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BackgroundNegative mood states are composed of symptoms of depression and anxiety, and by a third factor related to stress, tension and irritability. We sought to clarify the nature of the relationships between the factors by studying twin pairs.MethodA total of 503 monozygotic twin pairs completed the Depression Anxiety Stress Scales (DASS), an instrument that assesses symptoms of depression, anxiety and stress–tension. We applied a recently developed twin regression methodology – Inference about Causation from Examination of FAmiliaL CONfounding (ICE FALCON) – to test for evidence consistent with the existence of ‘causal’ influences between the DASS factors.ResultsThere was evidence consistent with the stress–tension factor having a causal influence on both the depression (p < 0.0001) and anxiety factors (p = 0.001), and for the depression factor having a causal influence on the anxiety factor (p < 0.001).ConclusionsOur findings suggest a critical role for stress–tension in the structure of negative mood states, and that interventions that target it may be particularly effective in reducing depression and anxiety symptoms. [ABSTRACT FROM PUBLISHER]

BackgroundImpairment in social cognition is an established finding in autism spectrum disorders (ASD). Emerging evidence suggests that attention-deficit/hyperactivity disorder (ADHD) might be also associated with deficits in theory of mind (ToM) and emotion recognition. However, there are inconsistent findings, and it has been debatable whether such deficits persist beyond childhood and how similar social cognitive deficits are in ADHD v. ASD.MethodWe conducted a meta-analysis of social cognition, including emotion recognition and ToM, studies in ADHD compared with healthy controls and ASD. The current meta-analysis involved 44 studies comparing ADHD (n = 1999) with healthy controls (n = 1725) and 17 studies comparing ADHD (n = 772) with ASD (n = 710).ResultsFacial and vocal emotion recognition (d = 0.40–0.44) and ToM (d = 0.43) abilities were significantly impaired in ADHD. The most robust facial emotion recognition deficits were evident in anger and fear. Social cognitive deficits were either very subtle (emotion recognition) or non-significant (ToM) in adults with ADHD. Deficits in social cognition, especially ToM, were significantly more pronounced in ASD compared with ADHD. General cognitive impairment has contributed to social cognitive deficits in ADHD.ConclusionsPerformance of individuals with ADHD on social cognition lies intermediate between ASD and healthy controls. However, developmental trajectories of social cognition probably differ between ADHD and ASD as social cognitive deficits in ADHD might be improving with age in most individuals. There is a need for studies investigating a potential subtype of ADHD with persistent social cognitive deficits and exploring longitudinal changes in social cognition during development. [ABSTRACT FROM PUBLISHER]

Although the underlying neurobiology of emerging psychotic disorders is not well understood, evidence from structural imaging and other studies support the notion that schizophrenia arises as a consequence of both an 'early neurodevelopmental' disturbance, as well as 'late neurodevelopmental' changes occurring during the initial stages of a psychotic illness, including around the time of transition to illness. In line with this, our longitudinal MRI findings in individuals at ultra-high risk for developing a psychotic illness show that there are excessive neuroanatomical changes in those who convert to psychosis. These aberrant changes are observed most prominently in medial temporal and prefrontal lobe regions. In a further series of longitudinal studies in first-episode psychosis, we have identified changes in prefrontal regions that indicate an accelerated loss of grey matter in patients compared to healthy control subjects. We suggest that the available evidence is consistent with the presence of subtle regionally and temporally specific neurobiological changes through the course of psychosis (Pantelis et al., 2005), including: (1) evidence for early (pre- and peri-natal) neurodevelopmental anomalies, (2) evidence for progressive grey matter loss involving medial temporal and orbital prefrontal regions around the time of transition to illness, and (3) evidence of late (post-pubertal) neurodevelopmental changes soon after the onset of psychosis, involving an acceleration of normal brain maturational processes, associated with significant loss of grey matter in dorsal prefrontal regions. The pathological processes underlying such changes remain unclear and may reflect anomalies in genetic and/or other endogenous mechanisms responsible for brain maturation, the adverse effects of intense or prolonged stress, or other environmental factors. These findings suggest that early markers of impending illness may prove difficult to define, and that brain changes in psychosis may better be conceptualized as anomalous trajectories of brain development. Further, active changes during transition to illness may present the potential to intervene and ameliorate these changes with potential benefit clinically. [ABSTRACT FROM AUTHOR]

Abstract: Theoretical calculations of the elastic response of carbon composites and amorphous carbon are reported. The studied composites consist of crystalline nanoinclusions, either spherical diamonds or carbon nanotubes, embedded in amorphous carbon matrices. The elastic constants of the composites were calculated and found to systematically increase as the density increases. The elastic recovery under hydrostatic pressure for all structures was also investigated and was found to be significantly high for both nanocomposite and amorphous carbon, but decreases as the material becomes more dilute. [Copyright &y& Elsevier]

BACKGROUND: Behavioural syndromes (thought disturbance, social withdrawal, depressed behaviour and antisocial behaviour) offer a different perspective from that of symptomatic syndromes on the disability that may be associated with schizophrenia. Few studies have assessed their relationship with neuropsychological deficits. We hypothesized that these syndromes may represent behavioural manifestations of frontal-subcortical impairments, previously described in schizophrenia. METHOD: Long-stay inpatients (n=54) and community patients (n=43) with enduring schizophrenia were assessed, using measures of symptoms and behaviour and tests of executive functioning. The relationship between syndromes and neuropsychological function was assessed using multiple regression and logistic regression analyses. RESULTS: Significant associations were found between performance on the spatial working memory task and the psychomotor poverty symptomatic syndrome, and between attentional set-shifting ability and both disorganization symptoms and the thought disturbance behavioural syndrome. These results were not explained by the effect of premorbid IQ, geographical location, length of illness or antipsychotic medication. Length of illness was an independent predictor of attentional set-shifting ability but not of working memory performance. CONCLUSION: The specific relationship between negative symptoms and spatial working memory is consistent with involvement of the dorsolateral prefrontal cortex. The associations between difficulty with set-shifting ability and both disorganization symptoms and behaviours may reflect inability to generalize a rule that had been learned and impaired ability to respond flexibly. The specific relationship of illness duration to set-shifting ability may suggest progressive impairment on some executive tasks. The nature of these relationships and their neurobiological and rehabilitation implications are considered. [ABSTRACT FROM AUTHOR]

Presents a study on brain structure abnormalities before the onset of psychosis. Prevalence of grey matter in the cortex of individuals with psychosis; Application of magnetic resonance imaging in the study; Significance of the study.

