Fetal alcohol spectrum disorder (FASD) is a life-long condition, and few interventions have been developed to improve the neurodevelopmental course in this population. Early interventions targeting core neurocognitive deficits have the potential to confer long-term neurodevelopmental benefits. Time-targeted choline supplementation is one such intervention that has been shown to provide neurodevelopmental benefits that emerge with age during childhood. We present a long-term follow-up study evaluating the neurodevelopmental effects of early choline supplementation in children with FASD approximately 7 years on average after an initial efficacy trial. In this study, we examine treatment group differences in executive function (EF) outcomes and diffusion MRI of the corpus callosum using the Neurite Orientation Dispersion and Density Index (NODDI) biophysical model.

The initial study was a randomized, double-blind, placebo-controlled trial of choline vs. placebo in 2.5- to 5-year-olds with FASD. Participants in this long-term follow-up study included 18 children (9 placebo; 9 choline) seen 7 years on average following initial trial completion. The mean age at follow-up was 11 years old. Diagnoses were 28% fetal alcohol syndrome (FAS), 28% partial FAS, and 44% alcohol-related neurodevelopmental disorder. The follow-up evaluation included measures of executive functioning (WISC-V Picture Span and Digit Span; DKEFS subtests) and diffusion MRI (NODDI).

Children who received choline early in development outperformed those in the placebo group across a majority of EF tasks at long-term follow-up (effect sizes ranged from -0.09 to 1.27). Children in the choline group demonstrated significantly better performance on several tasks of lower-order executive function skills (i.e., DKEFS Color Naming [Cohen's d = 1.27], DKEFS Word Reading [Cohen's d = 1.13]) and showed potentially better white matter microstructure organization (as indicated by lower orientation dispersion; Cohen's d = -1.26) in the splenium of the corpus callosum compared to the placebo group. In addition, when collapsing across treatment groups, higher white matter microstructural organization was associated with better performance on several EF tasks (WISC-V Digit Span; DKEFS Number Sequencing and DKEFS Word Reading).

These findings highlight long-term benefits of choline as a neurodevelopmental intervention for FASD and suggest that changes in white matter organization may represent an important target of choline in this population. Unique to this study is the use of contemporary biophysical modeling of diffusion MRI data in youth with FASD. Findings suggest this neuroimaging approach may be particularly useful for identifying subtle white matter differences in FASD as well as neurobiological responses to early intervention associated with important cognitive functions.

Fetal alcohol spectrum disorder (FASD) is a common neurodevelopmental condition associated with deficits in cognitive functioning (executive functioning [EF], attention, working memory, etc.), behavioral impairments, and abnormalities in brain structure including cortical and subcortical volumes. Rates of comorbid attention-deficit/hyperactivity disorder (ADHD) are high in children with FASD and contribute to significant functional impairments. Sluggish cognitive tempo (SCT) includes a cluster of symptoms (e.g. underactive/slow-moving, confusion, fogginess, daydreaming) found to be related to but distinct from ADHD, and previous research suggests that it may be common in FASD. We explored SCT by examining the relationship between SCT and both brain volumes (corpus callosum, caudate, and hippocampus) and objective EF measures in children with FASD vs. typically developing controls.

This is a secondary analysis of a larger longitudinal CIFASD study that consisted of 35 children with prenatal alcohol exposure (PAE) and 30 controls between the ages of 9 to 18 at follow-up. Children completed a set of cognitive assessments (WISC-IV, DKEFS, & NIH Toolbox) and an MRI scan, while parents completed the Child Behavior Checklist (CBCL), which includes a SCT scale. We examined group differences between PAE and controls in relation to SCT symptoms, EF scores, and subcortical volumes. Then, we performed within-and between-group comparisons with and without controlling for total intracranial volume, age, attention problems, and ADHD problems between SCT and subcortical brain volumes. Finally, we performed correlations between SCT and EF measures for both groups.

