Previous work suggests that exposure to childhood adversity is associated with the combination of delusions and hallucinations. In the present study, associations between (severity of) auditory vocal hallucinations (AVH) and (i) social adversity [traumatic experiences (TE) and stressful events (SE)] and (ii) delusional ideation were examined.

A baseline case-control sample of children with and without AVH were re-assessed on AVH after 5 years and interviewed about the experience of social adversity and delusions.

A total of 337 children (mean age 13.1 years, s.d.=0.5) were assessed: 40 children continued to hear voices that were present at baseline (24%, persistent group), 15 heard voices only at follow-up (9%, incident group), 130 children no longer reported AVH that were present at baseline (remitted group) and 152 never heard voices (referent group). Both TE and SE were associated with both incident and persistent AVH, as well as with greater AVH severity and delusional ideation at follow-up. In addition, the combination of AVH and delusions displayed a stronger association with TE and SE compared with either AVH or delusions alone.

Early childhood AVH are mostly benign and transitory. However, experience of social adversity is associated with persistence, severity and onset of new AVH closer to puberty, and with delusional ideation.

Obsessive-compulsive disorder (OCD) has been associated with response inhibition deficits under motivationally neutral contingencies. We examined response inhibition performance in the presence of reward and punishment. We further investigated whether the hypothesized difficulties in flexibly updating behaviour based on external feedback in OCD would also lead to a reduced ability to adjust to changes in the reward and punishment contingencies.

Participants completed a go/no-go task that used punishments or rewards to promote response activation or suppression. The task was administered to OCD patients free of current Axis-I co-morbidities including major depression (n = 20) and a group of healthy controls (n = 32).

Compared with controls, patients with OCD had increased commission errors in punishment conditions, and failed to slow down immediately after receiving punishment. The punishment-induced increase in commission errors correlated with self-report measures of OCD symptom severity. Additionally, patients did not differ from controls in adapting their overall response style to the changes in task contingencies.

Individuals with OCD showed reduced response control selectively under punishment conditions, manifesting in an impulsive response style that was related to their current symptom severity. This stresses failures of cognitive control in OCD, particularly under negative motivational contingencies.

The relationship between prenatal tobacco exposure and hyperactivity remains controversial. To mitigate limitations of prior studies, we used a strategy involving comparison of maternal and paternal smoking reports in a historical sample where smoking during pregnancy was common.

Data were drawn from a longitudinally followed subsample of the Child Health and Development Study (n = 1752), a population-based pregnancy cohort ascertained in 1961–1963 in California. Maternal prenatal smoking was common (33.4%). Maternal and paternal smoking patterns were assessed at three time points by mother report. Hyperactivity was assessed at the mean of age of 10 years based on mother report to a personality inventory.

Unadjusted, maternal smoking during pregnancy was associated with offspring hyperactivity [β = 0.22, 95% confidence interval (CI) 0.11–0.33] and, to a similar degree, when the father smoked (β = 0.18, 95% CI 0.07–0.30). After adjustment, maternal smoking remained robustly predictive of offspring hyperactivity (β = 0.25, 95% CI 0.09–0.40) but father smoking was not (β = 0.02, 95% CI −0.20 to 0.24). When examined among the pairs matched on propensity score, mother smoking was robustly related to offspring hyperactivity whether the father smoked (β = 0.26, 95% CI 0.03–0.49) or did not smoke (β = 0.30, 95% CI 0.04–0.57). By number of cigarettes, associations with hyperactivity were present for 10–19 and 20+ cigarettes per day among mothers.

In a pregnancy cohort recruited in a time period in which smoking during pregnancy was common, we document associations between prenatal smoking exposure and offspring hyperactivity. Novel approaches to inferring causality continue to be necessary in describing the potential adverse consequences of prenatal smoking exposure later in life.

Mood and anxiety disorders are ubiquitous but current treatment options are ineffective for many sufferers. Moreover, a number of promising pre-clinical interventions have failed to translate into clinical efficacy in humans. Improved treatments are unlikely without better animal–human translational pipelines. Here, we translate a rodent measure of negative affective bias into humans, exploring its relationship with (1) pathological mood and anxiety symptoms and (2) transient induced anxiety.