Objective: Our objective was to determine the outcome of novel strategies in managing a case of severe polydipsia. Clinical picture: The patient was a 39-year-old male with a 20-year history of paranoid schizophrenia who, despite only mild residual psychotic symptoms, had been hospitalized for the previous 10 years because of severe polydipsic behaviour complicated by water intoxication. Treatment: Novel antipsychotic agents, risperidone and olanzapine, as well as the specific angiotensin-II receptor blocking drug, irbesartan were employed at selected intervals in a study lasting nearly 3 years. A strict behavioural management programme was ongoing, in which diurnal weight change and the number of breaches of weight limits, requiring management in a low-stimulus environment, were documented on a daily basis. Summary measures of diurnal weight change and behavioural intervention were charted against changes in treatment. Outcome: Polydipsic behaviour improved on risperidone up to 4 mg daily, but was not sustained. Olanzapine was similarly successful in stabilizing polydipsia, and improvement was achieved with the addition of irbesartan. Conclusion: We suggest that the D2-sparing profiles of receptor binding achieved with low-dose risperidone and olanzapine may account for this beneficial effect. The benefit derived with irbesartan implicates the involvement of brain angiotensin systems centrally in helping to regulate drinking behaviour. [ABSTRACT FROM AUTHOR]

• We investigated complement proteins relevant to classical pathway activation, alternative pathway amplification or regulation in matched blood and CSF in people with clinical high-risk (CHR) for psychosis, antipsychotic-naïve first episode psychosis (FEP) and healthy controls. • We provide evidence for increased activity of the peripheral, but not central, complement system in both CHR and antipsychotic-naïve FEP. • Activation of the peripheral complement system may have clinical implications, varying with clinical severity in FEP. Alterations in the complement system have been reported in some people with psychotic disorder, including in pre-psychotic individuals, suggesting that complement pathway dysregulation may be a feature of the early psychosis phenotype. Measurement of complement protein expression in psychosis has been largely restricted to the blood from patients with established illness who were taking antipsychotic medication. The present study examined a range of complement proteins in blood and cerebrospinal fluid (CSF) derived from individuals at clinical high-risk for psychosis (CHR), antipsychotic-naïve first-episode psychosis (FEP) and healthy controls. A panel of complement proteins (C1q, C3, C3b/iC3b, C4, factor B and factor H) were quantified in serum and matched CSF in 72 participants [n = 23 individuals at CHR, n = 24 antipsychotic-naïve FEP, n = 25 healthy controls] using a multiplex immunoassay. Analysis of covariance was used to assess between-group differences in complement protein levels in serum and CSF. Pearson's correlation was used to assess the relationship between serum and CSF proteins, and between complement proteins and symptom severity. In serum, all proteins, except for C3, were significantly higher in FEP and CHR. While a trend was observed, protein levels in CSF did not statistically differ between groups and appeared to be impacted by BMI and sample storage time. Across the whole sample, serum and CSF protein levels were not correlated. In FEP, higher levels of serum classical and alternative grouped pathway components were correlated with symptom severity. Our exploratory study provides evidence for increased activity of the peripheral complement system in the psychosis spectrum, with such elevations varying with clinical severity. Further study of complement in CSF is warranted. Longitudinal investigations are required to elucidate whether complement proteins change peripherally and/or centrally with progression of psychotic illness. [ABSTRACT FROM AUTHOR]

Sleep disturbances are increasingly recognized as cooccurring with psychotic symptoms. The potential importance of this relationship is complicated when considering the effects of anxiety and depressive symptoms which commonly present in early-stage illness states. This study aimed to investigate the relationship between self-reported sleep disturbance on the development of attenuated psychotic symptoms (APS) cross-sectionally and longitudinally while adjusting for roles of anxiety and depressive symptoms. Eight-hundred and two help-seeking young people aged 12 to 25 years who engaged with our Australian early intervention services were included in the study (the "Transitions" cohort). Cross sectional mediation and cross-lagged longitudinal (12-month) mediation models were developed with outcomes being different APS domains. Only baseline excessive daytime sleepiness predicted later APS when accounting for previous APS, anxiety and depressive symptomatology. Cross sectionally, self-reported sleep disturbance showed both direct and indirect predictive relationships with all APS domains. Partial mediation through anxiety and depression was shown for unusual thought content, perceptual abnormalities, and disorganised speech, while full mediation through depression was shown for non-bizarre ideas. The specificity of the relationship between self-reported sleep disturbance on APS highlights the potential for different roles in mechanistic models of psychotic symptom expression. This further indicates the need for further experimental research to illuminate potential causal pathways. Future research should continue to use continuous, symptom level approaches across a range of timeframes to more accurately model the complex dynamics present in the sleep-psychosis relationship. [ABSTRACT FROM AUTHOR]

Background: Research has yielded evidence for genetic and environmental factors influencing the risk of schizophrenia. Numerous environmental factors have been identified; however, the individual effects are small. The additive and interactive effects of multiple risk factors are not well elucidated. Twin pairs discordant for schizophrenia offer a unique opportunity to identify factors that differ between patients and unaffected co-twins, who are perfectly matched for age, sex and genetic background. Methods: Register data were combined with clinical data for 216 twins including monozygotic (MZ) and dizygotic (DZ) proband pairs (one or both twins having a schizophrenia spectrum diagnosis) and MZ/DZ healthy control (HC) pairs. Logistic regression models were applied to predict (1) illness vulnerability (being a proband v. HC pair) and (2) illness status (being the patient v. unaffected co-twin). Risk factors included: A polygenic risk score (PRS) for schizophrenia, birth complications, birth weight, Apgar scores, paternal age, maternal smoking, season of birth, parental socioeconomic status, urbanicity, childhood trauma, estimated premorbid intelligence and cannabis. Results: The PRS [odds ratio (OR) 1.6 (1.1–2.3)], childhood trauma [OR 4.5 (2.3–8.8)], and regular cannabis use [OR 8.3 (2.1–32.7)] independently predicted illness vulnerability as did an interaction between childhood trauma and cannabis use [OR 0.17 (0.03–0.9)]. Only regular cannabis use predicted having a schizophrenia spectrum diagnosis between patients and unaffected co-twins [OR 3.3 (1.1–10.4)]. Conclusion: The findings suggest that several risk factors contribute to increasing schizophrenia spectrum vulnerability. Moreover, cannabis, a potentially completely avoidable environmental risk factor, seems to play a substantial role in schizophrenia pathology. [ABSTRACT FROM AUTHOR]

