled. While mindfulness is the focus of Buddhist meditation reached by focusing sustained attention on the body, on breathing and on the content of the thoughts, reaching an ineffable state of nothigness accompanied by a loss of sense of self and duality (Samadhi) is the main focus of Hinduism-inspired meditation. It is possible that these different practices activate separate brain networks. We tested this hypothesis by conducting an activation likelihood estimation (ALE) meta-analysis of functional magnetic resonance imaging (fMRI) studies. The network related to Buddhism-inspired meditation (16 experiments, 263 subjects, and 96 activation foci) included activations in some frontal lobe structures associated with executive attention, possibly confirming the fundamental role of mindfulness shared by many Buddhist meditations. By contrast, the network related to Hinduism-inspired meditation (8 experiments, 54 activation foci and 66 subjects) triggered a left lateralized network of areas including the postcentral gyrus, the superior parietal lobe, the hippocampus and the right middle cingulate cortex. The dissociation between anterior and posterior networks support the notion that different meditation styles and traditions are characterized by different patterns of neural activation.

Family history of major depression and residual symptoms in responder and non-responder depressed patients.

BACKGROUND: Little is known about the extent to which a family history of major depression (MD) affects residual depressive symptoms in responder and non-responder patients suffering from MD. METHODS: Nine hundred eighty-six patients with MD were recruited within the context of a large multicenter project. Information about the family history of MD, as well as about total depressive symptoms and specific depressive clusters, was collected and analyzed. RESULTS: No significant difference was observed in overall depressive symptoms between patients with and those without a family history of MD. However, non-responder patients with a family history of MD showed significantly higher scores in core symptoms as compared with responder patients without a family history of MD. CONCLUSIONS: Non-responder MD patients with a positive family history of MD could represent a slightly different sub-group of MD patients with more consistent core depressive symptoms as compared with responder patients without a family history of MD. However, taking into account the retrospective assessment of data, the use of positive or negative family history as a dichotomous indicator of familial loading and the cross-sectional design of the present study, further research is needed to draw more definitive conclusions.

Are mindfulness-based interventions effective for substance use disorders? A systematic review of the evidence.

Mindfulness-based interventions (MBIs) are increasingly suggested as therapeutic approaches for effecting substance use and misuse (SUM). The aim of this article is to review current evidence on the therapeutic efficacy of MBIs for SUM. A literature search was undertaken using four electronic databases and references of retrieved articles. The search included articles written in English published up to December 2011. Quality of included trials was assessed. In total, 24 studies were included, three of which were based on secondary analyses of previously investigated samples. Current evidence suggests that MBIs can reduce the consumption of several substances including alcohol, cocaine, amphetamines, marijuana, cigarettes, and opiates to a significantly greater extent than waitlist controls, non-specific educational support groups, and some specific control groups. Some preliminary evidence also suggests that MBIs are associated with a reduction in craving as well as increased mindfulness. The limited generalizability of the reviewed findings is noted (i.e., small sample size, lack of methodological details, and the lack of consistently replicated findings). More rigorous and larger randomized controlled studies are warranted.

Psychological mechanisms of mindfulness-based interventions: what do we know?

Little is known about the psychological mechanisms underlying the clinical benefits of mindfulness-based interventions (MBIs). In the present review, we suggest that mindfulness-based interventions may enhance positive emotional regulation strategies, as well as self-compassion levels, and decrease rumination and experiential avoidance. These changes are, in turn, associated with several clinical benefits including the reduction of stress and depression levels, as well as the enhancement of positive emotions. Limitations and potential applications of these findings are discussed.

Lack of influence of rs4680 (COMT) and rs6276 (DRD2) on diagnosis and clinical outcomes in patients with major depression.

OBJECTIVE: The gene coding for the catechol-O-methyltransferase (COMT) and the one coding for the dopamine receptor 2 (DRD2) have been linked with major depression (MD) and with the response to antidepressants in several studies. However, contrasting findings have been reported as well. The aim of the present study is, therefore, to investigate possible influences of rs4680 within COMT and rs6276 within DRD2, analyzed both individually and in combination, on the diagnosis and clinical outcomes in a sample of Korean MD patients treated with antidepressants. METHODS: Totally, 184 Korean in-patients suffering from MD treated with either paroxetine or venlafaxine and 220 healthy control subjects were included in the present study. Depression severity was assessed by means of the Hamilton Rating Scale for Depression. RESULTS: We were not able to find any association between the two variants under investigation and diagnosis of MD, as well as with antidepressant response. CONCLUSIONS: Although limited by several factors, including the small sample size and the impossibility to extend our findings to patients treated with different antidepressants, the results of our study provide support to the notion that these variants might not play a major role in the etiology and clinical outcomes of MD.

