Probands with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for several psychiatric and neurodevelopmental disorders. The risk of these disorders among the siblings of probands has not been thoroughly assessed in a population-based cohort.

Every child born in Finland in 1991–2005 and diagnosed with ADHD in 1995–2011 were identified from national registers. Each case was matched with four controls on sex, place, and date of birth. The full siblings of the cases and controls were born in 1981–2007 and diagnosed in 1981–2013. In total, 7369 cases with 12 565 siblings and 23 181 controls with 42 753 siblings were included in the analyses conducted using generalized estimating equations.

44.2% of the cases and 22.2% of the controls had at least one sibling diagnosed with any psychiatric or neurodevelopmental disorder (risk ratio, RR = 2.1; 95% CI 2.0–2.2). The strongest associations were demonstrated for childhood-onset disorders including ADHD (RR = 5.7; 95% CI 5.1–6.3), conduct and oppositional disorders (RR = 4.0; 95% CI 3.5–4.5), autism spectrum disorders (RR = 3.9; 95% CI 3.3–4.6), other emotional and social interaction disorders (RR = 2.7; 95% CI 2.4–3.1), learning and coordination disorders (RR = 2.6; 95% CI 2.4–2.8), and intellectual disability (RR = 2.4; 95% CI 2.0–2.8). Also, bipolar disorder, unipolar mood disorders, schizophrenia spectrum disorders, other neurotic and personality disorders, substance abuse disorders, and anxiety disorders occurred at increased frequency among the siblings of cases.

The results offer potential utility for early identification of neurodevelopmental and psychiatric disorders in at-risk siblings of ADHD probands and also argue for more studies on common etiologies.

Depression and anxiety disorders (ADs) are highly co-morbid, but the reason for this co-morbidity is unclear. One possibility is that they predispose one another. An informative way to examine interactions between disorders without the confounds present in patient populations is to manipulate the psychological processes thought to underlie the pathological states in healthy individuals. In this study we therefore asked whether a model of the sad mood in depression can enhance psychophysiological responses (startle) to a model of the anxiety in ADs. We predicted that sad mood would increase anxious anxiety-potentiated startle responses.

In a between-subjects design, participants (n=36) completed either a sad mood induction procedure (MIP; n=18) or a neutral MIP (n=18). Startle responses were assessed during short-duration predictable electric shock conditions (fear-potentiated startle) or long-duration unpredictable threat of shock conditions (anxiety-potentiated startle).

Induced sadness enhanced anxiety- but not fear-potentiated startle.

This study provides support for the hypothesis that sadness can increase anxious responding measured by the affective startle response. This, taken together with prior evidence that ADs can contribute to depression, provides initial experimental support for the proposition that ADs and depression are frequently co-morbid because they may be mutually reinforcing.

Lesbian, gay, and bisexual (LGB) individuals report higher levels of depression and anxiety than heterosexual people. Genetic factors may be a ‘common cause’ of sexual minority status and psychological distress. Alternatively, these may be correlated because of non-genetic environmental factors (e.g. minority stressors). This study investigated minority stressors and distress in monozygotic twins discordant for sexual minority status. This design provides a test of the role of non-shared environmental factors while minimizing differences due to genetics.

Thirty-eight twin pairs in which one was heterosexual and the other was LGB completed a survey. Differences between twin pairs in minority stressors, rumination, psychological distress, and gender non-conformity were examined. Associations between these variables were also tested.

Although there were no significant group differences for distress, LGB twins had higher rumination, a vulnerability factor for distress, than heterosexual co-twins. LGB twins also had higher scores than heterosexual co-twins on expectations of rejection, active concealment, self-stigma, prejudice events, childhood gender non-conformity, and lower scores on sexual orientation disclosure. Differences between twin pairs in rumination were positively associated with differences in acceptance concerns and self-stigma. Finally, self-stigma was positively associated with rumination in the full sample of heterosexual co-twins and microaggressions were positively associated with rumination when looking at exclusively heterosexual co-twins.

These results support environmental factors as a causal explanation for disparities in rumination between LGB and heterosexual individuals. These factors likely include minority stressors. Rumination may also be associated with minority stressors in heterosexual MZ co-twins of LGB individuals.

Depression is a challenge to diagnose reliably and the current gold standard for trials of DSM-5 has been in agreement between two or more medical specialists. Research studies aiming to objectively predict depression have typically used brain scanning. Less expensive methods from cognitive neuroscience may allow quicker and more reliable diagnoses, and contribute to reducing the costs of managing the condition. In the current study we aimed to develop a novel inexpensive system for detecting elevated symptoms of depression based on tracking face and eye movements during the performance of cognitive tasks.

In total, 75 participants performed two novel cognitive tasks with verbal affective distraction elements while their face and eye movements were recorded using inexpensive cameras. Data from 48 participants (mean age 25.5 years, standard deviation of 6.1 years, 25 with elevated symptoms of depression) passed quality control and were included in a case-control classification analysis with machine learning.

