Linguistic style as a digital marker for depression severity: An ambulatory assessment pilot study in patients with depressive disorder undergoing sleep deprivation therapy.

BACKGROUND: Digital phenotyping and monitoring tools are the most promising approaches to automatically detect upcoming depressive episodes. Especially, linguistic style has been seen as a potential behavioral marker of depression, as cross-sectional studies showed, for example, less frequent use of positive emotion words, intensified use of negative emotion words, and more self-references in patients with depression compared to healthy controls. However, longitudinal studies are sparse and therefore it remains unclear whether within-person fluctuations in depression severity are associated with individuals' linguistic style. METHODS: To capture affective states and concomitant speech samples longitudinally, we used an ambulatory assessment approach sampling multiple times a day via smartphones in patients diagnosed with depressive disorder undergoing sleep deprivation therapy. This intervention promises a rapid change of affective symptoms within a short period of time, assuring sufficient variability in depressive symptoms. We extracted word categories from the transcribed speech samples using the Linguistic Inquiry and Word Count. RESULTS: Our analyses revealed that more pleasant affective momentary states (lower reported depression severity, lower negative affective state, higher positive affective state, (positive) valence, energetic arousal and calmness) are mirrored in the use of less negative emotion words and more positive emotion words. CONCLUSION: We conclude that a patient's linguistic style, especially the use of positive and negative emotion words, is associated with self-reported affective states and thus is a promising feature for speech-based automated monitoring and prediction of upcoming episodes, ultimately leading to better patient care.

Psychological, endocrine and polygenic predictors of emotional well-being during the COVID-19 pandemic in a longitudinal birth cohort.

The COVID-19 pandemic severely affected the lives of families and the well-being of both parents and their children. Various factors, including prenatal stress, dysregulated stress response systems, and genetics may have influenced how the stress caused by the pandemic impacted the well-being of different family members. The present work investigated if emotional well-being during the COVID-19 pandemic could be predicted by developmental stress-related and genetic factors. Emotional well-being of 7-10 year-old children (n = 263) and mothers (n = 241) (participants in a longitudinal German birth cohort (POSEIDON)) was assessed during the COVID-19 pandemic using the CRISIS questionnaire at two time periods (July 2020-October 2020; November 2020-February 2021). Associations of the children's and mothers' well-being with maternal perceived stress, of the children's well-being with their salivary and morning urine cortisol at 45 months, and polygenic risk scores (PRSs) for depression, schizophrenia, loneliness were investigated. Lower emotional well-being was observed in both children and mothers during compared to before the pandemic, with the children's but not the mothers' emotional well-being improving over the course of the pandemic. A positive association between the child and maternal emotional well-being was found. Prenatally assessed maternal perceived stress was associated with a lower well-being in children, but not in mothers. Cortisol measures and PRSs were not significantly associated with the children's emotional well-being. The present study confirms that emotional well-being of children and mothers are linked, and were negatively affected by the COVID-19 pandemic, with differences in development over time.

Longitudinal relationships of psychotic-like experiences with suicidal ideation and self-harm in adolescents.

Research in adolescents suggests associations between psychotic-like experiences (PLEs) and self-injurious thoughts and behaviors (SITBs), but insights into their temporal relationship, which may inform prediction, have been limited. Psychological distress (PD; symptoms of depression and anxiety) has been related to both PLEs and SITBs, and may modulate this relationship. Given that PLEs have been linked to the development of several mental disorders, and the relationships between SITBs and suicide, it is important to better understand their relationship. The present study sought to investigate these factors using a longitudinal school-based design. Adolescents (n = 1685, ages 12-18) completed annual self-report assessments (6 time points) on PLEs, SITBs (suicidal ideation (SI) and self-harm (SH)), as well as PD. The longitudinal associations between PLEs and SITBs were analyzed, employing two cross-lagged panel models (CLPMs), with and without adjustment for PD. Unadjusted CLPMs revealed significant bidirectional temporal associations between PLEs and SITBs (both SI and SH), suggesting that PLEs both predicted and were predicted by SITBs. When adjusting for PD, the effect of SI on PLEs remained significant, but not PLEs on SI; bidirectional associations between PLEs and SH also remained significant. A bidirectional longitudinal relationship where both PLEs and SITBs can precede (and perhaps predict) each other was suggested in adolescents. PD may play a particular role in situations where PLEs are followed by SI. Heightened awareness about relationships between these phenotypes may be an important step toward facilitating timely interventions for both mental disorders and suicide.

Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders.

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development.

Alcohol solution strength preference predicts compulsive-like drinking behavior in rats.

BACKGROUND: Understanding compulsive drinking behavior is key to improving outcomes in the treatment of addiction. In the present study, we investigated compulsive-like drinking in alcohol-addicted rats using the alcohol deprivation effect (ADE) model of relapse behavior, which involves repeated deprivation and reintroduction phases; the latter approximate relapse. METHODS: High-resolution longitudinal drinking and locomotor data were measured while rats (n = 30) underwent a four-bottle (water, 5%, 10%, 20% alcohol v/v) free-choice ADE paradigm. Alcohol bottles were adulterated with the bitter compound quinine during a reintroduction phase to test for compulsive behavior. We characterized how drinking and locomotor behavior during ADE + quinine differed from a regular ADE and how, at the individual level, behavioral parameters extracted from the regular ADE related to compulsive-like drinking. Associations of drinking with locomotor activity were also examined. RESULTS: In the ADE with quinine, we observed reduced consumption of alcohol and a shift to preference for stronger alcohol. Quinine acted by decreasing both the access size and frequency of drinking of 5% alcohol while increasing the frequency of consumption of 20% alcohol. Preference for higher alcohol concentrations prior to the quinine challenge was associated with greater compulsive-like drinking behavior; higher baseline consumption of 20% alcohol correlated with more drinking of quinine-adulterated solutions while high frequency and amount of 5% alcohol consumption at baseline were correlated with being more strongly affected by quinine. Associations between locomotor activity and drinking behavior were observed at the hourly level. These associations reflected changing preferences across experimental phases. CONCLUSION: Drinking patterns, and specifically solution preference, may offer insights into the presentation of compulsive-like drinking. The findings provide a preclinical basis for observations from epidemiological studies that link higher risk and burden of alcohol-related disease to stronger alcohol concentrations and encourage further translational studies to better understand the underlying mechanisms.

Microbiome profiles are associated with cognitive functioning in 45-month-old children.

Prenatal, perinatal, and postnatal factors have been shown to shape neurobiological functioning and alter the risk for mental disorders later in life. The gut microbiome is established early in life, and interacts with the brain via the brain-immune-gut axis. However, little is known about how the microbiome relates to early-life cognitive functioning in children. The present study, where the fecal microbiome of 380 children was characterized using 16S rDNA and metagenomic sequencing aimed to investigate the association between the microbiota and cognitive functioning of children at the age of 45 months measured with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). Overall the microbiome profile showed a significant association with cognitive functioning. A strong correlation was found between cognitive functioning and the relative abundance of an unidentified genus of the family Enterobacteriaceae. Follow-up mediation analyses revealed significant mediation effects of the level of this genus on the association of maternal smoking during pregnancy and current cigarette smoking with cognitive function. Metagenomic sequencing of a subset of these samples indicated that the identified genus was most closely related to Enterobacter asburiae. Analysis of metabolic potential showed a nominally significant association of cognitive functioning with the microbial norspermidine biosynthesis pathway. Our results indicate that alteration of the gut microflora is associated with cognitive functioning in childhood. Furthermore, they suggest that the altered microflora might interact with other environmental factors such as maternal cigarette smoking. Interventions directed at altering the microbiome should be explored in terms of improving cognitive functioning in young children.

A survey of mental health literacy in Japanese high school teachers.

BACKGROUND: School teachers are well-positioned to recognize mental health problems in their students and to help them seek appropriate help. Therefore, teachers need to have high levels of mental health literacy (MHL). In East Asia, however, few studies have examined MHL levels in teachers. In this study, MHL levels were investigated in Japanese teachers. METHODS: Teachers (n = 665) from 27 Japanese high schools answered a self-administered questionnaire which assessed (a) knowledge about mental health/illnesses, (b) correct recognition of specific illnesses (depression, schizophrenia and panic disorder), (c) confidence in helping students with depressive symptoms, and (d) confidence in teaching mental health knowledge to students. RESULTS: The average proportion of correct answers to the knowledge questions (n = 20) was 58.1%. The proportion of those who correctly answered about the presence of a sharp increase of mental illnesses in adolescence was 51.7%. Few teachers correctly answered about the life-time prevalences of major mental illness in general (21.9%), depression (37.8%) and schizophrenia (19.8%). Depression, schizophrenia and panic disorder in vignette were correctly recognized by 54.1, 35.3 and 78.0% of teachers, respectively. Correct recognition was significantly lower in male than in female teachers. Only a small proportion of teachers had confidence in helping depressed students (19.9%) and in teaching mental health knowledge to students (11.1%). CONCLUSIONS: MHL in Japanese high school teachers appears to be low. Education programs should be developed and implemented to improve teacher MHL with the aim of helping them to support students suffering from mental health problems.