Compared to controls, participants with PAE showed significantly more SCT symptoms on the CBCL (t [57] = 3.66, p = 0.0006), more parent-rated attention problems and ADHD symptoms, lower scores across several EF measures (DKEFS Trail-Making and Verbal Fluency; WISC-IV Digit Span, Symbol Search, and Coding; effect sizes ranging from 0.44 to 1.16), and smaller regional volumes in the caudate, hippocampus, and posterior areas of the corpus callosum. In the PAE group, a smaller hippocampus was associated with more SCT symptoms (controlling for parent-rated attention problems and ADHD problems, age, and intracranial volume). However, in the control group, a larger mid posterior and posterior corpus callosum were significantly associated with more SCT symptoms (controlling for parent-rated attention problems, intracranial volume, and age; r [24] = 0.499, p = 0.009; r [24] = 0.517, p = 0.007). In terms of executive functioning, children in the PAE group with more SCT symptoms performed worse on letter sequencing of the Trail-Making subtest (controlling attention problems & ADHD symptoms). In comparison, those in the control group with more SCT symptoms performed better on letter sequencing and combined number letter sequencing of the Trail-Making subtest (controlling attention problems).

Findings suggest that children with FASD experience elevated SCT symptoms compared to typically developing controls, which may be associated with worse performance on EF tasks and smaller subcortical volumes (hippocampus) when taking attention difficulties and ADHD symptoms into account. Additional research into the underlying causes and correlates of SCT in FASD could result in improved tailoring of interventions for this population.

In recent years much focus has been put on the role of immune/inflammatory alterations in affecting Major Depression (MDD) development and antidepressant efficacy. Neutrophil-to-lymphocyte ratio (NLR) is an inexpensive inflammatory marker shown to be elevated in depressed patients, with large population studies reporting this effect only in women. However, its relation to treatment response is much less clear. Reduced hippocampal volumes (HV) are among the few consistent brain structural predictors of poor treatment response, and they have been shown to be influenced by inflammatory status.

To investigate the effect of NLR on treatment response in MDD patients, testing a possible moderating role of sex. To investigate the effect of NLR on HV and test a possible mediating role of the latter in the relation between NLR and treatment response.

Our study was performed on a sample of 120 MDD inpatients suffering from a non psychotic depressive episode (F=78; M=42). Depression severity was assessed via the Hamilton Depression Rating Scale (HDRS), both at admission and discharge; as a measure of treatment response, delta HDRS was calculated subtracting the two scores. NLR was calculated for each subject. Patients underwent 3T MRI acquisition and bilateral HV were estimated.

We found a significant moderating effect of sex on the relationship between NLR and Delta HDRS (p < 0.001): a negative relation was found in women (p < 0.001) and a positive one in men (p = 0.042). NLR was found to negatively affect left HV in the whole sample (p = 0.027) and in women (p = 0.038). A positive effect on Delta HDRS was found for both left (p = 0.038) and right (p = 0.027) HV. Finally, we found a significant indirect effect of NLR values on Delta HDRS through left HV in women (95% BCa CI [- 0.948, -0.017]); the direct effect of NLR on Delta HDRS also remained significant (p = 0.002).

Sex was found to moderate the relation between NLR and treatment response. The detrimental effect in women is in line with previous reports linking inflammation to hampered antidepressant effect; the positive one in men is more surprising: however, the only studies to date on the effect of NLR on antidepressant efficacy report a positive effect in patients with psychotic depression. In women we found NLR to affect treatment response partially through its effect on left HV, providing a possible, albeit incomplete, mechanistic explanation of the effect of inflammatory status on antidepressant efficacy.

None Declared

Non-pharmacological treatment like psychotherapy is associated with less side effects than pharmacological treatment and is often considered first-line treatment towards psychiatric disorders. The extent and variation of psychotherapy treatment offered in Danish psychiatric clinics over time has not previously been studied.

To examine the nationwide use of psychotherapy treatment during 2001-2020 in individuals assigned with a psychiatric disorder diagnosis at Danish psychiatric clinics.

All Danish individuals aged ≥ 3 years, who were registered with 1) a psychiatric disorder diagnosis (F10-F99) or 2) had a first psychotherapy treatment during the study period 1 January 2001 to 31 December 2020, were identified in the Danish National Patient Registry.