Adult participants (age = 29 ± 11) who met criteria for mood or anxiety disorder symptomatology according to a face-to-face neuropsychiatric interview were included in the symptomatic group. Study 1 included N = 77 (47 = asymptomatic [female = 21]; 30 = symptomatic [female = 25]), study 2 included N = 47 asymptomatic participants (25 = female). Outcome measures were choice ratios, reaction times and parameters recovered from a computational model of reaction time – the drift diffusion model (DDM) – from a two-alternative-forced-choice task in which ambiguous and unambiguous auditory stimuli were paired with high and low rewards.

Both groups showed over 93% accuracy on unambiguous tones indicating intact discrimination, but symptomatic individuals demonstrated increased negative affective bias on ambiguous tones [proportion high reward = 0.42 (s.d. = 0.14)] relative to asymptomatic individuals [0.53 (s.d. = 0.17)] as well as a significantly reduced DDM drift rate. No significant effects were observed for the within-subjects anxiety-induction.

Humans with pathological anxiety symptoms directly mimic rodents undergoing anxiogenic manipulation. The lack of sensitivity to transient anxiety suggests the paradigm might be more sensitive to clinically relevant symptoms. Our results establish a direct translational pipeline (and candidate therapeutics screen) from negative affective bias in rodents to pathological mood and anxiety symptoms in humans.

Suicide is a leading cause of death and has been strongly associated with affective disorders. The influence of affective disorder polarity on subsequent suicide attempts or completions and any differential effect of suicide risk factors by polarity were assessed in a prospective cohort.

Participants with major affective disorders in the National Institute of Mental Health (NIMH) Collaborative Depression Study (CDS) were followed prospectively for up to 25 years. A total of 909 participants meeting prospective diagnostic criteria for major depressive and bipolar disorders were followed through 4204 mood cycles. Suicidal behavior was defined as suicide attempts or completions. Mixed-effects, grouped-time survival analysis assessed risk of suicidal behavior and differential effects of risk factors for suicidal behavior by polarity. In addition to polarity, the main effects of age, gender, hopelessness, married status, prior suicide attempts and active substance abuse were modeled, with mood cycle as the unit of analysis.

After controlling for age of onset, there were no differences in prior suicide attempts by polarity although bipolar participants had more prior severe attempts. During follow-up, 40 cycles ended in suicide and 384 cycles contained at least one suicide attempt. Age, hopelessness and active substance abuse but not polarity predicted suicidal behavior. The effects of risk factors did not differ by polarity.

Bipolarity does not independently influence risk of suicidal behavior or alter the influence of well-established suicide risk factors within affective disorders. Suicide risk assessment strategies may continue to appraise these common risk factors without regard to mood polarity.

The effects of cannabis use on neuropsychological indices that show characteristic disturbances in schizophrenia are unclear. The effect of cannabis use on these cognitive functions is of particular interest given the hypothesized association between cannabis use and schizophrenia. Therefore, this study aimed to examine the effects of cannabis use on attentional control, working memory and executive functioning, in both healthy individuals and patients with schizophrenia.

Neuropsychological performance was assessed in 36 cannabis users who were otherwise healthy, 35 healthy non-users, 22 cannabis-using patients with schizophrenia, and 49 non-using patients with schizophrenia. Participants were administered the Stroop task, the letter–number sequencing and spatial span subtests of the Wechsler Memory Scale, and the Wisconsin Card Sorting Test (WCST).

Patients with schizophrenia (both cannabis users and non-users) showed significantly poorer performance across all neuropsychological tasks, relative to controls; however, there were no significant differences between schizophrenic cannabis users and schizophrenic non-users on any measures, with the exception of increased non-perseverative errors on the WCST in cannabis-using patients. Similarly, healthy cannabis users showed no significant differences from healthy non-users in any of the cognitive domains, with the exception of a schizophrenic-like increase in perseveration on the WCST.