A quasi-cluster randomized controlled trial of a classroom-based mental health literacy educational intervention to promote knowledge and help-seeking/helping behavior in adolescents.

INTRODUCTION: School-based education is a potentially effective approach for improving mental health literacy (MHL) in adolescents. This study evaluated the effects of the "Short MHL Program (SMHLP)", a brief (50 min), school teacher-led program, on MHL in adolescents in a quasi-cluster randomized controlled trial. METHODS: A total of 975 high school first graders (age 15-16) in Japan were allocated to classes such that gender and academic achievement ratios were almost equivalent at the time of admission to the high school. They were assigned at the class level to the SMHLP (n = 364 from 10 classes) or a control group (n = 611 from 17 classes). The program consisted of a 50-minute session and was delivered by a school teacher. The students completed a self-report questionnaire at 3 time points: pre-, (immediately) post- and 2-month follow-up. Outcomes included "Knowledge about mental health/illnesses", "Recognition of the necessity to seek help", "Intention to seek help", and "Intention of helping peers". Mixed effects modeling was employed for analyses. RESULTS: Scores of all outcomes were significantly improved in the intervention group compared to the control group post-intervention (p < .001). These improvements were maintained at 2-months follow-up for all outcomes (p < .001-.05). Questionnaire scores did not differ between groups at baseline. CONCLUSIONS: The effect of the SMHLP was confirmed in grade 10 students. Brief, yet effective programs can be a viable option to promote understanding of mental health problems and have the potential to be incorporated into regular school curriculum. ".

Neural Mechanisms for Adaptive Learned Avoidance of Mental Effort.

Humans tend to avoid mental effort. Previous studies have demonstrated this tendency using various demand-selection tasks; participants generally avoid options associated with higher cognitive demand. However, it remains unclear whether humans avoid mental effort adaptively in uncertain and nonstationary environments. If so, it also remains unclear what neural mechanisms underlie such learned avoidance and whether they remain the same regardless of cognitive-demand types. We addressed these issues by developing novel demand-selection tasks where associations between choice options and cognitive-demand levels change over time, with two variations using mental arithmetic and spatial reasoning problems (males/females: 29:4 and 18:2). Most participants showed avoidance, and their choices depended on the demand experienced on multiple preceding trials. We assumed that participants updated the expected cost of mental effort through experience, and fitted their choices by reinforcement learning models, comparing several possibilities. Model-based fMRI analyses revealed that activity in the dorsomedial and lateral frontal cortices was positively correlated with the trial-by-trial expected cost for the chosen option commonly across the different types of cognitive demand. Analyses also revealed a trend of negative correlation in the ventromedial prefrontal cortex. We further identified correlates of cost-prediction error at time of problem presentation or answering the problem, the latter of which partially overlapped with or were proximal to the correlates of expected cost at time of choice cue in the dorsomedial frontal cortex. These results suggest that humans adaptively learn to avoid mental effort, having neural mechanisms to represent expected cost and cost-prediction error, and the same mechanisms operate for various types of cognitive demand.SIGNIFICANCE STATEMENT In daily life, humans encounter various cognitive demands and tend to avoid high-demand options. However, it remains unclear whether humans avoid mental effort adaptively under dynamically changing environments. If so, it also remains unclear what the underlying neural mechanisms are and whether they operate regardless of cognitive-demand types. To address these issues, we developed novel tasks where participants could learn to avoid high-demand options under uncertain and nonstationary environments. Through model-based fMRI analyses, we found regions whose activity was correlated with the expected mental effort cost, or cost-prediction error, regardless of demand type. These regions overlap, or are adjacent with each other, in the dorsomedial frontal cortex. This finding helps clarify the mechanisms for cognitive-demand avoidance, and provides empirical building blocks for the emerging computational theory of mental effort.