Classification accuracy using cross-validation (within-study replication) reached 79% (sensitivity 76%, specificity 82%), when face and eye movement measures were combined. Symptomatic participants were characterised by less intense mouth and eyelid movements during different stages of the two tasks, and by differences in frequencies and durations of fixations on affectively salient distraction words.

Elevated symptoms of depression can be detected with face and eye movement tracking during the cognitive performance, with a close to clinically-relevant accuracy (~80%). Future studies should validate these results in larger samples and in clinical populations.

Endophenotypes are laboratory-based measures hypothesized to lie in the causal chain between genes and clinical disorder, and to serve as a more powerful way to identify genes associated with the disorder. One promise of endophenotypes is that they may assist in elucidating the neurobehavioral mechanisms by which an associated genetic polymorphism affects disorder risk in complex traits. We evaluated this promise by testing the extent to which variants discovered to be associated with schizophrenia through large-scale meta-analysis show associations with psychophysiological endophenotypes.

We genome-wide genotyped and imputed 4905 individuals. Of these, 1837 were whole-genome-sequenced at 11× depth. In a community-based sample, we conducted targeted tests of variants within schizophrenia-associated loci, as well as genome-wide polygenic tests of association, with 17 psychophysiological endophenotypes including acoustic startle response and affective startle modulation, antisaccade, multiple frequencies of resting electroencephalogram (EEG), electrodermal activity and P300 event-related potential.

Using single variant tests and gene-based tests we found suggestive evidence for an association between contactin 4 (CNTN4) and antisaccade and P300. We were unable to find any other variant or gene within the 108 schizophrenia loci significantly associated with any of our 17 endophenotypes. Polygenic risk scores indexing genetic vulnerability to schizophrenia were not related to any of the psychophysiological endophenotypes after correction for multiple testing.

The results indicate significant difficulty in using psychophysiological endophenotypes to characterize the genetically influenced neurobehavioral mechanisms by which risk loci identified in genome-wide association studies affect disorder risk.

Very little is known about the phenotypic expression of schizotypal traits in individuals with 22q11.2 deletion syndrome (22q11DS). The main purpose was to analyse the factorial structure, internal consistency and temporal stability of schizotypal traits, as well as their associations with prodromal states and clinical psychotic symptoms in adolescents with 22q11DS.

The sample comprised 61 adolescents with 22q11DS (mean = 14.95 years, s.d. = 2.13; n = 24 at follow-up). An age-matched comparison group (n = 61, mean = 15.44 years, s.d. = 1.76) was also included. The Schizotypal Personality Questionnaire (SPQ), the Structured Interview for Prodromal Syndromes, the Positive and Negative Syndrome Scale, and the Brief Psychiatric Rating Scale were used.

Adolescents with 22q11DS scored higher than the control group on the interpersonal dimension and suspiciousness subscale of the SPQ. The analysis of the internal structure of the SPQ in the sample of 22q11DS participants yielded a three-component solution (cognitive–perceptual, interpersonal, and disorganized). In addition, internal consistency coefficients ranged between 0.63 and 0.91. The schizotypal traits were highly stable across a 3.6-year interval, and ranged from 0.50 to 0.63. Self-reported schizotypal traits correlated with interview-based ratings of prodromal states and psychotic symptoms.

These results indicate that the SPQ may be a valid tool to assess schizotypal traits in adolescents with 22q11DS. The identification of a reliable self-report instrument for use in individuals with learning disabilities and at genetic high risk for psychosis could be useful in clinical and research settings. Assessment of schizotypal traits may be used as a distal risk marker and in a close-in strategy in high-risk genetic samples to enhance the possibility of early detection of psychosis.

Larger grey matter volume of the inferior frontal gyrus (IFG) is among the most replicated biomarkers of genetic risk for bipolar disorders (BD). However, the IFG is a heterogeneous prefrontal region, and volumetric findings can be attributable to changes in cortical thickness (CT), surface area (SA) or gyrification. Here, we investigated the morphometry of IFG in participants at genetic risk for BD.

We quantified the IFG cortical grey matter volume in 29 affected, 32 unaffected relatives of BD probands, and 42 controls. We then examined SA, CT, and cortical folding in subregions of the IFG.

We found volumetric group differences in the right IFG, with the largest volumes in unaffected high-risk and smallest in control participants (F2,192 = 3.07, p = 0.01). The volume alterations were localized to the pars triangularis of the IFG (F2,97 = 4.05, p = 0.02), with no differences in pars opercularis or pars orbitalis. Pars triangularis volume was highly correlated with its SA [Pearson r(101) = 0.88, p < 0.001], which significantly differed between the groups (F2,97 = 4.45, p = 0.01). As with volume, the mean SA of the pars triangularis was greater in unaffected (corrected p = 0.02) and affected relatives (corrected p = 0.05) compared with controls. We did not find group differences in pars triangularis CT or gyrification.

These findings strengthen prior knowledge about the volumetric findings in this region and provide a new insight into the localization and topology of IFG alterations. The unique nature of rIFG morphology in BD, with larger volume and SA early in the course of illness, could have practical implications for detection of participants at risk for BD.

