Evaluation of Phenotypic and Genotypic Variations of Drug Metabolising Enzymes and Transporters in Chronic Pain Patients Facing Adverse Drug Reactions or Non-Response to Analgesics: A Retrospective Study.

This retrospective study evaluates the link between an adverse drug reaction (ADR) or a non-response to treatment and cytochromes P450 (CYP), P-glycoprotein (P-gp) or catechol-O-methyltransferase (COMT) activity in patients taking analgesic drugs for chronic pain. Patients referred to a pain center for an ADR or a non-response to an analgesic drug between January 2005 and November 2014 were included. The genotype and/or phenotype was obtained for assessment of the CYPs, P-gp or COMT activities. The relation between the event and the result of the genotype and/or phenotype was evaluated using a semi-quantitative scale. Our analysis included 243 individual genotypic and/or phenotypic explorations. Genotypes/phenotypes were mainly assessed because of an ADR (n = 145, 59.7%), and the majority of clinical situations were observed with prodrug opioids (n = 148, 60.9%). The probability of a link between an ADR or a non-response and the genotypic/phenotypic status of the patient was evaluated as intermediate to high in 40% and 28.2% of all cases, respectively. The drugs in which the probability of an association was the strongest were the prodrug opioids, with an intermediate to high link in 45.6% of the cases for occurrence of ADRs and 36.0% of the cases for non-response. This study shows that the genotypic and phenotypic approach is useful to understand ADRs or therapeutic resistance to a usual therapeutic dosage, and can be part of the evaluation of chronic pain patients.

Long-Term Quality of Prescription for ST-Segment Elevation Myocardial Infarction (STEMI) Patients: A Real World 1-Year Follow-Up Study.

AIM: American and European associations of cardiology published specific guidelines about recommended drugs for secondary prevention in ST-segment elevation myocardial infarction (STEMI) patients. Our aim was to assess whether drug prescription for STEMI patients was in accordance with the guidelines at discharge and after 1 year. METHOD: We used data of 361 patients admitted for STEMI in a tertiary hospital in Switzerland from 2014 to 2016. We assessed the adequacy of prescription of recommended drugs at two time points: discharge and after 1 year. Medications assessed were aspirin, P2Y12 inhibitors, statin, angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) and ß-blockers. We took into account several criteria like statin dosage (low versus high intensity) and presence of contraindication for consideration of optimal therapy. Predictors of incomplete prescription of guideline medications were then assessed with multivariate logistic regression models. RESULTS: From discharge (n = 358) to 1-year follow-up (n = 303), rate of optimal prescription was reduced from 98.6 to 91.7% for aspirin, from 93.9 to 79.1% for P2Y12 inhibitors, from 83.8 to 65.7% for statins, from 98.6 to 95.6% for ACEIs/ARBs, and from 97.1 to 96.9% for ß-blockers. Predictors of incomplete prescription of guideline medications at discharge were female sex (odds ratio [OR] 2.54, p = 0.007), active or former smoker status (OR 2.29, p = 0.017), multivessel disease (OR 2.07, p = 0.022), left ventricular ejection fraction < 40% (OR 2.49, p = 0.008), and transfer to cardiac surgery (OR 9.66, p = 0.018). At 1 year, age > 65 (OR 1.92, p = 0.036) remained the only significant predictor. CONCLUSION: The present study showed a high prescription rate of guideline-recommended medications in a referral center for primary percutaneous coronary intervention. At discharge, women and co-morbid patients were at the highest risk of incomplete prescription of guideline medications, whereas long-term prescription was suboptimal for elderly. A drug lacking at time of discharge was rarely introduced within the year, which underscores the paramount importance of optimal prescription at time of discharge. Strategies like implementing a standardized prescription could reduce the proportion of suboptimal prescription. It could therefore be one way to improve the long-term quality of care of our patients to the highest level. This study used local data from AMIS Plus-National Registry of Acute Myocardial Infarction in Switzerland (NCT01305785).

