The author has not supplied his declaration of competing interest.

The author has not supplied his declaration of competing interest.

Persistent pondering over negative self-related thoughts is a central feature of depressive psychopathology.

In the present study, we sought to investigate the neural correlates of abnormal negative self-referential processing (SRP) in patients with major depressive disorder (MDD) and its impact on subsequent cognitive control-related neuronal activation.

We hypothesized aberrant activation dynamics during the period of negative and neutral SRP in the rostral anterior cingulate cortex (rACC) and in the amygdala in patients with MDD. We assumed abnormal activation in the fronto-cingulate network during Stroop task execution.

Nineteen depressed patients and 20 healthy controls participated in the study. Using an event-related fMRI design, negative, positive and neutral self-referential statements were displayed for 6.5s and followed by incongruent or congruent Stroop conditions.

In contrast to controls, patients did not exhibit valence-dependent rACC activation differences during SRP. A novel finding was the significant activation of the amygdala and the reward-processing network during presentation of neutral self-referential stimuli relative to baseline and to affective stimuli in patients. The fMRI analysis of the Stroop task revealed a reduced BOLD activation in the right frontoparietal network of patients in the incongruent condition after negative SRP only.

Thus, the inflexible activation in the rACC may correspond to the inability of depressed patients to shift their attention away from negative self-related stimuli. The accompanying negative affect and task-irrelevant emotional processing may compete for neuronal resources with cognitive control processes and lead thereby to deficient cognitive performance associated with decreased frontoparietal activation.

The authors have not supplied their declaration of competing interest.

A recent study did not find clear-cut sex differences in psychotic symptoms. Studies investigating altered stress reactivity more consistently report differences between the sexes, although the results are contradicting in suggesting either men or women to be more stress-sensitive. We assessed self-reported experiences in the context of real-life to more fully understand the nature of sex differences in psychosis.

We employed the Experience Sampling Method, a structured diary technique, to investigate in real-life:

– symptoms;

– behavior in context;

– underlying mechanisms in 283 healthy controls, 268 subjects at risk for psychosis and 232 patients with psychotic disorder.

Multilevel regression analyses revealed no differences in symptom expression between the sexes. Similarly, men and women did not differ in their level of social interaction and overall activity. However, men at increased risk of psychosis were more often alone and were less involved in goal-directed activities compared to women. Finally, women reported more emotional reactivity to daily life stress then men but women also reported more positive affect when pleasant events had happened.

The data thus suggest only minor differences between men and women in psychotic symptoms and actual behavior. However, whenever differences were apparent, they consistently pointed towards more severe symptoms and more deficiencies in men compared to women. In contrast, increased environmental reactivity in women (to both negative and positive environments) in addition to more social contacts may constitute a protective factor for the development of more severe psychopathology.

The authors have not supplied their declaration of competing interest.

Sex and gender differences in schizophrenic psychoses have often been described but treatment approaches so far have hardly taken them into account.

To describe the most important sex and gender differences in schizophrenic psychoses with clinical implications.

Review.

Schizophrenic disorders show a later age of onset in women and a slightly better course, especially in young women. As to pathogenesis, there is some evidence that the age difference might be at least partly due to the female sex hormone estradiol being a protective factor. Differences in course might also have to do with this biological factor, but at the same time with the psychosocial advantages of a higher age of onset and other psychosocial factors.

These gender differences have important implications for assessment and therapy. Thus, we have to consider gender differences in coping behaviour as well as psychosocial burdens and needs deriving from differing roles in partnership, family, household and profession, from dependent relationships, potential abuse and violence. Furthermore, there are specific biological risks such as gonadal dysfunction we have to deal with in both sexes differently. Thus, e.g. women with psychosis can also have very special needs regarding fertility, pregnancy and motherhood. Also, around menopause we have to consider special measures such as replacement of physiological 17-b-estradiol.

Women, but also men, with schizophrenic psychoses should get a gender-sensitive assessment and treatment.