Amongst both healthy individuals and patients with schizophrenia there appears to be little difference in cognitive performance between cannabis users and non-users, suggesting that cannabis use has only subtle effects on the neurocognitive performance indices assessed here, which have been well established to be disturbed in schizophrenia.

An imbalance in appetite-regulating neuropeptides of the central nervous system has been associated with anorexia nervosa (AN), but the mechanisms of action are poorly understood. Agouti-related protein (AGRP), an orexigenic mediator of the hypothalamus, increases food intake and decreases energy expenditure in times of negative energy balance. The aim of the present study was to investigate AGRP in acute and fully weight-restored patients with AN, as well as during weight gain.

Plasma AGRP and leptin levels were assessed using an enzyme-linked immunosorbent assay kit in a total of 175 female participants, including 75 patients with acute AN, 37 weight-restored AN patients and 63 healthy controls. Of the patients with acute AN, 33 were reassessed after partial weight gain.

In weight-restored AN patients plasma AGRP levels were similar to those in healthy controls, whereas in patients with acute AN, AGRP was elevated. AGRP was inversely correlated with indicators of undernutrition such as body mass index and plasma leptin. In addition, AGRP levels normalized during weight gain of longitudinally assessed AN patients.

Our results underline the significance of undernutrition and hypoleptinemia for the interpretation of peripheral AGRP concentrations. This provides support for the hypothesis that abnormal AGRP plasma levels in AN patients reflect undernutrition, rather than disease-specific traits.

Whether temperament and character differ between bipolar disorder (BD) and major depressive disorder (MDD) patients and general population subjects, or between BD I and BD II patients, remains unclear.

BD patients (n=191) from the Jorvi Bipolar Study and MDD patients (n=266) from the Vantaa Depression Study (VDS) and the Vantaa Primary Care Depression Study were interviewed at baseline, at 6 and 18 months, and in the VDS at 5 years. A general population comparison group (n=264) was surveyed by mail. BD patients' scores on the Temperament and Character Inventory-Revised were compared at an index interview, when levels of depression and mania were lowest, with scores of MDD patients and controls. BD I (n=99) and BD II (n=92) patients were compared.

Compared with controls, both BD and MDD patients had higher harm avoidance [odds ratio (OR) 1.027, p<0.001 and OR 1.047, p<0.001, respectively] and lower persistence (OR 0.983, p=0.006 and OR 0.968, p<0.001, respectively) scores. Moreover, BD patients had lower self-directedness (OR 0.979, p=0.003), MDD patients lower reward dependence (OR 0.976, p=0.002) and self-transcendence (OR 0.966, p<0.001) scores. BD patients scored lower in harm avoidance (OR 0.980, p=0.002) and higher in novelty seeking (OR 1.027, p<0.001) and self-transcendence (OR 1.028, p<0.001) than MDD patients. No differences existed between BD I and II patients.

The patterns of temperament and character dimensions differed less between BD and MDD patients, than patients from their controls. The most pronounced difference was higher novelty seeking in BD than MDD patients. The dimensions investigated are unlikely to differ between BD I and BD II patients.

Individuals with a borderline personality disorder (BPD) suffer from a constellation of rapidly shifting emotional, interpersonal, and behavioral symptoms. The menstrual cycle may contribute to symptom instability among females with this disorder.

Fifteen healthy, unmedicated females with BPD and without dysmenorrhea reported daily symptoms across 35 days. Urine luteinizing hormone and salivary progesterone (P4) were used to confirm ovulation and cycle phase. Cyclical worsening of symptoms was evaluated using (1) phase contrasts in multilevel models and (2) the Carolina Premenstrual Assessment Scoring System (C-PASS), a protocol for evaluating clinically significant cycle effects on symptoms.

