Changes in Psychotropic Drug Concentrations Across the Menstrual Cycle: A Pilot Study.

BACKGROUND: The escalating prescription of psychopharmacological medications to women of reproductive age underscores the growing significance of sex-specific variations in pharmacotherapy. Despite this, clinical trials have largely overlooked these differences. Preliminary data indicate sex-specific variations in the neurobiology of affective disorders and in the metabolism, pharmacodynamics, and kinetics of therapeutic drugs. This underscores the imperative for a more nuanced exploration of menstrual cycle-dependent fluctuations in psychotropic drugs. This pilot study aimed to investigate drug and hormone fluctuations in female patients with affective disorders, aiming to enhance comprehension of the interplay between cycle-related hormone fluctuations and pharmacokinetics. The ultimate goal is to facilitate more effective and safer pharmacological therapy in the future. METHODS: Blood samples were collected from 27 patients and 27 age-matched control participants at 3 distinct time points (early follicular phase, ovulation, and late luteal phase) during each menstrual cycle. Depressive and manic symptoms were assessed, and hormone concentrations were measured in the entire sample, while drug concentrations were assessed solely in the affective disorder sample using mass spectrometry. RESULTS: Significant variations in drug concentration were observed throughout the menstrual cycle for bupropion, with a trend toward altered concentration for venlafaxine. Moreover, notable differences in hormone concentrations were identified between patients and controls, even after accounting for the impact of contraceptive use, diagnoses, and medication. CONCLUSIONS: This pilot study reinforces previously reported data, underscoring the significance of sex-specific pharmacological therapy approaches. It provides further evidence supporting the interaction among sex hormones, drugs, and symptoms of affective disorders.

Paternal bonding is influenced by prenatal paternal depression and trait-anxiety.

BACKGROUND: Even though the development of an emotional bond to the child involves both parents, studies on the development of paternal bonding and the influencing factors are scarce. This pilot study examines the quality of paternal postnatal bonding in association with paternal depressive and anxiety symptoms before and after birth. Methods: Expecting parents (n = 81) were recruited from maternity services in Frankfurt, Germany. At recruitment and 3 months postpartum (pp) mothers and fathers completed an interview including sociodemographic and pregnancy data. Depressive and anxiety symptoms were screened using the Edinburgh Postnatal Depression Scale and the State-Trait Anxiety Inventory. At 3-month pp, fathers also completed the Postpartum Bonding Questionnaire for the assessment of bonding difficulties. A total of 63 couples, from whom data were available for both time points, were included in the final study group. RESULTS: Depressive and anxiety symptoms before birth are the best predictors for the quality of paternal bonding pp (Total score R2 .402 p = .001; Impaired bonding R2 .299 p = .019; Rejection and Anger R2 .353 p = .005; Anxiety about care R2 .457 p = .000). Maternal depression and sociodemographic variables were not significantly associated. LIMITATIONS: High selected small study group. CONCLUSIONS: Paternal depressive and anxiety symptoms during pregnancy are highly predictive for the quality of bonding as well as for the presence of depressive and anxiety symptoms 3 month pp. It is necessary to identify these symptoms as soon as possible in order to prevent later negative impacts on parental mental health and on child developmental outcomes.

Psychotropic medication in pregnancy and lactation and early development of exposed children.

There is still limited knowledge about alterations of blood concentrations of psychotropic drugs during pregnancy, the transfer of psychotropic drugs into breastmilk and the effects on exposed children. We investigated changes in concentrations of psychopharmacological medication during pregnancy and lactation in serum and breastmilk at different time points in a naturalistic sample of 60 mothers and observed the development of the exposed children in the first 12 months. We found a decrease in serum concentrations from the first to the second trimester of amitriptyline, duloxetine, escitalopram, quetiapine and sertraline. Citalopram stayed rather stable during pregnancy, sertraline levels interestingly increased again from the second to the third trimester. High concentration-by-dose ratios in breastmilk were found for venlafaxine as well as lamotrigine, low for quetiapine and clomipramine. Similarly, clomipramine and quetiapine showed low milk/serum-penetration ratios. Regarding the birth outcome measures in children, we found no significant differences between in utero exposed compared to nonexposed newborns. There were no significant differences in the development in the first 12 months. Psychotropic medication in the peripartum needs a balancing of risks and benefits and a continuous therapeutic drug monitoring can be a guidance for clinicians to monitor drug alteration patterns, which are likely to occur due to physiological pregnancy-associated changes in pharmacokinetics. Accordingly, therapeutic drug monitoring can optimize a medication in pregnancy and lactation with the lowest effective dose.

