The amygdala and subgenual anterior cingulate cortex (sACC) are key brain regions for the generation of negative affect. In this longitudinal fMRI study of adolescents we investigated how amygdala–sACC connectivity was correlated with negative affectivity (NA) both cross-sectionally and longitudinally, and examined its relationship to the onset of first-episode depression.

Fifty-six adolescents who were part of a larger longitudinal study of adolescent development were included. They had no history of mental illness at the time of their baseline scan (mean age 16.5 years) and had a follow-up scan 2 years later (mean age 18.8 years). We used resting-state functional-connectivity MRI to investigate whether cross-sectional and change measures of amygdala–sACC connectivity were (i) correlated with NA and its change over time, and (ii) related to the onset of first-episode depression.

The magnitude of amygdala connectivity with sACC showed significant positive correlation with NA at both time-points. Further analysis confirmed that change in amygdala–sACC connectivity between assessments was correlated with change in NA. Eight participants developed a first episode of depression between the baseline and follow-up assessments: they showed increased amygdala–sACC connectivity at follow-up.

Amygdala–sACC connectivity is associated with NA in adolescence, with change in connectivity between these regions showing positive correlation with change in NA. Our observation that the onset of depression was associated with an increase in connectivity between the regions provides support for the neurobiological ‘scar’ hypothesis of depression.

Posttraumatic stress disorder (PTSD) and stress/trauma exposure are cross-sectionally associated with advanced DNA methylation age relative to chronological age. However, longitudinal inquiry and examination of associations between advanced DNA methylation age and a broader range of psychiatric disorders is lacking. The aim of this study was to examine if PTSD, depression, generalized anxiety, and alcohol-use disorders predicted acceleration of DNA methylation age over time (i.e. an increasing pace, or rate of advancement, of the epigenetic clock).

Genome-wide DNA methylation and a comprehensive set of psychiatric symptoms and diagnoses were assessed in 179 Iraq/Afghanistan war veterans who completed two assessments over the course of approximately 2 years. Two DNA methylation age indices (Horvath and Hannum), each a weighted index of an array of genome-wide DNA methylation probes, were quantified. The pace of the epigenetic clock was operationalized as change in DNA methylation age as a function of time between assessments.

Analyses revealed that alcohol-use disorders (p = 0.001) and PTSD avoidance and numbing symptoms (p = 0.02) at Time 1 were associated with an increasing pace of the epigenetic clock over time, per the Horvath (but not the Hannum) index of cellular aging.

This is the first study to suggest that posttraumatic psychopathology is longitudinally associated with a quickened pace of the epigenetic clock. Results raise the possibility that accelerated cellular aging is a common biological consequence of stress-related psychopathology, which carries implications for identifying mechanisms of stress-related cellular aging and developing interventions to slow its pace.

Longitudinal studies indicate that future schizophrenia patients exhibit lower IQ than healthy controls. Recent studies suggest that future patients with other mental illnesses obtain lower pre-morbid IQ. The aims of this study were to compare pre-morbid IQ among five diagnostic categories and normal controls, to examine the distribution of pre-morbid IQ, and to investigate the relationship between pre-morbid IQ and risk of mental illness.

A total of 7486 individuals hospitalized with psychiatric disease and 20 531 controls. IQ was measured at the draft board and hospital diagnoses [schizophrenia (Sz), non-schizophrenic, non-affective psychoses (NSAP), affective (AD), personality (PD) and neurotic/stress disorders (ND)] were followed up to ages 43–54 years. Individuals hospitalized ⩽1 year after appearing before the draft board were excluded.

All future patients obtained significantly lower pre-morbid IQ than controls (3–7 IQ points), AD had the highest IQ and PD the lowest. In each diagnostic category, decreasing IQ was associated with an increasing risk of becoming a patient [odds ratios (ORs) 0.5–2.5 over the full IQ spectrum]. IQ distributions was nearly normal and uni-modal.

IQ deficits in each diagnostic category may reflect different functional patterns and temporal vicissitudes of the specific pathogenetic processes involved in different mental disorders.

The present study aimed to (a) characterize 10-year trajectory patterns of depressive symptoms and (b) investigate the association between depressive trajectory and subsequent obesity, metabolic function and cortisol level.