A total of 120,916 (27 %) study participants received psychotherapy treatment during the study period, most commonly individual psychotherapy (65 %) followed by group therapy (25 %). Adults (≥18 years) were more likely to receive therapy (34 %) than children and adolescents aged 3-17 years (15 %). The proportion of treated patients was highest among women (67 %) compared with men (33 %). The median age at first psychotherapy was 25 years (ranging from 19 to 33). 59 % of patients receiving psychotherapy had filled a psychotropic prescription within one year prior to therapy onset, particularly antidepressants (44 %) and antipsychotics (22 %).

The use of psychotherapy for treatment of psychiatric disorders is limited among Danish patients, although national clinical guidelines recommend it as first-line treatment of common conditions such as depressive, anxiety and obsessive-compulsive disorders.

No significant relationships.

To ensure rational drug use, there is a need to continuously monitor the use of ADHD medication among children and adolescents.

To describe the use of ADHD medication among Danish children and adolescents from 2010-2020.

Using the Danish national healthcare registries, we extracted data on filled prescriptions of ADHD medication (including methylphenidate, atomoxetine, guanfacine, dexamphetamine, and lisdexamphetamine) among children (age 6-12 years) and adolescents (age 13-17 years) between 2010-2020. We examined the annual incidence rate and prevalence proportion of ADHD drug use, and the proportion of children and adolescents having an ADHD diagnosis when initiating ADHD medication.

From 2010-2020, the incidence followed a u-shaped trend with an incidence rate of 4.9/1,000 children and 4.4/1,000 adolescents in 2010, decreasing to 3.2/1,000 children and 3.0/1,000 adolescents in 2013, and rising to 4.9/1,000 children and 4.8/1,000 adolescents in 2020. The prevalence for children showed a similar trend, shifting from 17/1,000 in 2010, to 15/1,000 in 2016, and peaking at 19/1,000 children in 2020. However, among adolescents the prevalence increased steadily from 19/1,000 in 2010 to 29/1,000 in 2020. 67% of children and 53% of adolescents initiating ADHD medication had an ADHD diagnosis.

After an initial decline in incidence rates of ADHD medication use among Danish children and adolescents, there has been a rise in use the last five years. The same trend applied for the prevalence among children, whereas the prevalence among adolescents increased steadily over the entire period. More than half of children and adolescents initiating ADHD medication were diagnosed with ADHD.

No significant relationships.

There is a lack of longitudinal studies of patients with bipolar disorder (BD) or unipolar depression (UD) in terms of psychological well-being as measured by the WHO-5 and the correlation to symptom scores. It is of interest to investigate whether the WHO-5 is useful in monitoring patients with mood disorders over time, as a tool in measurement-based care, and as a supplement to other psychometric measures.

In this study we investigate the correlation at baseline between the depressive symptom scores according to the 6-item Hamilton Depression Score (HDS-6) and the WHO-5 scores in outpatients treated for BD or UD. Furthermore, in patients with BD we investigate correlations between manic symptom scores according to the modified Bech-Rafaelsen Mania Scale (MAS-M) and the WHO-5 scores. Lastly, in patients with BD or UD, we investigate the correlations between endpoint-baseline change in WHO-5 and change in MAS-M and HDS-6.

A longitudinal study of 200 outpatients diagnosed and treated for either BD or UD. Patients will be measured at baseline and at least four weeks later. Baseline data are presented as frequencies, means and standard deviations or medians with interquartile ranges as appropriate. All correlations are presented as scatter plots and a Spearman correlation analysis

The study is ongoing, but the results will be available for presentation at the EPA in 2021.

The WHO-5 may represent a relevant outcome measure in the treatment of BD and UD.

No significant relationships.

Patients with schizophrenia have a four-fold increased all-cause and a doubled cardiovascular mortality rate as compared to the general population.

The study overall investigates the point-prevalence and prospective changes in cardiovascular risk factors in patients with schizophrenia, with baseline demographics of participants presented here.

A prospective study of patients diagnosed with schizophrenia divided into two subpopulations consisting of newly diagnosed (≤2 years from baseline in study (group A)) or chronic (diagnosed ≥10 years from baseline in study (group B)).