A pilot study of multilevel analysis of BDNF in paternal and maternal perinatal depression.

Depression in the perinatal period is common in mothers worldwide. Emerging research indicates that fathers are also at risk of developing perinatal depression. However, knowledge regarding biological risk factors and pathophysiological mechanisms of perinatal depression is still scarce, particularly in fathers. It has been suggested that the neurotrophin BDNF may play a role in maternal perinatal depression; however, there is currently no data regarding paternal perinatal depression. For this pilot study, 81 expecting parents were recruited and assessed at several time points. We screened for depression using EPDS and MADRS, investigated several psychosocial variables, and took blood samples for BDNF val66met genotyping, epigenetic, and protein analysis. Between pregnancy and 12 months postpartum (pp), we found that 3.7 to 15.7% of fathers screened positive for depression, and 9.6 to 24% of mothers, with at least a twofold increased prevalence in both parents using MADRS compared with EPDS. We also identified several psychosocial factors associated with perinatal depression in both parents. The data revealed a trend that lower BDNF levels correlated with maternal depressive symptoms at 3 months pp. In the fathers, no significant correlations between BDNF and perinatal depression were found. Pregnant women demonstrated lower BDNF methylation and BDNF protein expression compared with men; however, these were found to increase postpartum. Lastly, we identified correlations between depressive symptoms and psychosocial/neurobiological factors. The data suggest that BDNF may play a role in maternal perinatal depression, but not paternal.

Lithium Medication in Pregnancy and Breastfeeding-A Case Series.

Lithium salts are the first-line prophylaxis treatment for bipolar disorder in most guidelines. The majority of bipolar women are treated with mood stabilizers at the time they wish to get pregnant. One reason for this is the rising average age at first childbirth, at least in the high-income countries, which increases in general the likelihood of a medication with psychotropic drugs. Previously, lithium exposition during pregnancy was thought to strongly increase the risk of severe cardiac malformation. However, recent studies only point to a low teratogenic risk, so nowadays an increasing number of women are getting pregnant with ongoing lithium treatment. Regarding lithium medication during breastfeeding, there is evidence that lithium transfers to the breastmilk and can also be detected in the infants' serum. The influence on the infant is still a largely understudied topic. Regular monitoring of the infants' renal clearance, thyroid function, and lithium levels is warranted when breastfeeding under lithium exposure. In this case series, we present three case reports of bipolar mothers who were treated with lithium during pregnancy and breastfeeding to add to the scarce literature on this important topic. In short, we strengthen the importance of therapeutic drug monitoring due to fluctuating plasma levels during pregnancy and after birth, and we can report the birth and development of three healthy infants despite lithium medication during pregnancy and breastfeeding.

Parental ADHD in pregnancy and the postpartum period - A systematic review.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders worldwide, and in the majority of patients persists into adulthood. However, it remains unclear how maternal ADHD could affect pregnancy and birth as well as early mother-(father)-child interaction. There are several studies investigating the effect of depressed or anxious parents on parent-child-interactions in early infancy, but data about the influence of parental ADHD is lacking although it is a common mental disorder in parents. Additionally, the prescription of stimulant and other ADHD medication for adult ADHD patients is rising due to improved diagnostic procedures and a greater awareness of this disorder in adulthood among psychiatrists and psychologists. However, this leads to increased numbers of treated ADHD women that wish to have children or experience unplanned pregnancies while taking stimulant medication. In our systematic review we aimed at analysing the current evidence for the association of maternal ADHD with pregnancy and birth outcomes, pregnancy risks and health behaviour in pregnancy, as well as the association of parental ADHD with early parent-child interaction and early child development in the first 3 years. Furthermore, we reviewed recent evidence on the risks of stimulant and non-stimulant treatment for ADHD in pregnancy and lactation.