In a prospective study of Taiwanese adults aged ⩾60 years (n=3922) between 1989 and 1999, depression was assessed using a 10-item short-form of the Center for Epidemiologic Studies Depression Scale and information on body mass index (BMI) was collected by self-report. A subsample (n=445) of the original cohort in 1989 was drawn to assess metabolic variables and cortisol levels in a 2000 follow-up. After trajectory analyses were performed, multinomial logistic regression analyses were used to estimate the association estimates.

We identified four distinctive trajectories of depressive symptoms: class 1 (persistent low, 41.8%); class 2 (persistent mild, 46.8%); class 3 (late peak, 4.2%); and class 4 (high-chronic, 7.2%). The results from both complete cases and multiple imputation analyses indicated that the odds of obesity were lower in the class 2, 3 or 4 elderly, as compared with those in class 1, while the odds of underweight were higher. The classes of older adults with more and persistent depressive symptoms showed a trend toward having both a lower BMI (p=0.01) and a higher cortisol level (p=0.04) compared with those with low depressive symptoms.

Incremental increases in depressive symptoms over time were associated with reduced risk of obesity and higher cortisol levels.

Patients with bipolar disorder exhibit consistent deficits in facial affect identification at both behavioral and neural levels. However, little is known about which stages of facial affect processing are dysfunctional.

Event-related potentials (ERPs), including amplitude and latency, were used to evaluate two stages of facial affect processing: N170 to examine structural encoding of facial features and N250 to examine decoding of facial features in 57 bipolar disorder patients, 30 schizophrenia patients and 30 healthy controls. Three conditions were administered: participants were asked to identify the emotion of a face, the gender of a face, or whether a building was one or two stories tall.

Schizophrenia patients' emotion identification accuracy was lower than that of bipolar patients and healthy controls. N170 amplitude was significantly smaller in schizophrenia patients compared to bipolar patients and healthy controls, which did not differ from each other. Both patient groups had significantly longer N170 latency compared to healthy controls. For N250, both patient groups showed significantly smaller amplitudes compared with controls, but did not differ from each other. Bipolar patients showed longer N250 latency than healthy controls; patient groups did not differ from each other.

Bipolar disorder patients have relatively intact structural encoding of faces (N170) but are impaired when decoding facial features for complex judgments about faces (N250 latency and amplitude), such as identifying emotion or gender.

There are still uncertainties on the psychometric validity of the DSM-5 attention deficit hyperactivity disorder (ADHD) criteria for its use in the adult population. We aim to describe the adult ADHD phenotype, to test the psychometric properties of the DSM-5 ADHD criteria, and to calculate the resulting prevalence in a population-based sample in their thirties.

A cross-sectional evaluation using the DSM-5 ADHD criteria was carried out in 3574 individuals from the 1982 Pelotas Birth Cohort. Through receiver operator curve, latent and regression analyses, we obtained parameters on construct and discriminant validity. Still, prevalence rates were calculated for different sets of criteria.

The latent analysis suggested that the adult ADHD phenotype is constituted mainly by inattentive symptoms. Also, inattention symptoms were the symptoms most associated with impairment. The best cut-off for diagnosis was four symptoms, but sensitivity and specificity for this cut-off was low. ADHD prevalence rates were 2.1% for DSM-5 ADHD criteria and 5.8% for ADHD disregarding age-of-onset criterion.

The bi-dimensional ADHD structure proposed by the DSM demonstrated both construct and discriminant validity problems when used in the adult population, since inattention is a much more relevant feature in the adult phenotype. The use of the DSM-5 criteria results in a higher prevalence of ADHD when compared to those obtained by DSM-IV, and prevalence would increase almost threefold when considering current ADHD syndrome. These findings suggest a need for further refinement of the criteria for its use in the adult population.

DSM-5 proposes an Attenuated Psychosis Syndrome (APS) for further investigation, based upon the Attenuated Positive Symptom Syndrome (APSS) in the Structured Interview for Psychosis-Risk Syndromes (SIPS). SIPS Unusual Thought Content, Disorganized Communication and Total Disorganization scores predicted progression to psychosis in a 2015 NAPLS-2 Consortium report. We sought to independently replicate this in a large single-site high-risk cohort, and identify baseline demographic and clinical predictors beyond current APS/APSS criteria.

We prospectively studied 200 participants meeting criteria for both the SIPS APSS and DSM-5 APS. SIPS scores, demographics, family history of psychosis, DSM Axis-I diagnoses, schizotypy, and social and role functioning were assessed at baseline, with follow-up every 3 months for 2 years.