Tobacco craving and withdrawal symptoms in psychiatric patients during a motivational enhancement intervention based on a 26-hour smoking abstinence period.

INTRODUCTION: In psychiatric patients, tobacco withdrawal symptoms are frequently seen as a barrier to smoking cessation; however, further studies are warranted in this specific population. METHODS: Patients receiving in- or out-patient mental health care participated in a motivational enhancement program including a 26-hour tobacco abstinence experience with professional support and optional nicotine replacement therapy. The study included 174 subjects, of whom 159 were evaluated 1 week before and at the end of the 26-hour abstinence period. Repeated assessments included the Minnesota Nicotine Tobacco Withdrawal Scale Revised (MNWS-R), two items of the Mood and Physical Symptoms Scale (MPSS) regarding craving, the State-Trait Anxiety Inventory (STAI-S), the Beck Depression Inventory (BDI-21), and the World Health Organization Well-Being Index (WHO-5). RESULTS: More than half the participants (52.3%) succeeded in 26-hour smoking abstinence. Craving was the most frequent MNWS-R withdrawal symptom (28.3% scored ≥3 on a 0-4 scale). Comparison of pre- and post-intervention data revealed significant improvements in 13 of 16 MNWS-R symptoms as well as craving (MPSS) and well-being, and significant decreases in anxiety and depression. Increasing MNWS-R craving scores and greater depression were both significantly associated with lower success in the 26-hour smoking abstinence period. CONCLUSIONS: The negative effects of tobacco withdrawal symptoms in psychiatric patients may be substantially overestimated. Participation in a supportive structured motivational intervention with a 26-hour smoking cessation experience was well tolerated and contributed to temporary improvements in mental state. Craving is an interesting symptom to evaluate during smoking cessation attempts.

Efficacy and Safety of a Rapid Intravenous Injection of Ketamine 0.5 mg/kg in Treatment-Resistant Major Depression: An Open 4-Week Longitudinal Study.

BACKGROUND: Ketamine has been documented for its rapid antidepressant effects. However, optimal dose and delivery route have not yet been thoroughly investigated. The objectives of this study were to document the safety and test the antidepressant and antisuicidal effects of a single rapid 1-minute injection of ketamine 0.5 mg/kg in treatment-resistant depression (TRD). METHODS: Ten patients with TRD were included in an open, noncontrolled 4-week study and received a rapid intravenous dose of ketamine 0.5 mg/kg. Main outcome measure was the Montgomery-Åsberg Depression Rating Scale and suicidality was assessed using the Scale for Suicide Ideation. RESULTS: Rapid injection of ketamine elicited transient increase of blood pressure and altered states of consciousness in all patients and mild psychotomimetic effects in 4 patients, which all resolved without any intervention. Decrease of depression severity was observed from 40-minute postinjection until day 15. Eight patients became responders within 1 day and all were nonresponders after 4 weeks. The decrease of suicidal ideation was significant until day 7. Analysis indicated that higher severity of depression and anxiety at baseline predicted a larger Montgomery-Åsberg Depression Rating Scale decrease after 4 weeks. CONCLUSIONS: This study suggests that in well-controlled medical settings with adequate monitoring, a single rapid 1-minute injection of ketamine 0.5 mg/kg can be well tolerated and is efficacious in rapidly reducing depression symptoms and suicidal thoughts in outpatients with TRD. These findings are relevant to the practice of general clinical psychiatry and emergency departments were ketamine can have a place in acute management of TRD. Larger studies are necessary to confirm these results.

Phenotypic Assessment of Drug Metabolic Pathways and P-Glycoprotein in Patients Treated With Antidepressants in an Ambulatory Setting.