Background. Theory of mind (ToM) dysfunction is prominent in a number of psychiatric disorders, in particular, autism and schizophrenia, and can play a significant role in poor functioning. There is now emerging evidence suggesting that ToM abilities are also impaired in bipolar disorder (BP); however, the relationship between ToM deficits and mood state is not clear. Method. We conducted a meta-analysis of ToM studies in BP. Thirty-four studies comparing 1214 patients with BP and 1097 healthy controls were included. BP groups included remitted (18 samples, 545 BP patients), subsyndromal (12 samples, 510 BP patients), and acute (manic and/or depressed) (10 samples, 159 BP patients) patients. Results. ToM performance was significantly impaired in BP compared to controls. This impairment was evident across different types of ToM tasks (including affective/cognitive and verbal/visual) and was also evident in strictly euthymic patients with BP (d = 0.50). There were no significant differences between remitted and subsyndromal samples. However, ToM deficit was significantly more severe during acute episodes (d = 1.23). ToM impairment was significantly associated with neurocognitive and particularly with manic symptoms. Conclusion. Significant but modest sized ToM dysfunction is evident in remitted and subsyndromal BP. Acute episodes are associated with more robust ToM deficits. Exacerbation of ToM deficits may contribute to the more significant interpersonal problems observed in patients with acute or subsyndromal manic symptoms. There is a need for longitudinal studies comparing the developmental trajectory of ToM deficits across the course of the illness. [ABSTRACT FROM AUTHOR]

Abstract: The personality dimension of schizotypy is well established, and schizotypal traits can be taken to represent a proneness toward developing psychosis. Yet, there are competing theories about the latent structure of schizotypy. More specifically, there is controversy over the extent to which this propensity toward psychosis is present only in a small proportion of the population, or whether it is spread dimensionally throughout the general community. On the basis of accumulating research findings the present article argues for a fully dimensional model of schizotypy. It describes recent neurobiological, neuropsychological, social and environmental evidence supporting the idea that schizotypy in healthy populations, and disorders on the schizophrenia spectrum are fundamentally linked. Directions for further research are also considered. [Copyright &y& Elsevier]

Background and Aim: Little is known about the relationship between neurocognitive performance and functional outcome before the onset of frank psychosis. This longitudinal study aimed to investigate neurocognitive predictors of poor functional outcome in a group identified as ultra-high risk (UHR) for psychosis between two and 13 years prior.Method: Individuals (N=230) identified as UHR for psychosis at the PACE Clinic in Melbourne completed assessment of psychopathology, functioning and neurocognition at baseline and follow-up. The mean length of follow-up was 7.26 years (SD 3.05).Results: Forty-one individuals with the poorest functional outcome were identified. Only 48.8% of this group had transitioned to psychosis. Poor functional outcome was associated with reduced performance at baseline in the specific neurocognitive domains of verbal learning and memory, processing speed and attention, and verbal fluency, but not global cognitive impairment. Reduced performance on a verbal story recall task, in combination with higher negative symptoms at baseline, was the best predictor of later poor outcome. Baseline positive psychotic symptoms and GAF scores were not associated with later poor outcome.Discussion: To date, this is the longest follow-up study of an UHR sample. Poor functional outcome was associated with specific neurocognitive decrements, regardless of transition to psychosis. The detection of individuals with poor functioning at follow-up, against a background of previously identified risk factors for psychotic disorder, may yield a valid group in which to study biomarkers and treatment of schizophrenia. [ABSTRACT FROM AUTHOR]

Bora E, Yücel M, Pantelis C, Berk M. Meta-analytic review of neurocognition in bipolar II disorder. The clinical distinction between bipolar II disorder (BD II) and bipolar I disorder (BD I) is not clear-cut. Cognitive functioning offers the potential to explore objective markers to help delineate this boundary. To examine this issue, we conducted a quantitative review of the cognitive profile of clinically stable patients with BD II in comparison with both patients with BD I and healthy controls. Meta-analytical methods were used to compare cognitive functioning of BD II disorder with both BD I disorder and healthy controls. Individuals with BD II were less impaired than those with BD I on verbal memory. There were also small but significant difference in visual memory and semantic fluency. There were no significant differences in global cognition or in other cognitive domains. Patients with BD II performed poorer than controls in all cognitive domains. Our findings suggest that with the exception of memory and semantic fluency, cognitive impairment in BD II is as severe as in BD I. Further studies are needed to investigate whether more severe deficits in BD I are related to neurotoxic effects of severe manic episodes on medial temporal structures or neurobiological differences from the onset of the illness. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to critically review the literature in order to determine if Theory of Mind (ToM) impairment can be considered a trait-marker for schizophrenia spectrum disorders and bipolar disorder (BD). Method: After a thorough literature search, we reviewed the empirical studies investigating ToM impairments in remitted schizophrenia patients, first episode patients, subjects at high-risk (HR) for psychosis and first-degree relatives of schizophrenia patients. Studies investigating ToM impairment in other schizophrenia spectrum conditions, affective psychosis and BD were also reviewed. Results: ToM abnormalities exist at onset and continue throughout the course of schizophrenia, persist into remission, and while less severe, are apparent in HR populations. Mentalizing impairments are also observed in other forms of psychotic illness and BD. Conclusion: Mentalizing impairment in schizophrenia spectrum disorders and BD might reflect underlying general cognitive deficits and residual symptom expression, rather than representing a specific trait-marker. [ABSTRACT FROM AUTHOR]

Abstract: Ultra-nanocrystalline diamond is a polycrystalline material with crystalline diamond grains in the nanometer size regime. We study the structure and mechanical properties of this material as a function of the average grain size, employing atomistic simulations. From the calculated elastic constants and the estimated hardness, we observe softening of the material as the size of its grains decreases. We attribute the observed softening to the enhanced fraction of interfacial atoms as the average grain size becomes smaller. We provide a fitting formula for the scaling of the cohesive energy and bulk modulus with respect to the average grain size. We find that both these properties scale as quadratic polynomials of the inverse grain size. Our formulas yield correct values for bulk diamond in the limit of large grain sizes. [Copyright &y& Elsevier]

Verbal fluency was compared in Huntington's disease (n=12), Parkinson's disease (n=25) and schizophrenia (n=18) with a series of fluency tasks evaluating the effects on productivity of cuing with subordinate categories and alternation between fluency probes Findings indicated reduced output in the patient groups across all tasks consistent with a difficulty in intrinsic generation A significant group interaction was observed with cue provision, but not with alternation The facilitation of performance with cuing in all groups suggests a common mechanism of disruption in these disorders, most likely reflecting interruption of the prefrontal modulation of retrieval processes To explain the observed pattern, we propose that the semantic retrieval anomaly in these disorders reflects a difficulty in intrinsic extra-dimensional shift Verbal productivity was significantly associated with negative dimensions of schizophrenia, such as poverty of speech and flattened affect, a finding that is discussed in terms of the neurocognitive heterogeneity of schizophrenia and theories of cognitive dysfunction in subtypes of this disorder. [ABSTRACT FROM AUTHOR]