The author has not supplied his declaration of competing interest.

The authors have not supplied their declaration of competing interest.

The findings of meta-analyses and randomized placebo-controlled treatment studies indicate that a range of approaches are efficacious in acute treatment. Pharmacological and psychological treatments, when delivered singly, have broadly similar efficacy in acute treatment. However, acute treatment with cognitive therapy (group or individual) may be associated with a reduced risk of symptomatic relapse at follow-up. Cognitive behaviour therapy is efficacious in adults and children: cognitive therapy appears superior to exposure therapy, but the evidence for the efficacy of social skills training is less strong. It is unlikely that the combination of pharmacological with psychological treatments is associated with greater overall efficacy than with either treatment, when given alone, as only 1 of 4 studies of the relative efficacy of combination treatment found evidence for superior efficacy.

Antidepressant drugs with proven efficacy include most SSRIs, the SNRI venlafaxine, the MAOI phenelzine and the RIMA moclobemide: the potential efficacy of tricyclic antidepressants is unknown. Some benzodiazepines and anticonvulsants and the antipsychotic olanzapine also appear efficacious in acute treatment. A number of small single-dose placebo-controlled crossover studies together suggest that beta-blockers can be beneficial in reducing anxiety symptoms in individuals with ‘performance anxiety’ (for example, when speaking in public), which overlaps with mild non-generalized social anxiety disorder. Acute treatment studies indicate that the proportion of responding patients increases steadily over time. A post-hoc analysis of the clinical trial database with paroxetine indicates that many non-responders to treatment at 8 weeks become responders with a further 4 weeks of double-blind treatment: however a post-hoc analysis of the clinical trial database for escitalopram indicates that response is unlikely if there is no onset of clinical effect within the first 4 weeks of treatment.

The findings of randomized placebo-controlled relapse prevention studies in patients who have responded to previous acute treatment reveal a significant advantage for staying on active medication (clonazepam, escitalopram, paroxetine, pregabalin, sertraline) for up to six months. Fixed-dose randomized controlled trials do not provide consistent evidence of a dose-response relationship with antidepressant drugs: but a fixed-dose study of pregabalin found that only the higher daily dosage was efficacious. A double-blind randomized controlled dosage escalation trial found no advantage for increasing to a higher daily dosage (of duloxetine), when compared to continuing treatment with a lower dosage. Switching between treatments with proven efficacy may be helpful. An uncontrolled study of augmentation of SSRI treatment with buspirone found some evidence of beneficial effects; but a placebo-controlled crossover-study of the augmentation of paroxetine with pindolol found no evidence of efficacy. A small placebo-controlled study of the augmentation of paroxetine with clonazepam found the combination was marginally short of superiority, when compared to paroxetine alone.

The author has not supplied his declaration of competing interest.

The author has not supplied his declaration of competing interest.

The authors have not supplied their declaration of competing interest.

People displaying persistent, full-blown psychotic experiences without a need-for-care in the general population are an ideal group to investigate to differentiate those factors that are linked to distress and dysfunction from those that are merely associated with benign anomalous experiences. The UNIQUE study investigated the cognitive and social processes predicted by cognitive models of psychosis to differentiate between benign and pathological outcomes of psychotic experiences (PEs).

Two hundred and fifty-nine individuals were recruited (84 clinical participants with PEs; 92 non-clinical participants with PEs; 83 controls without PEs) from urban (South-East London) and rural (North Wales) UK sites. The three groups were compared on clinical and psychological measures, on reasoning tasks, and on their appraisals of experimental tasks inducing anomalous experiences (of thought interference symptoms and auditory hallucinations).

The clinical picture demonstrated a distinctive pattern of similarities and differences on PEs between the clinical and non-clinical groups, while their demographic and psychological profiles were markedly different. As predicted, the clinical group showed a ‘jump-to-conclusions’ reasoning style, and endorsed more threatening appraisals ratings of the experimentally-induced anomalous experiences than the non-clinical group, who did not differ from the controls.

