In an effort to group mental disorders on the basis of aetiology, five clusters have been proposed. In this paper, we consider the validity of the first cluster, neurocognitive disorders, within this proposal. These disorders are categorized as ‘Dementia, Delirium, and Amnestic and Other Cognitive Disorders’ in DSM-IV and ‘Organic, including Symptomatic Mental Disorders’ in ICD-10.

We reviewed the literature in relation to 11 validating criteria proposed by a Study Group of the DSM-V Task Force as applied to the cluster of neurocognitive disorders.

‘Neurocognitive’ replaces the previous terms ‘cognitive’ and ‘organic’ used in DSM-IV and ICD-10 respectively as the descriptor for disorders in this cluster. Although cognitive/organic problems are present in other disorders, this cluster distinguishes itself by the demonstrable neural substrate abnormalities and the salience of cognitive symptoms and deficits. Shared biomarkers, co-morbidity and course offer less persuasive evidence for a valid cluster of neurocognitive disorders. The occurrence of these disorders subsequent to normal brain development sets this cluster apart from neurodevelopmental disorders. The aetiology of the disorders is varied, but the neurobiological underpinnings are better understood than for mental disorders in any other cluster.

Neurocognitive disorders meet some of the salient criteria proposed by the Study Group of the DSM-V Task Force to suggest a classification cluster. Further developments in the aetiopathogenesis of these disorders will enhance the clinical utility of this cluster.

Accumulating evidence suggests that fetal growth restriction may increase risk of later schizophrenia but this issue has not been addressed directly in previous studies. We examined whether the degree of fetal growth restriction was linearly related to risk of schizophrenia, and also whether maternal pre-eclampsia, associated with both placental dysfunction and poor fetal growth, was related to risk of schizophrenia.

A population-based cohort of single live births in the Medical Birth Registry of Norway (MBRN) between 1967 and 1982 was followed to adulthood (n = 873 612). The outcome was schizophrenia (n=2207) registered in the National Insurance Scheme (NIS). The degree of growth restriction was assessed by computing sex-specific z scores (standard deviation units) of ‘birth weight for gestational age’ and ‘birth length for gestational age’. Analyses were adjusted for potential confounders. Maternal pre-eclampsia was recorded in the Medical Birth Registry by midwives or obstetricians using strictly defined criteria.

The odds ratio (OR) for schizophrenia increased linearly with decreasing birth weight for gestational age z scores (p value for trend = 0.005). Compared with the reference group (z scores 0.01–1.00), the adjusted OR [95% confidence interval (CI)] for the lowest z-score category (< − 3.00) was 2.0 (95% CI 1.2–3.5). A similar pattern was observed for birth length for gestational age z scores. Forty-nine individuals with schizophrenia were identified among 15 622 births with pre-eclampsia. The adjusted OR for schizophrenia following maternal pre-eclampsia was 1.3 (95% CI 1.0–1.8).

Associations of schizophrenia risk with degree of fetal growth restriction and pre-eclampsia suggest future research into schizophrenia etiology focusing on mechanisms that influence fetal growth, including placental function.

Much is still unclear about the role of personality in the structure of common psychiatric disorders such as depressive/anxiety disorders and alcohol dependence. This study will therefore examine whether various traits of negative emotionality and impulsivity showed shared or specific associations with these disorders.

Cross-sectional data were used from the Netherlands Study of Depression and Anxiety (NESDA), including individuals with no DSM-IV psychiatric disorder (n = 460), depressive/anxiety disorder only (i.e. depressive and/or anxiety disorder; n = 1398), alcohol dependence only (n = 32) and co-morbid depressive/anxiety disorder plus alcohol dependence (n = 358). Aspects of negative emotionality were neuroticism, hopelessness, rumination, worry and anxiety sensitivity, whereas aspects of impulsivity included disinhibition, thrill/adventure seeking, experience seeking and boredom susceptibility.

Aspects of negative emotionality formed a homogeneous dimension, which was unrelated to the more heterogeneous construct of impulsivity. Although all aspects of negative emotionality were associated with alcohol dependence only, associations were much stronger for depressive/anxiety disorder only and co-morbid depressive/anxiety disorder with alcohol dependence. The results for impulsivity traits were less profound and more variable, with disinhibition and boredom susceptibility showing modest associations with both depressive/anxiety disorder and alcohol dependence, whereas low thrill/adventure seeking and high disinhibition were more strongly related with the first and the latter, respectively.