Background: Childhood adverse experiences (CAE) are associated with clinical psychiatric disorders and symptoms, and with volumetric abnormalities in the amygdala-hippocampus complex (AmHiC) and frontal lobe (FroL) in adulthood.Aim: To study whether CAE are associated with reduced AmHiC and FroL and whether these structures mediate the effect of CAE on social anxiety and depression.Method: In seven European centres, 374 patients with recent onset of psychosis (n = 127), clinical high-risk to psychosis (n = 119) or recent onset of depression (n = 128) were scanned with MRI and their FroL and AmHiC volumes were measured. They all completed self-report scales for assessment of CAE, social anxiety and depression.Results: Of the CAE domains, physical abuse was associated specifically with reduced grey and white matter volumes of FroL and AmHiC in psychotic and high-risk patients. After controlling intracranial volume, PhyAb associated significantly with FroL and its grey matter volume in high-risk patients only. In mediation analyses, the effect of physical abuse on social anxiety was mediated via reduced FroL grey mater volume in high-risk patients. In them, when the effects of AmHiC and depression were controlled, the effect of physical abuse on social anxiety was mediated via FroL grey matter volume reduction.Conclusions: Childhood physical abuse is associated with reduced frontal lobe and amygdala-hippocampus complex volume in adult subjects with psychotic symptoms. Reduced frontal lobe and amygdala-hippocampus complex volume mediate the effect of physical abuse on social anxiety in high-risk patients. The effect of physical abuse on depression-independent social anxiety is mediated via reduced frontal lobe. [ABSTRACT FROM AUTHOR]

A tough material commonly used in coatings is diamond-like carbon (DLC), that is, amorphous carbon with content in four-fold coordinated C higher than ∼70%, and its composites with metal inclusions. This study aims to offer useful guidelines for the design and development of metal-containing DLC coatings for solar collectors, where the efficiency of the collector depends critically on the performance of the absorber coating. We use first-principles calculations based on density functional theory to study the structural, electronic, optical, and elastic properties of DLC and its composites with Ag and Cu inclusions at 1.5% and 3.0% atomic concentration, to evaluate their suitability for solar thermal energy harvesting. We find that with increasing metal concentration optical absorption is significantly enhanced while at the same time, the composite retains good mechanical strength: DLC with 70-80% content in four-fold coordinated C and small metal concentrations (<3 at. %) will show high absorption in the visible (absorption coefficients higher than 105 cm-1) and good mechanical strength (bulk and Young's modulus higher than 300 and 500 GPa, respectively). [ABSTRACT FROM AUTHOR]

Background. Aneurysms of the extracranial vertebral artery are rare and can provide a diagnostic and therapeutic challenge. Methods. We reviewed the clinical history of a patient presenting with cervical radiculopathy, who harboured an extracranial vertebral artery aneurysm eroding the cervical spine. Results. CT Angiography andMR Angiography set the diagnosis, by revealing a left C5-C6 vertebral artery aneurysm with cervical root impingement. Bony reconstruction depicted enlargement of the C6 transverse foramen and a marked enlargement of the C6-C7 intravertebral foramen. The lesion was treated by intravascular proximal vertebral artery occlusion. Conclusions. Extracranial vertebral artery aneurysms require a high index of clinical suspicion. This is the first report of a vertebral artery pseudoaneurysm presenting with bony erosion, which supports a less minacious portrayal of vertebral artery aneurysms. [ABSTRACT FROM AUTHOR]

Objective: Protocol for clozapine rechallenge in patients with a history of clozapine-induced myocarditis.Method: Clozapine-related cardiovascular adverse effects including myocarditis and cardiomyopathy have limited its widespread use in treatment-resistant schizophrenia. Here, we present a case of clozapine-induced myocarditis and successful cautious rechallenge. Ms. AA, a young female patient with severe psychosis developed myocarditis during her initial clozapine titration phase, which was thus discontinued. Subsequent response to other medications was poor, and she remained significantly disabled. We reviewed blood-based biomarkers identified during the emergence of her index episode of myocarditis and developed a successful clozapine rechallenge protocol, based on careful monitoring of changes in these indices and a very slow clozapine re-titration.Results and Conclusions: This protocol may have utility in the management of patients with a history of clozapine-induced myocarditis. [ABSTRACT FROM AUTHOR]

Background: Previous reviews suggest there is minimal evidence for an association between duration of untreated psychosis (DUP) and neurocognition. This is based on tallied findings of studies with small samples and neurocognition viewed as a single construct. We aimed to conduct a systematic review and meta-analysis examining the association between DUP and individual neurocognitive domains and tests in first-episode psychosis (FEP). Method: MOOSE and PRISMA guidelines were followed. Forty-three studies involving 4647 FEP patients were included. For studies providing correlations between DUP and neurocognition, 12 separate meta-analyses were performed based on neurocognitive domains/indices. The influence of demographic/clinical variables was tested using weighted linear meta-regression analyses. Results: The relationship between DUP and most neurocognitive domains/indices was not significant. Longer DUP was associated with a larger cognitive deterioration index, i.e. current minus premorbid intellectual functioning (N = 4; mean ES −0.213, 95% confidence interval (CI) (−0.344 to −0.074), p = 0.003). Findings were homogeneous, with no evidence of publication bias or significant influence from moderators. For studies providing mean and standard deviations for neurocognitive measures and DUP, 20 meta-regressions were performed on individual neurocognitive tests. One significant finding emerged showing that longer DUP was associated with fewer Wisconsin Card Sorting Test-perseverative errors (mean ES −0.031, 95% CI (−0.048 to −0.013), p < 0.001). Exploratory meta-regressions in studies with mean DUP <360 days showed longer DUP was significantly associated with poorer performance on Trail Making Test A and B and higher Full-Scale IQ. Conclusion: There may not be a generalised association between DUP and neurocognition, however, specific cognitive functions may be associated with longer DUP or delayed help-seeking. [ABSTRACT FROM AUTHOR]