Attitudes toward the right to autonomous decision-making in psychiatric genetic testing: Controversial and context-dependent.

Recent breakthroughs in psychiatric genetics have identified genetic risk factors of yet unknown clinical value. A main ethical principal in the context of psychiatric research as well as future clinical genetic testing is the respect for a person's autonomy to decide whether to undergo genetic testing, and whom to grant access to genetic data. However, experience within the psychiatric genetic research setting has indicated controversies surrounding attitudes toward this ethical principal. This study aimed to explore attitudes concerning the right of individuals to self-determine testing and disclosure of results, and to determine whether these attitudes are context-dependent, that is, not directly related to the test result but rather to specific circumstances. N = 160 individuals with major depression or bipolar disorder and n = 29 relatives of individuals with either illness completed an online-questionnaire assessing attitudes toward genetic testing, genetic research, disclosure of results, incidental findings, and access to psychiatric genetic test results. Generally, the right of the person's autonomy was considered very important, but attitudes varied. For example, half of those who considered that children should have the right to refuse psychiatric genetic testing even against their parents' will, also state that they should be tested upon their parents' wishes. Also, the majority of respondents considered the physician entitled to disregard their stated wishes concerning the disclosure of incidental findings in case of good treatment options. Thus, researchers and clinicians must be aware that attitudes toward psychiatric genetic testing are often mutable and should discuss these prior to testing.

Evidence for increased genetic risk load for major depression in patients assigned to electroconvulsive therapy.

Electroconvulsive therapy (ECT) is the treatment of choice for severe and treatment-resistant depression; disorder severity and unfavorable treatment outcomes are shown to be influenced by an increased genetic burden for major depression (MD). Here, we tested whether ECT assignment and response/nonresponse are associated with an increased genetic burden for major depression (MD) using polygenic risk score (PRS), which summarize the contribution of disease-related common risk variants. Fifty-one psychiatric inpatients suffering from a major depressive episode underwent ECT. MD-PRS were calculated for these inpatients and a separate population-based sample (n = 3,547 healthy; n = 426 self-reported depression) based on summary statistics from the Psychiatric Genomics Consortium MDD-working group (Cases: n = 59,851; Controls: n = 113,154). MD-PRS explained a significant proportion of disease status between ECT patients and healthy controls (p = .022, R2 = 1.173%); patients showed higher MD-PRS. MD-PRS in population-based depression self-reporters were intermediate between ECT patients and controls (n.s.). Significant associations between MD-PRS and ECT response (50% reduction in Hamilton depression rating scale scores) were not observed. Our findings indicate that ECT cohorts show an increased genetic burden for MD and are consistent with the hypothesis that treatment-resistant MD patients represent a subgroup with an increased genetic risk for MD. Larger samples are needed to better substantiate these findings.

Dynamical state transitions into addictive behaviour and their early-warning signals.

The theory of critical transitions in complex systems (ecosystems, climate, etc.), and especially its ability to predict abrupt changes by early-warning signals based on analysis of fluctuations close to tipping points, is seen as a promising avenue to study disease dynamics. However, the biomedical field still lacks a clear demonstration of this concept. Here, we used a well-established animal model in which initial alcohol exposure followed by deprivation and subsequent reintroduction of alcohol induces excessive alcohol drinking as an example of disease onset. Intensive longitudinal data (ILD) of rat drinking behaviour and locomotor activity were acquired by a fully automated drinkometer device over 14 weeks. Dynamical characteristics of ILD were extracted using a multi-scale computational approach. Our analysis shows a transition into addictive behaviour preceded by early-warning signals such as instability of drinking patterns and locomotor circadian rhythms, and a resultant increase in low frequency, ultradian rhythms during the first week of deprivation. We find evidence that during prolonged deprivation, a critical transition takes place pushing the system to excessive alcohol consumption. This study provides an adaptable framework for processing ILD from clinical studies and for examining disease dynamics and early-warning signals in the biomedical field.

Appetite loss as a potential predictor of suicidal ideation and self-harm in adolescents: A school-based study.