Our results suggest that depressive/anxiety disorder and alcohol dependence result from shared as well as specific aetiological pathways as they showed the same associations with all aspects of negative emotionality, disinhibition and boredom susceptibility as well as specific associations with thrill/adventure seeking and disinhibition.

Accumulating evidence links blood pressure variability (BPV) with white matter hyperintensities (WMH) and stroke. The longitudinal association between BPV with late onset depression (LOD) and cognitive decline remains unexplored.

Prospective cohort study of 2812 participant's age ⩾65 years (median age 72 years, 63.6% female) without dementia or stroke. Serial clinic visits assessed blood pressure, cognitive function, depression disorder, and depressive symptoms. A brain magnetic resonance imaging (MRI) substudy was performed in 1275 persons to examine possible associations with WMH.

The interaction between symptomatic LOD and systolic BPV was associated with cognitive decline on the Isaac Set Test [slope −4.45; 95% confidence interval (CI) −8.92 to −0.16, p = 0.04], Benton Visual Retention Test (slope −0.89; 95% CI −1.77 to −0.01, p = 0.049), Mini Mental State Examination (slope −1.08; 95% CI −1.86 to −0.30, p = 0.007) and Finger Tapping Test (slope −7.53; 95% CI −13.71 to −1.34, p = 0.017) but not Trail Making Test-A or -B/A. The MRI substudy demonstrated that systolic BPV was associated with cognitive decline via interactions with depression and total WMH volume, but this was not dependent on either deep or periventricular WMH volumes.

The findings show that the interaction between systolic BPV with symptomatic depression and WMH increases cognitive decline in persons ⩾65 years of age. Future work could extend these findings by examining systolic BPV in relation to cognitive decline and WMH in older populations with depression.

The cross-sectional association between impaired glucose/diabetes and depression is inconsistent. We examined the longitudinal associations between diabetes, indicators of glucose metabolism and depressive symptoms over 2 years of follow-up.

Participants were 4338 men and women from the English Longitudinal Study of Ageing, a prospective study of community-dwelling older adults [aged 62.9 (s.d.=9.0) years, 45.2% men]. Depressive symptoms were assessed at baseline and after 2 years of follow-up using the eight-item Centre of Epidemiological Studies – Depression (CES-D) scale. Glycated haemoglobin (HbA1c) levels, fasting glucose and other biological and behavioural risk factors were also assessed at baseline.

Approximately 11.5% of the sample were categorized with elevated depressive symptoms at follow-up (a score ⩾4 on the CES-D). There was an association between HbA1c and depressive symptoms at follow-up [per unit increase, odds ratio (OR) 1.17, 95% confidence interval (CI) 1.03–1.33] after adjustment for age and baseline CES-D. Cross-sectionally, the probability of depressive symptoms increased with increasing HbA1c levels until the value of 8.0% after which there was a plateau [p(curve)=0.03]. Compared with those with normal fasting glucose, participants with diabetes (confirmed through self-report or elevated fasting blood glucose) at baseline had an elevated risk of depressive symptoms at follow-up (OR 1.52, 95% CI 1.01–2.30) after adjusting for depressive symptoms at baseline, behavioural and sociodemographic variables, adiposity and inflammation.

These data suggest that poor glucose metabolism and diabetes are risk factors for future depression in older adults. There was no evidence of a U-shaped association.

Attenuated inhibitory control is one of the most robust findings in the neuropsychology of attention-deficit/hyperactivity disorder (ADHD). However, it is unclear whether this represents a deficit in outright stopping (reactive inhibition), whether it relates to a deficit in anticipatory response slowing (proactive inhibition), or both. In addition, children with other development disorders, such as autism spectrum disorder (ASD), often have symptoms of inattention, impulsivity, and hyperactivity similar to children with ADHD. These may relate to similar underlying changes in inhibitory processing.

In this study, we used a modified stop-signal task to dissociate reactive and proactive inhibition. We included not only children with ADHD, but also children primarily diagnosed with an ASD and high parent-rated levels of ADHD symptoms.