OBJECTIVE: Drug-metabolizing enzymes (DMEs), such as cytochrome P450 (CYP) enzymes, and transporters have emerged as major determinants of variability in drug metabolism and response. This study investigated the association between CYP and P-glycoprotein activities and plasma antidepressant concentration in an outpatient clinical setting. Secondary outcomes were antidepressant efficacy and tolerance. We also describe phenotypes in patients treated with antidepressants and evaluate the tolerance of a minimally invasive phenotyping approach. METHODS: From January 2015 to August 2015, 64 patients on a stable antidepressant regimen underwent a simultaneous assessment of steady-state antidepressant concentration and DME (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A) and P-glycoprotein transporter activity using a cocktail phenotyping approach. Psychiatric diagnoses were in accordance with DSM-5. RESULTS: We observed a high proportion of subjects (> 20%) with reduced activity of CYP2C19, CYP2D6, CYP3A4, and P-glycoprotein. As expected, higher CYP activity for major metabolic pathways was associated with lower concentration of the parent compound (CYP2C19 and escitalopram, P = .025; CYP2D6 and fluoxetine, P < .001; CYP2C19 and sertraline, P = .001), higher concentration of the metabolite (CYP2D6 and O-desmethylvenlafaxine, P = .007), and higher metabolite-to-parent drug ratio (CYP2C19 and escitalopram, P = .03; CYP2D6 and fluoxetine, P < .001; CYP2C19 and sertraline, P = .048; CYP2B6 and sertraline, P = .006). Phenotyping also highlighted the relevance of a minor metabolic pathway for venlafaxine (CYP3A4). Insufficient response and adverse reactions to antidepressants were not significantly associated with plasma antidepressant concentration, DME, or P-glycoprotein activity. Tolerance of the phenotypic test in ambulatory settings was found to be excellent. CONCLUSIONS: The phenotypic assessment of DMEs and a transporter is a valuable, well-tolerated method to explore the interindividual variability in drug disposition in clinical settings. The method is able to account for the inhibitory activity of antidepressants themselves and for polymedication, which is frequent in this population of refractory depressed patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02438072.

Measuring racing thoughts in healthy individuals: The Racing and Crowded Thoughts Questionnaire (RCTQ).

Racing thoughts refer to an acceleration and overproduction of thoughts, which have been associated with manic and mixed episodes. Phenomenology distinguishes 'crowded' from 'racing' thoughts, associated with mixed depression and mania, respectively. Recent data suggest racing thoughts might also be present in healthy individuals with sub-affective traits and symptoms. We investigated this assumption, with a 34-item self-rating scale, the Racing and Crowded Thoughts Questionnaire (RCTQ), and evaluated its reliability, factor structure, and concurrent validity. 197 healthy individuals completed the RCTQ, the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego - autoquestionnaire (TEMPS-A), the Beck Depression Inventory (BDI), the Altman Self-Rating Mania scale (ASRM), and the Ruminative Response Scale (RRS). Exploratory factor analysis yielded a three-factor solution, labeled 'thought overactivation', 'burden of thought overactivation', and 'thought overexcitability'. Internal consistency of each of the three subscales of the RCTQ was excellent. The TEMPS-A cyclothymia score was associated with the three factors, suggesting good concurrent validity. The 'thought activation' subscale was selectively associated with current elated mood and included items conveying both the notion of increased amount and velocity of thoughts, whereas the 'burden of thought overactivation' subscale was associated with current low mood. The 'thought overexcitability' subscale included items conveying the notion of distractibility, and was associated with both elated and low mood. Rumination was not a significant predictor of RCTQ subscores. These results suggest that the RCTQ has good psychometric properties. Racing and crowded thoughts, as measured by the RCTQ, are a multi-faceted phenomenon, distinct from rumination, and particularly associated with mood instability even in its milder forms.

Subjective Distress Associated with Adult ADHD: evaluation of a new self-report.