Suicide is a leading cause of death in adolescents, but detection of its risk is often challenging. Many mental illnesses share the common symptom of appetite loss and it is also known that people who suffer from these illnesses are at greater risk of suicide. However, the relationship between appetite loss and suicide risk has yet to be examined. For adolescents in particular, questions about appetite loss may be easier to answer than sensitive questions regarding mental health. The present study aims to investigate the association of appetite loss with suicidal ideation and self-harm in adolescents. Rates of adolescents with suicidal ideation or self-harm associated with appetite-loss were examined in 18,250 Japanese junior and senior high school students (aged 12-18) using a self-report questionnaire. Insomnia, a physical symptom which has previously been associated with suicide risk, was also controlled for in the analysis. Results showed that rates of adolescents with suicidal ideation or self-harm significantly increased according to the degree of self-reported appetite loss. Similar results were observed for insomnia. Odds ratios (ORs) for suicidal ideation and self-harm were 5.5 and 4.1 for adolescents with appetite loss compared to those without it, and the ORs were 5.5 and 3.5 for those with insomnia compared to those without it, respectively, adjusting for sex and age (p < 0.001). ORs remained statistically significant after adjusting for depression/anxiety (General Health Questionnaire-12 score). In conclusion, self-reported appetite loss was highly associated with suicidal ideation and self-harm in adolescents; adolescents reporting physical symptoms such as loss of appetite or insomnia should be given careful attention.

Prefrontal mechanisms in preference and non-preference-based judgments.

When we decide between two options, we can make our decision based on what we prefer, (preference-based choice), or we can also choose based on which option we want to avoid more (non-preference-based choice). Most decision making research has examined preference-based choice but has not differentiated it from non-preference-based choice. The decision making process can be decomposed into multiple value-based computational processes, which are shown to be subserved by different regions in the prefrontal cortex (PFC). Here we show that the same decision circuits within the PFC are configured differently depending on whether decisions are made based on preference or non-preference criteria (decision rule). Activation in the dorsolateral PFC changed depending on both the values of the two choice options and decision rule. We also found that activation in the medial and lateral PFC was modulated linearly according to the difference in value between the two items and according to the value of the chosen item, respectively. In the medial and lateral PFC, there were distinct patterns of activation between dorsal and ventral regions: in dorsal regions value-related changes in activation were modulated by the decision rule, whereas in ventral regions activation patterns were not modulated. We propose that preference and non-preference decision rules represented in the dorsal PFC differently configure decision processes, resulting in context-specific significance being attached to the choice values represented in the ventral PFC.

Reduced heart rate variability is related to fluctuations in psychological stress levels in daily life.

Laboratory-based studies have shown that psychological stress caused by response to various stressors triggers acute changes in the cardiovascular system. A better understanding is needed of the emerging evidence on temporal associations between psychological stress and cardiovascular responses in natural settings. This study examined the association of psychological stress and heart rate variability (HRV) in daily life, at high resolution over 2 weeks, taking the effect of physical activity into account. Participants (n = 34) completed ecological momentary assessments (EMA) 6 times per day, reporting levels of perceived stress, low-arousal negative affect (LNA), and high-arousal negative affect. Chest-mounted heart-rate monitors were worn to assess HRV. Multilevel models were used to examine the association between psychological stress levels and preceding/subsequent HRV. Reduced time domain HRV measures (mean and standard deviation of R-wave to R-wave intervals) during the prior hour predicted higher levels of perceived stress. Frequency domain HRV measures higher low to high frequency (LF/HF) and lower HF to total power (HF nu) ratios during the preceding 10 min predicted higher perceived stress levels, suggesting the dominance of sympathetic nervous system activity. EMA reports of higher perceived stress levels were associated with reduced time domain HRV measures during the following 10 min. On the other hand, higher LNA were related to increased HRV measures, such as lower LF/HF and higher HF nu during the following hour. The dynamic associations observed may have therapeutic implications for 'just-in-time' interventions in the management of daily stress and cardiovascular health.

Haplotype phasing of CYP2D6: an allelic ratio method using Agena MassARRAY data.