We replicated the well-documented finding of attenuated reactive inhibition in children with ADHD. In addition, we found a similar deficit in children with ASD and a similar level of ADHD symptoms. In contrast, we found no evidence for deficits in proactive inhibition in either clinical group.

These findings re-emphasize the role of reactive inhibition in children with ADHD and ADHD symptoms. Moreover, our findings stress the importance of a trans-diagnostic approach to the relationship between behavior and neuropsychology.

Functional imaging studies in relatives of schizophrenic patients have had inconsistent findings, particularly with respect to altered dorsolateral prefrontal cortex activation. Some recent studies have also suggested that failure of deactivation may be seen.

A total of 28 patients with schizophrenia, 28 of their siblings and 56 healthy controls underwent functional magnetic resonance imaging during performance of the n-back working memory task. An analysis of variance was fitted to individual whole-brain maps from each set of patient–relative–matched pair of controls. Clusters of significant difference among the groups were then used as regions of interest to compare mean activations and deactivations among the groups.

In all, five clusters of significant differences were found. The schizophrenic patients, but not the relatives, showed reduced activation compared with the controls in the lateral frontal cortex bilaterally, the left basal ganglia and the cerebellum. In contrast, both the patients and the relatives showed significant failure of deactivation compared with the healthy controls in the medial frontal cortex, with the relatives also showing less failure than the patients. Failure of deactivation was not associated with schizotypy scores or presence of psychotic-like experiences in the relatives.

Both schizophrenic patients and their relatives show altered task-related deactivation in the medial frontal cortex. This in turn suggests that default mode network dysfunction may function as a trait marker for schizophrenia.

Post-traumatic stress disorder (PTSD) involves maladaptive long-term memory formation which underlies involuntary intrusive thoughts about the trauma. Preventing the development of such maladaptive memory is a key aim in preventing the development of PTSD. We examined whether the N-methyl d-aspartate receptor (NMDAR) antagonist gas nitrous oxide (N2O) could reduce the frequency of intrusive memories by inhibiting NMDAR-dependent memory consolidation in a laboratory analogue of psychological trauma.

Participants were randomized to inhale N2O (N = 25) or medical air (N = 25) after viewing a negatively valenced emotional film clip (‘trauma film’). Participants subsequently completed a daily diary assessing frequency of intrusive thoughts relating to the film clip. A week later, participants completed an explicit memory recall task related to the film.

Post-encoding N2O sped the reduction in intrusive memory frequency, with a significant reduction by the next day in the N2O group compared to 4 days later in the air group. N2O also interacted with post-film dissociation, producing increased intrusion frequency in those who were highly dissociated at baseline. Sleep length and quality the night after viewing the film did not differ between the groups.

N2O speeds the reduction of intrusive analogue trauma memory in a time-dependent manner, consistent with sleep-dependent long-term consolidation disruption. Further research with this drug is warranted to determine its potential to inoculate against enduring effects of psychological trauma; however, caution is also urged in dissociated individuals where N2O may aggravate PTSD-like symptomatology.

Several psychosocial risk factors for complicated grief have been described. However, the association of complicated grief with cognitive and biological risk factors is unclear. The present study examined whether complicated grief and normal grief are related to cognitive performance or structural brain volumes in a large population-based study.

The present research comprised cross-sectional analyses embedded in the Rotterdam Study. The study included 5501 non-demented persons. Participants were classified as experiencing no grief (n = 4731), normal grief (n = 615) or complicated grief (n = 155) as assessed with the Inventory of Complicated Grief. All persons underwent cognitive testing (Mini-Mental State Examination, Letter–Digit Substitution Test, Stroop Test, Word Fluency Task, word learning test – immediate and delayed recall), and magnetic resonance imaging to measure general brain parameters (white matter, gray matter), and white matter lesions. Total brain volume was defined as the sum of gray matter plus normal white matter and white matter lesion volume. Persons with depressive disorders were excluded and analyses were adjusted for depressive symptoms.

Compared with no-grief participants, participants with complicated grief had lower scores for the Letter–Digit Substitution Test [Z-score −0.16 v. 0.04, 95% confidence interval (CI) −0.36 to −0.04, p = 0.01] and Word Fluency Task (Z-score −0.15 v. 0.03, 95% CI −0.35 to −0.02, p = 0.02) and smaller total volumes of brain matter (933.53 ml v. 952.42 ml, 95% CI −37.6 to −0.10, p = 0.04).