Influence of family history of major depression, bipolar disorder, and suicide on clinical features in patients with major depression and bipolar disorder.

The extent to which a family history of mood disorders and suicide could impact on clinical features of patients suffering from major depression (MD) and bipolar disorder (BD) has received relatively little attention so far. The aim of the present work is, therefore, to assess the clinical implications of the presence of at least one first- and/or second-degree relative with a history of MD, BD and suicide in a large sample of patients with MD or BD. One thousand one hundred and fifty-seven subjects with MD and 686 subjects with BD were recruited within the context of two large projects. The impact of a family history of MD, BD, and suicide-considered both separately and together-on clinical and socio-demographic variables was investigated. A family history of MD, BD, and suicide was more common in BD patients than in MD patients. A positive family history of mood disorders and/or suicide as well as a positive family history of MD and BD separately considered, but not a positive history of suicide alone, were significantly associated with a comorbidity with several anxiety disorders and inversely associated with age of onset. The clinical implications as well as the limitations of our findings are discussed.

Influence of BDNF variants on diagnosis and response to treatment in patients with major depression, bipolar disorder and schizophrenia.

AIM: The present study aimed to explore whether some single nucleotide polymorphisms (SNPs) within the BDNF gene could be associated with major depression (MD), bipolar disorder (BD) and schizophrenia, and whether they could predict clinical outcomes in Korean inpatients treated with antidepressants, mood stabilizers and antipsychotics, respectively. METHODS: One hundred and forty-five patients with MD, 132 patients with BD, 221 patients with schizophrenia and 170 psychiatrically healthy controls were genotyped for 5 BDNF SNPs (rs2030324, rs7103873, rs10835210, rs11030101 and rs6265). Baseline and final clinical measures--including the Montgomery-Asberg Depression Rating Scale, Young Mania Rating Scale and Positive and Negative Symptoms Scale for patients with MD, BD and schizophrenia, respectively--were recorded. RESULTS: rs10835210 CA and rs11030101 AT genotype frequencies were higher in BD and schizophrenia patients than in healthy and MD subjects. No significant association was found with clinical improvement. DISCUSSION: Our findings provide evidence of an association between BDNF and BD and schizophrenia. However, taking into account the several limitations of our study, including the moderately small sample size, further research is needed to draw more definitive conclusions.

Failure to replicate influence of GRIK4 and GNB3 polymorphisms on treatment outcome in major depression.

In the present study, we aimed to confirm the previous finding of an association between GRIK4 and GNB3 variants (rs195478 and rs5443) and remission and treatment resistance in major depression, using a multicenter sample of 223 patients. We did not find any supporting evidence for such associations. These conflicting data may result from difficulties in the replication of candidate gene association studies.

Influence of GRIA1, GRIA2 and GRIA4 polymorphisms on diagnosis and response to treatment in patients with major depressive disorder.

The present study is aimed to exploring whether some single nucleotide polymorphisms (SNPs) within GRIA1, GRIA2 and GRIA4 could be associated with major depressive disorder (MDD) and whether they could predict clinical outcomes in Korean in-patients, respectively, treated with antidepressants. One hundred forty-five (145) patients with MDD and 170 healthy controls were genotyped for 17 SNPs within GRIA1, GRIA2 and GRIA4. Baseline and final clinical measures, including the Montgomery-Asberg Depression Rating Scale (MADRS) for patients with MDD, were recorded. No association was observed between alleles, genotypes and haplotypes under investigation and clinical and demographical variables. As a secondary finding, a marginal association was observed between rs4302506 and rs4403097 alleles within GRIA2 and age of onset in patients with MDD. Our findings provide evidence for a possible association between rs4302506 and rs4403097 SNPs and age of onset in patients with MDD. However, taking into account that the several limitations of our study including the moderately small sample size of our study, our findings should be considered with caution and further research is needed to draw more definitive conclusions.