BackgroundTwo single-nucleotide polymorphisms (SNPs) (rs4281084 and rs12155594) within the neuregulin-1 (NRG1) gene have been associated with psychosis transition. However, the neurobiological changes associated with these SNPs remain unclear. We aimed to determine what relationship these two SNPs have on lateral ventricular volume and white matter integrity, as abnormalities in these brain structures are some of the most consistent in schizophrenia.MethodsStructural (n = 370) and diffusion (n = 465) magnetic resonance imaging data were obtained from affected and unaffected individuals predominantly of European descent. The SNPs rs4281084, rs12155594, and their combined allelic load were examined for their effects on lateral ventricular volume, fractional anisotropy (FA) as well as axial (AD) and radial (RD) diffusivity. Additional exploratory analyses assessed NRG1 effects on gray matter volume, cortical thickness, and surface area throughout the brain.ResultsIndividuals with a schizophrenia age of onset ⩽25 and a combined allelic load ⩾3 NRG1 risk alleles had significantly larger right (up to 50%, padj = 0.01) and left (up to 45%, padj = 0.05) lateral ventricle volumes compared with those with allelic loads of less than three. Furthermore, carriers of three or more risk alleles, regardless of age of onset and case status, had significantly reduced FA and elevated RD but stable AD in the frontal cortex compared with those carrying fewer than three risk alleles.ConclusionsOur findings build on a growing body of research supporting the functional importance of genetic variation within the NRG1 gene and complement previous findings implicating the rs4281084 and rs12155594 SNPs as markers for psychosis transition. [ABSTRACT FROM AUTHOR]

Objective: The question of how to best conceptualize health anxiety (HA) from a diagnostic and etiological perspective remains debated. The aim was to examine the relationship between HA and the symptoms of anxiety and obsessive–compulsive‐related disorders in a normative twin population. Method: Four hundred and ninety‐six monozygotic adult twin pairs from the Australian Twin Registry participated in the study (age, 34.4 ± 7.72 years; 59% females). Validated scales were used to assess each domain. We applied a twin regression methodology—ICE FALCON—to determine whether there was evidence consistent with ‘causal’ relationships between HA and other symptoms by fitting and comparing model estimates. Results: Estimates were consistent with higher levels of obsessing (‘unwanted thoughts’) (P = 0.008), social anxiety (P = 0.03), and body dysmorphic symptoms (P = 0.008) causing higher levels of HA symptoms, and with higher levels of HA symptoms causing higher levels of physical/somatic anxiety symptoms (P = 0.001). Conclusion: Obsessional thoughts, body dysmorphic concerns, and social anxiety symptoms may have a causal influence on HA. To report physical/somatic anxiety appears to be a consequence of the underlying presence of HA‐related fears. Should our results be confirmed by longitudinal studies, the evaluation and treatment of HA may benefit from the consideration of these identified risk factors. [ABSTRACT FROM AUTHOR]

Background. Cognitive deficits are a core feature of schizophrenia, and impairments in most domains are thought to be stable over the course of the illness. However, cross-sectional evidence indicates that some areas of cognition, such as visuospatial associative memory, may be preserved in the early stages of psychosis, but become impaired in later established illness stages. This longitudinal study investigated change in visuospatial and verbal associative memory following psychosis onset. Methods. In total 95 first-episode psychosis (FEP) patients and 63 healthy controls (HC) were assessed on neuropsychological tests at baseline, with 38 FEP and 22 HCs returning for follow-up assessment at 5-11 years. Visuospatial associative memory was assessed using the Cambridge Neuropsychological Test Automated Battery Visuospatial Paired-Associate Learning task, and verbal associative memory was assessed using Verbal Paired Associates subtest of the Wechsler Memory Scale - Revised. Results. Visuospatial and verbal associative memoryat baseline did not differ significantly between FEP patients and HCs. However, over follow-up, visuospatial associative memory deteriorated significantly for the FEP group, relative to healthy individuals. Conversely, verbal associative memory improved to a similar degree observed in HCs. In the FEP cohort, visuospatial (but not verbal) associative memory ability at baseline was associated with functional outcome at follow-up. Results. Visuospatial and verbal associative memoryat baseline did not differ significantly between FEP patients and HCs. However, over follow-up, visuospatial associative memory deteriorated significantly for the FEP group, relative to healthy individuals. Conversely, verbal associative memory improved to a similar degree observed in HCs. In the FEP cohort, visuospatial (but not verbal) associative memory ability at baseline was associated with functional outcome at follow-up. [ABSTRACT FROM AUTHOR]

BackgroundWhite matter disruptions in schizophrenia have been widely reported, but it remains unclear whether these abnormalities differ between illness stages. We mapped the connectome in patients with recently diagnosed and chronic schizophrenia and investigated the extent and overlap of white matter connectivity disruptions between these illness stages.MethodsDiffusion-weighted magnetic resonance images were acquired in recent-onset (n = 19) and chronic patients (n = 45) with schizophrenia, as well as age-matched controls (n = 87). Whole-brain fiber tracking was performed to quantify the strength of white matter connections. Connections were tested for significant streamline count reductions in recent-onset and chronic groups, relative to separate age-matched controls. Permutation tests were used to assess whether disrupted connections significantly overlapped between chronic and recent-onset patients. Linear regression was performed to test whether connectivity was strongest in controls, weakest in chronic patients, and midway between these extremities in recent-onset patients (controls > recent-onset > chronic).ResultsCompared with controls, chronic patients displayed a widespread network of connectivity disruptions (p < 0.01). In contrast, connectivity reductions were circumscribed to the anterior fibers of the corpus callosum in recent-onset patients (p < 0.01). A significant proportion of disrupted connections in recent-onset patients (86%) coincided with disrupted connections in chronic patients (p < 0.01). Linear regression revealed that chronic patients displayed reduced connectivity relative to controls, while recent-onset patients showed an intermediate reduction compared with chronic patients (p < 0.01).ConclusionsConnectome pathology in recent-onset patients with schizophrenia is confined to select tracts within a more extensive network of white matter connectivity disruptions found in chronic illness. These findings may suggest a trajectory of progressive deterioration of connectivity in schizophrenia. [ABSTRACT FROM PUBLISHER]

BackgroundCurrent group-average analysis suggests quantitative but not qualitative cognitive differences between schizophrenia (SZ) and bipolar disorder (BD). There is increasing recognition that cognitive within-group heterogeneity exists in both disorders, but it remains unclear as to whether between-group comparisons of performance in cognitive subgroups emerging from within each of these nosological categories uphold group-average findings. We addressed this by identifying cognitive subgroups in large samples of SZ and BD patients independently, and comparing their cognitive profiles. The utility of a cross-diagnostic clustering approach to understanding cognitive heterogeneity in these patients was also explored.MethodHierarchical clustering analyses were conducted using cognitive data from 1541 participants (SZ n = 564, BD n = 402, healthy control n = 575).ResultsThree qualitatively and quantitatively similar clusters emerged within each clinical group: a severely impaired cluster, a mild-moderately impaired cluster and a relatively intact cognitive cluster. A cross-diagnostic clustering solution also resulted in three subgroups and was superior in reducing cognitive heterogeneity compared with disorder clustering independently.ConclusionsQuantitative SZ–BD cognitive differences commonly seen using group averages did not hold when cognitive heterogeneity was factored into our sample. Members of each corresponding subgroup, irrespective of diagnosis, might be manifesting the outcome of differences in shared cognitive risk factors. [ABSTRACT FROM PUBLISHER]