The current study aims at documenting the psychometric properties of the Subjective Distress Associated with Adult ADHD-Self-Report (SDAAA-SR), a newly developed instrument for the assessment of psychological suffering in ADHD adults. The SDAAA-SR was administered to 247 students and 142 ADHD adults. Factor structure, internal consistency, test-retest reliability, convergent validity and discriminant validity were assessed. Sensitivity to change was examined in a subsample of 25 ADHD patients who participated in a 1-year therapy. The initial pool of 62 items was reduced to 33 items distributed in a three-component structure. Internal consistency was excellent for the "distress due to inattention/disorganization" subscale and good for the "distress due to hyperactivity/impulsivity" and "distress due to self-esteem deficit" subscales. Test-retest reliability in a subsample of 98 students was substantial for all three subscales. ADHD patients scored significantly higher than students on distress due to "inattention/disorganization" and "hyperactivity/impulsivity," but no difference was observed for "self-esteem deficit." The components "inattention/disorganization" and "hyperactivity/impulsivity" displayed moderate to large correlations with the corresponding dimensions of the Adult Self-Report Scale for ADHD (ASRS-V1.1). Distress due to "inattention/disorganization" and "self-esteem deficit" was significantly associated with lower satisfaction with social behaviors (QFS, social functioning questionnaire) and quality of life (WHOQOL-BREF). Distress due to "inattention/disorganization" and "self-esteem deficit" significantly decreased after a 1-year therapy. The SDAAA-SR represents a reliable and valid measure of adult ADHD-associated distress, an important but often undocumented parameter in the clinical setting. Its use as an outcome variable in psychological interventions deserves further investigation.

Determinants of Suicidality and of Treatment Modalities in a Community Psychiatry Sample of Asylum Seekers.

A high prevalence of mental illness has been reported in asylum seekers. The present cross-sectional study examined suicidal thoughts, treatment modalities (outpatient crisis intervention, inpatient care), and their determinants in asylum seekers (n = 119) and permanent residents (n = 120) attending the same outpatient clinic in Geneva, Switzerland. The most frequent diagnoses were depressive disorders (64.7%) and posttraumatic stress disorder (34.5%) in asylum seekers and psychotic (55.0%) and depressive disorders (33.3%) in permanent residents. The frequency of suicidal thoughts was similar in both groups (>30%). Asylum seekers benefited from outpatient crisis intervention more frequently than residents did (26.9% vs. 5.8%), whereas inpatient care was less frequent (25.2% vs. 44.2%). In asylum seekers, acute suicidal thoughts were associated with increased frequency of outpatient crisis interventions, and, suicidal thoughts, psychosis, or personality disorders were associated with higher rates of hospitalization. Documenting clinical characteristics and service utilization of asylum seekers is a prerequisite to organizing targeted interventions.

Maternal PTSD and corresponding neural activity mediate effects of child exposure to violence on child PTSD symptoms.

The aim of this study was to examine the relationship of maternal interpersonal violence-related posttraumatic stress disorder (IPV-PTSD), associated neural activity in response to mother-child relational stimuli, and child psychopathology indicators at child ages 12-42 months and one year later. The study tested the hypothesis that decreased maternal neural activity in regions that subserve emotion regulation would be associated with child symptoms associated with emotional dysregulation at both time points. Functional magnetic resonance imaging of 42 mothers with or without violence-exposure and associated IPV-PTSD were assessed. Their child's life-events and symptoms/behaviors indicative of high-risk subsequent PTSD diagnosis on a maternal-report questionnaire were measured one year later. Maternal IPV-PTSD severity was significantly associated with decreased ventromedial prefrontal cortex (vmPFC) activation in response to mother-child relational stimuli. Maternal IPV-PTSD severity and decreased vmPFC activation were then significantly associated with a child attachment disturbance at 12-42 months and symptoms/behaviors one year later, that were correlated with emotional dysregulation and risk for child PTSD. Maternal IPV-PTSD and child exposure to IPV were both predictive of child PTSD symptoms with maternal IPV-PTSD likely mediating the effects of child IPV exposure on child PTSD symptoms. These findings suggest that maternal IPV-PTSD severity and associated decreased vmPFC activity in response to mother-child relational stimuli are predictors of child psychopathology by age 12-42 months and one-year later. Significant findings in this paper may well be useful in understanding how maternal top-down cortico-limbic dysregulation promotes intergenerational transmission of IPV and related psychopathology and, thus should be targeted in treatment.