Emotion processing and regulation in major depressive disorder: A 7T resting-state fMRI study.

Dysfunctions in bottom-up emotion processing (EP), as well as top-down emotion regulation (ER) are prominent features in pathophysiology of major depressive disorder (MDD). Nonetheless, it is not clear whether EP- and ER-related areas are regionally and/or connectively disturbed in MDD. In addition, it is yet to be known how EP- and ER-related areas are interactively linked to regulatory behavior, and whether this interaction is disrupted in MDD. In our study, regional amplitude of low frequency fluctuations (ALFF) and whole-brain functional connectivity (FC) of meta-analytic-driven EP- and ER-related areas were compared between 32 healthy controls (HC) and 20 MDD patients. Then, we aimed to investigate whether the EP-related areas can predict the ER-related areas and regulatory behavior in both groups. Finally, the brain-behavior correlations between the EP- and ER-related areas and depression severity were assessed. We found that: (a) affective areas are regionally and/or connectively disturbed in MDD; (b) EP-ER interaction seems to be disrupted in MDD; overburden of emotional reactivity in amygdala may inversely affect cognitive control processes in prefrontal cortices, which leads to diminished regulatory actions. (c) Depression severity is correlated with FC of affective areas. Our findings shed new lights on the neural underpinning of affective dysfunctions in depression.

Attachment-specific speech patterns induce dysphoric mood changes in the listener as a function of individual differences in attachment characteristics and psychopathology.

OBJECTIVES: Early childhood experiences influence cognitive-emotional development, with insecure attachment predisposing to potential psychopathologies. We investigated whether narratives containing attachment-specific speech patterns shape listeners' emotional responses and social intentions. DESIGN: First, 149 healthy participants listened to three narratives characteristic for secure, insecure-preoccupied, and insecure-dismissing attachment. Following each narrative, the well-being and interpersonal reactivity as a particular aspect of emotional reactivity of the listener were assessed. Likewise, psychopathological aspects of personality were evaluated. A follow-up study compared 10 psychosomatic patients with a current depressive episode and/or personality disorder with distinct depressive symptoms and 10 age- and gender-matched healthy controls. METHODS: Effects of narratives on listeners' mental state were tested with repeated-measures AN(C)OVA. Mediating effects in the listener (attachment characteristics in the context of personality traits) were explored. Narrative effects were compared between patients and controls. RESULTS: Listening to insecure attachment narratives reduced well-being in controls. Nevertheless, tendency for social interaction was highest following the insecure-preoccupied narrative. Importantly, listeners' individual attachment characteristics mediated the relationship between well-being/interpersonal reactivity following the insecure-preoccupied narrative and levels of psychopathology. Furthermore, compared with healthy participants, patients showed higher emotional reactivity following exposure to the insecure-preoccupied narrative, represented by lower well-being and lower estimation of friendliness towards the narrator. CONCLUSIONS: Exposure to attachment-specific speech patterns can result in dysphoric mood changes. Specifically, the insecure-preoccupied narrative influenced the listeners' emotional state, which was further mediated by the individual attachment patterns and psychopathological personality characteristics. This deepens the understanding of interpersonal processes, especially in psychotherapeutic settings. PRACTITIONER POINTS: In clinical populations, insecure-preoccupied attachment has a high prevalence. In this study, listening to a narrative characteristic of insecure-preoccupied speech patterns resulted in reduced well-being in healthy listeners. Patients with depressive symptoms showed a higher emotional reactivity towards the insecure-preoccupied narrative compared to healthy controls. While working on (childhood) traumata, for example, in group therapy or inpatient settings, therapists should raise awareness to possible mood changes through discourse-conveyed attachment characteristics in listeners as a 'side effect'.

Dorsal and Ventral Posterior Cingulate Cortex Switch Network Assignment via Changes in Relative Functional Connectivity Strength to Noncanonical Networks.