The results of this study identified a number of specific factors that may be protective against transition to psychosis in individuals with persistent PEs. They also provide robust experimental evidence for the key role of appraisals in determining outcome, as postulated by cognitive models of psychosis.

Medical research Council, UK.

The authors have not supplied their declaration of competing interest.

The author has not supplied his declaration of competing interest.

The author has not supplied his declaration of competing interest.

Meta-analyses link childhood trauma to depression, mania, anxiety, and psychosis. It is unclear, however, whether these outcomes truly represent distinct disorders following childhood trauma, or that childhood trauma is associated with admixtures of affective, psychotic, anxiety and manic psychopathology throughout life.

To investigate the impact of trauma on psychopathological phenotype, functional outcome, and daily life stress reactivity.

We used data from a representative general population sample (NEMESIS-2; n = 6646), of whom respectively 1577 and 1120 had a lifetime diagnosis of mood or anxiety disorder, as well as from a sample of patients with a diagnosis of schizophrenia (GROUP; n = 825). Multinomial logistic regression was used to assess whether childhood trauma was more strongly associated with isolated affective/psychotic/anxiety/manic symptoms than with their admixture. Additionally, we examined these groups in terms of social functioning, clinical severity, and quality of life. In a separate sample (n = 621), daily life (emotional and cortisol) stress reactivity was assessed, using ambulatory assessment.

In all samples, childhood trauma was considerably more strongly associated with an admixture of symptoms of depression, anxiety, psychosis, and mania, rather than with these symptoms in isolation. Individuals exposed to childhood trauma, who also had an admixture of symptoms, had a lower quality of life, more help-seeking behaviour, higher prevalence of substance use disorders, and lower social functioning, compared with individuals not exposed to trauma, without an admixture of symptoms, or neither. Furthermore, trauma-exposed individuals with an admixed psychopathological phenotype show a higher daily emotional stress reactivity.

Childhood trauma increases the likelihood of a specific admixture of affective, anxiety and psychotic symptoms cutting across traditional diagnostic boundaries. Stratifying according to childhood trauma exposure thus identifies an admixed phenotype, possibly induced by continuous daily life stress reactivity, that has important clinical relevance. Identification of functionally meaningful aetiological subgroups may aid clinical practice.

The authors have not supplied their declaration of competing interest.

The author has not supplied his declaration of competing interest.

The author has not supplied his declaration of competing interest.

The author has not supplied his declaration of competing interest.

Genetic risk and outcome of psychoses (GROUP) is a 6 year longitudinal cohort study that focus on gene–environment vulnerability and resilience in patients with psychotic disorders, their unaffected family members and non-related controls. Its main aim is to elucidate etiological and pathogenetic factors that influence the onset and course of psychotic disorders. In this substudy, we will examine medication use over time, its relation with (the change in) metabolic syndrome status and effects on the brain.

A consortium of four university psychiatric centers and their affiliated mental health care institutions, conducted the GROUP study. At baseline, 1120 patients, 1057 siblings, 919 parents and 590 healthy controls were included. After inclusion, participants, except parents, were evaluated again after three and six years of follow-up. Extensive assessment of genetic factors, environmental factors, medication use, metabolic parameters and outcome were performed. Moreover, brain imaging was performed in a subset of participants, using a 1.5 Tesla MRI scanner.

At baseline 65% of patients used atypical antipsychotics, 16% used conventional antipsychotics and 19% used clozapine. Siblings and controls used no antipsychotics. Forty-three percent of patients, 21.3% of siblings and 9.1% of controls used antidepressants; 43.9% of patients, 2.1% of siblings and none of the controls used a mood stabilizer. We are currently analyzing the medication data over time in relation to (change in) metabolic syndrome status and the effects on the brain.