Self-Reported Long-Term Benefits of Mindfulness-Based Cognitive Therapy in Patients with Bipolar Disorder.

OBJECTIVES: This study focused on patients with bipolar disorder (BD), several years after their participation in mindfulness-based cognitive therapy (MBCT). It aimed at documenting sustained mindfulness practice, perceived long-term benefit from the program, and changes regarded as direct consequences of the intervention. DESIGN: This cross-sectional survey took place at least 2 years after MBCT for 70.4% of participants. LOCATION: It was conducted in two specialized outpatient units for BDs that are part of the Geneva University Hospitals (Switzerland) and the Sainte-Anne Hospital in Paris (France). SUBJECTS: Eligibility criteria were a diagnosis of BD according to DSM-IV and participation in at least four MBCT sessions. Response rate was 66.4%. The final sample included 71 outpatients (71.8% bipolar I, 28.2% bipolar II). OUTCOME MEASURES: A questionnaire retrospectively assessed patient-perceived change, benefit from MBCT, and current mindfulness practice. RESULTS: Proportions of respondents who practiced mindfulness at least once a week were 54.9% for formal practice (body scan, sitting meditation, mindful walking, or movements) and 57.7% for informal practice (mindful daily activities). Perceived benefit for the prevention of relapse was moderate, but patients acknowledged long-lasting effects and persistent changes in their way of life. Formal mindfulness practice at least once a week tended to be associated with increased long-lasting effects (p = 0.052), whereas regular informal practice and mindful breathing were significantly associated with persistent changes in daily life (p = 0.038) and better prevention of depressive relapse (p = 0.035), respectively. The most frequently reported positive change was increased awareness of being able to improve one's health. CONCLUSIONS: Despite methodological limitations, this survey allowed documenting mindfulness practice and perceived sustained benefit from MBCT in patients with BD. Participants particularly valued increased awareness that they can influence their own health. Both informal and formal practices, when sustained in the long term, might promote long-lasting changes.

Screening for genotypic and phenotypic variations in CYP450 activity in patients with therapeutic problems in a psychiatric setting, a retrospective study.

OBJECTIVES: This retrospective study aimed to assess to what extent an adverse drug reaction (ADR), an abnormal therapeutic drug monitoring (TDM) or a non-response, was attributable to an abnormal cytochrome P450 activity in a psychiatric setting. METHOD: We collected the results of investigations performed in these situations related to psychotropic drugs between January 2005 and November 2014. Activities of different cytochrome P450 were assessed by genotyping and/or phenotyping. Two experienced clinical pharmacologists assessed independently the possible association between the event and the results of the investigations. RESULTS: One hundred and thirty eight clinical or biological situations had a complete assessment of all major metabolic pathways of the target drug. A majority of clinical or biological situations were observed with antidepressants (n=93, 67.4%), followed by antipsychotics (n=28, 20.3%), benzodiazepines and hypnotics (n=13, 9.4%), and psychostimulants (n=4, 2.9%). Genotype and/or phenotype determination was mainly performed because of ADRs (n=68, 49.3%) or non-response (n=46, 33.3%). Inter-rate reliability of the scoring system between the pharmacologists was excellent (kappa=0.94). The probability of an association between ADR, TDM or non-response and metabolic status was rated as intermediate to high in 34.7% of all cases, with proportions of 30.4% and 36.7%, for non-response and ADR respectively. CONCLUSION: When indicated by clinical pharmacologists, ADR, TDM or non-response may be attributable to a variation of the metabolic status with an intermediate to high probability in 34.7% of patients, based on the congruent assessment made by two clinical pharmacologists. Further studies assessing the clinical relevance of prospective explorations and clarifying the appropriate method according to the clinical context are needed.

Increased Reward-Related Behaviors during Sleep and Wakefulness in Sleepwalking and Idiopathic Nightmares.