Most symptoms demonstrated midluteal worsening, a perimenstrual peak, and resolution of symptoms in the follicular or ovulatory phase. Post-hoc correlations with person-centered progesterone revealed negative correlations with most symptoms. Depressive symptoms showed an unexpected delayed pattern in which baseline levels of symptoms were observed in the ovulatory and midluteal phases, and exacerbations were observed during both the perimenstrual and follicular phases. The majority of participants met C-PASS criteria for clinically significant (⩾30%) symptom exacerbation. All participants met the emotional instability criterion of BPD, and no participant met DSM-5 criteria for premenstrual dysphoric disorder (PMDD).

Females with BPD may be at elevated risk for perimenstrual worsening of emotional symptoms. Longitudinal studies with fine-grained hormonal measurement as well as hormonal experiments are needed to determine the pathophysiology of perimenstrual exacerbation in BPD.

The DSM-IV symptom criteria for major depressive disorder (MDD) are somewhat lengthy, with many studies showing that treatment providers have difficulty recalling all nine symptoms. Moreover, the criteria include somatic symptoms that are difficult to apply in patients with medical illnesses. In a previous report, we developed a briefer definition of MDD that was composed of the mood and cognitive symptoms of the DSM-IV criteria, and found high levels of agreement between the simplified and full DSM-IV definitions. The goal of the present study was to replicate these findings in another large sample of psychiatric out-patients and to extend the findings to other patient samples.

We interviewed 1100 psychiatric out-patients and 210 pathological gamblers presenting for treatment and 1200 candidates for bariatric surgery. All patients were interviewed by a diagnostic rater who administered a semi-structured interview. We inquired about all symptoms of depression for all patients.

In all three samples high levels of agreement were found between the DSM-IV and the simpler definition of MDD. Summing across all 2510 patients, the level of agreement between the two definitions was 95.5% and the κ coefficient was 0.87.

After eliminating the four somatic criteria from the DSM-IV definition of MDD, a high level of concordance was found between this simpler definition and the original DSM-IV classification. This new definition offers two advantages over the current DSM-IV definition – it is briefer and it is easier to apply with medically ill patients because it is free of somatic symptoms.

Aberrant emotional biases have been reported in bipolar disorder (BD), but results are inconsistent. Despite the clinical relevance of chronic mood variability in BD, there is no previous research investigating how the extent of symptom fluctuations in bipolar disorder might relate to emotional biases. This exploratory study investigated, in a large cohort of bipolar patients, whether instability in weekly mood episode symptoms and other clinical and demographic factors were related to emotional bias as measured in a simple laboratory task.

Participants (N = 271, BDI = 206, BDII = 121) completed an ‘emotional categorization and memory’ task. Weekly self-reported symptoms of depression and mania were collected prospectively. In linear regression analyses, associations between cognitive bias and mood variability were explored together with the influence of demographic and clinical factors, including current medication.

Greater accuracy in the classification of negative words relative to positive words was associated with greater instability in depressive symptoms. Furthermore, greater negative bias in free recall was associated with higher instability in manic symptoms. Participants diagnosed with BDII, compared with BDI, showed overall better word recognition and recall. Current antipsychotic use was associated with reduced instability in manic symptoms but this did not impact on emotional processing performance.

Emotional processing biases in bipolar disorder are related to instability in mood. These findings prompt further investigation into the underpinnings as well as clinical significance of mood instability.

Episodes of depression and anxiety (D&A) during the transition from late adolescence to adulthood, particularly when persistent, are predictive of long-term disorders and associated public health burden. Understanding risk factors at this time is important to guide intervention. The current objective was to investigate the associations between maternal symptoms of D&A with offspring symptoms during their transition to adulthood.

Data from a large population-based birth cohort study, in South Brazil, were used. Prospective associations between maternal D&A and offspring risk of these symptoms during the transition to adulthood (18/19, 24 and 30 years) were estimated.

Maternal D&A in adolescence was associated with offspring symptoms across the transition to adulthood, associations were consistently stronger for females than for males. Daughters whose mothers reported D&A were 4.6 times (95% confidence interval 2.71–7.84) as likely to report D&A at all three time-points, than daughters of symptom-free mothers.

Maternal D&A is associated with persistent D&A during the daughter's transition to adulthood. Intervention strategies should consider the mother's mental health.