Case-control association study for 10 genes in patients with schizophrenia: influence of 5HTR1A variation rs10042486 on schizophrenia and response to antipsychotics.

The aim of this study is to investigate possible associations between a set of single-nucleotide polymorphisms (SNPs) within 10 genes with Schizophrenia (SCZ) and response to antipsychotics in Korean in-patients treated with antipsychotics. Two hundred and twenty-one SCZ in-patients and 170 psychiatrically healthy controls were genotyped for 42 SNPs within ABCB1, ABCB4, TAP2, CLOCK, CPLX1, CPLX2, SYN2, NRG1, 5HTR1A and GPRIN2. Baseline and final clinical measures, including the Positive and Negative Symptoms Scale (PANSS), were recorded. Rs10042486 within 5HTR1A was associated with both SCZ and clinical improvement on PANSS total scores as well as on PANSS positive and PANSS negative scores. The haplotype analyses focusing on the four, three and two blocks' haplotypes within 5HTR1A confirmed such findings as well. We did not observe any significant association between the remaining genetic variants under investigation in this study and clinical outcomes. Our preliminary findings suggest that rs10042486 within 5HTR1A promoter region could be associated with SCZ and with clinical improvement on PANSS total, positive and negative scores in Korean patients with SCZ. However, taking into account the several limitations of our study, further research is needed to draw more definitive conclusions.

Case-control association study of GRIA1, GRIA2 and GRIA4 polymorphisms in bipolar disorder.

OBJECTIVE: The present study aimed to investigate whether some single nucleotide polymorphisms (SNPs) within GRIA1, GRIA2 and GRIA4 could be associated with bipolar disorder (BD) and they could predict clinical outcomes in in-patients with BD treated with mood stabilizers. METHODS: One hundred and thirty-two (132) patients with BD and 170 healthy controls were genotyped for 17 SNPs within GRIA1, GRIA2 and GRIA4. Baseline and final clinical measures including Young Mania Rating Scale for patients with BD were recorded. Statistical significance was set at the 0.005 level in order to reduce the likelihood of false positive results. RESULTS: We failed to show an evidence for a possible association of GRIA1, GRIA2 and GRIA4 with BD patients, in terms of influences on diagnosis and treatment outcomes, although this was the first study to explore the influence of such genes for bipolar disorder. CONCLUSION: Our results suggest that 17 SNPs within GRIA1, GRIA2 and GRIA4 may not be associated with the development and treatment outcomes in BD. However, taking into account that the several limitations of our study including the moderately small sample size of our study, our findings should be considered with caution and further research is needed to draw more definitive conclusions.

Novel antidepressants and panic disorder: evidence beyond current guidelines.

AIM: The aim of the present review is to summarize available evidence about the efficacy and side effects of novel antidepressants for the treatment of panic disorder. METHODS: A literature search was undertaken using MEDLINE, ISI web of knowledge and references of retrieved articles. The search included articles published in English up to September 2009. Both controlled and uncontrolled trials were included. The quality of the reviewed articles was also assessed. RESULTS: Fourteen mainly poor-quality studies were included. Mirtazapine showed some efficacy in reducing the number and the severity of panic symptoms in many uncontrolled studies and was comparable to selective serotonin reputake inhibitors (SSRIs) in direct-comparison studies. Reboxetine was significantly more efficacious than placebo but less effective than SSRIs. Further uncontrolled studies suggested preliminary evidence for the use of milnacipran and duloxetine as well. All drugs were usually well tolerated. DISCUSSION: Current studies do not yet provide convincing evidence supporting the efficacy of mirtazapine, reboxetine, milnacipran and duloxetine for the treatment of panic disorder patients. However, on account of positive preliminary results, further research is warranted.

Mindfulness based cognitive therapy for psychiatric disorders: a systematic review and meta-analysis.

Mindfulness- based Cognitive Therapy (MBCT) is a meditation program based on an integration of Cognitive behavioural therapy and Mindfulness-based stress reduction. The aim of the present work is to review and conduct a meta-analysis of the current findings about the efficacy of MBCT for psychiatric patients. A literature search was undertaken using five electronic databases and references of retrieved articles. Main findings included the following: 1) MBCT in adjunct to usual care was significantly better than usual care alone for reducing major depression (MD) relapses in patients with three or more prior depressive episodes (4 studies), 2) MBCT plus gradual discontinuation of maintenance ADs was associated to similar relapse rates at 1year as compared with continuation of maintenance antidepressants (1 study), 3) the augmentation of MBCT could be useful for reducing residual depressive symptoms in patients with MD (2 studies) and for reducing anxiety symptoms in patients with bipolar disorder in remission (1 study) and in patients with some anxiety disorders (2 studies). However, several methodological shortcomings including small sample sizes, non-randomized design of some studies and the absence of studies comparing MBCT to control groups designed to distinguish specific from non-specific effects of such practice underscore the necessity for further research.