BACKGROUND: We previously suggested that abnormal sleep behaviors, i.e., as found in parasomnias, may often be the expression of increased activity of the reward system during sleep. Because nightmares and sleepwalking predominate during REM and NREM sleep respectively, we tested here whether exploratory excitability, a waking personality trait reflecting high activity within the mesolimbic dopaminergic (ML-DA) system, may be associated with specific changes in REM and NREM sleep patterns in these two sleep disorders. METHODS: Twenty-four unmedicated patients with parasomnia (12 with chronic sleepwalking and 12 with idiopathic nightmares) and no psychiatric comorbidities were studied. Each patient spent one night of sleep monitored by polysomnography. The Temperament and Character Inventory (TCI) was administered to all patients and healthy controls from the Geneva population (n = 293). RESULTS: Sleepwalkers were more anxious than patients with idiopathic nightmares (Spielberger Trait anxiety/STAI-T), but the patient groups did not differ on any personality dimension as estimated by the TCI. Compared to controls, parasomnia patients (sleepwalkers together with patients with idiopathic nightmares) scored higher on the Novelty Seeking (NS) TCI scale and in particular on the exploratory excitability/curiosity (NS1) subscale, and lower on the Self-directedness (SD) TCI scale, suggesting a general increase in reward sensitivity and impulsivity. Furthermore, parasomnia patients tended to worry about social separation persistently, as indicated by greater anticipatory worry (HA1) and dependence on social attachment (RD3). Moreover, exploratory excitability (NS1) correlated positively with the severity of parasomnia (i.e., the frequency of self-reported occurrences of nightmares and sleepwalking), and with time spent in REM sleep in patients with nightmares. CONCLUSIONS: These results suggest that patients with parasomnia might share common waking personality traits associated to reward-related brain functions. They also provide further support to the notion that reward-seeking networks are active during human sleep.

Group Psychoeducation for Relatives of Persons With Bipolar Disorder: Perceived Benefits for Participants and Patients.

Psychoeducation is a key element in the management of patients with bipolar disorders. The present study explored the perception of patients and family members with respect to group psychoeducation for relatives. Patients (n = 20) and relatives (n = 26) were assessed with questionnaires about perceived benefits and quality of life (median 4 years after participation). A large majority (>80%) of relatives acknowledged benefits with respect to easier detection of the early warning signs of relapse, improved quality of life, feeling more involved, and engaging in higher quality caregiving activities. Patients were less positive in general, but agreed that the program had helped them deal with crises, increased their feeling of being understood by relatives, and promoted positive changes in the family (>60%). Perceived positive changes in the family were associated with higher quality of life for relatives and patients. The present study highlights the importance of communication enhancement in group psychoeducation for relatives.

Electrocardiographic Screening for Prolonged QT Interval to Reduce Sudden Cardiac Death in Psychiatric Patients: A Cost-Effectiveness Analysis.

IMPORTANCE: Sudden cardiac death is a leading cause of mortality in psychiatric patients. Long QT (LQT) is common in this population and predisposes to Torsades-de-Pointes (TdP) and subsequent mortality. OBJECTIVE: To estimate the cost-effectiveness of electrocardiographic screening to detect LQT in psychiatric inpatients. DESIGN, SETTING, AND PARTICIPANTS: We built a decision analytic model based on a decision tree to evaluate the cost-effectiveness and utility of LQT screening from a health care perspective. LQT proportion parameters were derived from an in-hospital cross-sectional study. We performed experts' elicitation to estimate the risk of TdP, given extent of QT prolongation. A TdP reduction of 65% after LQT detection was based on positive drug dechallenge rate and through adequate treatment and electrolyte adjustments. The base-case model uncertainty was assessed with one-way and probabilistic sensitivity analyses. Finally, the TdP related mortality and TdP avoidance parameters were varied in a two-way sensitivity analysis to assess their effect on the Incremental Cost-Effectiveness Ratio (ICER). MAIN OUTCOMES AND MEASURES: Costs, Quality Ajusted Life Year (QALY), ICER, and probability of cost effectiveness thresholds ($ 10,000, $25,000, and $50,000 per QALY). RESULTS: In the base-case scenario, the numbers of patients needed to screen were 1128 and 2817 to avoid one TdP and one death, respectively. The ICER of systematic ECG screening was $8644 (95%CI, 3144-82 498) per QALY. The probability of cost-effectiveness was 96% at a willingness-to-pay of $50,000 for one QALY. In sensitivity analyses, results were sensitive to the case-fatality of TdP episodes and to the TdP reduction following the diagnosis of LQT. CONCLUSION AND RELEVANCE: In psychiatric hospitals, performing systematic ECG screening at admission help reduce the number of sudden cardiac deaths in a cost-effective fashion.

