Brain imaging studies have shown altered amygdala activity during emotion processing in children and adolescents with oppositional defiant disorder (ODD) and conduct disorder (CD) compared to typically developing children and adolescents (TD). Here we aimed to assess whether aggression-related subtypes (reactive and proactive aggression) and callous-unemotional (CU) traits predicted variation in amygdala activity and skin conductance (SC) response during emotion processing.

We included 177 participants (n = 108 cases with disruptive behaviour and/or ODD/CD and n = 69 TD), aged 8–18 years, across nine sites in Europe, as part of the EU Aggressotype and MATRICS projects. All participants performed an emotional face-matching functional magnetic resonance imaging task.

Differences between cases and TD in affective processing, as well as specificity of activation patterns for aggression subtypes and CU traits, were assessed. Simultaneous SC recordings were acquired in a subsample (n = 63). Cases compared to TDs showed higher amygdala activity in response to negative faces (fearful and angry) v. shapes. Subtyping cases according to aggression-related subtypes did not significantly influence on amygdala activity; while stratification based on CU traits was more sensitive and revealed decreased amygdala activity in the high CU group. SC responses were significantly lower in cases and negatively correlated with CU traits, reactive and proactive aggression.

Our results showed differences in amygdala activity and SC responses to emotional faces between cases with ODD/CD and TD, while CU traits moderate both central (amygdala) and peripheral (SC) responses. Our insights regarding subtypes and trait-specific aggression could be used for improved diagnostics and personalized treatment.

We sought to explore whether obstetric complications (OCs) are more likely to occur in the presence of familial/genetic susceptibility for schizophrenia or whether they themselves represent an independent environmental risk factor for schizophrenia.

The presence of OCs was assessed through maternal interview on 216 subjects, comprising 36 patients with schizophrenia from multiply affected families, 38 of their unaffected siblings, 31 schizophrenic patients with no family history of psychosis, 51 of their unaffected siblings and 60 normal comparison subjects. We examined the familiality of OCs and whether OCs were commoner in the patient and sibling groups than in the control group.

OCs tended to cluster within families, especially in multiply affected families. Patients with schizophrenia, especially those from multiply affected families, had a significantly higher rate of OCs compared to normal comparison subjects, but there was no evidence for an elevated rate of OCs in unaffected siblings.

Our data provides little evidence for a link between OCs and genetic susceptibility to schizophrenia. If high rates of OCs are related to schizophrenia genes, this relationship is weak and will only be detected by very large sample sizes.

Neuropsychological deficits are considered endophenotypes for schizophrenia, because they are not only found in patients but also in many of their unaffected relatives, albeit in attenuated form. It is not yet clear which of these deficits in relatives are related to genetic or to environmental causes. We tested effects of inferred genetic liability for schizophrenia on neurocognitive variables to address this problem.

Twenty-eight patients with schizophrenia, 129 non-affected biological parents and 143 matched controls were assessed with an extensive neuropsychological test battery including tests of attention, memory, executive functioning and motor soft signs. Twenty-two parents had an ancestral history of schizophrenia and therefore were hypothesized to be more likely than their spouses without such a history (n = 17) to carry a genetic risk for schizophrenia.

Unaffected parents of schizophrenic patients showed significant deficits in a wide array of neuropsychological tasks and task domains. However, comparison of more likely and less likely carriers of illness-related genes showed specifically attentional and executive functioning, but not memory, to vary with degree of inferred genetic loading.

Attentional and executive (frontal) impairments vary with genetic loading for schizophrenia and can be considered true endophenotypes for this disorder. Consequently, these functions are particularly suited to evaluate the functional impact of candidate genes for schizophrenia in future studies.

The consequences of Childhood trauma (CT) become increasingly apparent. The available data suggest that (1) CT is related to persisting alterations of HPA activity, (2) CT is related to psychopathology in patients with substance use disorders (SUD), and (3) alterations of HPA activity are related to craving and psychopathology. However, none of the existing studies have tried to integrate these different perspectives.