A total of 199 patients (57 diagnosed ≤2 years preceding baseline and 142 diagnosed ≥10 years ago) were included. Group A had been diagnosed for an average of 1.13±0.58 years and 21.19±7.62 years in group B. The majority (n=135 (67.8%)) were diagnosed with paranoid schizophrenia. At baseline PANSS total (median[Q1;Q3]) for group A was 61.0[51.0;76.0] and 60.0[48.0;76.0] for group B, with PANNS Positive being 17.0[13.0;20.0] and 15.0[12;19], PANSS Negative being 16.0[11.0;20.0] and 14.5[10.0;20.0], and PANSS General being 28.0[22.0;35.0] and30.0 [25.0;37.0], respectively. No difference in Clinical Global Impression was observed between groups ((median[Q1;Q3): 4.0[3.0;4.0] in both groups). Lastly, global assessment of function was similar between groups ((median[Q1;Q3): group A symptom: 38.5[37.0;46.0] and group B 41.0[37.0;52.0], and with function being 48.0[44.5;53.5] in group A and 45.5[41.0;53.0] in group B).

Prospective studies investigating prevalence of and prospective changes in cardiovascular risk in patients with schizophrenia are essential to understand the increased all-cause and cardiovascular specific mortality. Demographic descriptions of participants are essential to estimate generalizability in different treatment settings.

No significant relationships.

Patients with schizophrenia have a reduced life expectancy compared to the general population, and cardiovascular diseases contribute to this. Peripheral arterial disease (PAD) is associated with excess all-cause mortality and specifically with cardiovascular morbidity and mortality. The risk factors for PAD, such as diabetes, smoking, hypertension, dyslipidaemia and obesity, are more common among patients with schizophrenia which could contribute to a possibly higher prevalence of PAD among patients with schizophrenia.

To investigate PAD utilizing toe brachial index (TBI) in a population of patients diagnosed with schizophrenia with the purpose of establishing prevalence rates amongst newly diagnosed as well as more chronic patients.

A cross-sectional study of patients with schizophrenia (ICD10-diagnosis F20 or F25) with a study population of 57 patients diagnosed with schizophrenia within the last 2 years, psychiatric healthy controls matched by age, sex and smoking status and 142 patients with a schizophrenia diagnosis more than 10 years ago. The primary outcome is TBI in patients with schizophrenia stratified to the two subpopulations. The TBI will be calculated from the arm and toe systolic pressures. The toe pressures were measured using photoplethysmography (SysToe®, Atys Medical).

No results are available yet. The cohort will be described by age, sex, smoking status, body fat percentage and physical comorbidities. The TBI of the two subpopulations will be compared with psychiatrically healthy controls using paired t-tests if data is normally distributed. If transformation is unsuitable, Wilcoxon test will be carried out instead.

No results are available yet. Results will be presented at the EPA’s congress 2021.

No significant relationships.

Virus outbreaks such as the current SARS-CoV-2 pandemic are challenging for health care workers (HCWs), affecting their workload and their mental health. Since both, workload and HCW's well-being are related to the quality of care, continuous monitoring of working hours and indicators of mental health in HCWs is of relevance during the current pandemic. The existing investigations, however, have been limited to a single study period. We examined changes in working hours and mental health in Swiss HCWs at the height of the pandemic (T1) and again after its flattening (T2).

We conducted two cross-sectional online studies among Swiss HCWs assessing working hours, depression, anxiety, and burnout. From each study, 812 demographics-matched participants were included into the analysis. Working hours and mental health were compared between the two samples.

Compared to prior to the pandemic, the share of participants working less hours was the same in both samples, whereas the share of those working more hours was lower in the T2 sample. The level of depression did not differ between the samples. In the T2 sample, participants reported more anxiety, however, this difference was below the minimal clinically important difference. Levels of burnout were slightly higher in the T2 sample.

Two weeks after the health care system started to transition back to normal operations, HCWs' working hours still differed from their regular hours in non-pandemic times. Overall anxiety and depression among HCWs did not change substantially over the course of the current SARS-CoV-2 pandemic.