Pharmacogenomics aims to use the genetic information of an individual to personalize drug prescribing. There is evidence that pharmacogenomic testing before prescription may prevent adverse drug reactions, increase efficacy, and reduce cost of treatment. CYP2D6 is a key pharmacogene of relevance to multiple therapeutic areas. Indeed, there are prescribing guidelines available for medications based on CYP2D6 enzyme activity as deduced from CYP2D6 genetic data. The Agena MassARRAY system is a cost-effective method of detecting genetic variation that has been clinically applied to other genes. However, its clinical application to CYP2D6 has to date been limited by weaknesses such as the inability to determine which haplotype was present in more than one copy for individuals with more than two copies of the CYP2D6 gene. We report application of a new protocol for CYP2D6 haplotype phasing of data generated from the Agena MassARRAY system. For samples with more than two copies of the CYP2D6 gene for which the prior consensus data specified which one was present in more than one copy, our protocol was able to conduct CYP2D6 haplotype phasing resulting in 100% concordance with the prior data. In addition, for three reference samples known to have more than two copies of CYP2D6 but for which the exact number of CYP2D6 genes was unknown, our protocol was able to resolve the number for two out of the three of these, and estimate the likely number for the third. Finally, we demonstrate that our method is applicable to CYP2D6 hybrid tandem configurations.

Association between number of confidants and adolescent anxiety/depression: a school-based study.

BACKGROUND: Having no or few confidants is found to be associated with more severe mental health problems and a higher prevalence of depression in adults, but research examining this association in adolescents is scarce. Social relationships may be particularly critical during adolescence, as it is an important developmental period during which vulnerability to mental health problems increases. The present study examined the relationship between having no or few confidants and anxiety/depressive symptoms in adolescents. METHODS: Cross-sectional self-report survey targeting 7-12th grade students (age range: 12-18) was conducted in public junior and senior high schools in Mie and Kochi, Japan. Data from 17,829 students (49.7% boys) were analyzed. Associations between anxiety/depressive symptoms (12-item General Health Questionnaire; score range: 0-12) and the number of confidants (None, 1-3, or ≥ 4) were examined using multilevel regression analyses. The analyses were stratified by gender and school level (junior/senior high), and adjusted for experiences of being physically abused and bullied and the interactions of these experiences with the number of confidants. RESULTS: Having no or 1-3 confidants was associated with more anxiety/depressive symptoms, compared to having ≥ 4 confidants (p < 0.001) in all stratified groups. Having no confidants was associated with more anxiety/depressive symptoms than having 1-3 confidants (p < 0.001); in senior high boys, no difference was observed between having no confidants and having 1-3 confidants. In addition, in senior high boys, victims of bullying who have confidants reported significantly less anxiety/depressive symptoms than the victims who have no confidants (p < 0.01). CONCLUSIONS: Adolescents who had no or few confidants had more anxiety/depressive symptoms. Attention needs to be paid to better identify these adolescents, and avenues to support them need to be established.

A survey of mental health literacy in parents and guardians of teenagers.

Introduction: Parents and guardians (hereafter caregivers) of teenagers need high levels of mental health literacy (MHL) to manage mental health problems arising in teenagers in their care. Previous studies assessing MHL levels in caregivers of teenagers have reported mixed results, making it difficult to clearly estimate caregiver MHL levels. This study aimed to investigate MHL levels in Japanese caregivers of regular teenagers. Methods: Responses from caregivers (n = 1,397) of students entering junior and senior high schools to a self-administered online questionnaire were analyzed. The questionnaire assessed (a) knowledge about mental health/illnesses and (b) attitudes towards mental health problems in teens in their care (e.g., recognition of depression as a medical illness and intention to engage in helping behaviors). Results: The average proportion of correct answers to the knowledge questions (n = 7) was 55.4%; about one tenth (9.2%) of caregivers correctly answered only one or none of the questions. Few caregivers correctly answered about the life-time prevalence of any mental illnesses (46.1%) and appropriate sleep duration for teenagers' health (16.5%). The proportions of caregivers who had the intention to listen to the teen in their care, consult another person, and seek professional medical help if the teen suffered from depression were 99.5%, 91.5% and 72.7%, respectively. Conclusions: Many teenagers' caregivers appeared to be willing to help the teens in their care if they were suffering from mental health problems. However, there was much room for improvement in knowledge on mental health/illnesses and intention to seek help from medical professionals. Efforts toward better education should be made.

Speech Features as Predictors of Momentary Depression Severity in Patients With Depressive Disorder Undergoing Sleep Deprivation Therapy: Ambulatory Assessment Pilot Study.