Traumatized individuals and particularly post-traumatic stress disorder (PTSD) patients are characterized by memory disturbances that suggest altered memory control. The present study investigated the issue using an item method, directed forgetting (DF) paradigm in 51 civil war victims in Uganda. All participants had been exposed to severe traumatic stress and 26 additionally suffered from PTSD.

In an item cued, DF paradigm photographs were presented, each followed by an instruction to either remember or forget it. A recognition test for all initially presented photographs and thematically similar distracters followed. DF patterns were compared between the non-PTSD and the PTSD groups. Post-experimental ratings of picture valence and arousal were collected and correlated with DF.

Results revealed DF, that is, reduced recognition for ‘to-be-forgotten’ items in the non-PTSD but not in the PTSD group. Moreover, in the non-PTSD, but not in the PTSD group, false alarms were reduced for ‘to-be-remembered’ items. Finally, DF was reduced in those participants who rated the pictures as more arousing, the PTSD group giving, on average, higher arousal ratings.

Data indicate that DF is reduced in PTSD and that the reduction is related to stimulus arousal. Furthermore, individuals with PTSD are characterized by a more global encoding style than individuals without PTSD, reflected in a higher false alarm rate. In sum, traumatized individuals with (but not without) PTSD are impaired in their ability to selectively control episodic memory encoding. This impairment may contribute to clinical features of the disorder such as intrusions and flashbacks.

Childhood trauma is a risk factor for psychosis. Deficits in response inhibition are common to psychosis and trauma-exposed populations, and associated brain functions may be affected by trauma exposure in psychotic disorders. We aimed to identify the influence of trauma-exposure on brain activation and functional connectivity during a response inhibition task.

We used functional magnetic resonance imaging to examine brain function within regions-of-interest [left and right inferior frontal gyrus (IFG), right dorsolateral prefrontal cortex, right supplementary motor area, right inferior parietal lobule and dorsal anterior cingulate cortex], during the performance of a Go/No-Go Flanker task, in 112 clinical cases with psychotic disorders and 53 healthy controls (HCs). Among the participants, 71 clinical cases and 21 HCs reported significant levels of childhood trauma exposure, while 41 clinical cases and 32 HCs did not.

In the absence of effects on response inhibition performance, childhood trauma exposure was associated with increased activation in the left IFG, and increased connectivity between the left IFG seed region and the cerebellum and calcarine sulcus, in both cases and healthy individuals. There was no main effect of psychosis, and no trauma-by-psychosis interaction for any other region-of-interest. Within the clinical sample, the effects of trauma-exposure on the left IFG activation were mediated by symptom severity.

Trauma-related increases in activation of the left IFG were not associated with performance differences, or dependent on clinical diagnostic status; increased IFG functionality may represent a compensatory (overactivation) mechanism required to exert adequate inhibitory control of the motor response.

Prevalence rates of post-traumatic stress disorder (PTSD) following the experience of war have been shown to be high. However, little is known about the course of the disorder in people who remained in the area of conflict and in refugees.

We studied a representative sample of 522 adults with war-related PTSD in five Balkan countries and 215 compatriot refugees in three Western European countries. They were assessed on average 8 years after the war and reinterviewed 1 year later. We established change in PTSD symptoms, measured on the Impact of Events Scale – Revised (IES-R), and factors associated with more or less favourable outcomes.

During the 1-year period, symptoms decreased substantially in both Balkan residents and in refugees. The differences were significant for IES-R total scores and for the three subscales of intrusions, avoidance and hyperarousal. In multivariable regressions adjusting for the level of baseline symptoms, co-morbidity with depression predicted less favourable symptom change in Balkan residents. More pre-war traumatic events and the use of mental health services within the follow-up period were associated with less improvement in refugees.

Several years after the war, people with PTSD reported significant symptom improvement that might indicate a fluctuating course over time. Co-morbid depression may have to be targeted in the treatment of people who remained in the post-conflict regions whereas the use of mental health services seems to be linked to the persistence of symptoms among refugees.

Relationships between performance on various tests of executive functions and positive symptoms, especially delusions and hallucinations, have not been found consistently. This may be related to method of rating symptoms, to possible interactions between them, as well as to the low specificity of the cognitive test measures used. In this study, we have investigated the relationships between different aspects of positive symptomatology and several executive subprocesses.

Stable schizophrenia patients (n=96) were assessed for disorganization, delusion and hallucination symptoms rated from the Scale for Assessment of Positive Symptoms and the Scale for Assessment of Negative Symptoms. Interference sensitivity, inhibition and flexibility were assessed using the Wickens paradigm. The relationships between symptom dimensions as well as with cognitive and other potentially confounding variables were assessed using Pearson correlations and (simple and partial) stepwise regressions.

Generally consistent with the cognitive constructs used to account for positive symptoms, the results indicated relationships between delusions, disorganization and inhibition, and between hallucinations and interference sensitivity. However, these relationships appeared more complex than expected, with some being dependent on interactions between symptoms.

These results suggest: (i) that the global measures usually employed may not be appropriate for demonstrating specific relationships between symptoms and executive functions and (ii) that it is necessary to take into account the interactions between positive symptoms as well as with other factors to reveal these relationships.