The posterior cingulate cortex (PCC) is often used as a seed region for probing default-mode network (DMN) connectivity. However, there is evidence for a functional segregation between its dorsal (dPCC) and ventral (vPCC) subregions, which suggests differential involvements of d-/vPCC in regulating cognitive demands. Our paradigm included functional magnetic resonance imaging measures for baseline resting state, affective or cognitive tasks, and post-task resting states. We investigated the effect of task demands on intra-PCC coupling and d-/vPCC network assignment to major intrinsic connectivity networks (ICNs), which was estimated via edge weights of a graph network encompassing DMN, dorsal-attention network, and central-executive network (CEN). Although PCC subregions were functionally coupled during both resting-state conditions and cognitive tasks, they decoupled during affective stimulation. For dPCC, functional connectivity strength (FCS) to CEN was higher than to the other two ICNs; whereas for vPCC, FCS to DMN was the highest. We, hence, defined CEN and DMN as the canonical networks at rest for dPCC and vPCC, respectively. Switching from rest to affective stimulation, however, induced the strongest effects to relative network assignments between non-canonical networks of dPCC and vPCC. Although vPCC showed a durable functional connectivity (FC) to DMN, dPCC played a crucial role during switches of between-network FC depending on cognitive versus affective task requirements. Our results underline that it is crucial for future seed-based FC studies to consider these two subregions separately in terms of seed location and discussion of findings. Finally, our findings highlight the functional importance of connectivity changes toward regions outside the canonical networks.

Exposure to attachment narratives dynamically modulates cortical arousal during the resting state in the listener.

BACKGROUND: Affective stimulation entails changes in brain network patterns at rest, but it is unknown whether exogenous emotional stimulation has a prolonged effect on the temporal dynamics of endogenous cortical arousal. We therefore investigated differences in cortical arousal in the listener following stimulation with different attachment-related narratives. METHODS: Resting-state EEG was recorded from sixteen healthy subjects for ten minutes each with eyes closed: first at baseline and then after passively listening to three affective narratives from strangers about their early childhood experiences (prototypical for insecure-dismissing, insecure-preoccupied, and secure attachment). Using the VIGALL 2.1 algorithm, low or high vigilance stages in consecutive EEG segments were classified, and their dynamic profile was analyzed. Questionnaires assessed the listeners' emotional response to the content of the narrative. RESULTS: As a general effect of preceding affective stimulation, vigilance following the stimulation was significantly elevated compared to baseline rest, and carryover effects in dynamic vigilance profiles were observed. A difference between narrative conditions was revealed for the insecure-dismissing condition, in which the decrease in duration of high vigilance stages was fastest compared to the other two conditions. The behavioral data supported the observation that especially the insecure narratives induced a tendency in the listener to affectively disengage from the narrative content. DISCUSSION: This study revealed carryover effects in endogenous cortical arousal evoked by preceding affective stimulation and provides evidence for attachment-specific dynamic alterations of brain states and individual differences in emotional reactivity.

Delayed increase of thrombocyte levels after a single sub-anesthetic dose of ketamine - A randomized trial.

Recently, ketamine has been investigated as a potential antidepressant option for treatment resistant depression. Unlike traditional drugs, it yields immediate effects, most likely via increased glutamatergic transmission and synaptic plasticity. However, ketamine administration in humans is systemic and its long-term impact on blood parameters has not yet been described in clinical studies. Here we investigated potential sustained effects of ketamine administration (0.5 mg/kg ketamine racemate) on hematological and biochemical values in plasma and serum in a randomized double-blinded study. 80 healthy young participants were included and whole blood samples were collected 5 days before, and 14 days after the infusion. To assess the group effect, repeated measure analyses of co-variance (rmANCOVA) were conducted for the following blood parameters: levels of sodium, potassium, calcium, hemoglobin and number of erythrocytes, lymphocytes, and thrombocytes. RmANCOVA revealed a significant time by treatment effect on thrombocyte levels (F1, 74 = 13.54, p < 0.001, eta = 0.155), driven by an increase in the ketamine group (paired t-test, t = -3.51, df = 38, p = 0.001). Specificity of thrombocyte effect was confirmed by logistic regression, and in addition, no other coagulation parameters showed significant interaction. Moreover, the relative increase in the ketamine group was stable across sexes and not predicted by age, BMI, smoking, alcohol or drug use, and contraception. Our results describe aftereffects of sub-anesthetic ketamine administration on blood coagulation parameters, which should be considered especially when targeting psychiatric populations with relevant clinical comorbidities.