BACKGROUND: The use of mobile devices to continuously monitor objectively extracted parameters of depressive symptomatology is seen as an important step in the understanding and prevention of upcoming depressive episodes. Speech features such as pitch variability, speech pauses, and speech rate are promising indicators, but empirical evidence is limited, given the variability of study designs. OBJECTIVE: Previous research studies have found different speech patterns when comparing single speech recordings between patients and healthy controls, but only a few studies have used repeated assessments to compare depressive and nondepressive episodes within the same patient. To our knowledge, no study has used a series of measurements within patients with depression (eg, intensive longitudinal data) to model the dynamic ebb and flow of subjectively reported depression and concomitant speech samples. However, such data are indispensable for detecting and ultimately preventing upcoming episodes. METHODS: In this study, we captured voice samples and momentary affect ratings over the course of 3 weeks in a sample of patients (N=30) with an acute depressive episode receiving stationary care. Patients underwent sleep deprivation therapy, a chronotherapeutic intervention that can rapidly improve depression symptomatology. We hypothesized that within-person variability in depressive and affective momentary states would be reflected in the following 3 speech features: pitch variability, speech pauses, and speech rate. We parametrized them using the extended Geneva Minimalistic Acoustic Parameter Set (eGeMAPS) from open-source Speech and Music Interpretation by Large-Space Extraction (openSMILE; audEERING GmbH) and extracted them from a transcript. We analyzed the speech features along with self-reported momentary affect ratings, using multilevel linear regression analysis. We analyzed an average of 32 (SD 19.83) assessments per patient. RESULTS: Analyses revealed that pitch variability, speech pauses, and speech rate were associated with depression severity, positive affect, valence, and energetic arousal; furthermore, speech pauses and speech rate were associated with negative affect, and speech pauses were additionally associated with calmness. Specifically, pitch variability was negatively associated with improved momentary states (ie, lower pitch variability was linked to lower depression severity as well as higher positive affect, valence, and energetic arousal). Speech pauses were negatively associated with improved momentary states, whereas speech rate was positively associated with improved momentary states. CONCLUSIONS: Pitch variability, speech pauses, and speech rate are promising features for the development of clinical prediction technologies to improve patient care as well as timely diagnosis and monitoring of treatment response. Our research is a step forward on the path to developing an automated depression monitoring system, facilitating individually tailored treatments and increased patient empowerment.

Biological aging markers in blood and brain tissue indicate age acceleration in alcohol use disorder.

BACKGROUND: Alcohol use disorder (AUD) is associated with increased mortality and morbidity risk. A reason for this could be accelerated biological aging, which is strongly influenced by disease processes such as inflammation. As recent studies of AUD show changes in DNA methylation and gene expression in neuroinflammation-related pathways in the brain, biological aging represents a potentially important construct for understanding the adverse effects of substance use disorders. Epigenetic clocks have shown accelerated aging in blood samples from individuals with AUD. However, no systematic evaluation of biological age measures in AUD across different tissues and brain regions has been undertaken. METHODS: As markers of biological aging (BioAge markers), we assessed Levine's and Horvath's epigenetic clocks, DNA methylation telomere length (DNAmTL), telomere length (TL), and mitochondrial DNA copy number (mtDNAcn) in postmortem brain samples from Brodmann Area 9 (BA9), caudate nucleus, and ventral striatum (N = 63-94), and in whole blood samples (N = 179) of individuals with and without AUD. To evaluate the association between AUD status and BioAge markers, we performed linear regression analyses while adjusting for covariates. RESULTS: The majority of BioAge markers were significantly associated with chronological age in all samples. Levine's epigenetic clock and DNAmTL were indicative of accelerated biological aging in AUD in BA9 and whole blood samples, while Horvath's showed the opposite effect in BA9. No significant association of AUD with TL and mtDNAcn was detected. Measured TL and DNAmTL showed only small correlations in blood and none in brain. CONCLUSIONS: The present study is the first to simultaneously investigate epigenetic clocks, telomere length, and mtDNAcn in postmortem brain and whole blood samples in individuals with AUD. We found evidence for accelerated biological aging in AUD in blood and brain, as measured by Levine's epigenetic clock, and DNAmTL. Additional studies of different tissues from the same individuals are needed to draw valid conclusions about the congruence of biological aging in blood and brain.