Background: People with schizophrenia have high rates of substance use which contributes to co-morbidity and premature mortality. Some evidence suggests people at-risk for psychosis have high rates of substance use. We aimed to assess substance use in a help-seeking cohort, comparing those at-risk and not at-risk for psychosis, and to establish any relationship with clinical symptoms.Method: Participants were help-seeking youth presenting to mental health services in Sydney and Melbourne. 279 (34.8%) were at-risk for psychosis, and 452 (56.4%) did not meet criteria for a psychotic disorder or risk for psychosis. The excluded individuals were made up of 59 (7.4%) young people who met criteria for a psychotic disorder and 11 (1.4%) who were unable to be evaluated. We assessed the association of substance use involvement with risk status and clinical symptoms using multivariate regression.Results: Individuals at-risk for psychosis had significantly higher tobacco, alcohol and cannabis use than those not at-risk. Multivariate analysis revealed at-risk status was significantly associated with higher alcohol involvement scores when adjusting for age and gender, but no association was found for cannabis or tobacco. At-risk status was no longer associated with alcohol involvement when cannabis or tobacco use was added into the analysis.Conclusion: Tobacco smoking, alcohol consumption and cannabis use are common in help-seeking youth, particularly those at-risk for psychosis. It is important to consider co-occurring use of different substances in adolescents. Early substance misuse in this phase of illness could be targeted to improve physical and mental health in young people. [ABSTRACT FROM AUTHOR]

Schizophrenia is a debilitating disorder that typically begins in adolescence and is characterized by perceptual abnormalities, delusions, cognitive and behavioural disturbances and functional impairments. While current treatments can be effective, they are often insufficient to alleviate the full range of symptoms. Schizophrenia is associated with structural brain abnormalities including grey and white matter volume loss and impaired connectivity. Recent findings suggest these abnormalities follow a neuroprogressive course in the earliest stages of the illness, which may be associated with episodes of acute relapse. Neuroinflammation has been proposed as a potential mechanism underlying these brain changes, with evidence of increased density and activation of microglia, immune cells resident in the brain, at various stages of the illness. We review evidence for microglial dysfunction in schizophrenia from both neuroimaging and neuropathological data, with a specific focus on studies examining microglial activation in relation to the pathology of grey and white matter. The studies available indicate that the link between microglial dysfunction and brain change in schizophrenia remains an intriguing hypothesis worthy of further examination. Future studies in schizophrenia should: (i) use multimodal imaging to clarify this association by mapping brain changes longitudinally across illness stages in relation to microglial activation; (ii) clarify the nature of microglial dysfunction with markers specific to activation states and phenotypes; (iii) examine the role of microglia and neurons with reference to their overlapping roles in neuroinflammatory pathways; and (iv) examine the impact of novel immunomodulatory treatments on brain structure in schizophrenia. [ABSTRACT FROM AUTHOR]

Background Cognitive deficits have been reported during the early stages of bipolar disorder; however, the role of medication on such deficits remains unclear. The aim of this study was to compare the effects of lithium and quetiapine monotherapy on cognitive performance in people following first episode mania. Methods The design was a single-blind, randomised controlled trial on a cohort of 61 participants following first episode mania. Participants received either lithium or quetiapine monotherapy as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive cognitive assessment battery conducted at baseline, month 3 and month 12 follow-up time-points. Results There was a significant interaction between group and time in phonemic fluency at the 3-month and 12-month endpoints, reflecting greater improvements in performance in lithium-treated participants relative to quetiapine-treated participants. After controlling for multiple comparisons, there were no other significant interactions between group and time for other measures of cognition. Conclusion Although the effects of lithium and quetiapine treatment were similar for most cognitive domains, the findings imply that early initiation of lithium treatment may benefit the trajectory of cognition, specifically verbal fluency in young people with bipolar disorder. Given that cognition is a major symptomatic domain of bipolar disorder and has substantive effects on general functioning, the ability to influence the trajectory of cognitive change is of considerable clinical importance. [ABSTRACT FROM AUTHOR]

Background.Dysregulation of the striatum and altered corticostriatal connectivity have been associated with psychotic disorders. Social anhedonia has been identified as a predictor for the development of schizophrenia spectrum disorders. The aim of the present study was to examine corticostriatal functional connectivity in individuals with high social anhedonia.Method.Twenty-one participants with high social anhedonia score and 30 with low social anhedonia score measured by the Chinese version of the Revised Social Anhedonia Scale were recruited from university undergraduates (age 17–21 years) to undergo resting-state functional MRI scans. Six subdivisions of the striatum in each hemisphere were defined as seeds. Voxel-wise functional connectivity analyses were conducted between each seed and the whole brain voxels, followed by repeated-measures ANOVA for the group effect.Results.Participants with high social anhedonia showed hyper-connectivity between the ventral striatum and the anterior cingulate cortex and the insula, and between the dorsal striatum and the motor cortex. Hypo-connectivity in participants with high social anhedonia was also observed between the ventral striatum and the posterior cingulate cortex. Partial correlation analyses further showed that the functional connectivity between the ventral striatum and the prefrontal cortex was associated with pleasure experience and emotional suppression.Conclusions.Our findings suggest that altered corticostriatal connectivity can be found in participants with high levels of social anhedonia. Since social anhedonia has been considered a predictor for schizophrenia spectrum disorders, our results may provide novel evidence on the early changes in brain functional connectivity in at-risk individuals. [ABSTRACT FROM PUBLISHER]

Aim An estimated 75% of mental disorders begin before the age of 24 and approximately 25% of 13-24-year-olds are affected by mental disorders at any one time. To better understand and ideally prevent the onset of post-pubertal mental disorders, a clinical staging model has been proposed that provides a longitudinal perspective of illness development. This heuristic model takes account of the differential effects of both genetic and environmental risk factors, as well as markers relevant to the stage of illness, course or prognosis. The aim of the Transitions Study is to test empirically the assumptions that underpin the clinical staging model. Additionally, it will permit investigation of a range of psychological, social and genetic markers in terms of their capacity to define current clinical stage or predict transition from less severe or enduring to more severe and persistent stages of mental disorder. Method This paper describes the study methodology, which involves a longitudinal cohort design implemented within four headspace youth mental health services in Australia. Participants are young people aged 12-25 years who have sought help at headspace and consented to complete a comprehensive assessment of clinical state and psychosocial risk factors. A total of 802 young people (66% female) completed baseline assessments. Annual follow-up assessments have commenced. Conclusions The results of this study may have implications for the way mental disorders are diagnosed and treated, and progress our understanding of the pathophysiologies of complex mental disorders by identifying genetic or psychosocial markers of illness stage or progression. [ABSTRACT FROM AUTHOR]