We assessed anxiety (STAI), depression (BDI) and craving (OCDS-D) in a consecutive sample of 42 patients with alcohol dependence (37% female, 63% male) on day 1 (t1) and day 14 (t2) after their admission to a detoxification unit. Morning plasma levels of cortisol and ACTH were assessed and a standard dexamethasone test (DST) was performed (t2). Finally, the Childhood Trauma Questionnaire was administered.

At t1, cortisol levels correlated significantly with anxiety (r=.34*) and sexual abuse (r=.38*). An inverse relationship was found between ACTH levels and both, emotional abuse and emotional neglect (t1: r=-.33*, r=-.39*; t2: r=-.32*, r=-.51**). This relationship persisted when controlling for depression. Craving was related to anxiety and depression (t1: r=.53**, r=.60**; t2: r=.39*, r=.35*), but not to cortisol or ACTH levels. No relationships existed between CT and the DST outcome.

Our results give first evidence that CT is related to changes of the HPA activity in SUD patients, but they could not be further clarified by the DST. Psychopathology was related to both, early trauma and craving. Future studies should try to further examine these complex relationships.

Prolactin (PRL) data from adolescents treated with olanzapine are presented.

Data from 454 adolescents (13-18, mean=15.9 yrs) with schizophrenia or bipolar mania were pooled from 4 olanzapine (2.5-20.0mg/day) studies (4-32 weeks; 2 double-blind, placebo-controlled studies [combined for acute phase endpoint PRL levels] with open-label extensions; 2 open-label studies). Age- and sex-specific Covance reference ranges defined normal PRL; categorical increases were based on multiples of the upper limit of normal (ULN). Baseline-to-endpoint PRL changes in adolescents were compared with data pooled from 84 olanzapine clinical trials in adults with schizophrenia or bipolar disorder.

Olanzapine-treated adolescents had mean PRL increases at both the acute (11.4μg/L) and open-label endpoints (4.7μg/L). Of those patients with normal PRL levels at baseline (N=311), high PRL occurred in 54.7% at anytime; 32.2% at endpoint. The percentage of patients in which PRL levels shifted from normal-to-abnormal was smaller at endpoint than at anytime during treatment; 26.7% shifted to a higher category. Among patients with normal baseline PRL, 32.7% remained <=1X ULN; 32.3% increased to 1¬<=2X; 6.0%, >2-<=3X; and 1.2%, >3X at anytime; 4.6% had at >=1 potentially PRL-related adverse event. Adolescents had significantly higher mean changes at endpoint (p=.004), and a greater incidence of high PRL levels at anytime during olanzapine treatment (p<.001) versus adults.

Incidence of high PRL was significantly higher, and mean increases in PRL were significantly greater in adolescents versus adults. Mean increases and high PRL incidence were lower at the open-label compared with the acute phase endpoint.

The changes in metabolic parameters in olanzapine-treated adolescents were examined.

Data from 454 adolescents (13–18, mean=15.9 years) with schizophrenia or bipolar I disorder were pooled from 4 olanzapine (2.5–20.0mg/day) studies (4–32 weeks). Changes in metabolic parameters in adolescents were compared with those of olanzapine-treated adults (pooled from 84 clinical trials); changes in weight and BMI were compared with US age- and sex-adjusted standardized growth curves.

Olanzapine-treated adolescents had significant increases from baseline-to-endpoint in fasting glucose (p=.021); total cholesterol, LDL, and triglycerides (p<.001); and significant decreases in HDL (p<.001). Significantly more adolescents gained >=7% of their baseline weight versus adults (65.1% vs. 35.6%, p<.001); mean change from baseline-to-endpoint in weight was significantly greater in adolescents (7.0 vs. 3.3kg, p<.001). Adolescents had significantly lower mean changes from baseline-to-endpoint in fasting glucose (0.3 vs. 0.1mmol/L, p=.002) and triglycerides (0.3 vs. 0.2mmol/L, p=.007) versus adults. Significantly more adults experienced treatment-emergent normal-to-high changes at anytime in fasting glucose (4.8% vs. 1.2%, p=.033), total cholesterol (6.9% vs. 1.1%, p=.001), LDL (5.8% vs. 1.5%, p=.014), and triglycerides (25.7% vs. 17.4%, p=.030). Compared with standardized growth curves, olanzapine-treated adolescents had greater increases from baseline-to-endpoint in weight (1.0 vs. 7.1kg, p<.001), height (0.5 vs. 0.7cm, p<.001), and BMI (0.2 vs. 2.2kg/m2, p<.001).