Generalized anxiety disorder (GAD) and social anxiety disorder (SAD) are co-morbid and associated with similar neural disruptions during emotion regulation. In contrast, the lack of optimism examined here may be specific to GAD and could prove an important biomarker for that disorder.

Unmedicated individuals with GAD (n = 18) and age-, intelligence quotient- and gender-matched SAD (n = 18) and healthy (n = 18) comparison individuals were scanned while contemplating likelihoods of high- and low-impact negative (e.g. heart attack; heartburn) or positive (e.g. winning lottery; hug) events occurring to themselves in the future.

As expected, healthy subjects showed significant optimistic bias (OB); they considered themselves significantly less likely to experience future negative but significantly more likely to experience future positive events relative to others (p < 0.001). This was also seen in SAD, albeit at trend level for positive events (p < 0.001 and p < 0.10, respectively). However, GAD patients showed no OB for positive events (t17 = 0.82, n.s.) and showed significantly reduced neural modulation relative to the two other groups of regions including the medial prefrontal cortex (mPFC) and caudate to these events (p < 0.001 for all). The GAD group further differed from the other groups by showing increased neural responses to low-impact events in regions including the rostral mPFC (p < 0.05 for both).

The neural dysfunction identified here may represent a unique feature associated with reduced optimism and increased worry about everyday events in GAD. Consistent with this possibility, patients with SAD did not show such dysfunction. Future studies should consider if this dysfunction represents a biomarker for GAD.

In unipolar depressed patients participating in trials on antidepressants, we investigated if illness characteristics at baseline could predict conversion to bipolar disorder.

A long-term register-based follow-up study of 290 unipolar depressed patients with a mean age of 50.8 years (SD = 11.9) participating in three randomized trials on antidepressants conducted in the period 1985–1994. The independent effects of explanatory variables were examined by applying Cox regression analyses.

The overall risk of conversion was 20.7%, with a mean follow-up time of 15.2 years per patient. The risk of conversion was associated with an increasing number of previous depressive episodes at baseline, [HR 1.18, 95% CI (1.10–1.26)]. No association with gender, age, age at first depressive episode, duration of baseline episode, subtype of depression or any of the investigated HAM-D subscales included was found.

The patients were followed-up through the Danish Psychiatric Central Research Register, which resulted in inherent limitations such as possible misclassification of outcome.

In a sample of middle-aged hospitalized unipolar depressed patients participating in trials on antidepressants, the risk of conversion was associated with the number of previous depressive episodes. Therefore, this study emphasizes that unipolar depressed patients experiencing a relatively high number of recurrences should be followed more closely, or at least be informed about the possible increased risk of conversion.

Social anxiety disorder involves fear of social objects or situations. Social referencing may play an important role in the acquisition of this fear and could be a key determinant in future biomarkers and treatment pathways. However, the neural underpinnings mediating such learning in social anxiety are unknown. Using event-related functional magnetic resonance imaging, we examined social reference learning in social anxiety disorder. Specifically, would patients with the disorder show increased amygdala activity during social reference learning, and further, following social reference learning, show particularly increased response to objects associated with other people's negative reactions?

A total of 32 unmedicated patients with social anxiety disorder and 22 age-, intelligence quotient- and gender-matched healthy individuals responded to objects that had become associated with others’ fearful, angry, happy or neutral reactions.

During the social reference learning phase, a significant group × social context interaction revealed that, relative to the comparison group, the social anxiety group showed a significantly greater response in the amygdala, as well as rostral, dorsomedial and lateral frontal and parietal cortices during the social, relative to non-social, referencing trials. In addition, during the object test phase, relative to the comparison group, the social anxiety group showed increased bilateral amygdala activation to objects associated with others’ fearful reactions, and a trend towards decreased amygdala activation to objects associated with others’ happy and neutral reactions.

These results suggest perturbed observational learning in social anxiety disorder. In addition, they further implicate the amygdala and dorsomedial prefrontal cortex in the disorder, and underscore their importance in future biomarker developments.