Background We have previously reported that olfactory identification (OI) deficits are a promising premorbid marker of transition from ultra-high risk (UHR) to schizophrenia, but not to psychotic illness more generally. Whether this remains the case at longer follow-up, and whether there is decline in OI ability are unclear. Method The University of Pennsylvania Smell Identification Test (UPSIT) was administered to 81 participants at baseline (identification of risk for psychosis) and 254 individuals at follow-up. Forty-nine participants underwent UPSIT assessment at both time points. UPSIT scores were investigated at an average of 7.08 years after identification of risk in relation to transition to psychosis, a diagnosis of schizophrenia, and psychosocial/functional outcome. Results UPSIT scores at baseline and follow-up did not differ between participants who transitioned to psychosis and those who did not. Similarly, there were no significant differences on UPSIT scores at baseline or follow-up between individuals with a diagnosis of schizophrenia and transitioned individuals without schizophrenia. Those with a poor functional outcome showed significantly lower baseline UPSIT scores than participants with good outcome. There was no significant association between functional outcome and follow-up UPSIT scores. There were no significant changes in UPSIT over time for any group. Conclusions These results suggest that impaired OI is not a good marker of the onset of psychosis and schizophrenia, but may differentiate UHR individuals who experience a poor functional outcome, regardless of transition status. [ABSTRACT FROM AUTHOR]

BackgroundWhether there are differential effects of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) on the brain is currently debated. Although some studies report that FGAs reduce grey matter more than SGAs, others do not, and research to date is limited by a focus on schizophrenia spectrum disorders. To address this limitation, this study investigated the effects of medication in patients being treated for first-episode schizophrenia or affective psychoses.MethodCortical thickness was compared between 52 first-episode psychosis patients separated into diagnostic (i.e. schizophrenia or affective psychosis) and medication (i.e. FGA and SGA) subgroups. Patients in each group were also compared to age- and sex-matched healthy controls (n = 28). A whole-brain cortical thickness interaction analysis of medication and diagnosis was then performed. Correlations between cortical thickness with antipsychotic dose and psychotic symptoms were examined.ResultsThe effects of medication and diagnosis did not interact, suggesting independent effects. Compared with controls, diagnostic differences were found in frontal, parietal and temporal regions. Decreased thickness in FGA-treated versus SGA-treated groups was found in a large frontoparietal region (p < 0.001, corrected). Comparisons with healthy controls revealed decreased cortical thickness in the FGA group whereas the SGA group showed increases in addition to decreases. In FGA-treated patients cortical thinning was associated with higher negative symptoms whereas increased cortical thickness in the SGA-treated group was associated with lower positive symptoms.ConclusionsOur results suggest that FGA and SGA treatments have divergent effects on cortical thickness during the first episode of psychosis that are independent from changes due to illness. [ABSTRACT FROM PUBLISHER]

Objective It is likely that cognitive deficits are vulnerability markers for developing schizophrenia, as these deficits are already well-established findings in first-episode psychosis. Studies at-risk adolescents and young adults are likely to provide information about cognitive deficits that predate the onset of the illness. Method We conducted meta-analyses of studies comparing familial-high risk ( FHR) or ultra-high risk ( UHR; n = 2113) and healthy controls ( n = 1748) in youth studies in which the mean age was between 15 and 29. Results Compared with controls, high risk subjects were impaired in each domain in both UHR ( d = 0.34-0.71) and FHR ( d = 0.24-0.81). Heterogeneity of effect sizes across studies was modest, increasing confidence to the findings of the current meta-analysis ( I2 = 0-0.18%). In both risk paradigms, co-occurrence of genetic risk with attenuated symptoms was associated with more severe cognitive dysfunction. In UHR, later transition to psychosis was associated with more severe cognitive deficits in all domains ( d = 0.31-0.49) except sustained attention. However, cognitive impairment has a limited capacity to predict the outcome of high-risk patients. Conclusion Cognitive deficits are already evident in adolescents and young adults who have familial or clinical risk for psychosis. Longitudinal developmental studies are important to reveal timing and trajectory of emergence of such deficits. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) depends on a clinical interview with no biomarkers to aid diagnosis. The current investigation interrogated single-nucleotide polymorphisms (SNPs) of individuals with ASD from the Autism Genetic Resource Exchange (AGRE) database. SNPs were mapped to Kyoto Encyclopedia of Genes and Genomes (KEGG)-derived pathways to identify affected cellular processes and develop a diagnostic test. This test was then applied to two independent samples from the Simons Foundation Autism Research Initiative (SFARI) and Wellcome Trust 1958 normal birth cohort (WTBC) for validation. Using AGRE SNP data from a Central European (CEU) cohort, we created a genetic diagnostic classifier consisting of 237 SNPs in 146 genes that correctly predicted ASD diagnosis in 85.6% of CEU cases. This classifier also predicted 84.3% of cases in an ethnically related Tuscan cohort; however, prediction was less accurate (56.4%) in a genetically dissimilar Han Chinese cohort (HAN). Eight SNPs in three genes (KCNMB4, GNAO1, GRM5) had the largest effect in the classifier with some acting as vulnerability SNPs, whereas others were protective. Prediction accuracy diminished as the number of SNPs analyzed in the model was decreased. Our diagnostic classifier correctly predicted ASD diagnosis with an accuracy of 71.7% in CEU individuals from the SFARI (ASD) and WTBC (controls) validation data sets. In conclusion, we have developed an accurate diagnostic test for a genetically homogeneous group to aid in early detection of ASD. While SNPs differ across ethnic groups, our pathway approach identified cellular processes common to ASD across ethnicities. Our results have wide implications for detection, intervention and prevention of ASD. [ABSTRACT FROM AUTHOR]