The conversion rate was 30% (n = 60), or 37.7% excluding participants who were followed under 2 years. This rate was stable across time. Conversion time averaged 7.97 months for 60% who developed schizophrenia and 15.68 for other psychoses. Mean conversion age was 20.3 for males and 23.5 for females. Attenuated odd ideas and thought disorder appear to be the positive symptoms which best predict psychosis in a logistic regression. Total negative symptom score, Asian/Pacific Islander and Black/African-American race were also predictive. As no Axis-I diagnosis or schizotypy predicted conversion, the APS is supported as a distinct syndrome. In addition, cannabis use disorder did not increase risk of conversion to psychosis.

NAPLS SIPS findings were replicated while controlling for clinical and demographic factors, strongly supporting the validity of the SIPS APSS and DSM-5 APS diagnosis.

Deficits in sustained attention and reaction time are core features of attention deficit hyperactivity disorder (ADHD). However, little is known about attention performance in unaffected siblings. Hence, we examined sustained attention and reaction time in youths with ADHD, unaffected siblings and controls to test whether impaired performance in attention tasks can be a potential endophenotype of ADHD.

We recruited 438 probands with clinical diagnosis of ADHD according to DSM-IV criteria, 180 unaffected siblings, and 173 healthy controls without lifetime ADHD. They were assessed using psychiatric interviews, Conners’ Continuous Performance Test, and the tasks involving attention performance of the Cambridge Neuropsychological Test Automated Battery (CANTAB): Rapid Visual Information Processing (RVP), Reaction Time (RTI) and Match to Sample Visual Search (MTS). Multi-level models were used for data analysis.

Compared with the controls, probands with ADHD and unaffected siblings had significantly higher total misses, lower probability of hits in the RVP task and probands with ADHD performed worse in the RTI and MTS tasks after controlling for sex, age, co-morbidity, parental educational levels and IQ. The duration of methylphenidate use and IQ but not psychiatric co-morbidity or current use of methylphenidate were associated with deficits in sustained attention in probands with ADHD.

Our findings suggest that attention performance assessed by the RVP task, but not the RTI or MTS tasks, of the CANTAB may be a useful cognitive endophenotype for ADHD genetic studies.

The clinical care of psychiatric patients is often guided by perceptions of suicide risk. The aim of this study was to examine the methods and results of studies reporting high-risk models for inpatient suicide.

We conducted a registered meta-analysis according to PRISMA guidelines. We searched for relevant peer-reviewed cohort and controlled studies indexed in Medline, EMBASE and PsychINFO.

The pooled odds ratio (OR) among 18 studies reporting high-risk models for inpatient suicide was 7.1 [95% confidence interval (CI) 4.2–12.2]. Between-study heterogeneity in ORs was very high (range 0–94.8, first quartile 3.4, median 8.8, third quartile 26.1, prediction interval 0.80–63.1, I2 = 88.1%). The meta-analytically derived sensitivity was 53.1% (95% CI 38.2–67.5%, I2 = 95.9%) and specificity was 84.2% (95% CI 71.6–91.9%, I2 = 99.9%) with an associated meta-analytic area under the curve of 0.83. The positive predictive value of risk categorization among six cohort studies was 0.43% (95% CI 0.014–1.3%, I2 = 95.9%). A history of suicidal behavior and depressive symptoms or affective disorder was included in the majority of high-risk models.

Despite the strength of the pooled association between high-risk categorization and suicide, the very high degree of observed heterogeneity indicates uncertainty about our ability to meaningfully distinguish inpatients according to suicide risk. The limited sensitivity and low positive predictive value of risk categorization suggest that suicide risk models are not a suitable basis for clinical decisions in inpatient settings.

Obsessive–compulsive disorder (OCD) has been linked to functional abnormalities in fronto-striatal networks as well as impairments in decision making and learning. Little is known about the neurocognitive mechanisms causing these decision-making and learning deficits in OCD, and how they relate to dysfunction in fronto-striatal networks.

We investigated neural mechanisms of decision making in OCD patients, including early and late onset of disorder, in terms of reward prediction errors (RPEs) using functional magnetic resonance imaging. RPEs index a mismatch between expected and received outcomes, encoded by the dopaminergic system, and are known to drive learning and decision making in humans and animals. We used reinforcement learning models and RPE signals to infer the learning mechanisms and to compare behavioural parameters and neural RPE responses of the OCD patients with those of healthy matched controls.