Influence of TPH2 variants on diagnosis and response to treatment in patients with major depression, bipolar disorder and schizophrenia.

The present study is aimed at exploring whether some single nucleotide polymorphisms (SNPs) within the tryptophan hydroxylase 2 gene (TPH2) could be associated with major depression (MD), bipolar disorder (BD) and schizophrenia and whether they could predict clinical outcomes in Korean in-patients treated with antidepressants, mood stabilizers and antipsychotics, respectively. One hundred forty-five patients with MD, 132 patients with BD, 221 patients with schizophrenia and 170 psychiatrically healthy controls were genotyped for six TPH2 SNPs (rs4570625, rs10748185, rs11179027, rs1386498, rs4469933, and rs17110747). Baseline and final clinical measures, including the Montgomery-Åsberg Depression Rating Scale (MADRS), Young Mania Rating Scale and Positive and Negative Syndrome Scale, for patients with MD, BD and schizophrenia, respectively were recorded. None of the SNPs under investigation were associated with MD, BD and schizophrenia. However, in patients with MD, the rs4570625-rs10748185 G-A haplotype was significantly associated with higher endpoint MADRS severity, though not with response. Our results suggest that TPH2 variants neither have a major role in MD, BD and schizophrenia nor in response to treatments.

No influence of PTGS2 polymorphisms on response and remission to antidepressants in major depression.

In the present study, aimed at investigating whether a set of single nucleotide polymorphisms (SNPs) within PTGS2 gene (rs4648276, rs2066826 and rs689466) could be associated with antidepressant response, remission and treatment resistance in a sample of major depression patients, we did not find evidence supporting any of such associations.

Mindfulness-based approaches: are they all the same?

Mindfulness-based approaches are increasingly employed as interventions for treating a variety of psychological, psychiatric and physical problems. Such approaches include ancient Buddhist mindfulness meditations such as Vipassana and Zen meditations, modern group-based standardized meditations, such as mindfulness-based stress reduction and mindfulness-based cognitive therapy, and further psychological interventions, such as dialectical behavioral therapy and acceptance and commitment therapy. We review commonalities and differences of these interventions regarding philosophical background, main techniques, aims, outcomes, neurobiology and psychological mechanisms. In sum, the currently applied mindfulness-based interventions show large differences in the way mindfulness is conceptualized and practiced. The decision to consider such practices as unitary or as distinct phenomena will probably influence the direction of future research.

DAOA variants and schizophrenia: influence on diagnosis and treatment outcomes.

OBJECTIVE: The present study explored whether d-amino acid oxidase activator (DAOA) variants were associated with schizophrenia and whether they could predict the clinical outcomes of patients treated with various antipsychotics. METHODS: Two hundred and twenty-one (221) patients with schizophrenia and 170 psychiatrically healthy controls were genotyped for seven DAOA single-nucleotide polymorphisms (SNPs) (rs3916966, rs3916967, rs2391191, rs3916968, rs7139958, rs9558571 and rs778293). We also administered baseline and final clinical measures, including the Positive and Negative Symptoms Scale (PANSS), to patients with schizophrenia. RESULTS: None of the SNPs under investigation was associated with the development of schizophrenia. However, the rs7139958 AA and rs9558571 TT as well as the rs7139958 A and rs9558571 T genotypes were associated with higher scores on the PANSS positive subscale among patients with schizophrenia, possibly reflecting their greater susceptibility to the development of more severe positive symptoms. No other allele, genotype, or haplotype under investigation was significantly associated with any of the clinical parameters, including clinical improvement, in patients with schizophrenia. CONCLUSION: Our results suggested that rs7139958 and rs9558571 SNPs may be associated with more severe baseline positive symptoms in patients with schizophrenia. However, further research is needed to draw more definitive conclusions given the limitations of our study.