BackgroundGrey matter volume and cortical thickness represent two complementary aspects of brain structure. Several studies have described reductions in grey matter volume in people at ultra-high risk (UHR) of psychosis; however, little is known about cortical thickness in this group. The aim of the present study was to investigate cortical thickness alterations in UHR subjects and compare individuals who subsequently did and did not develop psychosis.MethodWe examined magnetic resonance imaging data collected at four different scanning sites. The UHR subjects were followed up for at least 2 years. Subsequent to scanning, 50 UHR subjects developed psychosis and 117 did not. Cortical thickness was examined in regions previously identified as sites of neuroanatomical alterations in UHR subjects, using voxel-based cortical thickness.ResultsAt baseline UHR subjects, compared with controls, showed reduced cortical thickness in the right parahippocampal gyrus (p < 0.05, familywise error corrected). There were no significant differences in cortical thickness between the UHR subjects who later developed psychosis and those who did not.ConclusionsThese data suggest that UHR symptomatology is characterized by alterations in the thickness of the medial temporal cortex. We did not find evidence that the later progression to psychosis was linked to additional alterations in cortical thickness, although we cannot exclude the possibility that the study lacked sufficient power to detect such differences. [ABSTRACT FROM AUTHOR]

BackgroundIndividuals at ultra-high risk (UHR) for psychosis show reduced neurocognitive performance across domains but it is unclear which reductions are associated with transition to frank psychosis. The aim of this study was to investigate differences in baseline neurocognitive performance between UHR participants with (UHR-P) and without transition to psychosis (UHR-NP) and a healthy control (HC) group and examine neurocognitive predictors of transition over the medium to long term.MethodA sample of 325 UHR participants recruited consecutively from the Personal Assessment and Crisis Evaluation (PACE) Clinic in Melbourne and 66 HCs completed a neurocognitive assessment at baseline. The UHR group was followed up between 2.39 and 14.86 (median = 6.45) years later. Cox regression was used to investigate candidate neurocognitive predictors of psychosis onset.ResultsThe UHR group performed more poorly than the HC group across a range of neurocognitive domains but only performance on digit symbol coding and picture completion differed between the groups. The risk of transition was only significantly associated with poorer performance on visual reproduction [hazard ratio (HR) 0.919, 95% confidence interval (CI) 0.876–0.965, p = 0.001] and matrix reasoning (HR 0.938, 95% CI 0.883–0.996, p = 0.037). These remained significant even after controlling for psychopathology at baseline.ConclusionsThis study is the longest follow-up of an UHR sample to date. UHR status was associated with poorer neurocognitive performance compared to HCs on some tasks. Cognition at identification as UHR was not a strong predictor of risk for transition to psychosis. The results suggests the need to include more experimental paradigms that isolate discrete cognitive processes to better understand neurocognition at this early stage of illness. [ABSTRACT FROM PUBLISHER]

BackgroundThere is evidence to suggest that cognitive deficits might persist beyond the acute stages of illness in major depressive disorder (MDD). However, the findings are somewhat inconsistent across the individual studies conducted to date. Our aim was to conduct a systematic review and meta-analysis of existing studies that have examined cognition in euthymic MDD patients.MethodFollowing a systematic search across several publication databases, meta-analyses were conducted for 27 empirical studies that compared euthymic adult MDD patients (895 participants) and healthy controls (997 participants) across a range of cognitive domains. The influence of demographic variables and confounding factors, including age of onset and recurrent episodes, was examined.ResultsCompared with healthy controls, euthymic MDD patients were characterized by significantly poorer cognitive functions. However, the magnitude of observed deficits, with the exception of inhibitory control, were generally modest when late-onset cases were excuded. Late-onset cases demonstrated significantly more pronounced deficits in verbal memory, speed of information processing and some executive functions.ConclusionsCognitive deficits, especially poor response inhibition, are likely to be persistent features, at least of some forms, of adult-onset MDD. More studies are necessary to examine cognitive dysfunction in remitted psychotic, melancholic and bipolar spectrum MDD. Cognitive deficits overall appear to be more common among patients with late-onset depression, supporting the theories suggesting that possible vascular and neurodegenerative factors play a role in a substantial number of these patients. [ABSTRACT FROM PUBLISHER]

Inelastic scattering experiments are key methods for mapping the full dispersion of fundamental excitations of solids in the ground as well as nonequilibrium states. A quantitative analysis of inelastic scattering in terms of phonon excitations requires identifying the role of multiphonon processes. Here, we develop an efficient first-principles methodology for calculating the all-phonon quantum mechanical structure factor of solids. We demonstrate our method by obtaining excellent agreement between measurements and calculations of the diffuse scattering patterns of black phosphorus, showing that multiphonon processes play a substantial role. The present approach constitutes a step towards the interpretation of static and time-resolved electron, x-ray, and neutron inelastic scattering data. [ABSTRACT FROM AUTHOR]

Memory-guided decision making is dynamic and context-dependent, even though many studies describe an enhancement of the P3 for recognized items in memory tasks ('old-new effect'). This study utilized a delay-dependent working memory task during which decision making could be optimized by focusing attention on detected changes instead of recognized similarities. Mean P3 amplitude and delta activity were analyzed from participants who classified probe stimuli as identical or modified. The P3 amplitudes were larger for modified than for identical probes, even when the probe occurred 4,000 ms after the primary stimulus. Enhanced single-trial amplitude, trial-by-trial consistency, and frontoparietal phase coherence of delta activity contributed to the larger P3 for the modified probe. Thus, context-dependent attentional resource allocation supporting memory-guided decisions might explain the enhancement of the P3 for specific probe types. [ABSTRACT FROM AUTHOR]

BackgroundAbnormalities in cortico-striatal-pallidal-thalamic (CSPT) circuits have been implicated in major depressive disorder (MDD). However, the robustness of these findings across studies is unclear, as is the extent to which they are influenced by demographic, clinical and pharmacological factors.MethodWith the aim of clarifying these questions, we conducted a meta-analysis to map the volumetric abnormalities that were most robustly identified in CSPT circuits of individuals with MDD. A systematic search identified 41 studies meeting our inclusion criteria.ResultsThere were significant volume reductions in prefrontal (especially orbitofrontal) and anterior cingulate cortices, and also in subcortical structures such as the caudate nucleus and putamen, with effect sizes ranging from small to moderate. The subgenual anterior cingulate and orbitofrontal cortices were significantly smaller in antidepressant-free samples compared to medicated patients. Late-life depression (LLD) tended to be associated with smaller volumes in circumscribed frontal and subcortical structures, with the most robust differences being found in thalamic volume.ConclusionsIndividuals with major depression demonstrate volumetric abnormalities of CSPT circuits. However, these observations may be restricted to certain subgroups, highlighting the clinical heterogeneity of the disorder. On the basis of this meta-analysis, CSPT abnormalities were more prominent in those with LLD whereas antidepressant use seemed to normalize certain cortical volumetric abnormalities. [ABSTRACT FROM PUBLISHER]