GROUP is a longitudinal cohort study in patients with psychotic disorders, their healthy siblings and controls without psychosis. This naturalistic substudy examines medication use, its association with (change of) metabolic status and effects on the brain in subjects with (high risk of) psychosis.

The authors have not supplied their declaration of competing interest.

Long-term functional outcome of dose-reduction/discontinuation strategies in first-episode psychosis (FEP) has not been studied before. The present study compared 7-year outcome of an early antipsychotic dose-reduction/discontinuation (DR) strategy with maintenance treatment (MT). Primary outcome was (symptomatic and functional) recovery; relapse rates, functional and symptomatic remission were secondary outcomes.

FEP patients (n = 128) symptomatically remitted for 6 m during their first treatment year who completed an 18 months trial comparing MT and DR were followed-up at 7 years. Symptomatic remission criteria were adopted from Andreasen et al., functional remission criteria were based on a functioning scale. Recovery was defined as meeting both criteria sets. MT or DR strategy, and baseline parameters were entered in a logistic regression analysis with symptom and functional remission and recovery at 7-years follow-up as dependent variables.

One hundred and three patients consented to participate. DR-patients showed twice the recovery-rate of MT-patients (40% against 18%), odds ratio 3.5 (P = .014). Symptomatic remission-rates were equal (69% and 67%). Better DR recovery-rates were attributable to higher functional remission-rates (46% vs. 20%) in DR. Predictors of recovery were DR, baseline living together and less severe negative symptoms. During the last 2 years of follow-up the mean daily dose in haloperidol equivalents was 2.20 mg in DR vs. 3.60 mg in MT (P = .031).

Relapse rates were initially higher in DR but leveled at 3 years; 61.5% relapsed in DR and 68.6% in MT in 7 years.

DR of antipsychotics during early stages of remitted FEP significantly improved 7-years outcome in terms of recovery and functional remission compared to maintenance treatment. Though initially relapse rates in GD were higher, these equalled those in MT from 3 years to the end of the study. While the necessity of immediate antipsychotic treatment in FEP and positive symptoms relapse is robustly demonstrated in a great number of studies, this study suggests that we are faced with a dilemma concerning the drawbacks of long-term maintenance antipsychotic treatment on functional capacity. Though antipsychotic discontinuation appears only feasible without relapse in a substantial minority of patients, guided dose-reduction as far as positive symptoms remain subsided and allow it, appears a feasible strategy in view of functional recovery, doing justice to both sides of the dilemma.

The authors have not supplied their declaration of competing interest.

ADHD is defined in DSM-5 by developmentally inappropriate and impairing levels of inattentive and hyperactive-impulsive symptoms. However, emotional dysregulation is considered to be an associated feature of the disorder that supports the diagnosis of ADHD. The common co-occurrence of emotional liability (EL) in ADHD raises the question of whether EL should be viewed as a component of ADHD or reflecting a comorbid condition.

To address the question of whether EL should be viewed as a third dimension of ADHD.

We investigated the association of EL with ADHD and impairment scores, in a sample of adults with ADHD that had been carefully selected for absence of comorbid conditions that could give rise to EL using both rating scale and experience sampling methods to measure emotional instability. We reviewed the effects of stimulants and atomoxetine on EL and the covariation of EL with ADHD inattention and hyperactivity-impulsivity. We further considered the phenotypic and genetic association of EL with ADHD using population twin data.

From these studies, we found that EL is strongly associated with ADHD even in non-comorbid cases and gives rise to additional impairments after ADHD symptoms are controlled for in the analysis. Stimulants and atomoxetine both improve EL and these improvements are correlated with changes in ADHD symptoms, indicating a shared treatment response. Genetic model fitting suggests a common pathway model, consistent with a single genetic liability for inattention, hyperactivity-impulsivity and EL.

Taken together these findings suggest that EL can be viewed as a third dimension of ADHD. Patients presenting with chronic emotional instability should always be screened for ADHD.

The author has not supplied his declaration of competing interest.

The authors have not supplied their declaration of competing interest.