Patients with OCD showed significantly increased RPE responses in the anterior cingulate cortex (ACC) and the putamen compared with controls. OCD patients also had a significantly lower perseveration parameter than controls.

Enhanced RPE signals in the ACC and putamen extend previous findings of fronto-striatal deficits in OCD. These abnormally strong RPEs suggest a hyper-responsive learning network in patients with OCD, which might explain their indecisiveness and intolerance of uncertainty.

The role of the cerebellum in obsessive-compulsive disorder (OCD) has drawn increasing attention. However, the functional connectivity between the cerebellum and the cerebral cortex has not been investigated in OCD, nor has the relationship between such functional connectivity and clinical symptoms.

A total of 27 patients with OCD and 21 healthy controls (HCs) matched on age, sex and education underwent magnetic resonance imaging (MRI). Seed-based connectivity analyses were performed to examine differences in cerebellar-cerebral connectivity in patients with OCD compared with HCs. Associations between functional connectivity and clinical features in OCD were analyzed.

Compared with HCs, OCD patients showed significantly decreased cerebellar-cerebral functional connectivity in executive control and emotion processing networks. Within the OCD group, decreased functional connectivity in an executive network spanning the right cerebellar Crus I and the inferior parietal lobule was positively correlated with symptom severity, and decreased connectivity in an emotion processing network spanning the left cerebellar lobule VI and the lingual gyrus was negatively correlated with illness duration.

Altered functional connectivity between the cerebellum and cerebral networks involved in cognitive-affective processing in patients with OCD provides further evidence for the involvement of the cerebellum in the pathophysiology of OCD, and is consistent with impairment in executive control and emotion regulation in this condition.

Studies of patients with anorexia nervosa (AN) have shown that they do not perform well in set-shifting tasks but little is known about the neurobiological correlates of this aspect of executive function. The aim of this study was to measure serum brain-derived neurotrophic factor (BDNF) and to establish whether set-shifting difficulties are present in people with current AN and in those recovered from AN, and whether serum BDNF concentrations are correlated with set-shifting ability.

Serum BDNF concentrations were measured in 29 women with current AN (AN group), 18 women who had recovered from AN (ANRec group) and 28 age-matched healthy controls (HC group). Set-shifting was measured using the Wisconsin Card Sorting Test (WCST). Eating-related psychopathology and depressive, anxiety and obsessive–compulsive symptomatology were evaluated using the Eating Disorder Examination Questionnaire (EDEQ), the Hospital Anxiety and Depression Scale (HADS), and the Maudsley Obsessive–Compulsive Inventory (MOCI) respectively.

Serum BDNF concentrations (mean±s.d.) were significantly lower in the AN group (11.7±4.9 ng/ml) compared to the HC group (15.1±5.5 ng/ml, p=0.04) and also compared to the ANRec group (17.6±4.8 ng/ml, p=0.001). The AN group made significantly more errors (total and perseverative) in the WCST relative to the HC group. There was no significant correlation between serum BDNF concentrations and performance on the WCST.

Serum BDNF may be a biological marker for eating-related psychopathology and of recovery in AN. Longitudinal studies are needed to explore possible associations between serum BDNF concentrations, illness and recovery and neuropsychological traits.

Although both cognitive therapy (CT) and interpersonal psychotherapy (IPT) have been shown to be effective treatments for major depressive disorder (MDD), it is not clear yet whether one therapy outperforms the other with regard to severity and course of the disorder. This study examined the clinical effectiveness of CT v. IPT in a large sample of depressed patients seeking treatment in a Dutch outpatient mental health clinic. We tested whether one of the treatments was superior to the other at post-treatment and at 5 months follow-up. Furthermore, we tested whether active treatment was superior to no treatment. We also assessed whether initial depression severity moderated the effect of time and condition and tested for therapist differences.

Depressed adults (n = 182) were randomized to either CT (n = 76), IPT (n = 75) or a 2-month waiting list control (WLC) condition (n = 31). Main outcome was depression severity, measured with the Beck Depression Inventory – II (BDI-II), assessed at baseline, 2, 3, and 7 months (treatment phase) and monthly up to 5 months follow-up (8–12 months).

No differential effects between CT and IPT were found. Both treatments exceeded response in the WLC condition, and led to considerable improvement in depression severity that was sustained up to 1 year. Baseline depression severity did not moderate the effect of time and condition.

Within our power and time ranges, CT and IPT appeared not to differ in the treatment of depression in the acute phase and beyond.