Methylation of NR3C1 is related to maternal PTSD, parenting stress and maternal medial prefrontal cortical activity in response to child separation among mothers with histories of violence exposure.

Prior research has shown that mothers with Interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) report greater difficulty in parenting their toddlers. Relative to their frequent early exposure to violence and maltreatment, these mothers display dysregulation of their hypothalamic pituitary adrenal axis (HPA-axis), characterized by hypocortisolism. Considering methylation of the promoter region of the glucocorticoid receptor gene NR3C1 as a marker for HPA-axis functioning, with less methylation likely being associated with less circulating cortisol, the present study tested the hypothesis that the degree of methylation of this gene would be negatively correlated with maternal IPV-PTSD severity and parenting stress, and positively correlated with medial prefrontal cortical (mPFC) activity in response to video-stimuli of stressful versus non-stressful mother-child interactions. Following a mental health assessment, 45 mothers and their children (ages 12-42 months) participated in a behavioral protocol involving free-play and laboratory stressors such as mother-child separation. Maternal DNA was extracted from saliva. Interactive behavior was rated on the CARE-Index. During subsequent fMRI scanning, mothers were shown films of free-play and separation drawn from this protocol. Maternal PTSD severity and parenting stress were negatively correlated with the mean percentage of methylation of NR3C1. Maternal mPFC activity in response to video-stimuli of mother-child separation versus play correlated positively to NR3C1 methylation, and negatively to maternal IPV-PTSD and parenting stress. Among interactive behavior variables, child cooperativeness in play was positively correlated with NR3C1 methylation. Thus, the present study is the first published report to our knowledge, suggesting convergence of behavioral, epigenetic, and neuroimaging data that form a psychobiological signature of parenting-risk in the context of early life stress and PTSD.

Long-term mental health outcome in post-conflict settings: Similarities and differences between Kosovo and Rwanda.

BACKGROUND: Few studies investigated the long-term mental health outcome in culturally different post-conflict settings. This study considers two surveys conducted in Kosovo 8 years after the Balkans war and in Rwanda 14 years after the genocide. METHODS: All participants (n = 864 in Kosovo; n = 962 in Rwanda) were interviewed using the posttraumatic stress disorder (PTSD) and major depressive episode (MDE) sections of the Mini International Neuropsychiatric Interview (MINI) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). RESULTS: Proportions of participants who met diagnostic criteria for either PTSD or MDE were 33.0% in Kosovo and 31.0% in Rwanda, with co-occurrence of both disorders in 17.8% of the Rwandan sample and 9.5% of the Kosovan sample. Among patients with PTSD, patterns of symptoms significantly differed in the two settings, with avoidance and inability to recall less frequent and sense of a foreshortened future and increased startle response more common in Rwanda. Significant differences were also observed in patients with MDE, with loss of energy and difficulties concentrating less frequent and suicidal ideation more common in Rwanda. Comorbid PTSD and MDE were associated with decreased SF-36 subjective mental and physical health scores in both settings, but significantly larger effects in Kosovo than in Rwanda. CONCLUSION: Culturally different civilian populations exposed to mass trauma may differ with respect to their long-term mental health outcome, including comorbidity, symptom profile and health perception.

How do maternal PTSD and alexithymia interact to impact maternal behavior?