Olanzapine-treated adolescents may gain significantly more weight compared with adults, but may have smaller changes in other metabolic parameters. Clinicians may want to consider both efficacy and changes in metabolic parameters when selecting treatment options for individual adolescent patients.

Self-reported activity restriction is an established correlate of depression in dementia caregivers (dCGs). It is plausible that the daily distribution of objectively measured activity is also altered in dCGs with depression symptoms; if so, such activity characteristics could provide a passively measurable marker of depression or specific times to target preventive interventions. We therefore investigated how levels of activity throughout the day differed in dCGs with and without depression symptoms, then tested whether any such differences predicted changes in symptoms 6 months later.

We examined 56 dCGs (mean age = 71, standard deviation (SD) = 6.7; 68% female) and used clustering to identify subgroups which had distinct depression symptom levels, leveraging baseline Center for Epidemiologic Studies of Depression Scale–Revised Edition and Patient Health Questionnaire-9 (PHQ-9) measures, as well as a PHQ-9 score from 6 months later. Using wrist activity (mean recording length = 12.9 days, minimum = 6 days), we calculated average hourly activity levels and then assessed when activity levels relate to depression symptoms and changes in symptoms 6 months later.

Clustering identified subgroups characterized by: (1) no/minimal symptoms (36%) and (2) depression symptoms (64%). After multiple comparison correction, the group of dCGs with depression symptoms was less active from 8 to 10 AM (Cohen’s d ≤ −0.9). These morning activity levels predicted the degree of symptom change on the PHQ-9 6 months later (per SD unit β = −0.8, 95% confidence interval: −1.6, −0.1, p = 0.03) independent of self-reported activity restriction and other key factors.

These novel findings suggest that morning activity may protect dCGs from depression symptoms. Future studies should test whether helping dCGs get active in the morning influences the other features of depression in this population (i.e. insomnia, intrusive thoughts, and perceived activity restriction).

Based on the vulnerability–stress model, we aimed to (1) determine new onset of depression in individuals who had not shown evidence of depression at baseline (5 years earlier) and (2) identify social, psychological, behavioral, and somatic predictors.

Longitudinal data of N = 10 036 participants (40–79 years) were evaluated who had no evidence of depression at baseline based on Patient Health Questionnaire (PHQ-9), no history of depression, or intake of antidepressants. Multivariate logistic regression models were used to predict the onset of depression.

Prevalence of new cases of depression was 4.4%. Higher rates of women (5.1%) than men (3.8%) were due to their excess incidence <60 years of age. Regression analyses revealed significant social, psychological, behavioral, and somatic predictors: loneliness [odds ratio (OR) 2.01; 95% confidence interval (CI) 1.48–2.71], generalized anxiety (OR 2.65; 1.79–3.85), social phobia (OR 1.87; 1.34–2.57), panic (OR 1.67; 1.01–2.64), type D personality (OR 1.85; 1.47–2.32), smoking (OR 1.35; 1.05–1.71), and comorbid cancer (OR 1.58; 1.09–2.24). Protective factors were age (OR 0.88; 0.83–0.93) and social support (OR 0.93; 0.90–0.95). Stratified by sex, cancer was predictive for women; for men smoking and life events. Entered additionally, the PHQ-9 baseline score was strongly predictive (OR 1.40; 1.34–1.47), generalized anxiety became only marginally, and panic was no longer predictive. Other predictors remained significant, albeit weaker.

Psychobiological vulnerability, stress, and illness-related factors were predictive of new onset of depression, whereas social support was protective. Baseline subclinical depression was an additional risk weakening the relationship between anxiety and depression by taking their overlap into account. Vulnerability factors differed between men and women.