Participants with complicated grief performed poorly in cognitive tests and had a smaller total brain volume. Although the effect sizes were small, these findings suggest that there may be a neurological correlate of complicated grief, but not of normal grief, in the general population.

The possible role of glutamate in the pathophysiology and treatment of depression is of intense current interest. Proton magnetic resonance spectroscopy (MRS) enables the detection of glutamate in the living human brain and meta-analyses of previous MRS studies in depressed patients have suggested that glutamate levels are decreased in anterior brain regions. Nevertheless, at conventional magnetic field strengths [1.5–3 Tesla (T)], it is difficult to separate glutamate from its metabolite and precursor, glutamine, with the two often being measured together as Glx. In contrast, MRS at 7 T allows clear spectral resolution of glutamate and glutamine.

We studied 55 un-medicated depressed patients and 50 healthy controls who underwent MRS scanning at 7 T with voxels placed in anterior cingulate cortex, occipital cortex and putamen (PUT). Neurometabolites were calculated using the unsuppressed water signal as a reference.

Compared with controls, depressed patients showed no significant difference in glutamate in any of the three voxels studied; however, glutamine concentrations in the patients were elevated by about 12% in the PUT (p < 0.001).

The increase in glutamine in PUT is of interest in view of the postulated role of the basal ganglia in the neuropsychology of depression and is consistent with elevated activity in the descending cortical glutamatergic innervation to the PUT. The basal ganglia have rarely been the subject of MRS investigations in depressed patients and further MRS studies of these structures in depression are warranted.

Obsessive-compulsive disorder (OCD) is common in clozapine-treated patients although the actual prevalence, phenomenology and risk factors remain unclear. The aim of the present study was to address the three aforementioned questions.

The electronic records of a large cohort of clozapine-medicated schizophrenia patients routinely screened for OCD were used. The Obsessive Compulsive Inventory Revised version (OCI-R) was available from 118 cases and a 21 points cut-off threshold for OCD was defined.

OCD prevalence was 47%, higher in patients on poly-pharmacy than on monotherapy (64% vs 31%; p = 0.001). Two OCI-R factors had significantly higher scores and distinct risk factors: checking behaviour (mean = 5.1; SD = 3.6) correlated with length of clozapine treatment (r = 0.21; p = 0.026), and obsessing factor (mean = 4.8; SD = 3.6) correlated with psychosis severity (r = 0.59; p = 0.001). These factors along with total OCI-R, did not correlate with either clozapine dose or plasma levels, after correcting for psychosis severity.

Screening for OCD in clozapine patients, and probably in those treated with structurally similar drugs with potent antiserotoninergic properties, should be widely adopted by clinicians. Further research is needed to understand the pathophysiology underlying repetitive behavior onset in clozapine-treated patients.

Impairments in key neuropsychological domains (e.g. working memory, attention) and social cognitive deficits have been implicated as intermediate (endo) phenotypes for bipolar disorder (BD), and should therefore be evident in unaffected relatives.

Neurocognitive and social cognitive ability was examined in 99 young people (age range 16–30 years) with a biological parent or sibling diagnosed with the disorder [thus deemed to be at risk (AR) of developing BD], compared with 78 healthy control (HC) subjects, and 52 people with a confirmed diagnosis of BD.

Only verbal intelligence and affective response inhibition were significantly impaired in AR relative to HC participants; the BD participants showed significant deficits in attention tasks compared with HCs. Neither AR nor BD patients showed impairments in general intellectual ability, working memory, visuospatial or language ability, relative to HC participants. Analysis of BD-I and BD-II cases separately revealed deficits in attention and immediate memory in BD-I patients (only), relative to HCs. Only the BD (but not AR) participants showed impaired emotion recognition, relative to HCs.

Selective cognitive deficits in the capacity to inhibit negative affective information, and general verbal ability may be intermediate markers of risk for BD; however, the extent and severity of impairment in this sample was less pronounced than has been reported in previous studies of older family members and BD cases. These findings highlight distinctions in the cognitive profiles of AR and BD participants, and provide limited support for progressive cognitive decline in association with illness development in BD.