Maternal interpersonal violence-related post-traumatic stress disorder (IPV-PTSD) is known to be associated with impairment of a mother's capacity to participate in mutual emotion regulation during her child's first years of life. This study tested the hypothesis that maternal difficulty in identifying feelings in self and other, as an important dimension of the construct of alexithymia, together with maternal IPV-PTSD, would be negatively associated with maternal sensitivity. Maternal sensitivity to child emotional communication is a marker of maternal capacity to engage in mutual regulation of emotion and arousal. Following diagnostic interviews and administration of the Toronto Alexithymia Scale, 56 mothers and their toddlers (ages 12-42 months) were filmed during free-play and separation/novelty-exposure. Observed maternal sensitivity was coded via the CARE-Index. Maternal IPV-PTSD severity, difficulty in identifying emotions, and lower socio-economic status were all associated with less maternal sensitivity, and also with more maternal controlling and unresponsive behavior on the CARE-Index.

Subjective experience of thought overactivation in mood disorders: beyond racing and crowded thoughts.

BACKGROUND: Racing thoughts, crowded thoughts and flight of ideas are frequent symptoms in mood disorders, but the underlying subjective experience of overactivation of thought processes remains poorly documented. METHODS: Qualitative analysis of audiotaped interviews explored subjective experience of thought overactivation in patients with mood disorders (sample 1, n = 45). Quantitative analysis considered the properties of a newly developed rating scale in sample 1, in an additional sample of patients with mood disorders (sample 2, n = 37) and in healthy subjects (sample 3, n = 38). RESULTS: Qualitative analysis of individual interviews revealed that 5 conceptual categories characterized thought overactivation: sequential thought flow, overstimulation, competition for resource allocation, unexpected/unexplained onset, and association with mood and emotions. A principal component analysis of the initial 16-item rating scale indicated that a single component explained 55.9% of the variance, with major and exclusive contributions from 9 items, which were retained in the final 9-item Subjective Thought Overactivation Questionnaire (STOQ; Cronbach's α = 0.95). Total score correlated significantly with activation, depression and perceived conflict subscales of the Internal State Scale (ISS; rs = 0.57-0.66, p < 0.001). It was associated with decreased well-being (ISS; rs = -0.48, p = 0.001) and increased state anxiety (State-Trait Anxiety Inventory; rs = 0.60, p < 0.001). The STOQ score was significantly higher in patients than in healthy subjects. It allowed distinguishing between ISS mood states, with the highest median score in mixed states. LIMITATIONS: Sample size, representativeness, possible bias in qualitative analysis, and quality of expert consensus. CONCLUSIONS: Qualitative analysis of clinical interviews, together with a new short rating scale, contributed to a documentation of subjective thought overactivation, an important but often undetected feature in mood disorders.

Staff representations and tobacco-related practices in a psychiatric hospital with an indoor smoking ban.

The present study describes representations about smoking and practices related to patient smoking among staff of a large public psychiatric hospital. A survey was performed using a specially designed questionnaire. The return rate was 72.4% (n = 155). A large proportion of staff recognized the importance of both smoking status and mental health for patient's well-being (46.9%), and believed that smoking cessation was possible for psychiatric patients (58.6%). However, the role of the psychiatric hospital was perceived as providing information (85.3%) and helping to diminish cigarette consumption (51%), rather than proposing smoking cessation (29.5%). Staff daily practice included reminding patients of smoking restrictions (43.9%), managing cigarettes (46.5%), and nicotine replacement therapy (24.3%). A principal component analysis of tobacco-related practices revealed two main factors (59.8% of variance): basic hospital actions (factor 1) and more specialized interventions (factor 2), which were significantly associated with higher worries about personally developing smoke-related illnesses (Spearman r = 0.38, P < 0.0001). Compared with non-smokers, smokers reported higher perceived vulnerability to develop an illness due to tobacco and a higher level of worry about this. The discussion highlights the need to redefine roles and expectancies of mental health staff, and improve training and collaboration with experts, in order to improve efficiency concerning tobacco issues.